Fatal overdose after ingestion of a transdermal fentanyl patch in two non-human primates.

PubMed

Deschamps, Jack-Yves; Gaulier, Jean-Michel; Podevin, Guillaume; Cherel, Yan; Ferry, Nicolas; Roux, Françoise A

2012-11-01

CASE HISTORY AND PRESENTATION: Two non-human primates (Macaca fascicularis), weight 3.5 kg, enrolled in an experimental protocol received a 25 μg hour(-1) transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. MANAGEMENT AND FOLLOW-UP: Attempted reversal with naloxone was ineffective. After several hours of ventilation, both primates eventually died, 7 and 15 hours after ketamine injection, respectively. In both cases, the patch was discovered in the animal's cheek pouch. Subsequent fentanyl serum concentration measurements (8.29 and 14.80 μg L(-1) ) confirmed fentanyl overdose. This report of two fatal intoxications in non-human primates secondary to ingestion of a transdermal fentanyl patch demonstrates that this method of analgesia is inappropriate for non-human primates, because of their tendency to chew almost anything they can reach. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

A case of overdose via tattoo.

PubMed

Borg, Roberta; Ashton, Antony

2015-08-01

Transdermal fentanyl patches are used frequently for the management of both acute and chronic pain. Adverse events with their use, in particular overdose, are not uncommon. We describe a case of fentanyl overdose from transdermal patch placed over a five-day old tattoo. The report will review the pharmacology of transdermal fentanyl and the physiology of tattooing, as well as the potential link between the two, which may have lead to the overdose.

Duragesic transdermal patch: postmortem tissue distribution of fentanyl in 25 cases.

PubMed

Anderson, D T; Muto, J J

2000-10-01

Fentanyl is a potent, short-acting narcotic analgesic widely used as a surgical anesthetic and for the control of pain when administered in the form of a transdermal patch. The success of the patch can be attributed to fentanyl's low molecular weight and its highly lipophilic nature, which enables it to be readily absorbed through the skin and subsequently distributed throughout the body. Over the past three years, the Los Angeles County Coroner's Toxicology Laboratory has encountered 25 cases involving Duragesic patches (fentanyl), and their postmortem tissue distributions are presented here. The analysis of fentanyl from postmortem specimens (3-mL or g sample size) consisted of an n-butyl chloride basic extraction followed by identification and quantitation on a gas chromatograph-mass spectrometer using the selected ion monitoring (SIM) mode. The fentanyl ions monitored were m/z 245, 146, and 189 and the internal standard, fentanyl-d5 ions, were m/z 250, 151, and 194 (quantitation ion underlined). The linear range of the assay was 1.67 microg/L to 500 microg/L with the limit of quantitation and detection of 1.67 microg/L. The postmortem tissue distribution ranges of fentanyl in the 25 fatalities were as follows: heart blood, 1.8-139 microg/L (23 cases); femoral blood, 3.1-43 microg/L (13 cases); vitreous, +<2.0-20 microg/L (4 cases); liver, 5.8-613 microg/kg (22 cases); bile, 3.5-262 microg/L (15 cases); urine, 2.9-895 microg/L (19 cases); gastric, 0-1200 microg total (17 cases); spleen, 7.8-79 microg/kg (3 cases); kidney, 11 microg/kg (1 case); and lung, 31 microg/kg (1 case). The age of the decedents in this study ranged from 19 to 84, with an average age of 46. The modes of death included 15 accidental, 5 natural, 3 suicidal, and 2 undetermined. The main objectives of this paper are to show the prevalence of fentanyl patches in our community and to aid the forensic toxicologist with the interpretation of postmortem fentanyl levels in casework.

PDPH in obstetric anesthesia: comparison of 24-gauge Sprotte and 25-gauge Quincke needles and effect of subarachnoid administration of fentanyl.

PubMed

Devcic, A; Sprung, J; Patel, S; Kettler, R; Maitra-D'Cruze, A

1993-01-01

Postdural puncture headache (PDPH) is a frequent complication of spinal anesthesia. Some investigators have recommended the use of the Sprotte needle to reduce the incidence of this serious complication. This study prospectively compared the incidence of PDPH with two spinal needles of different size and design: the 24-gauge Sprotte (noncutting point) versus the 25-gauge Quincke (diamond, cutting point). The hypothesis that subarachnoid fentanyl will reduce the incidence of PDPH, as suggested in the literature, was also studied. Only patients for emergency or elective cesarean delivery were studied. One hundred ninety four patients were randomly assigned to receive spinal anesthesia with one of the two needles (Sprotte, n = 96; Quincke, n = 98). Simultaneously, each patient was assigned to receive hyperbaric 0.75% bupivacaine local anesthetic or a combination of the same concentration of local anesthetic with 20 micrograms of fentanyl (Sprotte with fentanyl, n = 47; Sprotte without fentanyl, n = 49; Quincke with fentanyl, n = 49; Quincke without fentanyl, n = 49). All patients were evaluated during the first 4 postoperative days, and follow-up telephone interviews were conducted 3 weeks after discharge. Four patients (4.2%) in the Sprotte group and seven (7.1%) in the Quincke group developed PDPH. Three out of four patients with headache in the Sprotte and four out of seven in the Quincke group received fentanyl as an adjunct for spinal anesthesia. Two patients in the Sprotte group required an epidural blood patch as a therapy for PDPH. Two patients in the Quincke group had severe headache and required an epidural blood patch. In the current study, the use of the 24-gauge Sprotte spinal needle resulted in a low incidence of severe PDPH, but was not significantly different when compared with the use of a 25-gauge Quincke needle (oriented parallel to the longitudinal dural fibers). The addition of fentanyl to hyperbaric bupivacaine spinal anesthesia did not reduce the risk of PDPH.

Fatal fentanyl patch misuse in a hospitalized patient with a postmortem increase in fentanyl blood concentration.

PubMed

Moore, Philip W; Palmer, Robert B; Donovan, Joseph Ward

2015-01-01

Opioid-related mortality happens, even in healthcare settings. We describe serial postmortem fentanyl blood concentrations in a hospital inpatient who fatally abused transdermal fentanyl. This is a single-patient case report. A 42-year-old man with lymphoma was started on transdermal fentanyl therapy while hospitalized for chronic abdominal pain. The patient was last seen awake 1.3 h prior to being found apneic and cyanotic. During the resuscitation attempt, a small square-shaped film was removed from the patient's oropharynx. Femoral blood was collected 0.5 and 2 h postmortem, and the measured fentanyl concentration increased from 1.6 to 14 ng/mL. Study limitations include potential laboratory or collection errors and missing data. (i) Providers must be vigilant for signs of fentanyl patch abuse. (ii) Postmortem blood concentrations are not static postmortem, likely secondary to decreasing pH, increased aqueous solubility, and tissue redistribution, and are therefore unlikely to accurately represent antemortem blood concentrations. © 2014 American Academy of Forensic Sciences.

Management of an oral ingestion of transdermal fentanyl patches: a case report and literature review.

PubMed

Faust, Andrew C; Terpolilli, Ralph; Hughes, Darrel W

2011-01-01

Purpose. Fentanyl is available as a transdermal system for the treatment of chronic pain in opioid-tolerant patients; however, it carries a black box warning due to both the potency of the product and the potential for abuse. In this report, we describe a case of transbuccal and gastrointestinal ingestion of fentanyl patches and the management of such ingestion. Summary. A 32-year-old man was brought to the emergency department (ED) via emergency medical services for toxic ingestion and suicide attempt. The patient chewed and ingested two illegally purchased transdermal fentanyl patches. In the ED, the patient was obtunded, dizzy and drowsy. Initial vital signs showed the patient to be afebrile and normotensive with a heart rate of 63, respiratory rate of 16, and oxygen saturation of 100% on 2 liters nasal cannula after administration of 2 milligrams of intravenous naloxone. The patient was treated with whole bowel irrigation and continuous intravenous naloxone infusion for approximately 48 hours without complications. Conclusion. Despite numerous case reports describing oral ingestion of fentanyl patches, information on the management of such intoxication is lacking. We report successful management of such a case utilizing whole bowel irrigation along with intravenous push and continuous infusion naloxone.

Management of an Oral Ingestion of Transdermal Fentanyl Patches: A Case Report and Literature Review

PubMed Central

Faust, Andrew C.; Terpolilli, Ralph; Hughes, Darrel W.

2011-01-01

Purpose. Fentanyl is available as a transdermal system for the treatment of chronic pain in opioid-tolerant patients; however, it carries a black box warning due to both the potency of the product and the potential for abuse. In this report, we describe a case of transbuccal and gastrointestinal ingestion of fentanyl patches and the management of such ingestion. Summary. A 32-year-old man was brought to the emergency department (ED) via emergency medical services for toxic ingestion and suicide attempt. The patient chewed and ingested two illegally purchased transdermal fentanyl patches. In the ED, the patient was obtunded, dizzy and drowsy. Initial vital signs showed the patient to be afebrile and normotensive with a heart rate of 63, respiratory rate of 16, and oxygen saturation of 100% on 2 liters nasal cannula after administration of 2 milligrams of intravenous naloxone. The patient was treated with whole bowel irrigation and continuous intravenous naloxone infusion for approximately 48 hours without complications. Conclusion. Despite numerous case reports describing oral ingestion of fentanyl patches, information on the management of such intoxication is lacking. We report successful management of such a case utilizing whole bowel irrigation along with intravenous push and continuous infusion naloxone. PMID:21629807

Fatal overdose due to prescription fentanyl patches in a patient with sickle cell/beta-thalassemia and acute chest syndrome: A case report and review of the literature.

PubMed

Biedrzycki, Olaf J; Bevan, David; Lucas, Sebastian

2009-06-01

Introduced into clinical practice in the 1960s, the analgesic fentanyl is 100 times more potent than morphine. Various methods of administration exist including the transdermal Duragesic patch system, widely used in chronic pain and palliative care settings. Numerous, often imaginative methods of abuse of fentanyl patches have been reported; the majority of fatal fentanyl overdose cases resulting from deliberate abuse or suicide. We describe the accidental overdose of a young black male with sickle cell/beta-thalassemia who had been using the Duragesic system for almost 2 years.At autopsy the macroscopic findings were of nonspecific opiate overdose with congested heavy lungs. Histopathological examination revealed severe sickling of red blood cells in the lungs (acute chest syndrome). Toxicological examination revealed blood and urine fentanyl levels of 40 microg/L and 400 microg/L (10 fold and 100 fold higher than therapeutic levels). The mast cell tryptase was also significantly elevated at 76 microg/L, (Normal 2-14 microg/L). We discuss the relevance of these findings with regard to the cause of death, and stress the need to consider fentanyl when confronted with nonspecific signs of opiate overdose as it is not detected in routine toxicological drug screens.

Structural, Morphological, and Functional Correlates of Corneal Endothelial Toxicity Following Corneal Exposure to Sulfur Mustard Vapor

DTIC Science & Technology

2013-10-01

fentanyl patch (25 lg/h) was placed anterior to the scapula. On the day of exposure, rabbits were anesthetized with an intramuscular administration of 15 mg...sterile saline to flush residual agent. Rabbits were returned to cages and provided food and water ad libitum. Fentanyl patches were replaced after 72

Transdermal fentanyl in deliberate overdose in pediatrics.

PubMed

Lyttle, Mark D; Verma, Sapna; Isaac, Rhian

2012-05-01

The use of the fentanyl skin patch to provide pain relief in chronic pain conditions and oncology in adult practice has been common for several years, and an increase in use is now being seen in pediatric practice. Its use in drug misuse and suicide has also increased in recent years. We present the case of an adolescent who deliberately overdosed using fentanyl skin patches and describe the implications for management. This report serves to remind clinicians to consider this method of drug administration in children who display signs of opioid toxicity, where overdose may be subsequent to its use in therapy, recreation, or deliberate self-harm.

Reliability of postmortem fentanyl concentrations in determining the cause of death.

PubMed

Gill, James R; Lin, Peter T; Nelson, Lewis

2013-03-01

Transdermal fentanyl, an opioid used for management of marked pain, also is abused and may cause death. We reviewed medical examiner reports of 92 decedents who had one or more fentanyl transdermal patches on their body and had fentanyl detected in their postmortem toxicology analysis. The manners of death included 40 accidents, 36 natural, 8 suicides, 5 therapeutic complications, and 3 undetermined deaths. Among the accidental fentanyl intoxication deaths, 32 of 37 involved substance abuse. The majority (95 %) of the 37 accidental deaths involving fentanyl were multi-drug intoxications. The substance abuse deaths had a mean fentanyl blood concentration (26.4 ng/ml or μg/L) that was over twice that of the natural group (11.8 ng/ml). Our analysis suggests a relationship between total patch dosage and mean postmortem fentanyl concentration up to the 100-μg/h dose. The very wide and overlapping ranges of postmortem fentanyl concentrations effectively nullify the utility of correlating the dose and expected postmortem concentration for any particular death. Based on the variable relationship between dose and blood concentration, the antemortem dose cannot be reliably predicted based on the postmortem concentration. This does not, however, render the medical examiner/coroner unable to determine the cause and manner of death because the toxicology results are only one datum point among several that are considered. Although there was a weakly positive relationship between body mass index and fentanyl concentration, further research is needed to determine whether adipose tissue represents a significant depot for postmortem release of fentanyl.

Population pharmacokinetics of transdermal fentanyl in patients with cancer-related pain.

PubMed

Kokubun, Hideya; Ebinuma, Keiichi; Matoba, Motohiro; Takayanagi, Risa; Yamada, Yasuhiko; Yago, Kazuo

2012-06-01

Determining the appropriate dose of transdermal fentanyl (TDF) for the alleviation of cancer pain requires determining the factors causing variations in serum fentanyl concentration after TDF treatment. The objective of this study was to identify these factors and incorporate them into a formula that can be used to predict serum fentanyl concentration after application of a TDF patch. Blood samples of cancer patients treated with a TDF patch for the alleviation of pain were collected at 24, 48, and 72 hours after application to evaluate population pharmacokinetics using the nonlinear mixed-effect model (NONMEM). Based upon this evaluation, Child-Pugh Score and use of a cytochrome P450 3A4 (CYP3A4) inducer were identified as the most significant factors in variations in serum fentanyl concentration and incorporated into the following Final Model formula: CL(fenta) (L/h) = 3.53 × (15 - Child-Pugh Score) × (1 + 1.38 × use or no use of CYP3A4 inducer). Bootstrap evaluation of the Final Model revealed a high convergence rate, suggesting that the model formula is a reliable and useful tool for determining TDF dose for the alleviation of cancer pain.

75 FR 49992 - Peter W.S. Grigg, M.D.; Revocation of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-16

... denial of any pending application to renew or modify the registration on the ground that his ``continued... also unlawfully distributed four fentanyl 400 mg. tablets and one fentanyl transdermal patch 12 mcg./hr... legitimate medical purposes.'' Id. Respondent also admitted that on this date, he distributed to the officer...

Assisted suicide by fentanyl intoxication due to excessive transdermal application.

PubMed

Juebner, Martin; Fietzke, Mathias; Beike, Justus; Rothschild, Markus A; Bender, Katja

2014-11-01

Herein, we report a case of an assisted suicide committed by application of 34 matrix-based fentanyl-containing transdermal therapeutic systems (TTS) with different release rates. The TTS were supplied by the husband but administered by the deceased herself. Besides routine systematic toxicological analysis (STA), the concentrations of fentanyl and norfentanyl were determined in the blood (femoral and heart), urine, stomach content, brain, lung tissue, musculus iliopsoas, liver, kidney, bile and in some of the used TTS by LC-MS/MS. Blood levels of fentanyl were 60.6 μg/L in femoral blood and 94.1 μg/L in heart blood. These concentrations are in good concordance with levels described in cases with accidental or lethal suicidal fentanyl patch application. The organ distribution indicates an influence of post-mortem redistribution. The levels of residual fentanyl in the TTS were also determined. STA furthermore revealed supratherapeutic levels of bromazepam. Thus, the cause of death was a combination of fentanyl and bromazepam intoxication. However, considering the determined levels of fentanyl and norfentanyl in the entire set of specimens and the high toxicity in comparison to bromazepam, fentanyl was the leading toxic noxa.

Consumption of three strong opioids (morphine, oxycodone and fentanyl) in seven European countries during seven years (2003-2009).

PubMed

Hudec, R; Tisonova, J; Foltan, V; Kristova, V

2013-01-01

The aim was to analyse the consumption of selected strong opioid analgesics during a seven-year period of 2003-2009 in order to compare Slovak consumption with that in six other European countries and to determine our position. Drug consumption data from the State Institute for Drug Control in Slovak Republic were used. As to the data from other countries, annual health statistics published on websites were used in comparison. Obviously the consumption of one of studied opioid drugs with transdermal aplication route, particularly fentanyl, tended to increase in all countries during the observed period. Oxycodone tends to yield a rapid increase in consumption as well. As opposed to the latter drugs, the consumption of morphine was decreasing throughout the observed period. The consumption of these drugs in Slovakia remains low (except for that of fentanyl). Our analysis confirmed a clear shift from oral to transdermal therapy as well as usage of newer drugs. Drug consumption data are a relatively new source of information for health research. Our analysis showed increasing trends in fentanyl (patch opioid) consumption in all compared countries as well as an increasing consumption of oxycodone and decreasing consumption of morphine (Fig. 3, Ref. 17).

Case report of severe bradycardia due to transdermal fentanyl.

PubMed

Hawley, Pippa

2013-09-01

This case report describes a patient who developed severe bradycardia due to transdermal fentanyl. There have been no prior case reports of this occurring in palliative care, but the frequency of association of fentanyl with bradycardia in the anesthesia setting suggests it may be more common than realized. Palliative care settings often have a policy of not routinely checking vital signs, and symptoms of bradycardia could be misinterpreted as the dying process. A patient with recurrent ovarian cancer was admitted with nausea and abdominal pain due to bowel obstruction and fever from a urinary tract infection. A switch from injectable hydromorphone to transdermal fentanyl resulted in symptomatic severe bradycardia within 36 h, without any other signs of opioid toxicity and with good analgesic effect. The fentanyl patch was removed. Atropine was not required. The patient made an uneventful recovery. Transdermal buprenorphine was subsequently used satisfactorily for long-term background pain control, with additional hydromorphone when needed. The delayed absorption of fentanyl via the transdermal route makes early identification of fentanyl-induced bradycardia key to prompt reversal. Patients with resting or relative bradycardia may be at higher than average risk.

A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

PubMed Central

Zandvliet, Maarten L.; Koolen, Stijn L. W.; Mathijssen, Ron H. J.; van der Rijt, Carin C. D.

2016-01-01

Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer‐related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter‐ and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. In elderly patients, current data suggest that we should carefully dose fentanyl due to alterations in absorption and metabolism. The influence of BMI and gender on fentanyl pharmacokinetics is questionable, most probably due to a large heterogeneity in the published studies. Pharmacogenetics, e.g. the CYP3A5*3 gene polymorphism, may influence fentanyl pharmacokinetics as well, although further study is warranted. Several other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetics. Unfortunately, most of the published papers that studied factors influencing fentanyl pharmacokinetics describe healthy volunteers instead of cancer patients. Results from the studies in volunteers may not be simply extrapolated to cancer patients because of multiple confounding factors. To handle fentanyl treatment in a population of cancer patients, it is essential that physicians recognize factors that influence fentanyl pharmacokinetics, thereby preventing potential side‐effects and increasing its efficacy. PMID:27619152

New Initiation of Long-Acting Opioids in Long-Stay Nursing Home Residents

PubMed Central

Pimentel, Camilla B.; Gurwitz, Jerry H.; Tjia, Jennifer; Hume, Anne L.; Lapane, Kate L.

2016-01-01

BACKGROUND Despite known risks of overdose and respiratory depression when treating opioid-naïve individuals with long-acting opioids, use of these potent agents may be common in nursing homes. OBJECTIVES To estimate prevalence of new initiation of long-acting opioids since national efforts to increase prescriber and public awareness on safe use of transdermal fentanyl patches. DESIGN Cross-sectional. SETTING US nursing homes. PARTICIPANTS 22,253 Medicare-enrolled long-stay nursing home residents. MEASUREMENTS The Minimum Data Set 3.0 linked with Medicare enrollment, hospital claims, and prescription drug transaction data (January–December 2011) were used to determine the prevalence of new initiation among nursing home residents who were prescribed a long-acting opioid in the nursing home. RESULTS Of nursing home residents who were prescribed a long-acting opioid within 30 days of a nursing home admission (n = 12,278), 9.4% (95% confidence interval [CI]: 8.9–9.9%) lacked a prescription drug claim for a short-acting opioid in the previous 60 days. The most common initial prescriptions of long-acting opioids were fentanyl patch (51.9% of opioid-naïve nursing home residents), morphine sulfate (28.1%), and oxycodone (17.2%). CONCLUSION New initiation of long-acting opioids—especially fentanyl patches that have been the subject of safety communications—persists in nursing homes. PMID:27487158

Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study.

PubMed

Barratt, Daniel T; Bandak, Benedikte; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Christrup, Lona L; Tuke, Jonathan; Somogyi, Andrew A

2014-04-01

This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl. CYP3A4*22 and CYP3A5*3 polymorphisms were analysed in 620 cancer pain patients receiving transdermal fentanyl (12.5-700 μg/h) from the European Pharmacogenetic Opioid Study. Using stepwise linear regression, CYP3A4/5 genetic variability was examined in combination with patient factors relating to organ drug elimination function and ABCB1 genetics for their association with serum fentanyl and norfentanyl concentrations and metabolic ratio (MR) (norfentanyl : fentanyl). Delivery rate-adjusted serum fentanyl concentrations (0.0012-1.1 nmol/l/μg.h) and MRs (0.08-499) varied widely. Only 43% of variability in serum fentanyl concentrations was accounted for by delivery rate and less than 50% by CYP3A4/5 genotypes and clinical variables (delivery rate, sex, comedications, kidney disease, BMI, serum albumin). CYP3A4*22 and CYP3A5*3 variants, CYP3A inhibitors and variables relating to liver and kidney function (serum albumin, glomerular filtration rate, kidney disease, BMI) were associated with MR, but accounted for only 14% of variability. Serum fentanyl concentrations and MR vary considerably between cancer pain patients on transdermal fentanyl patches. CYP3A4*22 and CYP3A5*3 genotypes, and multiple clinical factors, combine to influence transdermal fentanyl pharmacokinetics, but accounted for only a small proportion of variability in this study. Identification of the remaining factors determining serum fentanyl concentrations, and their relationship to efficacy and adverse effects may aid in improving the safety and effectiveness of transdermal fentanyl.

Medicines for back pain

MedlinePlus

... direct care, they can be effective in reducing pain. Examples of narcotics include: Codeine Fentanyl -- available as a patch Hydrocodone Hydromorphone Morphine Oxycodone Tramadol Possible side effects of these drugs include: Drowsiness ...

Transdermal fentanyl: pharmacology and toxicology.

PubMed

Nelson, Lewis; Schwaner, Robert

2009-12-01

To evaluate the underlying pharmacology, safety, and misuse/abuse of transdermal fentanyl, one of the cornerstone pharmacotherapies for patients with chronic pain. Literature was identified through searches of Medline (PubMed) and several textbooks in the areas of pharmacology, toxicology, and pain management. A bibliographical review of articles identified by these searches was also performed. Search terms included combinations of the following: fentanyl, transdermal, patch, pharmacology, kinetics, toxicity, and poisoning. All pertinent clinical trials, retrospective studies, and case reports relevant to fentanyl pharmacology and transdermal fentanyl administered by any route and published in English were identified. Each was reviewed for data regarding the clinical pharmacology, abuse, misuse, and safety of transdermal fentanyl. Data from these studies and information from review articles and pharmaceutical prescribing information were included in this review. Fentanyl is a high-potency opioid that has many uses in the treatment of both acute and chronic pain. Intentional or unintentional misuse, as well as abuse, may lead to significant clinical consequences, including death. Both the US Food and Drug Administration (FDA) and Health Canada have warned of potential pitfalls associated with transdermal fentanyl, although these have not been completely effective in preventing life-threatening adverse events and fatalities related to its inappropriate use. Clinically consequential adverse effects may occur unexpectedly with normal use of transdermal fentanyl, or if misused or abused. Misuse and therapeutic error may be largely preventable through better education at all levels for both the prescriber and patient. The prevention of intentional misuse or abuse may require regulatory intervention.

The use of rotation to fentanyl in cancer-related pain

PubMed Central

Dima, Delia; Tomuleasa, Ciprian; Frinc, Ioana; Pasca, Sergiu; Magdo, Lorand; Berindan-Neagoe, Ioana; Muresan, Mihai; Lisencu, Cosmin; Irimie, Alexandru; Zdrenghea, Mihnea

2017-01-01

Pain is commonly diagnosed with respect to cancer and heart diseases, being a major symptom in most neoplastic diseases. Uncontrolled pain leads to a decrease in the quality of life and an increase in the morbidity of the patient. Opioids represent the best analgetic supportive therapy and are frequently used in patients suffering from cancer and experiencing a high level of pain. Opioid treatment starts with a gradual titration of the dose until the minimum effective dose and the maximum tolerated dose are determined. Opioid rotation refers to the switch from one opioid to another in order to get a better response to analgetic therapy and reduce side effects. Fentanyl therapy is recommended to be continued during chemotherapy, radiotherapy, or in the case of surgical intervention. Rotation to fentanyl patches is an efficient and elegant solution for cancer patients, with reduced side effects. Opioid rotation, especially to fentanyl, was shown to increase the quality of life in patients with malignant disease. Finally, rotation to fentanyl is also advantageous from an economic point of view. PMID:28223843

Preparation and in vitro evaluation of a new fentanyl patch based on acrylic/silicone pressure-sensitive adhesive blends.

PubMed

Taghizadeh, Seyed Mojtaba; Soroushnia, Arezou; Mirzadeh, Hamid; Barikani, Mehdi

2009-04-01

In this study, the influence of the ratio of silicone (Si) to acrylic pressure-sensitive adhesive (PSA), polyvinyl pyrrolidone (PVP), and lauryl alcohol (LA) % (wt/wt) on the properties of a drug in adhesive patch containing 4% (wt/wt) fentanyl as model drug was evaluated. The dependent variables selected were drug solubility, in vitro drug release in the platforms as well as adhesion properties including peel strength and tack value. By using the central composite design of Design Expert software, it was found that the effect of each factor was different, yet all had influenced dependent variables significantly (p < .05). Quadratic model generated for various response variables using backward regression analysis was found to be statistically significant (p < .05). It was deduced that the presence of PVP and Si displayed similar trends on drug solubility and release. Each role played by Si with LA and PVP in release rate was separately investigated, and it was found that the presence of PVP and LA in lowering the amount of drug released was more dominant compared with that of Si. The release patterns at the early and later stages follow the Higuchi and semiempirical models, respectively. Effect of PVP as well as Si and LA were similar on tack value. The influence of LA compared to peeling characteristics of Si system was more pronounced.

Could chest wall rigidity be a factor in rapid death from illicit fentanyl abuse?

PubMed

Burns, Glenn; DeRienz, Rebecca T; Baker, Daniel D; Casavant, Marcel; Spiller, Henry A

2016-06-01

There has been a significant spike in fentanyl-related deaths from illicit fentanyl supplied via the heroin trade. Past fentanyl access was primarily oral or dermal via prescription fentanyl patch diversion. One factor potentially driving this increase in fatalities is the change in route of administration. Rapid intravenous (IV) fentanyl can produce chest wall rigidity. We evaluated post-mortem fentanyl and norfentanyl concentrations in a recent surge of lethal fentanyl intoxications. Fentanyl related deaths from the Franklin County coroner's office from January to September 2015 were identified. Presumptive positive fentanyl results were confirmed by quantitative analysis using liquid chromatography tandem mass spectrometry (LC/MS/MS) and were able to quantify fentanyl, norfentanyl, alfentanyl, and sufentanyl. 48 fentanyl deaths were identified. Mean fentanyl concentrations were 12.5 ng/ml, (range 0.5 ng/ml to >40 ng/ml). Mean norfentanyl concentrations were 1.9 ng/ml (range none detected to 8.3 ng/ml). No appreciable concentrations of norfentanyl could be detected in 20 of 48 cases (42%) and were less than 1 ng/ml in 25 cases (52%). Elevated fentanyl concentrations did not correlate with rises in norfentanyl levels. In several cases fentanyl concentrations were strikingly high (22 ng/ml and 20 ng/ml) with no norfentanyl detected. The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity. An alternate explanation could be a dose-related rapid onset of respiratory arrest. Deaths occurred with low levels of fentanyl in the therapeutic range (1-2 ng/ml) in apparent non-naïve opiate abusers. Acute chest wall rigidity is a well-recognized complication in the medical community but unknown within the drug abuse community. The average abuser of illicit opioids may be unaware of the increasing fentanyl content of their illicit opioid purchase. In summary we believe sudden onset chest wall rigidity may be a significant and previously unreported factor leading to an increased mortality, from illicit IV fentanyl use. Fentanyl and norfentanyl ratios and concentrations suggest a more rapid onset of death given the finding of fentanyl without norfentanyl in many of the fatalities. Chest wall rigidity may help explain the cause of death in these instances, in contrast to the typical opioid-related overdose deaths. Intravenous heroin users should be educated regarding this potentially fatal complication given the increasingly common substitution and combination with heroin of fentanyl.

Toxic leukoencephalopathy due to transdermal fentanyl overdose.

PubMed

Foy, Lindsey; Seeyave, Desiree M; Bradin, Stuart A

2011-09-01

Children with altered mental status who present to the emergency department have a broad differential diagnosis. We report a case of a 19-month-old girl who presented in coma and who was later found to have a fentanyl patch adhered to her back. She was found to have changes on brain magnetic resonance imaging consistent with a toxic spongiform leukoencephalopathy but had a good neurologic outcome. This case report illustrates the importance of a thorough physical examination in children in coma and a rarely reported magnetic resonance imaging finding that has been seen in opioid intoxication and is usually associated with severe morbidity and mortality.

[Dose-finding for treatment with a transdermal fentanyl patch : Titration with oral transmucosal fentanyl citrate and morphine sulfate].

PubMed

Mücke, M; Conrad, R; Marinova, M; Cuhls, H; Elsner, F; Rolke, R; Radbruch, L

2016-12-01

To date, no studies investigating titration with oral transmucosal fentanyl for the dose-finding of transdermal fentanyl treatment have been published. In an open randomized study 60 patients with chronic malignant (n = 39) or nonmalignant pain (n = 21), who required opioid therapy according to step three of the guidelines of the World Health Organization (WHO), were investigated. In two groups of 30 patients each titration with immediate release morphine (IRM) or oral transmucosal fentanyl citrate (OTFC) was undertaken. For measurement purposes the Brief Pain Inventory (BPI) and Minimal Documentation System (MIDOS) were used. After a 24-h titration phase, in which patients documented the intensity of pain, nausea, and tiredness, treatment with transdermal fentanyl was evaluated over a 10-day period by means of the necessary dose adaptation (responder ≤ 1 dose adaptation; conversion formula 1:1 [OTFC group] vs 100:1 [IRM group]).The pain reduction over the first 24 h (titration phase) did not differ significantly between the groups. The number of responders (17 OTFC vs. 21 IRM) over the 10-day period did not show any difference either. In both groups there was a significant reduction in pain intensity (p < 0.001). Over the course of the study, there were significantly more drop-outs because of adverse effects in the OTFC group than in the IRM group (8 vs 1, p = 0.028).Oral transmucosal fentanyl citrate can be applied for the titration of transdermal fentanyl, but it does not show any clinically relevant advantage. For example, the risk of side effects-induced drop-outs was greater in the present study. Whether the unnecessary opioid switching to treat chronic pain and breakthrough pain is advantageous with regard to minimizing conversion errors cannot be definitively answered within the scope of this study.

A novel approach to pharmaco-EEG for investigating analgesics: assessment of spectral indices in single-sweep evoked brain potentials.

PubMed

Gram, Mikkel; Graversen, Carina; Nielsen, Anders K; Arendt-Nielsen, Thomas; Mørch, Carsten D; Andresen, Trine; Drewes, Asbjørn M

2013-12-01

To compare results from analysis of averaged and single-sweep evoked brain potentials (EPs) by visual inspection and spectral analysis in order to identify an objective measure for the analgesic effect of buprenorphine and fentanyl. Twenty-two healthy males were included in a randomized study to assess the changes in EPs after 110 sweeps of painful electrical stimulation to the median nerve following treatment with buprenorphine, fentanyl or placebo patches. Bone pressure, cutaneous heat and electrical pain ratings were assessed. EPs and pain assessments were obtained before drug administration, 24, 48, 72 and 144 h after beginning of treatment. Features from EPs were extracted by three different approaches: (i) visual inspection of amplitude and latency of the main peaks in the average EPs, (ii) spectral distribution of the average EPs and (iii) spectral distribution of the EPs from single-sweeps. Visual inspection revealed no difference between active treatments and placebo (all P > 0.05). Spectral distribution of the averaged potentials showed a decrease in the beta (12-32 Hz) band for fentanyl (P = 0.036), which however did not correlate with pain ratings. Spectral distribution in the single-sweep EPs revealed significant increases in the theta, alpha and beta bands for buprenorphine (all P < 0.05) as well as theta band increase for fentanyl (P = 0.05). For buprenorphine, beta band activity correlated with bone pressure and cutaneous heat pain (both P = 0.04, r = 0.90). In conclusion single-sweep spectral band analysis increases the information on the response of the brain to opioids and may be used to identify the response to analgesics. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

PATIENTS' KNOWLEDGE OF MEDICAL PATCHES IN HUNGARY.

PubMed

Somogyi, Orsolya; Zelko, Romana

2016-11-01

Transdermal therapy with medical patches is a simple possibility in home medication. As the correct use of patches has a decisive impact from the point of its modulator effect.A questionnaire survey was developed to explore level of patients' knowledge of the correct use of transdermal patches. A survey was administered in thirteen Hungarian community pharmacies from October of 2012 to May of 2015. Most of the participants, men and women over 18 years of age (n = 233), used major analgesic patches (fentanyl); the remainder were given nitroglycerin, NSAID analgesics patches during the survey. For the hypothesis testing it was assumed that men were more likely to use a razor for skin depilation before patch application than women as their denser pelage hinders patch adhesion. The hypothesis testing showed no significant gender difference in razor use (X² = 0.201; p = 0.654). Pharmacists should direct patients to avoid using soap for skin cleansing before patch application because only 22 percent of the participants always avoided its use. Since only 9 tests were flawless from 233 completed questionnaires. Many patients do not understand how to correctly apply a transdermal dosage patch. Pharmacists should teach their correct application based on results.

LC-MS/MS analysis of fentanyl and norfentanyl in a fatality due to application of multiple Durogesic transdermal therapeutic systems.

PubMed

Coopman, Vera; Cordonnier, Jan; Pien, Karen; Van Varenbergh, Dirk

2007-07-04

Fentanyl is a potent synthetic narcotic analgesic administered in the form of a transdermal patch for the management of chronic pain. A 78-year-old woman with a history of cancer was found dead in bed. She was lying on her back. The external examination revealed 10 Durogesic transdermal therapeutic systems (100 microg/h fentanyl) on the body. Liquid-liquid extraction and liquid chromatography tandem mass spectrometry with electrospray source in positive ionization mode was applied for the quantitation of fentanyl and its major metabolite norfentanyl in the post-mortem samples. Fentanyl-d5 and norfentanyl-d5 were used as internal standards. Multiple reaction monitoring was used for specific detection. Calibration was performed by addition of standard solutions to drug-free matrix (blood, urine and liver) prior to extraction. The method showed good linearity for fentanyl and norfentanyl over a concentration range of 5-150 microg/L in reconstituted extracts with coefficients of determination equal or greater than 0.998. Percent mean within-day precision and accuracy of 0.9-1.0% and 99.4-101.1% for fentanyl and 2.0-4.5% and 93.1-101.0% for norfentanyl were obtained. Mean extraction recoveries varied between 95.5% and 100.3% for fentanyl and 39.2-57.4% for norfentanyl. The following fentanyl (norfentanyl) concentration in the post-mortem samples were measured; 28.6 microg/L (3.0 microg/L) in right and 28.2 microg/L (3.5 microg/L) in left subclavian blood, 21.3 microg/L (<2 microg/L) in right and 20.9 microg/L (<2 microg/L) in left femoral blood, 37.6 microg/L (4.2 microg/L) in right and 33.9 microg/L (4.4 microg/L) in left ventricular blood, 282.9 microg/L (121.2 microg/L) in urine, 688.2 microg/L in stomach contents, 122.5 microg/L (25.4 microg/L) in bile, 19.5 microg/L (< 2 microg/L) in vitreous humour, 203.0 microg/kg (26.6 microg/kg) in liver and 78.6 microg/kg (46.3 microg/kg) in kidney. We concluded that the woman's death was caused by acute intoxication with fentanyl. The manner of death was presumed to be suicide due to excessive administered Durogesic transdermal therapeutic systems.

Evaluation of the Coat-A-Count sup 125 I fentanyl RIA: Comparison of sup 12 5I RIA and GC/MS-SIM for quantification of fentanyl in case urine specimens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watts, V.W.; Caplan, Y.H.

The Coat-A-Count solid phase {sup 125}I Fentanyl Radioimmunoassay was evaluated with respect to linearity and precision using equine urine fortified with fentanyl and then compared with a gas chromatographic/mass spectrometric method for quantification of fentanyl in urine. The RIA assay was found to be linear over the urine fentanyl concentration range of 0.25 to 7.5 ng/mL and precise with coefficients of variation (CV) ranging from 9.6 to 19.3%. The RIA calibrators, ranging in fentanyl concentrations from 0.25 to 7.5 ng/mL, and controls, at mean fentanyl concentrations of 0.46 and 1.32 ng/mL, were compared by both the RIA and GC/MS methods.more » The cross-reactivity with the {sup 125}I RIA test was determined for the fentanyl metabolites, norfentanyl and hydroxyfentanyl, and found to be 5% and 35%, respectively. The illicit fentanyl analogs were found to show significant cross-reactivity, ranging from 20 to 100%. The {sup 125}I RIA was compared to GC/MS quantifications of fentanyl in 35 positive and 20 negative case urine specimens.« less

Comparison of abuse, suspected suicidal intent, and fatalities related to the 7-day buprenorphine transdermal patch versus other opioid analgesics in the National Poison Data System.

PubMed

Coplan, Paul M; Sessler, Nelson E; Harikrishnan, Venkatesh; Singh, Richa; Perkel, Charles

2017-01-01

Prescription opioid related abuse, suicide and death are significant public health problems. This study compares rates of poison center calls categorized as intentional abuse, suspected suicidal intent or fatality for the 7-day buprenorphine transdermal system/patch (BTDS) with other extended-release and long-acting (ER/LA) opioids indicated for chronic pain. Retrospective 24-month cohort study using National Poison Data System data from July 2012 through June 2014. BTDS was introduced in the United States in January 2011. Numbers and rates of calls of intentional abuse, suspected suicidal intent and fatalities were evaluated for BTDS, ER morphine, ER oxycodone, fentanyl patch, ER oxymorphone and methadone tablets/capsules, using prescription adjustment to account for community availability. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. Absolute numbers and prescription-adjusted rates of intentional abuse and suspected suicidal intent with BTDS were significantly lower (p < .0001) than for all other ER/LA opioid analgesics examined. No fatalities associated with BTDS exposure were reported. This post-marketing evaluation of BTDS indicates infrequent poison center calls for intentional abuse and suspected suicidal intent events, suggesting lower rates of these risks with BTDS compared to other ER/LA opioids.

Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy Greyhound dogs

PubMed Central

KuKanich, Butch; Allen, Philip

2014-01-01

The purpose of this study was to compare the pharmacokinetics of two highly protein bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy Greyhound dogs (3 males and 3 females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL/min/kg) was faster than buprenorphine (10.3 mL/min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including: octanol:water partition coefficient and pKa the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. PMID:24684621

A randomized controlled study comparing intrathecal hyperbaric bupivacaine-fentanyl mixture and isobaric bupivacaine-fentanyl mixture in common urological procedures

PubMed Central

Upadya, Madhusudan; Neeta, S; Manissery, Jesni Joseph; Kuriakose, Nigel; Singh, Rakesh Raushan

2016-01-01

Background and Aims: Bupivacaine is available in isobaric and hyperbaric forms for intrathecal use and opioids are used as additives to modify their effects. The aim of this study was to compare the efficacy and haemodynamic effect of intrathecal isobaric bupivacaine-fentanyl mixture and hyperbaric bupivacaine-fentanyl mixture in common urological procedures. Methods: One hundred American Society of Anesthesiologists physical status 1 and 2 patients undergoing urological procedures were randomized into two groups. Group 1 received 3 ml of 0.5% isobaric bupivacaine with 25 μg fentanyl while Group 2 received 3 ml of 0.5% hyperbaric bupivacaine with 25 μg fentanyl. The parameters measured include heart rate, blood pressure, respiratory rate, onset and duration of motor and sensory blockade. Student's unpaired t-test and the χ2 test were used to analyse the results, using the SPSS version 11.5 software. Results: The haemodynamic stability was better with isobaric bupivacaine fentanyl mixture (Group 1) than with hyperbaric bupivacaine fentanyl mixture (Group 2). The mean onset time in Group 1 for both sensory block (4 min) and motor block (5 min) was longer compared with Group 2. The duration of sensory block (127.8 ± 38.64 min) and motor block (170.4 ± 27.8 min) was less with isobaric bupivacaine group compared with hyperbaric bupivacaine group (sensory blockade 185.4 ± 16.08 min and motor blockade 201.6 ± 14.28 min). Seventy percent of patients in Group 2 had maximum sensory block level of T6 whereas it was 53% in Group 1. More patients in Group 1 required sedation compared to Group 2. Conclusion: Isobaric bupivacaine fentanyl mixture was found to provide adequate anaesthesia with minimal incidence of haemodynamic instability. PMID:26962255

Taking the alternative route: Women's experience of intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for labour analgesia.

PubMed

Fleet, Julie-Anne; Jones, Meril; Belan, Ingrid

2017-10-01

To compare women's experience of receiving either intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for labour analgesia. A content analysis was undertaken as part of the third phase of a larger randomised controlled trial, using the per-protocol dataset to examine women's experiences of treatment received. Healthy women birthing at term, who received intranasal fentanyl (n=41), subcutaneous fentanyl (n=37) and/or intramuscular pethidine (n=38) for labour analgesia, were contacted at 6 weeks postpartum to complete a phone questionnaire. A tertiary and regional maternity unit in South Australia. Over 80% of women who received intranasal or subcutaneous fentanyl reported that they would use the treatment again compared to 44.8% of women who had received pethidine (self-administered intranasal fentanyl provided more expressive responses emphasising the route provided a strong sense of control and enablement. Route of administration influenced the women's experience, more women who self-administered intranasal fentanyl reported positive emotional responses, with women reporting increased autonomy and satisfaction. Whereas, women who relied on the midwife to administer subcutaneous fentanyl or intramuscular pethidine, were more often focused on the physical effect of the drug. Pethidine was the least preferred option due to adverse effects. For women requesting parenteral analgesia, fentanyl administered by less invasive routes offers women additional options that may better meet their emotional, cognitive and physical needs than the current practice of administering intramuscular pethidine. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of intrapartum opioid use on breastfeeding experience at 6 weeks post partum: A secondary analysis.

PubMed

Fleet, Julie-Anne; Jones, Meril; Belan, Ingrid

2017-07-01

To examine breastfeeding experiences up to 6 weeks postpartum for mothers administered intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for intrapartum analgesia. A secondary analysis was undertaken using the per-protocol dataset to examine the third phase of a larger randomised controlled trial. This phase of the study examined breastfeeding intention and experience from the first hour of birth to 6 weeks postpartum. Medical records were audited and women were contacted at 6 weeks postpartum to complete a telephone questionnaire. Two maternity hospitals in South Australia. Healthy women birthing at term received intranasal fentanyl (n=37), subcutaneous fentanyl (n=37), or intramuscular pethidine (n=35). While maternal characteristics and birth outcomes were comparable between groups, women who received either intranasal fentanyl or subcutaneous fentanyl experienced fewer difficulties in establishing breastfeeding by 6 weeks postpartum when compared to intramuscular pethidine (p<0.01). Women who received fentanyl reported that their neonates had less difficulties establishing breastfeeding, compared to those who received pethidine. Therefore, for woman who intend to breastfeed, fentanyl should be the preferred opiate, for the relief of pain in labour. When providing education to women in relation to intrapartum pain relief it is important to consider the potential influence on breastfeeding experience. This research provides evidence that fentanyl is a suitable alternative to pethidine for women requesting parenteral analgesia in labour. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trans-Dermal Fentanyl Patches are a Cost-Effective Method of Long-Term Analgesic Delivery Following Corneal Exposure to Sulfur Mustard Vapor

DTIC Science & Technology

2012-01-01

SM) exposure in rabbits involves delivery of the opioid receptor agonist buprenorphine using subcutaneously implanted osmotic pumps. The...significantly lower than the costs of purchasing and loading an osmotic pump with buprenorphine . Pump implantation took approximately 10 min per...general distress than did the buprenorphine cohort. The elevated behavioral changes exhibited by the rabbits with implanted pumps were likely a

Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs.

PubMed

KuKanich, B; Allen, P

2014-12-01

The purpose of this study was to compare the pharmacokinetics of two highly protein-bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. © 2014 John Wiley & Sons Ltd.

Pharmacological Consequence of the A118G Mu Opioid Receptor Polymorphism on Morphine- and Fentanyl-mediated Modulation of Ca2+ Channels in Humanized Mouse Sensory Neurons

PubMed Central

Mahmoud, Saifeldin; Thorsell, Annika; Sommer, Wolfgang H.; Heilig, Markus; Holgate, Joan K.; Bartlett, Selena E.; Ruiz-Velasco, Victor

2011-01-01

Background The most common functional single nucleotide polymorphism of the human OPRM1 gene, A118G, has been shown to be associated with inter-individual differences in opioid analgesic requirements, particularly with morphine, in patients with acute postoperative pain. The purpose of the present study was to examine whether this polymorphism would modulate the morphine and fentanyl pharmacological profile of sensory neurons isolated from a humanized mouse model homozygous for either the 118A or 118G allele. Methods The coupling of wild-type and mutant mu opioid receptors to voltage-gated Ca2+ channels after exposure to either ligand was examined by employing the whole-cell variant of the patch-clamp technique in acutely dissociated trigeminal ganglion neurons. Morphine-mediated antinociception was measured in mice carrying either the 118AA or 118GG allele. Results The biophysical parameters (cell size, current density, and peak current amplitude potential) measured from both groups of sensory neurons were not significantly different. In 118GG neurons, morphine was approximately 5-fold less potent and 26% less efficacious than that observed in 118AA neurons. On the other hand, the potency and efficacy of fentanyl were similar for both groups of neurons. Morphine-mediated analgesia in 118GG mice was significantly reduced compared to the 118AA mice. Conclusions This study provides evidence to suggest that the diminished clinical effect observed with morphine in 118G carriers results from an alteration of the receptor’s pharmacology in sensory neurons. Additionally, the impaired analgesic response with morphine may explain why carriers of this receptor variant have an increased susceptibility to become addicted to opioids. PMID:21926562

Comparison of Butorphanol and Fentanyl for the Relief of Postoperative Shivering Associated with Spinal Anesthesia

PubMed Central

Manne, Venkata Sesha Sai Krishna; Gondi, Srinivasa Rao

2017-01-01

Aim: The aim of this study was to compare fentanyl and butorphanol for the relief of postoperative shivering in spinal anesthesia. Materials and Methods: A total of 100 American Society of Anesthesiologists physical status Class I and II patients aged 19–60 years belonging to both sexes who were posted for elective surgical procedures under spinal anesthesia were divided into two groups (fentanyl and butorphanol) and monitored intraoperatively for the occurrence of shivering and time taken to control shivering after administration of fentanyl and butorphanol drugs. Results: Relief of shivering is rapid and more effective with fentanyl than butorphanol. There is a significant increase in pulse rate, mean arterial pressure, respiratory rate (RR), and decreased in oxygen saturation at the onset of shivering and also a decrease in core body temperature. Sedation, nausea, vomiting, and recurrence of shivering are more with butorphanol with fentanyl. Conclusion: On the basis of the study, it is concluded that fentanyl is more effective and takes less time to control perioperative shivering as compared to butorphanol. PMID:28298762

Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting.

PubMed

Middleton, Paul M; Simpson, Paul M; Sinclair, Gary; Dobbins, Timothy A; Math, B; Bendall, Jason C

2010-01-01

To compare the effectiveness of intravenous (IV) morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane when administered by paramedics to patients with moderate to severe pain. We conducted a retrospective comparative study of adult patients with moderate to severe pain treated by paramedics from the Ambulance Service of New South Wales who received IV morphine, IN fentanyl, or inhaled methoxyflurane either alone or in combination between January 1, 2004, and November 30, 2006. We used multivariate logistic regression to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of > or = 30% of initial pain score using an 11-point verbal numeric rating scale (VNRS-11). The study population comprised 52,046 patients aged between 16 and 100 years with VNRS-11 scores of > or = 5. All analgesic agents were effective in the majority of patients (81.8%, 80.0%, and 59.1% for morphine, fentanyl, and methoxyflurane, respectively). There was very strong evidence that methoxyflurane was inferior to both morphine and fentanyl (p < 0.0001). There was strong evidence that morphine was more effective than fentanyl (p = 0.002). There was no evidence that combination analgesia was better than either fentanyl or morphine alone. Inhaled methoxyflurane, IN fentanyl, and IV morphine are all effective analgesic agents in the out-of-hospital setting. Morphine and fentanyl are significantly more effective analgesic agents than methoxyflurane. Morphine appears to be more effective than IN fentanyl; however, the benefit of IV morphine may be offset to some degree by the ability to administer IN fentanyl without the need for IV access.

The effect of inhalant anesthetic and body temperature on peri-anesthetic serum concentrations of transdermally administered fentanyl in dogs.

PubMed

Pettifer, Glenn R; Hosgood, Giselle

2004-04-01

To determine whether moderate hypothermia during anesthesia significantly affects the serum concentration of transdermally delivered fentanyl and whether halothane or isoflurane affect these concentrations. Randomized cross-over experimental trial. Six mature, healthy Beagles (three males, three females) weighing 10.6 +/- 0.43 kg. A 50-microg hour(-1) fentanyl patch was applied 36 hours prior to anesthesia. Anesthesia was induced at time 0 (t = 0). Each dog received four treatments: isoflurane + normothermia (ISO-NORM), isoflurane + hypothermia (ISO-HYPO), halothane + normothermia (HAL-NORM), and halothane + hypothermia (HAL-HYPO). Dogs were intubated and maintained at 1.5 times MAC. Animals in the hypothermia treatments were cooled to 35 degrees C during anesthesia. Serum fentanyl analysis was performed at -36, -24, -12, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 18, and 26 hours. Direct arterial blood pressures and arterial blood gases were monitored. The mean body temperatures (+/-SEM) during the anesthetic period for the four treatments were: ISO-NORM = 37.7 +/- 0.07 degrees C, ISO-HYPO = 35.8 +/- 0.1 degrees C, HAL-NORM = 37.7 +/- 0.06 degrees C, and HAL-HYPO = 35.8 +/- 0.13 degrees C. The mean (+/-SEM) serum fentanyl concentrations (SFC) for both hypothermia treatments were significantly lower than baseline concentrations at t = 1 hour and persisted for the duration of anesthesia for the ISO-HYPO treatment but only from t = 1 to 2 hours for the HAL-HYPO treatment. Serum fentanyl concentrations returned to baseline within one hour of the end of anesthesia, regardless of body temperature. There were no significant differences between treatments for systolic or diastolic blood pressure but mean blood pressures were higher during normothermia versus hypothermia during the last hour of anesthesia. Hypothermia during inhalation anesthesia produced a significant reduction in SFC using transdermal administration and was more protracted with isoflurane than halothane anesthesia. While significant reductions in SFC occurred, the SFC were still within the range believed to confer analgesia.

Fentanyl Ameliorates Severe Acute Pancreatitis-Induced Myocardial Injury in Rats by Regulating NF-κB Signaling Pathway

PubMed Central

Wang, Yayun; Chen, Manhua

2017-01-01

Background Acute pancreatitis (AP) is a sudden inflammation of the pancreas. It results in multiple, severe complications, and 15–20% of patients develop severe acute pancreatitis (SAP) with mortality as high as 30%. Consequently, it is imperative to develop an effective therapy for SAP. Material/Methods We used 30 adult male Sprague Dawley (SD) rats. Rats were randomly divided into 3 groups – sham, SAP, and fentanyl+SAP – with 10 rats in each group. An automatic biochemical analyzer was used to analyze the concentration of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay was applied to assess the cell apoptosis rate. Pathological changes in pancreas/heart were detected with hematoxylin and eosin (HE) staining. Western immunoblot assay was used to analyze protein levels of interleukin (IL)-1β, IL-6, and IκB. Results Fentanyl pre-treatment inhibits SAP-induced elevation of CK-MB/LDH concentrations in serum. Compared with the sham group, SAP generates a higher brown/yellow staining rate, which is abated by fentanyl. In the pancreas, SAP generated more serious interstitial edema/hemorrhage and fat necrosis than in the sham group, which are attenuated by fentanyl. Likewise, compared to the sham group, SAP generates swelled/disordered myocardial fibers and congested blood vessels in myocardium, which are ameliorated by fentanyl. In the sham group, there was little IL-1β/IL-6, and fentanyl significantly inhibited SAP-induced up-regulation of IL-1β/IL-6 levels. Compared with the sham group, SAP significantly reduced IκB level, which was rescued by fentanyl. Conclusions Fentanyl effectively alleviates SAP-induced pancreas and heart injuries through regulating the nuclear factor-κB (NF-κB) signaling pathway. PMID:28680032

Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

PubMed Central

Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

2012-01-01

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

PubMed Central

FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

2016-01-01

Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

Use of Fentanyl in Adolescents with Clinically Severe Obesity Undergoing Bariatric Surgery - a Pilot Study

PubMed Central

Vaughns, Janelle D.; Ziesenitz, Victoria C.; Williams, Elaine F.; Mushtaq, Alvina; Bachmann, Ricarda; Skopp, Gisela; Weiss, Johanna; Mikus, Gerd; van den Anker, Johannes N.

2018-01-01

Background The number of obese pediatric patients requiring anesthesia is rapidly increasing. Although fentanyl is a commonly used narcotic during surgery, there is no pharmacokinetic (PK) data available for optimal dosing of fentanyl in adolescents with clinically severe obesity. Materials and Methods An IRB-approved exploratory pilot study was conducted in 6 adolescents aged 14 to 19 years undergoing bariatric surgery. Mean total body weight (TBW) and mean BMI were 137.4 ± 14.3 kg, and 49.6 ± 6.4 kg/m2 (99.5th BMI percentile), respectively. Fentanyl was dosed intravenously for intraoperative analgesia based on ideal body weight per standard of care. PK blood samples were drawn over a 24 hour post-dose period. Fentanyl PK parameters were calculated by non-compartmental analysis. Results Mean fentanyl AUC0–∞ was 1.5 ± 0.5 h*ng/mL. Systemic clearance of fentanyl was 1522 ± 310 mL/min and 11.2 ± 2.6 mL/min*kg TBW. Volume of distribution was 635 ± 282 L and 4.7 ± 2.1 L/kg TBW. While absolute clearance was increased, absolute volume of distribution was comparable to previously established adult values. Conclusions These results suggest that fentanyl clearance is enhanced in adolescents with clinically severe obesity while volume of distribution is comparable to previously published studies. PMID:28238111

COMPARISON OF INTRAMUSCULAR FENTANYL-MIDAZOLAM, FENTANYL-MIDAZOLAM-KETAMINE, AND KETAMINE-MEDETOMIDINE FOR IMMOBILIZATION OF JAPANESE MACAQUES ( MACACA FUSCATA).

PubMed

Ølberg, Rolf-Arne; Sinclair, Melissa; Barker, Ian K; Crawshaw, Graham

2018-03-01

The combination of fentanyl and midazolam is commonly used as a sedative in humans. The objective of this study was to evaluate the sedative properties and physiological effects of fentanyl-midazolam and fentanyl-midazolam-ketamine compared with medetomidine-ketamine given intramuscularly in Japanese macaques ( Macaca fuscata). In a randomized crossover design, eight Japanese macaques were hand-injected with either 30 μg/kg fentanyl + 0.3 mg/kg midazolam (FM), 15 μg/kg fentanyl + 0.3 mg/kg midazolam + 5.0 mg/kg ketamine (FMK), or 0.05 mg/kg medetomidine + 5.0 mg/kg ketamine (MedK). Heart rate; indirect systolic, mean, and diastolic arterial pressure; respiratory rate; blood gas concentrations; rectal temperature; and duration of immobilization were recorded. Mixed linear models were used to evaluate the effects of drug treatment on all continuous variables, with a significance level of P < 0.05. Only three of seven animals receiving FM were successfully immobilized. All eight animals in both the FMK and MedK treatment groups had a rapid, smooth induction and were successfully immobilized. Both FMK and MedK treatments resulted in significant hypoxia and the animals required supplemental oxygen via face mask. The mean duration of FMK immobilization was 42 ± 10 min, significantly shorter than the 65 ± 14 min for the animals receiving MedK. Immobilization with MedK resulted in significantly lower heart rates, and significantly higher arterial pressure compared with FMK. Hypoventilation was significantly more pronounced in FMK-treated animals compared with MedK treatments. Immobilization with FMK resulted in a gradual, slow recovery whereas MedK-treated animals woke up more rapidly. Fentanyl-midazolam alone is not a useful sedative in Japanese macaques. A combination of fentanyl and midazolam with ketamine can be used as an alternative to medetomidine-ketamine in this species.

Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006).

PubMed

Algren, D Adam; Monteilh, Carolyn P; Punja, Mohan; Schier, Joshua G; Belson, Martin; Hepler, Bradford R; Schmidt, Carl J; Miller, Corinne E; Patel, Manish; Paulozzi, Leonard J; Straetemans, Masja; Rubin, Carol

2013-03-01

During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users. Baseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status. Monthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs were analyzed. The median age of decedents was 46 and 45 years for the fentanyl and non-fentanyl groups, respectively. Fentanyl-contaminated heroin-associated fatalities (FHFs) were more likely to be female (p = 0.003). Women aged over 44 years (OR = 4.67;95 % CI = 1.29-16.96) and divorced/widowed women (OR = 14.18;95 % CI = 1.59-127.01) were more likely to be FHFs when compared to women aged less than 44 years and single, respectively. A significant interaction occurred between gender and age, and gender and marital status. Most FHFs had central (heart) blood samples available for fentanyl testing (n = 96; 95 %): fentanyl was detected in most (n = 91; 95 %). Of these, close to half had no detectable heroin (or 6-acetylmorphine) concentrations (n = 37; 40.7 %). About half of these samples had detectable cocaine concentrations (n = 20; 54 %). Median fentanyl concentration in central blood samples was 0.02 μg/ml (n = 91, range <0.002-0.051 μg/ml) and 0.02 μg/ml (n = 32, range <0.004-0.069 μg/ml) in peripheral blood samples. The geometric mean of the ratio of central to peripheral values was 2.10 (median C/P = 1.75). At autopsy, pulmonary edema was the most frequently encountered finding for both groups (77 %). Illicit drugs may contain undeclared ingredients that may increase the likelihood of fatality in users. Gender differences in fentanyl-related mortality may be modified by age and/or marital status. These findings may help inform public health and prevention activities if fatalities associated with fentanyl-contaminated illicit drugs reoccur.

Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients.

PubMed

Bendall, Jason C; Simpson, Paul M; Middleton, Paul M

2011-01-01

To compare the effectiveness of intravenous morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane for managing moderate to severe pain in pediatric patients in the out-of-hospital setting. We conducted a retrospective comparative study of 3,312 pediatric patients aged between 5 and 15 years who had moderate to severe pain (pain score ≥ 5) and who received intravenous morphine, IN fentanyl, or inhaled methoxyflurane, either alone or in combination, between January 1, 2004, and November 30, 2006. Multivariate logistic regression was used to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of ≥ 30% of initial pain score using an 11-point verbal numeric rating scale. Effective analgesia was achieved in 82.5% of cases overall. All analgesic agents were effective in the majority of patients (87.5%, 89.5%, and 78.3% for morphine, fentanyl, and methoxyflurane, respectively). There was evidence that methoxyflurane was less effective than both morphine (odds ratio [OR] 0.52; 95% confidence interval [CI] 0.36-0.74) and fentanyl (OR 0.43; 95% CI 0.29-0.62; p < 0.0001). There was no clinical or statistical evidence of difference in the effectiveness of fentanyl and morphine in this population (OR 1.22; 95% CI 0.74-2.01). There was no evidence that combination analgesia was better than either fentanyl or morphine alone. Intranasal fentanyl and intravenous morphine are equally effective analgesic agents in pediatric patients with moderate to severe acute pain in the out-of-hospital setting. Methoxyflurane is less effective in comparison with both morphine and fentanyl, but is an effective analgesic in the majority of children.

Epidural Analgesia With Bupivacaine and Fentanyl Versus Ropivacaine and Fentanyl for Pain Relief in Labor

PubMed Central

Guo, Shanbin; Li, Bo; Gao, Chengjie; Tian, Yue

2015-01-01

Abstract The aim of this study was to compare the efficacy and safety of the combinational use of bupivacaine and fentanyl versus ropivacaine and fentanyl in epidural analgesia for labor. Multiple electronic databases were searched by using appropriate MeSH terms, and keywords for original research papers published before October 2014. Meta-analyses were based on mean differences between the groups as well as odds ratios. Statistical heterogeneity was tested by I2 index. Fifteen randomized controlled trials, recruiting 2097 parturient mothers overall, were selected for the meta-analyses. Concentrations of the preparations used (weight/volume; mean and standard deviations) were bupivacaine 0.1023% ± 0.0375%, ropivacaine 0.1095% ± 0.042%, and fentanyl 0.00021% ± 0.000089%. There were no statistically significant differences between both the combinations in the mean change in Visual Analog Score for pain during labor, incidence of instrumental or cesarean delivery, neonate Apgar score of <7, maternal satisfaction, duration of either first or second stage of labor, oxytocin use for induction, onset of analgesia, and duration of analgesia. Women who received ropivacaine and fentanyl had significantly lower incidence of motor blocks (odds ratio [95% CI] = 0.38 [0.30, 0.48] P < 0.00001, fixed effect and 0.38 [0.27, 0.54] P < 0.0001, random effects I2 30%) when compared with women who received bupivacaine and fentanyl. Incidence of side effects was similar for both the combinations. Analgesia with ropivacaine in combination with fentanyl at 0.1%:0.0002% ratio for labor pain relief is associated with lower incidence of motor blocks in comparison with analgesia with bupivacaine and fentanyl at similar ratio (0.1%: 0.0002%). PMID:26061307

[Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord].

PubMed

Abut, Yesim Cokay; Turkmen, Asli Zengin; Midi, Ahmet; Eren, Burak; Yener, Nese; Nurten, Asiye

2015-01-01

The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. In experiment, there were four groups with medication and a control group. Rats were injected 15μL saline or fentanyl 0.0005μg/15μL, levobupivacaine 0.25%/15μL and fentanyl 0.0005μg+levobupivacaine 0.25%/15μL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups. In neuropathologic investment, the fentanyl and fentanyl+levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

The Behavioral Effects of a Mixed Efficacy Antinociceptive Peptide, VRP26, Following Chronic Administration in Mice

PubMed Central

Anand, Jessica P.; Boyer, Brett T.; Mosberg, Henry I.; Jutkiewicz, Emily M.

2016-01-01

Rationale VRP26 displays mu opioid receptor agonist and delta opioid receptor antagonist activity in vitro, a pharmacological profile purported to produce reduced tolerance, dependence, and rewarding effects. We hypothesized that VRP26 would display reduced adverse effects after chronic administration as compared with the traditional opioid analgesic fentanyl. Objective To explore the development of tolerance, dependence and conditioned place preference of VRP26 as compared with the traditional opioid analgesic fentanyl. Methods The antinociceptive effects of VRP26 and fentanyl were assessed using the mouse warm water tail withdrawal (WWTW) assay. Measurement of antinociceptive tolerance and physical dependence occurred after seven days of continuous administration of either fentanyl (0.3 mg/kg/day) or VRP26 (10 mg/kg/day); tolerance was measured by a shift in the antinociceptive dose response curve in the WWTW assay. Physical dependence was determined by observation of withdrawal symptoms after precipitated withdrawal. Rewarding effects were measured by the ability of VRP26 or fentanyl to produce conditioned place preference. Results Fentanyl produced significant tolerance and dependence, as well as significant conditioned place preference. VRP26 produced neither tolerance nor physical dependence, nor did it produce significant conditioned place preference. Conclusions These results suggest that chronic treatment with VRP26 may produce less tolerance or physical dependence than chronic treatment with clinically available mu opioid analgesics such as fentanyl. Additionally, VRP26 produces less rewarding effects than fentanyl. This desirable in vivo profile may be due to the mixed efficacy nature of VRP26 and could provide the framework for safer opioid analgesics. PMID:27117141

Knee strength retention and analgesia with continuous perineural fentanyl infusion after total knee replacement: randomized controlled trial.

PubMed

Mangar, Devanand; Karlnoski, Rachel A; Sprenker, Collin J; Downes, Katheryne L; Taffe, Narrene; Wainwright, Robert; Gustke, Kenneth; Bernasek, Thomas L; Camporesi, Enrico

2014-04-01

Despite providing adequate pain relief, a femoral nerve block can induce postoperative muscle weakness after total knee arthoplasty (TKA). Fentanyl has been shown to have peripheral effects but has not been used as a perineural infusate alone after TKA. Sixty patients scheduled for TKA were randomized to one of three blinded groups: a continuous 24 h infusion of either fentanyl 3 μg/ml, ropivacaine 0.1%, or 0.9% normal saline through a femoral nerve sheath catheter at 10 ml/h. The main outcome was maximum voluntary isometric contraction (MVIC) in the quadriceps femoris (knee extension), measured by a handheld dynamometer (Nm/kg). Other variables assessed were preoperative and postoperative visual analog scale (VAS) scores, hamstrings MVIC (knee flexion), active range of motion of the operative knee, distance ambulated, incidence of knee buckling, supplemental morphine usage, postoperative side effects, and serum fentanyl levels. Quadriceps MVIC values were significantly greater in the fentanyl group compared to the group that received ropivacaine (median values, 0.08 vs. 0.03 Nm/kg; p = 0.028). The incidence of postoperative knee buckling upon ambulation was higher in the ropivacaine group compared to the fentanyl group, although not statistically significant (40% vs. 15 %, respectively; p = 0.077). VAS scores while ambulating were not significantly different between the fentanyl group and the ropivacaine group (p = 0.270). Postoperative morphine consumption, nausea and vomiting, and resting VAS scores were similar among the three groups. A continuous perineural infusion of fentanyl produced greater strength retention than ropivacaine post-TKA.

An Acute Butyr-Fentanyl Fatality: A Case Report with Postmortem Concentrations.

PubMed

McIntyre, Iain M; Trochta, Amber; Gary, Ray D; Wright, Jennifer; Mena, Othon

2016-03-01

In this case report, we present an evaluation of the distribution of postmortem concentrations of butyr-fentanyl in a fatality attributed principally to the drug. A man who had a history of intravenous drug abuse was found unresponsive on the bathroom floor of his home. Drug paraphernalia was located on the bathroom counter. Toxicology testing, which initially screened positive for fentanyl by enzyme-linked immunosorbent assay, subsequently confirmed butyr-fentanyl, which was then quantitated by gas chromatography-mass spectrometry-specific ion monitoring (GC-MS SIM) analysis following liquid-liquid extraction. The butyr-fentanyl peripheral blood concentration was quantitated at 58 ng/mL compared with the central blood concentration of 97 ng/mL. The liver concentration was 320 ng/g, the vitreous was 40 ng/mL, the urine was 670 ng/mL and the gastric contained 170 mg. Acetyl-fentanyl was also detected in all biological specimens tested. Peripheral blood concentration was quantitated at 38 ng/mL compared with the central blood concentration of 32 ng/mL. The liver concentration was 110 ng/g, the vitreous was 38 ng/mL, the urine was 540 ng/mL and the gastric contained <70 mg. The only other drug detected was a relatively low concentration of benzoylecgonine. The cause of death was certified as acute butyr-fentanyl, acetyl-fentanyl and cocaine intoxication, and the manner of death was certified as accident. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparing the Effect of Adding Fentanyl, Sufentanil, and Placebo with Intrathecal Bupivacaine on Duration of Analgesia and Complications of Spinal Anesthesia in Patients Undergoing Cesarean Section

PubMed Central

Farzi, Farnoush; Mirmansouri, Ali; Naderi Nabi, Bahram; Atrkar Roushan, Zahra; Ghazanfar Tehran, Samaneh; Nematollahi Sani, Mona; Makhlooghi Azad, Soodabe; Nemati, Maryam

2017-01-01

Background Spinal anesthesia is the method of choice for most elective and emergency Cesarean sections. To increase the duration of anesthesia and improve the quality of analgesia during and after surgery, intrathecal opioids, as adjuvant drugs, are used in combination with local anesthetics. Methods This was a double-blind clinical trial performed on 99 patients. Women were divided into 3 groups of fentanyl, sufentanil, and placebo. For fentanyl group, 12.5 mg of bupivacaine and 25 micrograms of fentanyl; for sufentanil group, 12.5 mg of bupivacaine and 2.5 micrograms of sufentanil; and for placebo group, 12.5 mg of bupivacaine and a half mL of normal saline were injected in subarachnoid space. The sensory and motor block, hemodynamic status (mean blood pressure and heart rate), and probable complications were assessed. Results There was no significant difference between the groups in demographic characteristics. Durations of analgesia were, respectively, 314 ± 42.95, 312.5 ± 34.44, and 116.1 ± 42.24 minutes in the fentanyl, sufentanil, and placebo groups (P = 0.0001). Duration of sensory and motor block was higher in fentanyl and sufentanil groups compared with the placebo group. The highest duration of sensory and motor block was noted in sufentanil group (P = 0.0001). No significant difference was found between the groups in the hemodynamic parameters (P > 0.05). The frequency of itching in the fentanyl group was higher than sufentanil and placebo groups (P = 0.003). Also, shivering was higher in the placebo group compared with other groups (P = 0.036). Conclusions According to the results, adding 25 microgram fentanyl or 2.5 microgram sufentanil to intrathecal bupivacaine increased the duration of analgesia and provided hemodynamic stability with no major complication. As administering intrathecal fentanyl had a similar duration of analgesia like sufentanil with faster return of motor block and ambulation, it seems that it is a preferred additive for Cesarean section surgery. PMID:29696107

Intrathecal versus IV fentanyl in pediatric cardiac anesthesia.

PubMed

Pirat, Arash; Akpek, Elif; Arslan, Gülnaz

2002-11-01

Systemic large-dose opioids are widely used in pediatric cardiac anesthesia, but there are no randomized, prospective studies regarding the use of intrathecal (IT) opioids for these procedures. In this randomized, prospective study, we compared cardiovascular and neurohumoral responses during IT or IV fentanyl anesthesia for pediatric cardiac surgery. Thirty children aged 6 mo to 6 yr were anesthetized with an IV fentanyl bolus of 10 micro g/kg. This was followed by a fentanyl infusion of 10 micro g. kg(-1). h(-1) (Group IV; n = 10), 2 micro g/kg of IT fentanyl (Group IT; n = 10), or combined IV and IT protocols (Group IV + IT; n = 10). Heart rate, mean arterial blood pressure, additional fentanyl doses, time to first analgesic requirement, COMFORT and Children's Hospital of Eastern Ontario Pain Scale scores, and extubation time were recorded. Blood cortisol, insulin, glucose, and lactate levels were measured presurgery, poststernotomy, during the rewarming phase of cardiopulmonary bypass (CPB), and 6 and 24 h after surgery. The patients' urinary cortisol excretion rates were also measured during the first postoperative day. The findings in all three groups were statistically similar, except for higher blood glucose levels during CPB in Group IT compared with Group IV (P < 0.004). Group IV + IT was the only group in which the increases in heart rate and mean arterial blood pressure from presurgery to poststernotomy were not significant. The 24-h urinary cortisol excretion rates ( micro g. kg(-1). d(-1)) were 61.51 +/- 39, 92.54 +/- 67.55, and 40.15 +/- 29.69 for Groups IV, IT, and IV + IT, respectively (P > 0.05). A single IT injection of fentanyl 2 micro g/kg offers no advantage over systemic fentanyl (10 micro g/kg bolus and 10 micro g. kg(-1). h(-1)) with regard to hemodynamic stability or suppression of stress response. The combination of these two regimens may provide better hemodynamic stability during the pre-CPB period and may be associated with a decreased 24-h urinary cortisol excretion rate. In this prospective, randomized study, we investigated the adequacy of a single intrathecal injection of fentanyl for intraoperative analgesia, compared the effects of IT and IV fentanyl on stress response, and assessed for an additive effect of IT and IV fentanyl administration in pediatric cardiac anesthesia. The results with these three different anesthetic regimens were similar regarding anesthesia depth and level of stress response. However, the combination of IT and IV routes may provide better hemodynamic stability and a less pronounced stress response, as reflected by 24-h urinary cortisol excretion.

Illicit Fentanyl-Related Fatalities in Florida: Toxicological Findings.

PubMed

Lee, Dayong; Chronister, Chris W; Broussard, Wilson A; Utley-Bobak, Suzanne R; Schultz, Daniel L; Vega, Russell S; Goldberger, Bruce A

2016-10-01

Fentanyl induces pharmacological effects and abuse liability comparable to other prescription opioids and heroin. A surge in fentanyl-related fatalities has been periodically reported throughout the USA. The University of Florida Forensic Toxicology Laboratory observed a significant increase in fentanyl-related deaths starting in mid-2014. The present report evaluated toxicological findings, demographics of the decedents and circumstances of death in the postmortem cases that were submitted to the laboratory for toxicological analysis from July 2014 to January 2015 and that were tested for fentanyl in biological specimens. The cases originated from 6 of the 24 Florida Medical Examiner Districts, with the majority from District 12 (Desoto, Manatee and Sarasota counties). The specimens were analyzed for fentanyl by gas chromatography-mass spectrometry; the limit of detection (LOD) was 0.62 ng/mL and the limit of quantification (LOQ) was 2.5 ng/mL. During the 7-month period, the laboratory tested 143 postmortem cases for fentanyl and 50% had quantifiable fentanyl in postmortem blood. Fentanyl concentrations ranged from 2.5 to 68 ng/mL (n = 66; median: 9.8 ng/mL); six cases were positive for fentanyl >LOD but

Synthesis and biological evaluation of some novel 1-substituted fentanyl analogs in Swiss albino mice

PubMed Central

Yadav, Shiv Kumar; Maurya, Chandra Kant; Gupta, Pradeep Kumar; Jain, Ajai Kumar; Ganesan, Kumaran

2014-01-01

Fentanyl [N-(1-phenethyl-4-piperidinyl)propionanilide] is a potent opioid analgesic agent, but a has narrow therapeutic index. We reported earlier on the synthesis and bioefficacy of fentanyl and its 1-substituted analogs (1–4) in mice. Here we report the synthesis and biological evaluation of four additional analogs, viz. N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6), isopropyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (7) and t-butyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (8). The median lethal dose (LD50) determined by intravenous, intraperitoneal and oral routes suggests these analogs to be comparatively less toxic than fentanyl. On the basis of observational assessment on spontaneous activities of the central, peripheral, and autonomic nervous systems, all the analogs were found to be similar to fentanyl. Naloxone hydrochloride abolished the neurotoxic effects of these analogs, thereby ascertaining their opioid receptor-mediated effects. All the analogs displayed significant analgesic effects, measured by formalin-induced hind paw licking and tail immersion tests at their respective median effective dose (ED50). They also exhibited 8–12 fold increase in therapeutic index over fentanyl. However, 5 and 6 alone produced lower ED50 (20.5 and 21.0 µg/kg, respectively) and higher potency ratio (1.37 and 1.33, respectively) compared to fentanyl. They could thus be considered for further studies on pain management. PMID:26109885

Effects of Pre-Existing Liver Disease on Acute Pain Management Using Patient-Controlled Analgesia Fentanyl With Parecoxib After Major Liver Resection: A Retrospective, Pragmatic Study.

PubMed

Lim, K I; Chiu, Y C; Chen, C L; Wang, C H; Huang, C J; Cheng, K W; Wu, S C; Shih, T H; Yang, S C; Juang, S E; Huang, C E; Jawan, B; Lee, Y E

2016-05-01

The aim of this study was to compare the outcomes of pain management with the use of patient-controlled analgesia (PCA) fentanyl with IV parecoxib between patients with healthy liver with patients with diseased liver undergoing major liver resection. Patients with healthy liver undergoing partial hepatectomy as liver donors for liver transplantation (group 1) and patients with liver cirrhosis (Child's criteria A) undergoing major liver resection for hepatoma (group 2) were identified retrospectively. Both groups routinely received post-operative IV PCA fentanyl and a single dose of parecoxib 40 mg. They were followed up for 3 days or until PCA fentanyl was discontinued post-operatively. Daily Visual Analog Scale, PCA fentanyl usage, rescue attempts, and common drug side effects were collected and analyzed with the use of SPSS version 20. One hundred one patients were included in the study: 54 in group 1, and 47 in group 2. There were no statistical differences between the two groups in terms of the daily and total fentanyl usage, VAS resting, and incidence of itchiness. The rate of rescue analgesia on post-operative day (POD) 1 was lower in group 2, with a value of P = .045. VAS dynamics were better on POD 1 and 2 for group 2, with P = .05 and P = .012, respectively. We found that combining a single dose of IV parecoxib 40 mg with PCA fentanyl is an easy and effective method of acute pain control after major liver resection. We propose the careful usage of post-operative fentanyl and parecoxib in patients with diseased liver, given the difference in effect as compared with healthy liver. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk of fentanyl-involved overdose among those with past year incarceration: Findings from a recent outbreak in 2014 and 2015.

PubMed

Brinkley-Rubinstein, Lauren; Macmadu, Alexandria; Marshall, Brandon D L; Heise, Andrew; Ranapurwala, Shabbar I; Rich, Josiah D; Green, Traci C

2018-04-01

Overdose is the leading cause of unintentional injury-related death. Rhode Island (RI) has the highest rate of illicit drug use nationally and the 5th highest overdose mortality rate. RI has experienced an outbreak of fentanyl-related overdoses. In incarcerated populations, risk of overdose is greatly elevated. However, little is known about fentanyl-related overdose post-release. In the current analyses, we identify changes in fentanyl-related fatal overdose among those who died in 2014 and 2015 who were incarcerated in the year before death. We linked data from the RI Office of the Medical Examiner with records from the RI Department of Corrections. We calculated risk ratios and 95% confidence intervals using log-binomial regression to compare risk of fentanyl-involved overdose death. We also compared median time to death since release, median sentence length, and median number of incarcerations in 2014 and 2015. Results indicate that the risk of dying of a fentanyl-related overdose increased (RR: 1.99 (95% CI: 1.11-3.57, p = 0.014)) from 2014 to 2015 among those with past year incarceration. This study is one of the first to describe fentanyl-related fatal overdose among those with past year incarceration. In 2015 the median sentence was longer among those with a fentanyl-related overdose death and the median time from release to death among all who had past year incarceration extended past 90 days. Access to medications for addiction treatment, overdose education, and naloxone should be available during community re-entry and extended beyond the early post-release period. Copyright © 2018. Published by Elsevier B.V.

Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

PubMed

da Luz, Vinicius Fernando; Otsuki, Denise Aya; Gonzalez, Maria Margarita Castro; Negri, Elnara Marcia; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Malbouisson, Luiz Marcelo Sá; Viana, Bruno Gonçalves; Vane, Matheus Fachini; Carmona, Maria Jose Carvalho

2015-10-01

The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline. © 2015 Wiley Publishing Asia Pty Ltd.

Study of the newborn feeding behaviors and fentanyl concentration in colostrum after an analgesic dose of epidural and intravenous fentanyl in cesarean section.

PubMed

Goma, Hala M; Said, Reem N; El-Ela, Amr M

2008-05-01

To compare the effects of epidural and intravenous fentanyl on breast feeding behaviors and fentanyl concentration in the colostrum after an analgesic dose. This study was conducted at the Obstetrics Department of Kasr El-Aini Hospital-Cairo University, Cairo, Egypt. The studied mothers were 100 multipara, who have been subjected to cesarean section, and have a previous history of successful breast feeding. The study was conducted from May 2005 to May 2007. They were divided into 2 groups: group I included 50 patients who received epidural anesthesia with fentanyl, and group II included 50 patients who received spinal anesthesia with intravenous fentanyl, and both groups were observed for initial breast feeding behaviors of newborns, and fentanyl concentration in the colostrum at 45 minutes, and 24 hours after birth. The study included 100 multipara, 2 samples of colostrum were taken from each patients at 45 minutes, and at 24 hours. The levels of fentanyl concentration were greatest at 45 minutes of the initial sampling time, reaching 0.40+/-0.059 ng/ml in the epidural group, and 0.19+/-0.019 ng/ml in intravenous fentanyl group. There was no statistical difference in breast feeding behaviors at birth, or at 24 hours of age in both groups. Although the levels of fentanyl concentration were greatest at 45 minutes of the initial sampling time, it can be used safely as intravenous or epidural without affecting the initial breast feeding behaviors of the newborn.

[Low-dose hypobaric spinal anesthesia for anorectal surgery in jackknife position: levobupivacaine-fentanyl compared to lidocaine-fentanyl].

PubMed

de Santiago, J; Santos-Yglesias, J; Girón, J; Jiménez, A; Errando, C L

2010-11-01

To compare the percentage of patients who were able to bypass the postoperative intensive care recovery unit after selective spinal anesthesia with lidocaine-fentanyl versus levobupivacaine-fentanyl for anorectal surgery in jackknife position. Randomized double-blind clinical trial comparing 2 groups of 30 patients classified ASA 1-2. One group received 18 mg of 0.6% lidocaine plus 10 microg of fentanyl while the other group received 3 mg of 0.1% levobupivacaine plus 10 microg of fentanyl. Intraoperative variables were time of start of surgery, maximum extension of sensory blockade, requirement for rescue analgesics, and hemodynamic events. The level of sensory blockade was recorded at 5, 10, and 15 minutes after the start of surgery and at the end of the procedure. The degrees of postoperative motor blockade and proprioception were recorded, as were the results of the Romberg test and whether or not the patient was able to bypass the postoperative recovery unit. Also noted were times of start of ambulation and discharge, complications, and postoperative satisfaction. Intraoperative variables did not differ significantly between groups, and all patients in both groups bypassed the postoperative recovery unit. Times until walking and discharge home, complications, and overall satisfaction after surgery were similar in the 2 groups. Both spinal anesthetic solutions provide effective, selective anesthesia and are associated with similar rates of recovery care unit bypass after anorectal surgery in jackknife position.

Synergism between fentanyl and tramadol in tonic inflammatory pain: the orofacial formalin test.

PubMed

Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

2012-06-01

Opioids have been used for long time to management of pain, the coadministration of two opioids may induce synergism. The present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent cutaneous nociception in the region innervated by the trigeminal nerve. The i.p. administration of tramadol and fentanyl induced a dose-dependent antinociception with an ED(50) of 2.97 ± 0.32 mg/kg for phase I and 1.79 ± 0.30 mg/kg for phase II and 0.062 ± 0.0040 mg/kg in phase I and 0.041 ± 0.0039 mg/kg in phase II, respectively. The coadministration of fentanyl with tramadol induced synergism in both phases of the test with an interaction index of 0.343 and 0.163 for phase I and phase II, respectively. This finding could be explained by the more complex pharmacology of tramadol compared to fentanyl.

Trends in opioid analgesics sales to community pharmacies and hospitals in Italy (2000-2010).

PubMed

Caraceni, A T; Brunelli, C; Rocco, P; Minghetti, P

2013-08-01

Opioid consumption data in Italy have been widely studied. However, only aggregate data can be found in the published literature, and differences are expected by distribution setting (community pharmacies and hospitals). The aim of our paper is to analyse opioids sales trends in Italy in the decade 2000-2010, in an effort to explore such differences. Quarterly sales data of opioid medicinal products sold by wholesalers to both community pharmacies (retail) and to hospitals (non-retail) during the time period 2000-2010 were supplied by IMS Italy. Data were standardized using the Defined Daily Doses per day per 1000 inhabitants (DDDd/1000). Opioid sales have steadily increased during the time period considered going from 1.04 DDDd/1000 in 2000 to 4.9 in 2010 (+292%). Nonetheless relevant differences can be found both by distribution setting and drug type. In particular retail sales have increased by 286 % for WHO Step II opioids and by 575% for WHO Step III drugs, while non-retail sales have increased by 48% and 263%, respectively. In 2010, fentanyl and buprenorphine transdermal patches and oxycodone are more widely prescribed than morphine, in the retail setting, with fentanyl at large in the first position. In hospitals morphine and fentanyl almost equally share the 75% of the market. Data suggest that morphine is no more the opioid of first choice for severe pain in Italy, at least for outpatients. This is contradicting most international guidelines available in the 2000-2010 decade.

Selective enhancement of fentanyl-induced antinociception by the delta agonist SNC162 but not by ketamine in rhesus monkeys: Further evidence supportive of delta agonists as candidate adjuncts to mu opioid analgesics.

PubMed

Banks, Matthew L; Folk, John E; Rice, Kenner C; Negus, S Stevens

2010-12-01

Mu-opioid receptor agonists such as fentanyl are effective analgesics, but their clinical use is limited by untoward effects. Adjunct medications may improve the effectiveness and/or safety of opioid analgesics. This study compared interactions between fentanyl and either the noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine or the delta-opioid receptor agonist SNC162 [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-phenyl)methyl]-N,N-diethylbenzamide] in two behavioral assays in rhesus monkeys. An assay of thermal nociception evaluated tail-withdrawal latencies from water heated to 50 and 54°C. An assay of schedule-controlled responding evaluated response rates maintained under a fixed-ratio 30 schedule of food presentation. Effects of each drug alone and of three mixtures of ketamine+fentanyl (22:1, 65:1, 195:1 ketamine/fentanyl) or SNC162+fentanyl (59:1, 176:1, 528:1 SNC162/fentanyl) were evaluated in each assay. All drugs and mixtures dose-dependently decreased rates of food-maintained responding, and drug proportions in the mixtures were based on relative potencies in this assay. Ketamine and SNC162 were inactive in the assay of thermal antinociception, but fentanyl and all mixtures produced dose-dependent antinociception. Drug interactions were evaluated using dose-addition and dose-ratio analysis. Dose-addition analysis revealed that interactions for all ketamine/fentanyl mixtures were additive in both assays. SNC162/fentanyl interactions were usually additive, but one mixture (176:1) produced synergistic antinociception at 50°C. Dose-ratio analysis indicated that ketamine failed to improve the relative potency of fentanyl to produce antinociception vs. rate suppression, whereas two SNC162/fentanyl mixtures (59:1 and 176:1) increased the relative potency of fentanyl to produce antinociception. These results suggest that delta agonists may produce more selective enhancement than ketamine of mu agonist-induced antinociception. Copyright © 2010 Elsevier Inc. All rights reserved.

Comparison of Dexmedetomidine and Fentanyl as an Adjuvant to Ropivacaine for Postoperative Epidural Analgesia in Pediatric Orthopedic Surgery.

PubMed

Park, Sang Jun; Shin, Seokyung; Kim, Shin Hyung; Kim, Hyun Woo; Kim, Seung Hyun; Do, Hae Yoon; Choi, Yong Seon

2017-05-01

Opioids are commonly used as an epidural adjuvant to local anesthetics, but are associated with potentially serious side effects, such as respiratory depression. The aim of this study was to compare the efficacy and safety of dexmedetomidine with that of fentanyl as an adjuvant to epidural ropivacaine in pediatric orthopedic surgery. This study enrolled 60 children (3-12 years old) scheduled for orthopedic surgery of the lower extremities and lumbar epidural patient-controlled analgesia (PCA). Children received either dexmedetomidine (1 μg/kg) or fentanyl (1 μg/kg) along with 0.2% ropivacaine (0.2 mL/kg) via an epidural catheter at 30 minutes before the end of surgery. Postoperatively, the children were observed for ropivacaine consumption via epidural PCA, postoperative pain intensity, need for rescue analgesics, emergence agitation, and other adverse effects. The mean dose of bolus epidural ropivacaine was significantly lower within the first 6 h after surgery in the dexmedetomidine group, compared with the fentanyl group (0.029±0.030 mg/kg/h vs. 0.053±0.039 mg/kg/h, p=0.012). The median pain score at postoperative 6 h was also lower in the dexmedetomidine group, compared to the fentanyl group [0 (0-1.0) vs. 1.0 (0-3.0), p=0.039]. However, there was no difference in the need for rescue analgesia throughout the study period between groups. The use of dexmedetomidine as an epidural adjuvant had a significantly greater analgesic and local anesthetic-sparing effect, compared to fentanyl, in the early postoperative period in children undergoing major orthopedic lower extremity surgery. © Copyright: Yonsei University College of Medicine 2017

Comparison of Dexmedetomidine and Fentanyl as an Adjuvant to Ropivacaine for Postoperative Epidural Analgesia in Pediatric Orthopedic Surgery

PubMed Central

Park, Sang Jun; Shin, Seokyung; Kim, Shin Hyung; Kim, Hyun Woo; Kim, Seung Hyun; Do, Hae Yoon

2017-01-01

Purpose Opioids are commonly used as an epidural adjuvant to local anesthetics, but are associated with potentially serious side effects, such as respiratory depression. The aim of this study was to compare the efficacy and safety of dexmedetomidine with that of fentanyl as an adjuvant to epidural ropivacaine in pediatric orthopedic surgery. Materials and Methods This study enrolled 60 children (3–12 years old) scheduled for orthopedic surgery of the lower extremities and lumbar epidural patient-controlled analgesia (PCA). Children received either dexmedetomidine (1 µg/kg) or fentanyl (1 µg/kg) along with 0.2% ropivacaine (0.2 mL/kg) via an epidural catheter at 30 minutes before the end of surgery. Postoperatively, the children were observed for ropivacaine consumption via epidural PCA, postoperative pain intensity, need for rescue analgesics, emergence agitation, and other adverse effects. Results The mean dose of bolus epidural ropivacaine was significantly lower within the first 6 h after surgery in the dexmedetomidine group, compared with the fentanyl group (0.029±0.030 mg/kg/h vs. 0.053±0.039 mg/kg/h, p=0.012). The median pain score at postoperative 6 h was also lower in the dexmedetomidine group, compared to the fentanyl group [0 (0–1.0) vs. 1.0 (0–3.0), p=0.039]. However, there was no difference in the need for rescue analgesia throughout the study period between groups. Conclusion The use of dexmedetomidine as an epidural adjuvant had a significantly greater analgesic and local anesthetic-sparing effect, compared to fentanyl, in the early postoperative period in children undergoing major orthopedic lower extremity surgery. PMID:28332374

Comparison of epidural butorphanol and fentanyl as adjuvants in the lower abdominal surgery: A randomized clinical study

PubMed Central

Kaur, Jasleen; Bajwa, Sukhminder Jit Singh

2014-01-01

Background: Epidural opioids acting through the spinal cord receptors improve the quality and duration of analgesia along with dose-sparing effect with the local anesthetics. The present study compared the efficacy and safety profile of epidurally administered butorphanol and fentanyl combined with bupivacaine (B). Materials and Methods: A total of 75 adult patients of either sex of American Society of Anesthesiologist physical status I and II, aged 20-60 years, undergoing lower abdominal under epidural anesthesia were enrolled into the study. Patients were randomly divided into three groups of 25 each: B, bupivacaine and butorphanol (BB) and bupivacaine + fentanyl (BF). B (0.5%) 20 ml was administered epidurally in all the three groups with the addition of 1 mg butorphanol in BB group and 100 μg fentanyl in the BF group. The hemodynamic parameters as well as various block characteristics including onset, completion, level and duration of sensory analgesia as well as onset, completion and regression of motor block were observed and compared. Adverse events and post-operative visual analgesia scale scores were also noted and compared. Data was analyzed using ANOVA with post-hoc significance, Chi-square test and Fisher's exact test. Value of P < 0.05 was considered significant and P < 0.001 as highly significant. Results: The demographic profile of patients was comparable in all the three groups. Onset and completion of sensory analgesia was earliest in BF group, followed by BB and B group. The duration of analgesia was significantly prolonged in BB group followed by BF as compared with group B. Addition of butorphanol and fentanyl to B had no effect on the time of onset, completion and regression of motor block. No serious cardio-respiratory side effects were observed in any group. Conclusions: Butorphanol and fentanyl as epidural adjuvants are equally safe and provide comparable stable hemodynamics, early onset and establishment of sensory anesthesia. Butorphanol provides a significantly prolonged post-operative analgesia. PMID:24843326

Alfentanil and memory function. A comparison with fentanyl for day case termination of pregnancy.

PubMed

Kennedy, D J; Ogg, T W

1985-06-01

Two groups of 20 patients undergoing day case vaginal termination of pregnancy received either methohexitone and alfentanil 7.5 micrograms/kg or methohexitone and fentanyl 1.5 micrograms/kg. Their recovery times and memory function at 1 and 2 hours after surgery were compared. No difference in the recovery of the 2 groups was noted but at 2 hours after operation the alfentanil group showed impairment of memory for new facts compared with pre-operative memory function testing. This was not evident in the fentanyl group. Apart from this finding alfentanil was adjudged to be a suitable agent for day case anaesthesia.

A Comparison of the Effects of Fentanyl and Remifentanil on Nausea, Vomiting, and Pain after Cesarean Section

PubMed Central

Jabalameli, Mitra; Rouholamin, Safoura; Gourtanian, Fatemeh

2011-01-01

Background: The effects of different opioids on postoperative nausea and vomiting (PONV) and pain have not been conclusively determined. The aim of this study was to compare the effects of fentanyl, remifentanil or fentanyl plus morphine on the incidence of PONV and pain in women subjected to cesarean section under general anesthesia. Methods: The study was a randomized clinical trial recruiting 96 parturients with American Society of Anesthesiologists (ASA) physical status I and II. They scheduled for cesarean section under general anesthesia using sodium thiopental, succynylcholine, and isoflurane O2/N2O 50/50 mixture. After clamping the umbilical cord, the patients were given fentanyl (2 µg/kg/h), remifentanil (0.05 µg/kg/h), or fentanyl (2 µg/kg) pulse morphine (0.1 mg/kg) intravenously. Visual analog scale for pain and nausea, frequency of PONV, meperidine and metoclopramide consumption were evaluated at recovery, and 4, 8, 12 and 24 hours after the surgery. Results: There was no significant difference between the three groups in terms of frequency of nausea, vomiting, and mean nausea and pain scores at any time points. None of the patients required the administration of metoclopramide. However, the mean VAS for pain in remifentanil-treated group was insignificantly more than that in fentanyl- or fentanyl plus morphine-treated group at recovery or 4 hours after the surgery. The mean mepridine consumption in remifentanil-treated group was significantly (P=0.001) more than that in fentanyl- or fentanyl plus morphine-treated group in 24 hours after the surgery respectively. There was no significant difference in hemodynamic parameters of the three groups in all measurements after the surgery. Conclusion: The findings of this study showed that early postoperative analgesia was better with fentanyl, and postoperative meperidine consumption was significantly less with fentanyl than with remifentanil or combined fentayl and morphine. PMID:23357939

Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose

PubMed Central

Griswold, Matthew K.; Chai, Peter R.; Krotulski, Alex J.; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W.; Logan, Barry K.; Babu, Kavita M.

2018-01-01

Objective To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. Methods This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and non-pharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Results Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Conclusions Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700). PMID:28681615

Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose.

PubMed

Griswold, Matthew K; Chai, Peter R; Krotulski, Alex J; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W; Logan, Barry K; Babu, Kavita M

2018-01-01

To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).

The distribution and redistribution of fentanyl & norfentanyl in post mortem samples.

PubMed

Chatterton, C N; Scott-Ham, M

2018-03-01

This article compares 249 post mortem case reports that were positive for fentanyl/norfentanyl. All the cases were submitted to, and analyzed by, the toxicology department of the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada. This study highlights the varied distribution of fentanyl in the body after death as a result of misadventure, i.e., these are accidental drug overdose cases as opposed to a study of analytical data resulting from fentanyl use/administration in a clinical environment and/or death as a result of suicide. Post mortem samples were collected from more than one anatomical site and analyzed for fentanyl and norfentanyl using liquid chromatography-tandem mass spectrometry. Ante-mortem samples were available in 4 of these cases and were also analyzed. Post mortem mean blood fentanyl concentrations were found to be 13.2ng/mL (femoral), 19.1ng/mL (iliac) and 42.0ng/mL (subclavian). For norfentanyl the mean concentrations were 4.6ng/mL (femoral), 4.6ng/mL (iliac) and 7.4ng/mL (subclavian). Mean vitreous fentanyl and norfentanyl concentrations were 10.8ng/mL and 3.5ng/mL respectively. Mean liver fentanyl and norfentanyl concentrations were found to be 185.5ng/g and 18.8ng/g respectively. This study demonstrates the importance of multi-site sample collection and subsequent analysis for a thorough post mortem toxicological investigation. The study also highlights the risks and limitations associated with the interpretation of post mortem analytical results concerning fentanyl. Copyright © 2018 Elsevier B.V. All rights reserved.

A Comparison of Fentanyl and Flurbiprofen Axetil on Serum VEGF-C, TNF-α, and IL-1ß Concentrations in Women Undergoing Surgery for Breast Cancer.

PubMed

Wen, Yiyun; Wang, Mingde; Yang, Jinfeng; Wang, Yichun; Sun, Huiping; Zhao, Jianghong; Liu, Weizhen; Zhou, Zhengyu; Deng, Hongwu; Castillo-Pedraza, Catalina; Zhang, Yi; Candiotti, Keith A

2015-07-01

Vascular endothelial growth factor-C (VEGF-C), tumor necrosis factor-α (TNF-α), and interleukin-1ß(IL-1ß) have been shown to be associated with the recurrence and metastasis of breast cancer after surgery. This study tested the hypothesis that patients undergoing surgery for breast cancer, who received postoperative analgesia with flurbiprofen axetil combined with small doses of fentanyl (FA), exhibited reduced levels of VEGF-C, TNF-α, and IL-1ß compared with those patients receiving fentanyl alone (F). Forty-women with primary breast cancer undergoing a modified radical mastectomy were randomized to receive postoperative analgesia with flurbiprofen axetil combined with fentanyl or fentanyl alone. Venous blood was sampled before anesthesia, at the end of surgery, and at 48 hours after surgery, and the serum was analyzed. The primary endpoint was changes in the VEGF-C concentrations in serum. Group FA patients reported similar analgesic effects as group F patients at 2, 24, and 48 hours. At 48 hours, mean postoperative concentrations of VEGF-C in group F patients were higher than in group FA patients, 730.9 versus. 354.1 pg/mL (P = 0.003), respectively. The mean postoperative concentrations of TNF-α in group F patients were also higher compared with group FA patients 27.1 vs. 15.8 pg/mL (P = 0.005). Finally, the mean postoperative concentrations of IL-1ß in group F were also significantly higher than in group FA 497.5 vs. 197.7 pg/mL (P = 0.001). In patients undergoing a mastectomy, postoperative analgesia with flurbiprofen axetil, combined with fentanyl, were associated with decreases in serum concentrations of VEGF-C, TNF-α, and IL-1ß compared with patients receiving doses of only fentanyl. © 2014 World Institute of Pain.

Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

PubMed Central

Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

2009-01-01

The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

Reinforcement of subarachnoid block by epidural volume effect in lower abdominal surgery: A comparison between fentanyl and tramadol for efficacy and block properties

PubMed Central

Mohan, Atiharsh; Singh, Preet Mohinder; Malviya, Deepak; Arya, Sunil Kumar; Singh, Dinesh Kumar

2012-01-01

Background: Epidural volume extension (EVE) is claimed to increase the block height and decrease the dose requirement for intrathecal drug. However, almost all studies have been done in obstetric population and none actually compares the effect of additional drugs added to epidural volume. Materials and Methods: Seventy-five (ASA I and II) patients scheduled for lower abdominal surgery were randomly divided into three groups. All groups received intrathecal 10 mg bupivacaine; two groups received additional 10 ml of normal saline epidurally with 25 mg tramadol or 25 mg of fentanyl. Groups were than compared for maximal block height, rate of sensory block regression to T10, and motor block regression to Bromage scale of 0. Time to first analgesia and adverse effects were also compared among the three groups. Materials and Methods: Seventy-five (ASA I and II) patients scheduled for lower abdominal surgery were randomly divided into three groups. All groups received intrathecal 10 mg bupivacaine; two groups received additional 10 ml of normal saline epidurally with 25 mg tramadol or 25 mg of fentanyl. Groups were than compared for maximal block height, rate of sensory block regression to T10, and motor block regression to Bromage scale of 0. Time to first analgesia and adverse effects were also compared among the three groups. Results: Groups with EVE had statistically significant higher block height, with a significant faster regression that the control group. However, both fentanyl and tramadol groups were inseparable in respect to motor or sensory block regression. Fentanyl group had maximal time to first analgesia, followed by tramadol and control groups. Hemodynamic alterations were also more common in EVE groups. Conclusion: EVE can increase the block height significantly, but it seems to be limited only to the physical property of additional volume in epidural space and fentanyl or tramadol do not seem to differ in their ability to alter block properties. PMID:25885615

Optimization of the radioimmunoassays for measuring fentanyl and alfentanil in human serum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuettler, J.; White, P.F.

Measurement of serum fentanyl and alfentanil concentrations by radioimmunoassay (RIA) may result in significant errors and high variability when the technique described in the available fentanyl and alfentanil RIA kits is used. The authors found a 29-94% overestimation of measured fentanyl and alfentanil serum levels when 3H-fentanyl or 3H-alfentanil was added lastly to the mixture of antiserum and sample. This finding is related to a reduction in binding sites for the labeled compounds after preincubation of sample and antiserum. If this sequence is used, it becomes necessary to extend the incubation period up to 6 h for fentanyl and upmore » to 10 h for alfentanil in order to achieve equilibration between unlabeled and labeled drug with respect to antiserum binding. However, when antiserum is added lastly to the mixture of sample and labeled drug, measurement accuracy and precision for fentanyl and alfentanil serum concentrations are enhanced markedly. In addition, it is important to perform the calibration curves and sample measurements using the same medium (i.e., serum alone or a serum/buffer dilution). In summary, to optimize the RIA for fentanyl and alfentanil, the authors recommend the following: 1) adding the antiserum lastly to the mixture of sample and labeled drug; 2) performing calibration curves using patient's blank serum when possible; 3) carefully examining and standardizing each step of the RIA procedure to reduce variability, and, finally; 4) comparing results with those of other established RIA laboratories.« less

Subcutaneous Fentanyl Administration: A Novel Approach for Pain Management in a Rural and Suburban Prehospital Setting.

PubMed

Lebon, Johann; Fournier, Francis; Bégin, François; Hebert, Denise; Fleet, Richard; Foldes-Busque, Guilaume; Tanguay, Alain

2016-01-01

To determine the feasibility, safety, and effectiveness of the subcutaneous route of fentanyl administration by Basic Life Support-Emergency Medical Technicians (BLS-EMT) in a rural and suburban region, with the support of an online pain management medical control center. Retrospective study of patients who received subcutaneous fentanyl and were transported by BLS-EMT to the emergency department (ED) of an academic hospital between July 1, 2013 and January 1, 2014, inclusively. Fentanyl orders were obtained from emergency physicians via an online medical control (OLMC) center. Effectiveness was defined by changes in pain scores 15 minutes, 30 minutes, and 45+ minutes after initial fentanyl administration. Safety was evaluated by measuring vital signs, Ramsay sedation scores, and adverse events subsequent to fentanyl administration. Feasibility was defined as successful fentanyl administration by BLS-EMT. SPSS-20 was used for descriptive statistics, and independent t-tests and Mann-Whitney U tests were used to determine inter- and intra-group differences based on transport time. Two hundred and eighty-eight patients (288; 14 to 93 years old) with pain scores ≥7 were eligible for the study. Of the 284 (98.6%) who successfully received subcutaneous fentanyl, 35 had missing records or data, and 249 (86.5%) were included in analyses. Average pain score pre-fentanyl was 8.9 ± 1.1. Patients <70 years old received a higher dose of fentanyl than those ≥70 years old (1.4 ± 0.3 vs, 0.8 ± 0.2 mcg/kg, p < 0.05). Pain scores decreased significantly post-fentanyl administration and the proportion of patients achieving pain relief increased significantly (p < 0.05) over the course of transport to ED (15 minutes, 30 minutes, 45+ minutes). Only 1.6% of patients experienced adverse events, including hypotension (n = 2; 0.8%), nausea (n = 1; 0.4%), and Ramsay level >3 (n = 1; 0.4%). Prehospital subcutaneous fentanyl administration by BLS-EMT with the support of an OLMC center is a safe and feasible approach to pain relief in prehospital settings, and is not associated with major adverse events. Effectiveness, subsequent to subcutaneous fentanyl administration is characterized by a decrease in pain over the course of transport to ED. Further studies are needed to compare the effectiveness of SC administration by EMS with other routes of administration and other analgesics.

On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl.

PubMed

Shin, Soo Hyeon; Ghosh, Priyanka; Newman, Bryan; Hammell, Dana C; Raney, Sam G; Hassan, Hazem E; Stinchcomb, Audra L

2017-09-01

At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The J max enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p < 0.05) among the three fentanyl TDSs. The J max enhancement ratios due to transient heat exposure were significantly different for the two nicotine TDSs, but not for the three fentanyl TDSs. Furthermore, the transient heat exposure affected the clearance of drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.

Pragmatic pharmacology: population pharmacokinetic analysis of fentanyl using remnant samples from children after cardiac surgery

PubMed Central

Van Driest, Sara L.; Marshall, Matthew D.; Hachey, Brian; Beck, Cole; Crum, Kim; Owen, Jill; Smith, Andrew H.; Kannankeril, Prince J.; Woodworth, Alison; Caprioli, Richard M.

2016-01-01

Aims One barrier contributing to the lack of pharmacokinetic (PK) data in paediatric populations is the need for serial sampling. Analysis of clinically obtained specimens and data may overcome this barrier. To add evidence for the feasibility of this approach, we sought to determine PK parameters for fentanyl in children after cardiac surgery using specimens and data generated in the course of clinical care, without collecting additional blood samples. Methods We measured fentanyl concentrations in plasma from leftover clinically‐obtained specimens in 130 paediatric cardiac surgery patients and successfully generated a PK dataset using drug dosing data extracted from electronic medical records. Using a population PK approach, we estimated PK parameters for this population, assessed model goodness‐of‐fit and internal model validation, and performed subset data analyses. Through simulation studies, we compared predicted fentanyl concentrations using model‐driven weight‐adjusted per kg vs. fixed per kg fentanyl dosing. Results Fentanyl clearance for a 6.4 kg child, the median weight in our cohort, is 5.7 l h–1 (2.2–9.2 l h–1), similar to values found in prior formal PK studies. Model assessment and subset analyses indicated the model adequately fit the data. Of the covariates studied, only weight significantly impacted fentanyl kinetics, but substantial inter‐individual variability remained. In simulation studies, model‐driven weight‐adjusted per kg fentanyl dosing led to more consistent therapeutic fentanyl concentrations than fixed per kg dosing. Conclusions We show here that population PK modelling using sparse remnant samples and electronic medical records data provides a powerful tool for assessment of drug kinetics and generation of individualized dosing regimens. PMID:26861166

A Novel Oral Fluid Assay (LC-QTOF-MS) for the Detection of Fentanyl and Clandestine Opioids in Oral Fluid After Reported Heroin Overdose.

PubMed

Griswold, Matthew K; Chai, Peter R; Krotulski, Alex J; Friscia, Melissa; Chapman, Brittany P; Varma, Neha; Boyer, Edward W; Logan, Barry K; Babu, Kavita M

2017-12-01

The adulteration of heroin with non-pharmaceutical fentanyl and other high-potency opioids is one of the factors contributing to striking increases in overdose deaths. To fully understand the magnitude of this problem, accurate detection methods for fentanyl and other novel opioid adulterant exposures are urgently required. The objective of this work was to compare the detection of fentanyl in oral fluid and urine specimens using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) in a population of heroin users presenting to the Emergency Department after overdose. This was a prospective observational study of adult Emergency Department patients who presented after a reported heroin overdose requiring naloxone administration. Participants provided paired oral fluid and urine specimens, which were prepared, extracted, and analyzed using a dual LC-QTOF-MS workflow for the identification of traditional and emerging drugs of abuse. Analytical instrumentation included SCIEX TripleTOF® 5600+ and Waters Xevo® G2-S QTOF systems. Thirty participants (N = 30) were enrolled during the study period. Twenty-nine participants had fentanyl detected in their urine, while 27 had fentanyl identified in their oral fluid (overall agreement 93.3%, positive percent agreement 93.1%). Cohen's Kappa (k) was calculated and demonstrated moderately, significant agreement (k = 0.47; p value 0.002) in fentanyl detection between oral fluid and urine using this LC-QTOF-MS methodology. Additional novel opioids and metabolites, including norfentanyl, acetylfentanyl, and U-47700, were detected during this study. In this study of individuals presenting to the ED after reported heroin overdose, a strikingly high proportion had a detectable fentanyl exposure. Using LC-QTOF-MS, the agreement between paired oral fluid and urine testing for fentanyl detection indicates a role for oral fluid testing in surveillance for nonpharmaceutical fentanyl. Additionally, the use of LC-QTOF-MS allowed for the detection of other clandestine opioids (acetylfentanyl and U-47700) in oral fluid.

Synergistic interaction between fentanyl and the histamine H3 receptor agonist R-(alpha)-methylhistamine, on the inhibition of nociception and plasma extravasation in mice.

PubMed

Poveda, Raquel; Fernández-Dueñas, Víctor; Fernández, Alejandro; Sánchez, Sílvia; Puig, Margarita M; Planas, Eulàlia

2006-07-10

Here we report a synergistic interaction between fentanyl and the histamine H(3) receptor agonist R-(alpha)-methylhistamine on the inhibition of nociception and plasma extravasation in mice. Chronic inflammation was induced by subplantar injection of Complete Freund's Adjuvant into the right hind paw, and the effect of the drugs was evaluated 7 days later. Nociception and plasma extravasation were assessed by hot-plate and Evans blue tests respectively. Subcutaneous administration of fentanyl (0.01-0.1 mg/kg) induced dose-related anti-nociceptive and anti-extravasation effects (E(max)=100% and 62%, respectively). R-(alpha)-methylhistamine administration (0.3-3 mg/kg) showed a dose-related inhibitory effect on extravasation (E(max)=65%) but not on nociception. To analyze possible interaction between these two drugs, a dose-response curve to fentanyl plus a fixed dose of R-(alpha)-methylhistamine (0.5 mg/kg) was obtained. The dose-response curve for the combined treatment showed a shift to the left compared with that for fentanyl alone. Our results confirm that fentanyl and R-(alpha)-methylhistamine interact in a synergic way, inhibiting nociception and plasma extravasation.

Fentanyl Buccal Tablet for the Treatment of Breakthrough Pain: Pharmacokinetics of Buccal Mucosa Delivery and Clinical Efficacy

PubMed Central

Darwish, Mona; Hamed, Ehab; Messina, John

2010-01-01

The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc.) employs OraVescent® drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP. PMID:20634985

Association between Genetic Polymorphisms in Cav2.3 (R-type) Ca2+ Channels and Fentanyl Sensitivity in Patients Undergoing Painful Cosmetic Surgery

PubMed Central

Fukuda, Ken-ichi; Kasai, Shinya; Hasegawa, Junko; Hayashida, Masakazu; Minami, Masabumi; Ikeda, Kazutaka

2013-01-01

Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, lead to different proper doses of fentanyl, which can hamper effective pain treatment. Voltage-activated Ca2+ channels (VACCs) play a crucial role in the nervous system by controlling membrane excitability and calcium signaling. Cav2.3 (R-type) VACCs have been especially thought to play critical roles in pain pathways and the analgesic effects of opioids. However, unknown is whether single-nucleotide polymorphisms (SNPs) of the human CACNA1E (calcium channel, voltage-dependent, R type, alpha 1E subunit) gene that encodes Cav2.3 VACCs influence the analgesic effects of opioids. Thus, the present study examined associations between fentanyl sensitivity and SNPs in the human CACNA1E gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. We first conducted linkage disequilibrium (LD) analyses of 223 SNPs in a region that contains the CACNA1E gene using genomic samples from 100 patients, and a total of 13 LD blocks with 42 Tag SNPs were observed within and around the CACNA1E gene region. In the preliminary study using the same 100 genomic samples, only the rs3845446 A/G SNP was significantly associated with perioperative fentanyl use among these 42 Tag SNPs. In a confirmatory study using the other 255 genomic samples, this SNP was also significantly associated with perioperative fentanyl use. Thus, we further analyzed associations between genotypes of this SNP and all of the clinical data using a total of 355 samples. The rs3845446 A/G SNP was associated with intraoperative fentanyl use, 24 h postoperative fentanyl requirements, and perioperative fentanyl use. Subjects who carried the minor G allele required significantly less fentanyl for pain control compared with subjects who did not carry this allele. Although further validation is needed, the present findings show the possibility of the involvement of CACNA1E gene polymorphisms in fentanyl sensitivity. PMID:23940630

Glasgow Coma Scale Scores, Early Opioids, and 4-year Psychological Outcomes among Combat Amputees

DTIC Science & Technology

2014-01-01

psychological outcomes, loss of consciousness, military and VA health data, morphine , posttraumatic stress disorder, traumatic brain injury. INTRODUCTION...appropriate for postinjury analgesia [15–17]. Unfortu- nately, little research has compared the psychological benefits of morphine or fentanyl...that morphine reduced PTSD compared with fentanyl because mor- phine produced more long-lasting pain relief and/or was more effective at blocking

Use of fentanyl and midazolam in mechanically ventilated children--Does the method of infusion matter?

PubMed

da Silva, Paulo Sérgio Lucas; Reis, Maria Eunice; de Aguiar, Vânia Euzébio; Fonseca, Marcelo Cunio Machado

2016-04-01

Benzodiazepines and opioids are commonly used in pediatric intensive care unit. However, there is no previous study assessing the use of administering these drugs combined (single solution) or separately. We sought to evaluate the impact of these 2 different methods of providing sedation/analgesia in pediatric intensive care unit. One hundred twelve patients mechanically ventilated for more than 48 hours were randomized to receive a protocolized sedation regime comprising midazolam and fentanyl either separately (group 1, 57 patients) or combined as a single solution (group 2, 55 patients). Primary end point variable was the cumulated dose of midazolam and fentanyl. The median cumulated doses of both fentanyl (0.19 vs 0.37 mg/kg, P < .05) and midazolam (28.8 vs 45.6 mg/kg, P < .05) required in group 2 were higher when compared with those of group 1. Moreover, group 2 patients had a significantly longer time of vasopressor drugs requirement and a higher number of patients developing tolerance. Patients who received a single solution of midazolam and fentanyl had a higher cumulated dose of compared with those patients who did not. The potential risk for long-term neurologic effects on developing brains associated with this finding should be considered. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes in blood glucose level during and after light sedations using propofol-fentanyl and midazolam-fentanyl in diabetic patients who underwent cataract surgery.

PubMed

Khalighinejad, Pooyan; Rahimi, Mojtaba; Naghibi, Khosro; Niknam, Negar

2015-01-01

Surgeries may trigger the stress response which leads to changes in blood glucose level, and studies suggest that different sedation and anesthesia methods have different effects on blood glucose level. The aim of this study was to investigate changes of blood glucose levels in diabetic patients and compare them in two sedation methods of propofol + fentanyl and midazolam + fentanyl. Totally, 80 diabetic candidates for cataract surgery who had all the inclusion criteria, underwent cataract surgery using two methods of propofol (1 mg/kg/h) + fentanyl (2 μg/kg) (Group P) and midazolam (0.03 mg/kg) + fentanyl (2 μg/kg) (Group M) for light sedation. In the end, 70 patients (Group P n = 35 and Group M n = 35) remained in the study. Patients' blood glucose levels, vital signs, and hemodynamic data were assessed 30 min prior to the surgery, each 15 min during surgery and at the end of surgery. Hemodynamic parameters did not have a statistically significant difference between the two groups mean blood glucose level in Group M was 149.15 mg/dl and in Group P was 149.2 mg/dl, and based on repeated measures analysis of variance test, significant differences were not observed between the two groups (P = 0.99). T-test showed no significant differences in the blood glucose level at any time of the study between the two groups. Light sedation methods of propofol + fentanyl and midazolam + fentanyl did not have any differences in alteration of blood glucose level.

A review: Fentanyl and non-pharmaceutical fentanyls.

PubMed

Suzuki, Joji; El-Haddad, Saria

2017-02-01

Fentanyl and non-pharmaceutical fentanyls (NPFs) have been responsible for numerous outbreaks of overdoses all over the United States since the 1970s. However, there has been a growing concern in recent years that NPFs are contributing to an alarming rise in the number of opioid-related overdoses. The authors conducted a narrative review of the published and grey literature on fentanyl and NPFs in PubMed, Google Scholar, and Google using the following search terms: "fentanyl", "non-pharmaceutical fentanyl", "fentanyl analogs", "fentanyl laced heroin" and "fentanyl overdose". References from relevant publications and grey literature were also reviewed to identify additional citations for inclusion. The article reviews the emergence and misuse of fentanyl and NPFs, their clinical pharmacology, and the clinical management and prevention of fentanyl-related overdoses. Fentanyl and NPFs may be contributing to the recent rise in overdose deaths in the United States. There is an urgent need to educate clinicians, researchers, and patients about this public health threat. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of preoperative incentive spirometry on fentanyl-induced cough: a prospective, randomized, controlled study.

PubMed

Goyal, Vipin Kumar; Bhargava, Suresh Kumar; Baj, Birbal

2017-10-01

Fentanyl-induced cough (FIC) has a reported incidence of 13-65% on induction of anesthesia. Incentive spirometry (IS) creates forceful inspiration, while stretching pulmonary receptors. We postulated that spirometry just before the fentanyl (F) bolus would decrease the incidence and severity of FIC. This study enrolled 200 patients aged 18-60 years and with American Society of Anesthesiologists status I or II. The patients were allocated to two groups of 100 patients each depending on whether they received preoperative incentive spirometry before fentanyl administration. Patients in the F+IS group performed incentive spirometry 10 times just before an intravenous bolus of 3 µg/kg fentanyl in the operating room. The onset time and number of coughs after fentanyl injection were recorded as primary outcomes. Any significant changes in blood pressure, heart rate, or adverse effects of the drug were recorded as secondary outcomes. Patients in the F+IS group had a significantly lower incidence of FIC than in the F group (6% vs. 26%) (P < 0.05). The severity of cough in the F+IS group was also significantly lower than that in group F (mild, 5 vs. 17; moderate 1 vs. 7; severe, 0 vs. 2) (P < 0.05). The median onset time was comparable in both groups (9 s [range: 6-12 s] in both groups). Preoperative incentive spirometry significantly reduces the incidence and severity of FIC when performed just before fentanyl administration.

Effect of preoperative incentive spirometry on fentanyl-induced cough: a prospective, randomized, controlled study

PubMed Central

Bhargava, Suresh Kumar; Baj, Birbal

2017-01-01

Background Fentanyl-induced cough (FIC) has a reported incidence of 13–65% on induction of anesthesia. Incentive spirometry (IS) creates forceful inspiration, while stretching pulmonary receptors. We postulated that spirometry just before the fentanyl (F) bolus would decrease the incidence and severity of FIC. Methods This study enrolled 200 patients aged 18–60 years and with American Society of Anesthesiologists status I or II. The patients were allocated to two groups of 100 patients each depending on whether they received preoperative incentive spirometry before fentanyl administration. Patients in the F+IS group performed incentive spirometry 10 times just before an intravenous bolus of 3 µg/kg fentanyl in the operating room. The onset time and number of coughs after fentanyl injection were recorded as primary outcomes. Any significant changes in blood pressure, heart rate, or adverse effects of the drug were recorded as secondary outcomes. Results Patients in the F+IS group had a significantly lower incidence of FIC than in the F group (6% vs. 26%) (P < 0.05). The severity of cough in the F+IS group was also significantly lower than that in group F (mild, 5 vs. 17; moderate 1 vs. 7; severe, 0 vs. 2) (P < 0.05). The median onset time was comparable in both groups (9 s [range: 6–12 s] in both groups). Conclusions Preoperative incentive spirometry significantly reduces the incidence and severity of FIC when performed just before fentanyl administration. PMID:29046775

Administration order of midazolam/fentanyl for moderate dental sedation.

PubMed

Lobb, Douglas; Clarke, Alix; Lai, Hollis

2018-02-01

The purpose of this study is to investigate the effects of administration order when a sedative drug (midazolam) and an opioid analgesic drug (fentanyl) is applied for moderate intravenous (IV) sedation in dentistry. A retrospective chart review was conducted in one dental clinic during its transition from a midazolam-first to a fentanyl-first protocol for dental procedures requiring moderate IV sedation. Physiological parameters, drug administration times, patient recovery times, drug dosages, and patient recall and satisfaction were investigated for differences. A total of 76 charts (40 midazolam-first and 36 fentanyl-first administrations), were used in the analysis. Administering midazolam first resulted in an average 4.38 min (52%) decrease in administration times (P < 0.001), and a decrease in procedural recollection immediately following the procedure (P = 0.03), and 24 to 48 hours later (P = 0.009). Administering fentanyl first required an average of 2.43 mg (29%) less midazolam (P < 0.001). No significant differences were found for change in vital signs, minimum oxygen saturation levels, recovery times, and patient satisfaction (P > 0.05). Oxygen saturation levels did not drop below 90% for either group; however, 5 cases in the fentanyl-first group fell to between 90% and 92%, compared with 0 cases in the midazolam-first group. The administration order of fentanyl and midazolam may have different effects on patients and the sedation procedure. Findings from this study should be used to facilitate discussion among dental practitioners and to guide additional research investigating this topic.

Effect of Fentanyl Nasal Packing Treatment on Patients With Acute Postoperative Pain After Nasal Operation: A Randomized Double-Blind Controlled Trial.

PubMed

Kim, Kwan-Sub; Yeo, Nam-Kyung; Kim, Seong-Su; Park, Woong-Sub; Kwak, Su-Hyun; Cho, Sang-Hyeon; Sung, Gyu-Wan; Kim, Hae-Sook; Yi, Sang-Wook; Cho, Hae Jun

2018-05-01

Nasal packing is an option for bleeding control after endoscopic sinus surgery and septoplasty. Although new packing materials have been developed, patients still suffer from pain and require additional analgesics treatments. In this study, a prospective, randomized, and double-blind controlled trial was designed to evaluate the effect of fentanyl-soaked packing on pain after endoscopic sinus surgery and septoplasty. One hundred fifty-two patients who underwent nasal surgeries due to chronic rhinosinusitis or nasal septal deviation were enrolled in this study. At the end of operation, 50 mcg fentanyl-soaked biodegradable synthetic polyurethane foams packing Nasopore or Merocel were applied to a group of 79 patients, and saline-soaked ones were applied to another group of 73 patients. To evaluate the influence of fentanyl on postoperative nasal pain, patients' conditions were assessed via means of Numeric Rating Scale, patient satisfaction, and Ramsay Sedation Scale. In addition, symptoms of headache or sore throat and any signs of cardiopulmonary-relevant indicators were monitored. The fentanyl group had significantly decreased Numeric Rating Scale and increased patient satisfaction in every operation type for the majority of postoperative time periods ( P < .05) with reduced postoperative headache and sore throat compared to the control group. The fentanyl group showed a higher score on Ramsay Sedation Scale than the control group ( P < .05 in group including endoscopic sinus surgery). There were no significant differences in cardiopulmonary-relevant indicators between the 2 groups ( P > .05). Fentanyl group showed significantly reduced postoperative pain without serious adverse effects. We suggest that topical fentanyl application to nasal packs can be a useful method to reduce pain during the early postoperative period after endoscopic sinus surgery and septoplasty.

A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats.

PubMed

Savić Vujović, Katarina R; Vučković, Sonja; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Vučetić, Čedomir; Džoljić, Eleonora; Prostran, Milica

2013-04-01

In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of μ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (±)-cis-3-methyl fentanyl (CM), (±)-cis-3-carbomethoxy fentanyl (C), (±)trans-3-carbomethoxy fentanyl (T) and (±)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27)>F(1)>C(0.35)≥T(0.11)≥B(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46)≥T(0.11)≥B(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-α,α,17-trimethyl-, (5α,7α) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)>O(5)≥T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3)≥T(2.3)>M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6-11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.

Effect of fentanyl and lidocaine on the end-tidal sevoflurane concentration preventing motor movement in dogs.

PubMed

Suarez, Martin A; Seddighi, Reza; Egger, Christine M; Rohrbach, Barton W; Cox, Sherry K; KuKanich, Butch K; Doherty, Thomas J

2017-01-01

OBJECTIVE To determine effects of fentanyl, lidocaine, and a fentanyl-lidocaine combination on the minimum alveolar concentration of sevoflurane preventing motor movement (MAC NM ) in dogs. ANIMALS 6 adult Beagles. PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals). Baseline MAC NM (MAC NM-B ) was determined starting 45 minutes after induction of anesthesia. Dogs then received 1 of 3 treatments IV: fentanyl (loading dose, 15 μg/kg; constant rate infusion [CRI], 6 μg/kg/h), lidocaine (loading dose, 2 mg/kg; CRI, 6 mg/kg/h), and the fentanyl-lidocaine combination at the same doses. Determination of treatment MAC NM (MAC NM-T ) was initiated 90 minutes after start of the CRI. Venous blood samples were collected at the time of each treatment MAC NM measurement for determination of plasma concentrations of fentanyl and lidocaine. RESULTS Mean ± SEM overall MAC NM-B for the 3 treatments was 2.70 ± 0.27 vol%. The MAC NM decreased from MAC NM-B to MAC NM-T by 39%, 21%, and 55% for fentanyl, lidocaine, and the fentanyl-lidocaine combination, respectively. This decrease differed significantly among treatments. Plasma fentanyl concentration was 3.25 and 2.94 ng/mL for fentanyl and the fentanyl-lidocaine combination, respectively. Plasma lidocaine concentration was 2,570 and 2,417 ng/mL for lidocaine and the fentanyl-lidocaine combination, respectively. Plasma fentanyl and lidocaine concentrations did not differ significantly between fentanyl and the fentanyl-lidocaine combination or between lidocaine and the fentanyl-lidocaine combination. CONCLUSIONS AND CLINICAL RELEVANCE CRIs of fentanyl, lidocaine, and the fentanyl-lidocaine combination at the doses used were associated with clinically important and significant decreases in the MAC NM of sevoflurane in dogs.

Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

PubMed Central

2010-01-01

Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist) and parecoxib (a selective cyclooxygenase-2 inhibitor) on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals) were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG) desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity), while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect. PMID:20089200

The fentanyl concentration required for immobility under propofol anesthesia is reduced by pre-treatment with flurbiprofen axetil.

PubMed

Kodaka, Mitsuharu; Tsukakoshi, Mikiko; Miyao, Hideki; Tsuzaki, Koichi; Ichikawa, Junko; Komori, Makiko

2013-12-01

We hypothesized that nonsteroidal anti-inflammatory drugs decrease the plasma fentanyl concentration required to produce immobility in 50% of patients in response to skin incision (Cp50incision) compared with placebo under target-controlled infusion (TCI) propofol anesthesia. Sixty-two unpremedicated patients scheduled to undergo gynecologic laparoscopy were randomly assigned to receive placebo (control group) or flurbiprofen axetil 1 mg·kg(-1) (flurbiprofen group) preoperatively. General anesthesia was induced with fentanyl and propofol, and intubation was performed after succinylcholine 1 mg·kg(-1). Propofol was administered via a target-controlled infusion (TCI) system (Diprifusor™) set at an effect-site concentration of 5 μg·mL(-1). Fentanyl was given by a TCI system using the STANPUMP software (Schafer model). The concentration for the first patient was set at 3 ng·mL(-1) and modified in each group according to the up-down method. Skin incision was performed after more than ten minutes equilibration time. Serum fentanyl concentration, bispectral index (BIS), and hemodynamic parameters were measured two minutes before and after skin incision. The Cp50incision of fentanyl was derived from the mean of the crossovers (i.e., the serum fentanyl concentrations of successive participants who responded and those who did not or vice versa). Ten and 11 independent crossover pairs were collected in the control and flurbiprofen groups, respectively, representing 42 of 62 enrolled patients. The mean (SD) fentanyl Cp50incision was less in the flurbiprofen group [0.84 (0.63) ng·mL(-1)] than in the control group [1.65 (1.15) ng·mL(-1)]; P = 0.007; however, there were no differences in BIS, blood pressure, or heart rate, between groups. Preoperative flurbiprofen axetil decreased the Cp50incision of fentanyl by 49% during propofol anesthesia without changing the BIS or hemodynamic variables.

Increase in Drug Overdose Deaths Involving Fentanyl-Rhode Island, January 2012-March 2014.

PubMed

Mercado, Melissa C; Sumner, Steven A; Spelke, M Bridget; Bohm, Michele K; Sugerman, David E; Stanley, Christina

2018-03-01

This study identified sociodemographic, substance use, and multiple opioid prescriber and dispenser risk factors among drug overdose decedents in Rhode Island, in response to an increase in overdose deaths (ODs) involving fentanyl. This cross-sectional investigation comprised all ODs reviewed by Rhode Island's Office of the State Medical Examiners (OSME) during January 2012 to March 2014. Data for 536 decedents were abstracted from OSME's charts, death certificates, toxicology reports, and Prescription Monitoring Program (PMP) databases. Decedents whose cause of death involved illicit fentanyl (N = 69) were compared with decedents whose causes of death did not involve fentanyl (other drug decedents; N = 467). Illicit-fentanyl decedents were younger than other drug decedents (P = 0.005). While more other-drug decedents than illicit fentanyl decedents had postmortem toxicological evidence of consuming heroin (31.9% vs 19.8%, P < 0.001) and various pharmaceutical substances (P = 0.002-0.027), third party reports indicated more recent heroin use among illicit fentanyl decedents (62.3% vs 45.6%, P = 0.002). Approximately 35% of decedents filled an opioid prescription within 90 days of death; of these, one-third had a mean daily dosage greater than 100 morphine milligram equivalents (MME/day). Most decedents' opioid prescriptions were filled at one to two dispensers (83.9%) and written by one to two prescribers (75.8%). Notably, 29.2% of illicit fentanyl and 10.5% of other drug decedents filled prescriptions for buprenorphine, which is used to treat opioid use disorders. Illicit-fentanyl deaths frequently involved other illicit drugs (e.g., cocaine, heroin). The proportion of all decedents acquiring greater than 100 MME/day prescription dosages written and/or filled by few prescribers and dispensers is concerning. To protect patients, prescribers and dispensers should review PMP records and substance abuse history prior to providing opioids.

Overdose Deaths Related to Fentanyl and Its Analogs - Ohio, January-February 2017.

PubMed

Daniulaityte, Raminta; Juhascik, Matthew P; Strayer, Kraig E; Sizemore, Ioana E; Harshbarger, Kent E; Antonides, Heather M; Carlson, Robert R

2017-09-01

Ohio is experiencing unprecedented loss of life caused by unintentional drug overdoses (1), with illicitly manufactured fentanyl (IMF) emerging as a significant threat to public health (2,3). IMF is structurally similar to pharmaceutical fentanyl, but is produced in clandestine laboratories and includes fentanyl analogs that display wide variability in potency (2); variations in chemical composition of these drugs make detection more difficult. During 2010-2015, unintentional drug overdose deaths in Ohio increased 98%, from 1,544 to 3,050.* In Montgomery County (county seat: Dayton), one of the epicenters of the opioid epidemic in the state, unintentional drug overdose deaths increased 40% in 1 year, from 249 in 2015 to 349 in 2016 (estimated unadjusted mortality rate = 57.7 per 100,000) (4). IMFs have not been part of routine toxicology testing at the coroner's offices and other types of medical and criminal justice settings across the country (2,3). Thus, data on IMF test results in the current outbreak have been limited. The Wright State University and the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory (MCCO/MVRCL) collaborated on a National Institutes of Health study of fentanyl analogs and metabolites and other drugs identified in 281 unintentional overdose fatalities in 24 Ohio counties during January-February 2017. Approximately 90% of all decedents tested positive for fentanyl, 48% for acryl fentanyl, 31% for furanyl fentanyl, and 8% for carfentanil. Pharmaceutical opioids were identified in 23% of cases, and heroin in 6%, with higher proportions of heroin-related deaths in Appalachian counties. The majority of decedents tested positive for more than one type of fentanyl. Evidence suggests the growing role of IMFs, and the declining presence of heroin and pharmaceutical opioids in unintentional overdose fatalities, compared with 2014-2016 data from Ohio and other states (3-5). There is a need to include testing for IMFs as part of standard toxicology panels for biological specimens used in the medical, substance abuse treatment, and criminal justice settings.

Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida

PubMed Central

Pearson, Julia; Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Mainland, Mary; Hair, Laura; Devers, Kelly; Chrostowski, Leszek; Arbefeville, Elise; Merves, Michele

2017-01-01

In the last two years, an epidemic of 40 fatal heroin overdose cases has occurred in the Tampa area of Florida. Of these cases, 14 involved fentanyl and acetyl fentanyl. Victim demographics, case histories, toxicology findings, and causes and manners of death for all 40 deaths are presented. In 26 deaths in which acetyl fentanyl or fentanyl were not involved, free and total peripheral blood morphine concentrations were consistent with fatal heroin intoxications, averaging 0.16 mg/L and 0.35 mg/L, respectively. In the heroin cases with fentanyl present (n=7), the average free morphine concentration was 0.040 mg/L, the average total morphine concentration was 0.080 mg/L, and the average fentanyl concentration was 0.012 mg/L. In the cases with heroin, fentanyl, and acetyl fentanyl (n=3), the average free morphine concentration was 0.010 mg/L, the average total morphine concentration was 0.030 mg/L, the average fentanyl concentration was 0.018 mg/L, and the average acetyl fentanyl concentration was 0.008 mg/L. In the cases involving only acetyl fentanyl (without heroin or fentanyl, n=4), the average acetyl fentanyl concentration was 0.47 mg/L and the average acetyl norfentanyl concentration was 0.053 mg/L. The presented cases, with associated drug concentrations, case histories, demographics, and causes and manners of death may help provide assistance with the interpretation of the postmortem findings. Based on case circumstances, autopsy results, and toxicology results, it is evident that fentanyl and/or acetyl fentanyl, when present, contributed to the cause of death. PMID:29034049

Two syringe spinal anesthesia technique for cesarean section: A controlled randomized study of a simple way to achieve more satisfactory block and less hypotension.

PubMed

Keera, Amr Aly Ismail; Elnabtity, Ali Mohamed Ali

2016-01-01

Multiple trials have been tried to prevent hypotension during spinal anesthesia. However, the drug choice and mode of administration is still a matter of debate. To compare the outcome of spinal injection of hyperbaric bupivacaine and fentanyl separately to standard injection of mixed fentanyl with hyperbaric bupivacaine. A randomized, controlled clinical trial. One hundred twenty-four parturient scheduled for elective cesarean section were randomly allocated into two groups, each 62 parturient: Group M received spinal anesthesia using 10 mg bupivacaine 0.5% premixed with 25 μg fentanyl in the same syringe and Group S received 25 μg fentanyl in one syringe and 10 mg bupivacaine 0.5% without barbotage in a second syringe. Patients with intraoperative pain that was controllable without the need for a shift to general anesthesia was significantly lower in Group S (3.2%) than in Group M (16.1%). The frequency of hypotension was significantly lower in Group S compared to Group M (P < 0.05). Time till the onset of sensory block was nonsignificantly shorter with nonsignificantly higher mean level of maximal sensory block in Group S compared to Group M (P > 0.05). There was no significant difference in the time till occurrence of hypotension, duration of hypotension, mean dose of ephedrine used for the treatment of hypotension and frequency of patients developed itching between the groups (P > 0.05). Separate intrathecal injection of fentanyl and hyperbaric bupivacaine provided a significant improvement in the quality of sensory block and significant reduction of the frequency of hypotension compared to injection of mixed medications.

Hyperbaric bupivacaine 2.5 mg prolongs analgesia compared with plain bupivacaine when added to intrathecal fentanyl 25 microg in advanced labor.

PubMed

Teoh, Wendy H L; Sia, Alex T H

2003-09-01

We investigated the effect of sequential administration of intrathecal (IT) hyperbaric bupivacaine (after the initial administration of IT hypobaric fentanyl) on the duration of spinal analgesia. Thirty-seven nulliparous parturients with a cervical dilation >/= 5 cm were randomized to receive either IT fentanyl 25 micro g and plain bupivacaine 2.5 mg (group P; n = 19) or IT fentanyl 25 micro g and hyperbaric (with 8% glucose) bupivacaine 2.5 mg (group H; n = 18). The two components of the IT injectate were administered sequentially (fentanyl 25 micro g diluted in 2 mL of normal saline, immediately followed by 0.5 mL of 0.5% bupivacaine). Patients were then positioned with their torso elevated at 30 degrees for 30 min. Pain scores using 0-100 visual analog scales were collected before combined spinal/epidural analgesia and at 5, 15, and 30 min after the block. Patients in Group H had a longer median duration of analgesia (122 min; range, 80-210 min) than Group P (95 min; range, 75-125 min) (P < 0.01). Group H also had a more limited dermatomal spread (median highest sensory level of T8 versus T4 in group P; P < 0.05). The side-effect profile was similar. Under these circumstances, hyperbaric bupivacaine conferred an increased duration of IT analgesia compared with plain bupivacaine.

Postmortem Tissue Distribution of Acetyl Fentanyl, Fentanyl and their Respective Nor-Metabolites Analyzed by Ultrahigh Performance Liquid Chromatography with Tandem Mass Spectrometry

PubMed Central

Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Mainland, Mary; Hair, Laura; Devers, Kelly; Chrostowski, Leszek; Arbefeville, Elise; Merves, Michele; Pearson, Julia

2015-01-01

In the last two years, an epidemic of fatal narcotic overdose cases has occurred in the Tampa area of Florida. Fourteen of these deaths involved fentanyl and/or the new designer drug, acetyl fentanyl. Victim demographics, case histories, toxicology findings and causes and manners of death, as well as, disposition of fentanyl derivatives and their nor-metabolites in postmortem heart blood, peripheral blood, bile, brain, liver, urine and vitreous humor are presented. In the cases involving only acetyl fentanyl (without fentanyl, n=4), the average peripheral blood acetyl fentanyl concentration was 0.467 mg/L (range 0.31 to .60 mg/L) and average acetyl norfentanyl concentration was 0.053 mg/L (range 0.002 to 0.086 mg/L). In the cases involving fentanyl (without acetyl fentanyl, n=7), the average peripheral blood fentanyl concentration was 0.012 mg/L (range 0.004 to 0.027 mg/L) and average norfentanyl blood concentration was 0.001 mg/L (range 0.0002 to 0.003 mg/L). In the cases involving both acetyl fentanyl and fentanyl (n=3), the average peripheral blood acetyl fentanyl concentration was 0.008 mg/L (range 0.006 to 0.012 mg/L), the average peripheral blood acetyl norfentanyl concentration was 0.001 mg/L (range 0.001 to 0.002 mg/L), the average peripheral blood fentanyl concentration was 0.018 mg/L (range 0.015 to 0.021 mg/L) and the average peripheral blood norfentanyl concentration was 0.002 mg/L (range 0.001 mg/L to 0.003 mg/L). Based on the toxicology results, it is evident that when fentanyl and/or acetyl fentanyl were present, they contributed to the cause of death. A novel ultrahigh performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS) method to identify and quantify acetyl fentanyl, acetyl norfentanyl, fentanyl and norfentanyl in postmortem fluids and tissues is also presented. PMID:26583960

Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015.

PubMed

Peterson, Alexis B; Gladden, R Matthew; Delcher, Chris; Spies, Erica; Garcia-Williams, Amanda; Wang, Yanning; Halpin, John; Zibbell, Jon; McCarty, Carolyn Lullo; DeFiore-Hyrmer, Jolene; DiOrio, Mary; Goldberger, Bruce A

2016-08-26

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEA's National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(†) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(§) and recent release from an institution such as a jail, rehabilitation facility, or hospital.

Fentanyl Law Enforcement Submissions and Increases in Synthetic Opioid-Involved Overdose Deaths - 27 States, 2013-2014.

PubMed

Gladden, R Matthew; Martinez, Pedro; Seth, Puja

2016-08-26

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC, respectively, issued nationwide alerts identifying illicitly manufactured fentanyl (IMF) as a threat to public health and safety (1,2). IMF is unlawfully produced fentanyl, obtained through illicit drug markets, includes fentanyl analogs, and is commonly mixed with or sold as heroin (1,3,4). Starting in 2013, the production and distribution of IMF increased to unprecedented levels, fueled by increases in the global supply, processing, and distribution of fentanyl and fentanyl-precursor chemicals by criminal organizations (3). Fentanyl is a synthetic opioid 50-100 times more potent than morphine (2).* Multiple states have reported increases in fentanyl-involved overdose (poisoning) deaths (fentanyl deaths) (2). This report examined the number of drug products obtained by law enforcement that tested positive for fentanyl (fentanyl submissions) and synthetic opioid-involved deaths other than methadone (synthetic opioid deaths), which include fentanyl deaths and deaths involving other synthetic opioids (e.g., tramadol). Fentanyl deaths are not reported separately in national data. Analyses also were conducted on data from 27 states(†) with consistent death certificate reporting of the drugs involved in overdoses. Nationally, the number of fentanyl submissions and synthetic opioid deaths increased by 426% and 79%, respectively, during 2013-2014; among the 27 analyzed states, fentanyl submission increases were strongly correlated with increases in synthetic opioid deaths. Changes in fentanyl submissions and synthetic opioid deaths were not correlated with changes in fentanyl prescribing rates, and increases in fentanyl submissions and synthetic opioid deaths were primarily concentrated in eight states (high-burden states). Reports from six of the eight high-burden states indicated that fentanyl-involved overdose deaths were primarily driving increases in synthetic opioid deaths. Increases in synthetic opioid deaths among high-burden states disproportionately involved persons aged 15-44 years and males, a pattern consistent with previously documented IMF-involved deaths (5). These findings, combined with the approximate doubling in fentanyl submissions during 2014-2015 (from 5,343 to 13,882) (6), underscore the urgent need for a collaborative public health and law enforcement response.

The effect of spinal hyperbaric bupivacaine-fentanyl or hyperbaric bupivacaine on uterine tone and fetal heart rate in labouring women: a randomised controlled study.

PubMed

Kuberan, A; Jain, K; Bagga, R; Makkar, J K

2018-07-01

The mechanism for fetal heart rate abnormalities following spinal opioids remains controversial. We evaluated uterine tone, using an intra-uterine pressure catheter, and fetal heart rate abnormalities in 30 women in spontaneous labour with cervical dilation of 3-5 cm having combined spinal-epidural analgesia. Women were randomly assigned to receive a spinal with 2.0 mg hyperbaric bupivacaine plus 15 μg fentanyl, or 2.5 mg hyperbaric bupivacaine. The primary outcome measure was an increase > 10 mmHg in baseline uterine tone in the 30-min period following spinal injection. Only three (20%) women who had a bupivacaine-fentanyl spinal showed a > 10 mmHg increase in baseline tone vs. none who had bupivacaine (p = 0.63). The mean (SD) baseline uterine tone after the spinal injection was 13.3 (7.0) mmHg in the bupivacaine-fentanyl group and 7.7 (2.5) mmHg in the bupivacaine group (p = 0.01). Seven (47%) in the bupivacaine-fentanyl group showed new onset fetal heart rate changes during the 30-min period after the spinal, compared with two (13%) in the bupivacaine group (p = 0.04); however, these were transient and responded to intra-uterine resuscitation. Pain scores, sensory and motor block as well as neonatal outcomes were comparable between the groups. We found that raised baseline uterine tone was not more frequent when using bupivacaine-fentanyl rather than bupivacaine in the spinal component of combined spinal-epidural, although absolute values of baseline tone were higher, and fetal heart rate changes more frequent, in the former group. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Index to Drug-Specific Information

MedlinePlus

... Factive (gemifloxacin) Felbamate Felbatol (felbamate) Fentanyl buccal soluble film Fentanyl buccal tablets Fentanyl nasal spray Fentanyl sublingual ... Onfi (clobazam) Onglyza (saxagliptin) Onsolis (fentanyl buccal soluble film) OptimarkM (gasoversetamide) Optison (perflutren protein-type A microspheres) ...

A toxicology-based review of fentanyl-related deaths in New Mexico (1986-2007).

PubMed

Krinsky, Clarissa S; Lathrop, Sarah L; Crossey, Michael; Baker, Ginger; Zumwalt, Ross

2011-12-01

Since its approval in the United States, fentanyl has become increasingly popular for the medical management of pain and as a substance of abuse. Fentanyl is unique among the opioids in its widespread use with a transdermal delivery system, which contributes to its unique pharmacokinetics and abuse potential. We examined the demographics of deaths with fentanyl identified on toxicologic analysis and reviewed specific challenges in the laboratory detection of postmortem fentanyl levels. The New Mexico Office of the Medical Investigator database was searched for all cases from January 1986 through December 2007 with fentanyl reported as present or quantified. Those deaths with a cause of death identified as drug overdose were then analyzed separately. From 1986 to 2007, 154 cases were identified with fentanyl present in postmortem samples, with 96 of the cases identified as fentanyl-related drug overdoses. The number of fentanyl-related deaths has increased over the past 20 years, corresponding to both statewide increases in the medical use of fentanyl and the abuse of prescription opioids. The demographics of these fentanyl-related overdoses showed that subjects were more likely to be female, white non-Hispanic, and older than those in previously described overdose deaths. Several cases were identified with central and peripheral blood samples and antemortem and postmortem samples available for fentanyl quantification. Given the uncharacteristic demographics of fentanyl-related deaths and the complexity of the laboratory analysis of fentanyl, forensic scientists must use caution in both the detection and interpretation of fentanyl concentrations.

Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

PubMed

Wajima, Zen'ichiro; Yoshikawa, Tatsusuke; Ogura, Akira; Imanaga, Kazuyuki; Shiga, Toshiya; Inoue, Tetsuo; Ogawa, Ryo

2002-04-01

Forskolin, a direct activator of adenylate cyclase, can relax airway smooth muscle, similar to other agents that increase intracellular cyclic adenine monophosphate. However, the potential usefulness of forskolin in treating bronchospasm is limited by its poor water solubility. Colforsin daropate is a novel and potent water-soluble forskolin derivative. No clinical data have been published on the bronchorelaxant effects of this drug. The aim of this study was to investigate whether intravenous colforsin daropate prevents thiamylal-fentanyl-induced bronchoconstriction. Double-blind, prospective, placebo-controlled randomized study. University teaching hospital. Thirty-six patients were allocated randomly to two groups: the control group (n = 18) and colforsin daropate group (n = 18). Intravenous administration of colforsin daropate or placebo (normal saline). Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg. A 15 mg x kg(-1) x hr(-1) continuous infusion of thiamylal followed anesthetic induction. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, the control group patients started to receive 7.5 mL/hr continuous infusion of normal saline, and the colforsin daropate group patients started to receive 0.75 microg x kg(-1) x min(-1) (7.5 mL/hr) continuous infusion of colforsin daropate for 60 min. After that, both groups received fentanyl 5 microg/kg. Systolic and diastolic arterial pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48) and 30 min after fentanyl injection (T60). At baseline, both groups had comparable Rawm, Rawe, and Cdyn values. In the control group, Rawm increased significantly at T36-60 compared with the baseline, Rawe increased significantly at T36-48 compared with the baseline, and Cdyn decreased significantly at T36-60 compared with the baseline. In the colforsin daropate group, there were no changes in Rawm, Rawe or Cdyn at T36-60. These observations suggest that intravenous colforsin daropate has a bronchodilator effect in humans.

Exposure to time varying magnetic fields associated with magnetic resonance imaging reduces fentanyl-induced analgesia in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teskey, G.C.; Prato, F.S.; Ossenkopp, K.P.

The effects of exposure to clinical magnetic resonance imaging (MRI) on analgesia induced by the mu opiate agonist, fentanyl, was examined in mice. During the dark period, adult male mice were exposed for 23.2 min to the time-varying (0.6 T/sec) magnetic field (TVMF) component of the MRI procedure. Following this exposure, the analgesic potency of fentanyl citrate (0.1 mg/kg) was determined at 5, 10, 15, and 30 min post-injection, using a thermal test stimulus (hot-plate 50 degrees C). Exposure to the magnetic-field gradients attenuated the fentanyl-induced analgesia in a manner comparable to that previously observed with morphine. These results indicatemore » that the time-varying magnetic fields associated with MRI have significant inhibitory effects on the analgesic effects of specific mu-opiate-directed ligands.« less

Pain Levels Within 24 Hours After UFE: A Comparison of Morphine and Fentanyl Patient-Controlled Analgesia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hyun S., E-mail: sikhkim@jhmi.edu; Czuczman, Gregory J.; Nicholson, Wanda K.

The purpose of this study was to assess the presence and severity of pain levels during 24 h after uterine fibroid embolization (UFE) for symptomatic leiomyomata and compare the effectiveness and adverse effects of morphine patient-controlled analgesia (PCA) versus fentanyl PCA. We carried out a prospective, nonrandomized study of 200 consecutive women who received UFE and morphine or fentanyl PCA after UFE. Pain perception levels were obtained on a 0-10 scale for the 24-h period after UFE. Linear regression methods were used to determine pain trends and differences in pain trends between two groups and the association between pain scoresmore » and patient covariates. One hundred eighty-five patients (92.5%) reported greater-than-baseline pain after UFE, and 198 patients (99%) required IV opioid PCA. One hundred thirty-six patients (68.0%) developed nausea during the 24-h period. Seventy-two patients (36%) received morphine PCA and 128 (64%) received fentanyl PCA, without demographic differences. The mean dose of morphine used was 33.8 {+-} 26.7 mg, while the mean dose of fentanyl was 698.7 {+-} 537.4 {mu}g. Using this regimen, patients who received morphine PCA had significantly lower pain levels than those who received fentanyl PCA (p < 0.0001). We conclude that patients develop pain requiring IV opioid PCA within 24 h after UFE. Morphine PCA is more effective in reducing post-uterine artery embolization pain than fentanyl PCA. Nausea is a significant adverse effect from opioid PCA.« less

Dose fentanyl injection for blunting the hemodynamic response to intubation increase the risk of reflex bradycardia during major abdominal surgery?

PubMed Central

Kim, Jin-Kyoung; Park, Jung-Min; Lee, Cheol-Hee

2012-01-01

Background Although supplemental fentanyl has been widely used to blunt the hemodynamic responses to laryngoscopic intubation, its residual vagotonic effect may increase the risk of reflex bradycardia. We compared the incidence and severity of significant reflex bradycardia after a bolus injection of equivalent doses of fentanyl and remifentanil (control drug). Methods In this prospective, randomized, double-blind study, 220 adult patients undergoing major abdominal surgery were randomly assigned to receive fentanyl (1.5 µg/kg) or remifentanil (1.5 µg/kg). No anticholinergic prophylaxis was administered. Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to < 50 beats per minute (bpm) or to 50-59 bpm associated with a systolic arterial pressure < 70 mmHg in connection with surgical maneuvers. If bradycardia or hypotension developed, atropine or ephedrine was administered following a predefined treatment protocol. Results In total, 188 subjects (remifentanil, 95; fentanyl, 93) were included. The proportion of subjects with symptomatic reflex bradycardia in the fentanyl group was similar to that in the remifentanil group (30.1% vs. 28.4%, respectively). Atropine and/or ephedrine were needed similarly in both groups. The differences between the group of 55 patients who presented with symptomatic reflex bradycardia were not statistically significant with respect to the lowest heart rate, anesthetic depth-related data (bispectral index and end-tidal sevoflurane concentration), or the proportion of causative surgical maneuvers. Conclusions Fentanyl (1.5 µg/kg) administered intravenously during anesthetic induction is unlikely to increase the incidence and severity of significant reflex bradycardia in patients undergoing major abdominal surgery. PMID:23198032

Administration order of midazolam/fentanyl for moderate dental sedation

PubMed Central

2018-01-01

Background The purpose of this study is to investigate the effects of administration order when a sedative drug (midazolam) and an opioid analgesic drug (fentanyl) is applied for moderate intravenous (IV) sedation in dentistry. Methods A retrospective chart review was conducted in one dental clinic during its transition from a midazolam-first to a fentanyl-first protocol for dental procedures requiring moderate IV sedation. Physiological parameters, drug administration times, patient recovery times, drug dosages, and patient recall and satisfaction were investigated for differences. Results A total of 76 charts (40 midazolam-first and 36 fentanyl-first administrations), were used in the analysis. Administering midazolam first resulted in an average 4.38 min (52%) decrease in administration times (P < 0.001), and a decrease in procedural recollection immediately following the procedure (P = 0.03), and 24 to 48 hours later (P = 0.009). Administering fentanyl first required an average of 2.43 mg (29%) less midazolam (P < 0.001). No significant differences were found for change in vital signs, minimum oxygen saturation levels, recovery times, and patient satisfaction (P > 0.05). Oxygen saturation levels did not drop below 90% for either group; however, 5 cases in the fentanyl-first group fell to between 90% and 92%, compared with 0 cases in the midazolam-first group. Conclusions The administration order of fentanyl and midazolam may have different effects on patients and the sedation procedure. Findings from this study should be used to facilitate discussion among dental practitioners and to guide additional research investigating this topic. PMID:29556559

Aerosol Stable Peptide-Coated Liposome Nanoparticles: A Proof-of-Concept Study with Opioid Fentanyl in Enhancing Analgesic Effects and Reducing Plasma Drug Exposure

PubMed Central

HOEKMAN, JOHN D; SRIVASTAVA, PRAMOD; HO, RODNEY J Y

2014-01-01

Previous we reported a novel pressurized olfactory drug (POD) delivery device that deposit aerosolized drug preferentially to upper nasal cavity. This POD device provided sustained CNS levels of soluble morphine analgesic effects. However, analgesic onset of less soluble fentanyl was more rapid but brief, likely due to hydrophobic fentanyl redistribution readily back to blood. To determine whether fentanyl incorporated into an aerosol stable liposome that binds to nasal epithelial cells will enhance CNS drug exposure and analgesic effects and reduce plasma exposure, we constructed RGD liposomes anchored with acylated integrin binding peptides (palmitoyl-GRGDS). The RGD liposomes, which assume gel-phase membrane structure at 25°C were stable under the stress of aerosolization as only 2.2 ± 0.5 % calcein leakage detected. The RGD mediated integrin binding of liposome is also verified to be unaffected by aerosolization. Rats treated with fentanyl in RGD-liposome and POD device exhibited greater analgesic effect, compared to the free drug counterpart (AUCeffect = 1387.l vs. 760.1 %MPE*min); while ~20% reduced plasma drug exposure was noted (AUC0-120 = 208.2 vs 284.8 ng*min/ml). Collectively, fentanyl incorporated in RGD-liposomes are physically and biologically stable under aerosolization, enhanced the overall analgesic effects and reduced plasma drug exposure for the first 2 hours. PMID:24909764

Spinal anaesthesia with midazolam in the rat.

PubMed

Bahar, M; Cohen, M L; Grinshpon, Y; Chanimov, M

1997-02-01

This study examined in an animal model whether intrathecal midazolam, alone or with fentanyl, can achieve anaesthesia sufficient for laparotomy, comparable to lidocaine. Effects on consciousness and whether anaesthesia was segmental were also examined. The haemodynamic and respiratory changes were compared with those of intrathecal lidocaine or intrathecal fentanyl alone. Sixty Wistar strain rats, with nylon catheters chronically implanted in the lumbar subarachnoid theca, were divided into six groups. Group 1 (n = 12) received 75 microL intrathecal lidocaine 2%. Group 2 (n = 12) received 75 microL intrathecal midazolam 0.1%, Group 3 (n = 12) received intrathecal 37.5 microL midazolam 0.1%, plus 37.5 microL fentanyl 0.005%. Group 4 (n = 12) received intrathecal 50 microL fentanyl 0.005%. Group 5 (n = 6) received 75 microL midazolam 0.1% iv. Group 6 (n = 6) received halothane 0.6% in oxygen by inhalation. Both groups that received intrathecal midazolam, alone or combined with fentanyl, developed effective segmental sensory and motor blockade of the hind limbs and abdominal wall, sufficient for a pain-free laparotomy procedure. Neither of these groups, unlike the group that received intrathecal lidocaine, developed a reduction in blood pressure or change in heart rate at the time of maximal sensory or motor blockade, nor were there changes in the arterial blood gases or respiratory rate. Midazolam, when injected intrathecally, produces reversible, segmental, spinally mediated antinociception, sufficient to provide balanced anaesthesia for abdominal surgery.

Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 - 10 States, July-December 2016.

PubMed

O'Donnell, Julie K; Halpin, John; Mattson, Christine L; Goldberger, Bruce A; Gladden, R Matthew

2017-11-03

Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July-December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.

Increases in self-reported fentanyl use among a population entering drug treatment: The need for systematic surveillance of illicitly manufactured opioids.

PubMed

Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

2017-08-01

Recent reports indicate a sharp increase in fentanyl-related overdose deaths across the United States, much of which is likely related to the introduction of cheap, illicitly manufactured fentanyl derivatives. In this study, we sought to estimate the magnitude of illicit fentanyl use from 2012 to 2016 using a national opioid abuse surveillance system. The study program surveyed 10,900 individuals entering substance abuse treatment for opioid use disorder, with participants asked to endorse past month 'use to get high' of fentanyl drugs, stratified by identifiable (i.e., branded) fentanyl formulations or a 'type unknown' drug alleged to contain fentanyl. Total past-month fentanyl-use rose modestly from 2012 to 2016. While use of known fentanyl products remained relatively stable (mean=10.9%; P=0.25), endorsements of 'unknown' fentanyl products nearly doubled from 9% in 2013 to 15.1% by 2016 (P<0.001). Data show no discernable indication that this increase is diminishing or stabilizing. This first attempt to assess the prevalence of illicit fentanyl use shows that recent increases in fentanyl use seem to be due almost entirely to 'unknown' fentanyl presumed to be illicitly manufactured. Given that it is difficult to assess the extent to which fentanyl may have been substituted for another drug (i.e., oxycodone, alprazolam, etc.) or was used as a heroin admixture, our data likely represent an underestimation of the full magnitude of illicit fentanyl abuse. As such, this growing public health problem requires immediate attention and more systematic efforts to identify and track its abuse. Copyright © 2017. Published by Elsevier B.V.

Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery

PubMed Central

Mather, Laurence E; Woodhouse, Annie; Ward, M Elizabeth; Farr, Stephen J; Rubsamen, Reid A; Eltherington, Lorne G

1998-01-01

Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist™, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. Methods Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMist™ and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. Results Plasma concentrations from SmartMist™ were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. Conclusions Fentanyl delivery using SmartMist™ can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae. PMID:9690947

Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy.

PubMed

Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan

2018-01-01

Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p < 0.05). Sedative effects were observed in three patients in the intranasal ketamine administration group. No such sedative effect was seen in the groups that received intranasal fentanyl and intravenous paracetamol in Wilson Sedation Scale (p < 0.05). Cognitive impairment, constipation, nausea, vomiting and bleeding were not observed in any of the groups. This study showed that either intranasal ketamine and intranasal fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats.

PubMed

Dahan, A; Yassen, A; Bijl, H; Romberg, R; Sarton, E; Teppema, L; Olofsen, E; Danhof, M

2005-06-01

There is evidence from animal studies suggesting the existence of a ceiling effect for buprenorphine-induced respiratory depression. To study whether an apparent ceiling effect exists for respiratory depression induced by buprenorphine, we compared the respiratory effects of buprenorphine and fentanyl in humans and rats. In healthy volunteers, the opioids were infused i.v. over 90 s and measurements of minute ventilation at a fixed end-tidal PCO2 of 7 kPa were obtained for 7 h. Buprenorphine doses were 0.7, 1.4, 4.3 and 8.6 microg kg(-1) (n=20 subjects) and fentanyl doses 1.1, 2.1, 2.9, 4.3 and 7.1 microg kg(-1) (n=21). Seven subjects received placebo. In rats, both opioids were infused i.v. over 20 min, and arterial PCO2 was measured 5, 10, 15 and 20 min after the start of fentanyl infusion and 30, 150, 270 and 390 min after the start of buprenorphine infusion. Doses tested were buprenorphine 0, 100, 300, 1000 and 3000 microg kg(-1) and fentanyl 0, 50, 68 and 90 microg kg(-1). In humans, fentanyl produced a dose-dependent depression of minute ventilation with apnoea at doses > or = 2.9 microg kg(-1); buprenorphine caused depression of minute ventilation which levelled off at doses > or = 3.0 microg kg(-1) to about 50% of baseline. In rats, the relationship of arterial PCO2 and fentanyl dose was linear, with maximum respiratory depression at 20 min (maximum PaCO2 8.0 kPa). Irrespective of the time at which measurements were obtained, buprenorphine showed a non-linear effect on PaCO2, with a ceiling effect at doses > 1.4 microg kg(-1). The effect on PaCO2 was modest (maximum value measured, 5.5 kPa). Our data confirm a ceiling effect of buprenorphine but not fentanyl with respect to respiratory depression.

21 CFR 522.800 - Droperidol and fentanyl citrate injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Droperidol and fentanyl citrate injection. 522.800... § 522.800 Droperidol and fentanyl citrate injection. (a) Specifications. Droperidol and fentanyl citrate injection is a sterile solution containing 20 milligrams of droperidol and 0.4 milligram of fentanyl citrate...

21 CFR 522.800 - Droperidol and fentanyl citrate injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Droperidol and fentanyl citrate injection. 522.800... § 522.800 Droperidol and fentanyl citrate injection. (a) Specifications. Droperidol and fentanyl citrate injection is a sterile solution containing 20 milligrams of droperidol and 0.4 milligram of fentanyl citrate...

21 CFR 522.800 - Droperidol and fentanyl citrate injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Droperidol and fentanyl citrate injection. 522.800... § 522.800 Droperidol and fentanyl citrate injection. (a) Specifications. Droperidol and fentanyl citrate injection is a sterile solution containing 20 milligrams of droperidol and 0.4 milligram of fentanyl citrate...

Acetyl fentanyl overdose fatalities--Rhode Island, March-May 2013.

PubMed

2013-08-30

In May 2013, the Rhode Island State Health Laboratories noticed an unusual pattern of toxicology results among 10 overdose deaths of suspected illicit drug users that had occurred during March 7-April 11, 2013. An enzyme-linked immunosorbent assay (ELISA) for fentanyl in blood was positive for fentanyl in all 10 cases, but confirmatory gas chromatography/mass spectrometry (GC/MS) did not detect fentanyl. The mass spectrum was instead consistent with acetyl fentanyl, a fentanyl analog. Acetyl fentanyl, a synthetic opioid, has not been documented in illicit drug use or overdose deaths, and is not available as a prescription drug anywhere. Animal studies suggest that acetyl fentanyl is up to five times more potent than heroin as an analgesic.

Radioreceptor assay for analysis of fentanyl and its analogs in biological samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alburges, M.E.

The assay is based on the competition of these drugs with ({sup 3}H) fentanyl for opioid receptors in membrane preparations of rat forebrain in vitro. The binding in stereospecific, reversible and saturable. Scatchard plots of saturation suggest the presence of high and low affinity binding sites. Morphine and hydromorphone complete with ({sup 3}H)fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of ({sup 3}H)fentanyl. Many other commonly abused drugs do not compete with ({sup 3}H)fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, ({plus minus})-cis-3-methylfentanyl, alpha-methylfentanyl, butyrylfentanyl and benzylfentanyl were analyzed by radioreceptormore » assay, radioimmunoassay, and gas chromatography/mass spectrometry. Urinary analysis of fentanyl showed a good correlation with these three methods; however, discrepancies were observed in the analysis of fentanyl analogs. This radioreceptor assay is well-suited as an initial assay for the detection of active analogs of fentanyl in urine with good correlation with other techniques in the analysis of fentanyl; however, there is substantial disagreement between techniques in the quantitation of fentanyl analogs. The implications of these discrepancies are discussed.« less

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

PubMed

Dehuisser, Virginie; Bosmans, Tim; Kitshoff, Adriaan; Duchateau, Luc; de Rooster, Hilde; Polis, Ingeborgh

2017-11-01

To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. Prospective, blinded, randomized, experimental study. A group of 12 intact female dogs. Following intramuscular dexmedetomidine (10 μg kg -1 ) and methadone (0.1 mg kg -1 ) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg -1 ) (group AP) or alfaxalone (2 mg kg -1 ) preceded by fentanyl (2 μg kg -1 ) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg -1 minute -1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 μg kg -1 hour -1 ) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg -1 minute -1 (group AP) versus 0.13 ± 0.01 mg kg -1 minute -1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Comparison between intravenous paracetamol and fentanyl for intraoperative and postoperative pain relief in dilatation and evacuation: Prospective, randomized interventional trial.

PubMed

Ali, Muhammad Asghar; Shamim, Faisal; Chughtai, Shakaib

2015-01-01

Dilatation and Evacuation procedure involves pain, for which pain control measures need to be undertaken. The purpose of this study was to compare paracetamol with fentanyl for pain relief in dilatation and curettage procedures. Sixty female patients were randomly included during the period from March 1, 2012 to February 28, 2013. All patients had received oral midazolam 7.5 mg as a premedication 30 min before procedure in the ward. Group P had received intravenous (IV) paracetamol 15 mg/kg in the waiting area of the operating room 15 min before starting the procedure. Group F had received IV fentanyl 2 ug/kg/min at induction of anesthesia. Pain scores on a numerical rating scale at 5, 15, and 30 min intervals after surgery were recorded. Mild pain was commonly observed in both groups, an insignificant difference between groups. The study demonstrates the usefulness of IV paracetamol which may be as effective as fentanyl in dilation and curettage procedures.

Exposure to fentanyl-contaminated heroin and overdose risk among illicit opioid users in Rhode Island: A mixed methods study.

PubMed

Carroll, Jennifer J; Marshall, Brandon D L; Rich, Josiah D; Green, Traci C

2017-08-01

Illicit fentanyl use has become wide spread in the US, causing high rates of overdose deaths among people who use drugs. This study describes patterns and perceptions of fentanyl exposure among opioid users in Rhode Island. A mixed methods study was conducted via questionnaire with a convenience sample of 149 individuals using illicit opioids or misusing prescription opioids in Rhode Island between January and November 2016. Of these, 121 knew of fentanyl and reported known or suspected exposure to fentanyl in the past year. Semi-structured interviews were conducted with the first 47 participants. Study participants were predominantly male (64%) and white (61%). Demographic variables were similar across sample strata. Heroin was the most frequently reported drug of choice (72%). Self-reported exposure to illicit fentanyl in the past year was common (50.4%, n=61). In multivariate models, regular (at least weekly) heroin use was independently associated with known or suspected fentanyl exposure in the past year (adjusted prevalence ratio (APR)=4.07, 95% CI: 1.24-13.3, p=0.020). In interviews, users described fentanyl as unpleasant, potentially deadly, and to be avoided. Participants reporting fentanyl exposure routinely experienced or encountered non-fatal overdose. Heroin users reported limited ability to identify fentanyl in their drugs. Harm reduction strategies used to protect themselves from fentanyl exposure and overdose, included test hits, seeking prescription opioids in lieu of heroin, and seeking treatment with combination buprenorphine/naloxone. Participants were often unsuccessful in accessing structured treatment programs. Among illicit opioid users in Rhode Island, known or suspected fentanyl exposure is common, yet demand for fentanyl is low. Fentanyl-contaminated drugs are generating user interest in effective risk mitigation strategies, including treatment. Responses to the fentanyl epidemic should be informed by the perceptions and experiences of local users. The rapid scale-up of buprenorphine/naloxone provision may slow the rate of fentanyl-involved overdose deaths. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Comparative study of fentanyl and morphine in addition to hyperbaric or isobaric bupivacaine in combined spinal anaesthesia for caesarean section

PubMed Central

Saracoglu, Ayten; Saracoglu, Kemal T.; Eti, Zeynep

2011-01-01

Introduction The aim of our study was to compare the effects of isobaric and hyperbaric bupivacaine combined with morphine or fentanyl in patients undergoing caesarean section. We assessed quality and spread of analgesia and anaesthesia, postoperative analgesic requirement and side effects. Material and methods Hundred patients with American Society of Anesthesiologists physical status (ASA) I-II, age 18 to 40 years, were randomized to 4 groups. The intrathecal solutions were isobaric bupivacaine + morphine (group A), isobaric bupivacaine + fentanyl (group B), heavy bupivacaine + + morphine (group C) and heavy bupivacaine + fentanyl (group D). Mean arterial pressure, heart rate, oxygen saturation, ephedrine consumption, analgesic requirement time and additional analgesic needs were recorded. Results The 1st min value of mean arterial pressure was the lowest one in all groups. Heart rate decreased significantly in group A at the 10th min but not in the other groups. The decrease of visual analogue scale (VAS) pain scores began in the groups after the 4th postoperative h (p < 0.05) and the VAS value of group B at the 8th h was significantly higher than the other groups. The first analgesic requirement time in the postoperative period was longer in patients who had intrathecal morphine than those who had fentanyl. The duration of analgesia with isobaric bupivacaine and morphine was the longest one. Conclusions We concluded that intrathecal morphine provides a long duration of postoperative analgesia but the duration gets longer when it is combined with plain bupivacaine instead of heavy bupivacaine. PMID:22291807

Effects of fentanyl administration on locomotor response in horses with the G57C μ-opioid receptor polymorphism.

PubMed

Wetmore, Lois A; Pascoe, Peter J; Shilo-Benjamini, Yael; Lindsey, Jane C

2016-08-01

OBJECTIVE To determine the locomotor response to the administration of fentanyl in horses with and without the G57C polymorphism of the μ-opioid receptor. ANIMALS 20 horses of various breeds and ages (10 horses heterozygous for the G57C polymorphism and 10 age-, breed-, and sex-matched horses that did not have the G57C polymorphism). PROCEDURES The number of steps each horse took was counted over consecutive 2-minute periods for 20 minutes to determine a baseline value. The horse then received a bolus of fentanyl (20 μg/kg, IV), and the number of steps was again counted during consecutive 2-minute periods for 60 minutes. The mean baseline value was subtracted from each 2-minute period after fentanyl administration; step counts with negative values were assigned a value of 0. Data were analyzed by use of a repeated-measures ANOVA. RESULTS Data for 19 of 20 horses (10 horses with the G57C polymorphism and 9 control horses without the G57C polymorphism) were included in the analysis. Horses with the G57C polymorphism had a significant increase in locomotor activity, compared with results for horses without the polymorphism. There was a significant group-by-time interaction. CONCLUSIONS AND CLINICAL RELEVANCE Horses heterozygous for the G57C polymorphism of the μ-opioid receptor had an increased locomotor response to fentanyl administration, compared with the response for horses without this polymorphism. The clinical impact of this finding should be investigated.

Isoflurane minimum alveolar concentration reduction by fentanyl.

PubMed

McEwan, A I; Smith, C; Dyar, O; Goodman, D; Smith, L R; Glass, P S

1993-05-01

Isoflurane is commonly combined with fentanyl during anesthesia. Because of hysteresis between plasma and effect site, bolus administration of fentanyl does not accurately describe the interaction between these drugs. The purpose of this study was to determine the MAC reduction of isoflurane by fentanyl when both drugs had reached steady biophase concentrations. Seventy-seven patients were randomly allocated to receive either no fentanyl or fentanyl at several predetermined plasma concentrations. Fentanyl was administered using a computer-assisted continuous infusion device. Patients were also randomly allocated to receive a predetermined steady state end-tidal concentration of isoflurane. Blood samples for fentanyl concentration were taken at 10 min after initiation of the infusion and before and immediately after skin incision. A minimum of 20 min was allowed between the start of the fentanyl infusion and skin incision. The reduction in the MAC of isoflurane by the measured fentanyl concentration was calculated using a maximum likelihood solution to a logistic regression model. There was an initial steep reduction in the MAC of isoflurane by fentanyl, with 3 ng/ml resulting in a 63% MAC reduction. A ceiling effect was observed with 10 ng/ml providing only a further 19% reduction in MAC. A 50% decrease in MAC was produced by a fentanyl concentration of 1.67 ng/ml. Defining the MAC reduction of isoflurane by all the opioids allows their more rational administration with inhalational anesthetics and provides a comparison of their relative anesthetic potencies.

Day-case anaesthesia for termination of pregnancy. Evaluation of a total intravenous anaesthetic technique.

PubMed

Ogg, T W; Jennings, R A; Morrison, C G

1983-11-01

An investigation was undertaken to assess the use of a total intravenous anaesthetic technique of fentanyl and methohexitone for outpatient vaginal termination of pregnancy. When compared with a technique of fentanyl, methohexitone, nitrous oxide and trichloroethylene the total intravenous method caused swifter recovery, minimal side-effects and no cardiovascular depression. However, both anaesthetic techniques produced significant postoperative reduction of memory for new facts when compared with a control group receiving no general anaesthesia. There is a need to continue the search for anaesthetic methods appropriate for day cases.

Isoflurane exerts neuroprotective actions at or near the time of severe traumatic brain injury.

PubMed

Statler, Kimberly D; Alexander, Henry; Vagni, Vincent; Holubkov, Richard; Dixon, C Edward; Clark, Robert S B; Jenkins, Larry; Kochanek, Patrick M

2006-03-03

Isoflurane improves outcome vs. fentanyl anesthesia, in experimental traumatic brain injury (TBI). We assessed the temporal profile of isoflurane neuroprotection and tested whether isoflurane confers benefit at the time of TBI. Adult, male rats were randomized to isoflurane (1%) or fentanyl (10 mcg/kg iv bolus then 50 mcg/kg/h) for 30 min pre-TBI. Anesthesia was discontinued, rats recovered to tail pinch, and TBI was delivered by controlled cortical impact. Immediately post-TBI, rats were randomized to 1 h of isoflurane, fentanyl, or no additional anesthesia, creating 6 anesthetic groups (isoflurane:isoflurane, isoflurane:fentanyl, isoflurane:none, fentanyl:isoflurane, fentanyl:fentanyl, fentanyl:none). Beam balance, beam walking, and Morris water maze (MWM) performances were assessed over post-trauma d1-20. Contusion volume and hippocampal survival were assessed on d21. Rats receiving isoflurane pre- and post-TBI exhibited better beam walking and MWM performances than rats treated with fentanyl pre- and any treatment post-TBI. All rats pretreated with isoflurane had better CA3 neuronal survival than rats receiving fentanyl pre- and post-TBI. In rats pretreated with fentanyl, post-traumatic isoflurane failed to affect function but improved CA3 neuronal survival vs. rats given fentanyl pre- and post-TBI. Post-traumatic isoflurane did not alter histopathological outcomes in rats pretreated with isoflurane. Rats receiving fentanyl pre- and post-TBI had the worst CA1 neuronal survival of all groups. Our data support isoflurane neuroprotection, even when used at the lowest feasible level before TBI (i.e., when discontinued with recovery to tail pinch immediately before injury). Investigators using isoflurane must consider its beneficial effects in the design and interpretation of experimental TBI research.

Analysis of fentanyl in urine by DLLME-GC-MS.

PubMed

Gardner, Michael A; Sampsel, Sheena; Jenkins, Werner W; Owens, Janel E

2015-03-01

Fentanyl is a synthetic narcotic anesthetic ∼80-100 times more potent than morphine. Owing to the potential for its abuse, the drug may be included in a forensic toxicology work-up, which requires fast, precise and accurate measurements. Here, the stability of fentanyl was assessed when stored at three different temperatures (-20, 4 and 25°C) in synthetic urine. Stability at those three temperatures was demonstrated over 12 weeks upon analysis by gas chromatography-mass spectrometry with a deuterated internal standard (fentanyl-D5) utilizing three different extraction techniques: liquid-liquid extraction (LLE), solid-phase extraction and dispersed liquid-liquid microextraction (DLLME). The DLLME method was then optimized before use in the analysis of fentanyl in urine samples obtained from autopsy cases at the El Paso County Coroner's Office. Accuracy of the DLLME method was assessed by completing spike and recovery studies at three different fortification levels (10, 100 and 250 ng/mL) with excellent recovery (89.9-102.6%). The excellent comparability between DLLME and LLE is demonstrated (Bland-Altman difference plot with a mean difference of 4.9 ng/mL) and the use of this methodology in the analysis of forensically relevant samples is discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Glasgow Coma Scores, Early Opioids, and Posttraumatic Stress Disorder Among Combat Amputees

DTIC Science & Technology

2014-04-01

icz, Johnson, & Mosely, 2008). Little research has compared how morphine and fentanyl might impact later psychological outcomes such as PTSD. In the...Fox, Saunders, Menk, & Middaugh, 1995). Because the analgesic effect of fentanyl is approximately 100 times more than morphine , the median Level 2...dosages administered to patients for these opioids appeared equivalent for analgesic effectiveness (Fox et al., 1995). Of the morphine -treated pa

Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients.

PubMed

Oosten, Astrid W; Abrantes, João A; Jönsson, Siv; de Bruijn, Peter; Kuip, Evelien J M; Falcão, Amílcar; van der Rijt, Carin C D; Mathijssen, Ron H J

2016-04-01

Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

PubMed Central

Lim, Stephen CB; Paech, Michael J; Sunderland, Bruce; Liu, Yandi

2013-01-01

Background The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. PMID:23596347

Frequent use of opioids in patients with dementia and nursing home residents: A study of the entire elderly population of Denmark.

PubMed

Jensen-Dahm, Christina; Gasse, Christiane; Astrup, Aske; Mortensen, Preben Bo; Waldemar, Gunhild

2015-06-01

Pain is believed to be undertreated in patients with dementia; however, no larger studies have been conducted. The aim was to investigate prevalent use of opioids in elderly with and without dementia in the entire elderly population of Denmark. A register-based cross-sectional study in the entire elderly (≥65 years) population in 2010 was conducted. Opioid use among elderly with dementia (N = 35,455) was compared with elderly without (N = 870,645), taking age, sex, comorbidity, and living status into account. Nursing home residents (NHRs) used opioids most frequently (41%), followed by home-living patients with dementia (27.5%) and home-living patients without dementia (16.9%). Buprenorphine and fentanyl (primarily patches) were commonly used among NHRs (18.7%) and home-living patients with dementia (10.7%) but less often by home-living patients without dementia (2.4%). Opioid use in the elderly Danish population was frequent but particularly in patients with dementia and NHR, which may challenge patient safety and needs further investigation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Subcutaneous administration of fentanyl in childbirth: an observational study on the clinical effectiveness of fentanyl for mother and neonate.

PubMed

Fleet, Julie; Jones, Meril; Belan, Ingrid

2014-01-01

to explore the maternal and neonatal effects of fentanyl administered subcutaneously to women during labour. two methods were used: (1) A retrospective audit of the birth register and maternal and neonatal records for the period from January 2000 to December 2007. (2) A pilot study was also conducted on a convenience sample of women between July 2008 and October 2008. this study was conducted within a maternity unit at a rural South Australian hospital where approximately 350 babies are birthed each year. audit participants included women who had uncomplicated pregnancies and birthed at term (37-42 weeks gestation). Women in the experimental group consisted of those who had utilised only subcutaneous fentanyl for pain relief (n=75), or nitrous oxide and oxygen prior to being administered subcutaneous fentanyl (n=196). Stratified random selection based on parity and age was used to determine the control group, which consisted of women who used no pharmacological pain relief (n=196). The pilot study involved a convenience sample of women (n=10) assessed to have an uncomplicated pregnancy and labour occurring at term (≥37 weeks gestation). audit variables examined included the women's age, parity, labour duration, mode of birth (spontaneous or assisted), analgesia used, total dosage, time administered prior to birth, time of birth, neonatal Apgar scores, time to establish breathing, naloxone use, days spent in hospital post-birth and breast-feeding outcomes upon discharge. The pilot study explored maternal effects assessed pre- and 30 minutes post-administration of subcutaneously administered fentanyl by observing pain scores, vital signs, sedation levels, nausea/vomiting scores and anti-emetic use. To assess possible adverse effects in the neonate Apgar scores, time to establish respiration, naloxone use, transfer to neonatal nursery and breast-feeding outcomes upon discharge were recorded. women in the experimental groups were more likely to be induced, experienced a longer duration of labour and had an increased likelihood of an assisted vaginal birth. The average total dose of fentanyl administered was 250 μg. Neonatal outcomes were comparable between groups when examining Apgar scores <7 at 1 and 5 minutes and time to establish breathing. There was, however, a significant difference with naloxone administration between the groups. There was no significant difference between groups in hospital stay or breast-feeding on discharge. The pilot study identified a clinically significant reduction in pain scores for 78% of women following the administration of subcutaneous fentanyl, with the average pain score decreasing from 8.4 (±1.4) to 7.2 (±1.1) (paired t-test, p=0.017). Vital signs were not affected, no anti-emetics were required and all women remained alert with no sedation noted. the audit identified fentanyl use was associated with a longer length of labour, but this may be explained by more women in the experimental groups requiring induction of labour than those in the control group. However, length of hospital stay, breast-feeding rates and neonatal outcomes were comparable amongst the three groups. Results of the pilot study are consistent with those of the audit in relation to the effects on mother and neonate. In addition, the pilot study begins to provide evidence that fentanyl is efficacious in providing pain relief. results of this study are the first to explore the effects of fentanyl administered subcutaneously to women during labour. This method of analgesia offers women an additional choice of pain relief during childbirth and may be particularly beneficial in remote and rural settings where resources are often limited and access to specialist services difficult. Further research, however, is required to be able to generalise the outcomes and provide further data to support the clinical effectiveness of this route of administration of fentanyl. Copyright © 2013 Elsevier Ltd. All rights reserved.

Two Different Epidural Analgesic Combinations: Morphine vs. Fentanyl/Bupivacaine or Fentanyl/Ropivacaine and Their Post Operative Effects

DTIC Science & Technology

2001-10-01

sensory and emotional experiences associated with actual or potential tissue damage,” (Taber, 1989, p. 1405). Pain has both physical and psychological...accentuating the pain response (Taber, 1989). In addition to the patients’ perception and experience of pain, the healthcare providers’ beliefs, biases...with quick recovery and pain-free postoperative experiences is a priority. The goal of this study was to compare the effectiveness of two

Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery

PubMed Central

Muraoka, Wataru; Nishizawa, Daisuke; Fukuda, Kenichi; Kasai, Shinya; Hasegawa, Junko; Wajima, Koichi; Nakagawa, Taneaki

2016-01-01

Background Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment. PMID:28256933

Transversus Abdominis Plane Block Versus Wound Infiltration for Analgesia After Cesarean Delivery: A Randomized Controlled Trial.

PubMed

Tawfik, Mohamed Mohamed; Mohamed, Yaser Mohamed; Elbadrawi, Rania Elmohamadi; Abdelkhalek, Mostafa; Mogahed, Maiseloon Mostafa; Ezz, Hanaa Mohamed

2017-04-01

Transversus abdominis plane (TAP) block and local anesthetic wound infiltration provide analgesia after cesarean delivery. Studies comparing the 2 techniques are scarce, with conflicting results. This double-blind, randomized controlled trial aimed to compare bilateral ultrasound-guided TAP block with single-shot local anesthetic wound infiltration for analgesia after cesarean delivery performed under spinal anesthesia. We hypothesized that the TAP block would decrease postoperative cumulative fentanyl consumption at 24 hours. Eligible subjects were American Society of Anesthesiologists physical status II parturients with full-term singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia. Exclusion criteria were: <19 years of age or >40 years of age; height <150 cm, weight <60 kg, body mass index ≥40 kg/m; contraindications to spinal anesthesia; history of recent opioid exposure; hypersensitivity to any of the drugs used in the study; significant cardiovascular, renal, or hepatic disease; and known fetal abnormalities. Eighty subjects were randomly allocated to 2 equal groups. In the infiltration group, participants received 15 mL of bupivacaine 0.25% in each side of the surgical wound (total 30 mL); and in the TAP group, participants received 20 mL of bupivacaine 0.25% bilaterally in the TAP block (total 40 mL). The TAP block and wound infiltration were performed by the primary investigator and the operating obstetrician, respectively. All participants received postoperative standard analgesia (ketorolac and paracetamol) and intravenous fentanyl via patient-controlled analgesia. Patients and outcome assessors were blinded to the study group. The primary outcome was the cumulative fentanyl consumption at 24 hours. Secondary outcomes were the time to the first postoperative fentanyl dose, cumulative fentanyl consumption at 2, 4, 6, and 12 hours, pain scores at rest and on movement at 2, 4, 6, 12, and 24 hours, the deepest level of sedation, the incidence of side effects (nausea and vomiting and pruritis), and patient satisfaction. Data from 78 patients (39 patients in each group) were analyzed. The mean ± SD of cumulative fentanyl consumption at 24 hours was 157.4 ± 63.4 μg in the infiltration group and 153.3 ± 68.3 μg in the TAP group (difference in means [95% confidence interval] is 4.1 [-25.6 to 33.8] μg; P = .8). There were no significant differences between the 2 groups in the time to the first postoperative fentanyl dose, cumulative fentanyl consumption at 2, 4, 6, and 12 hours, pain scores at rest and on movement at 2, 4, 6, 12, and 24 hours, the deepest level of sedation, and patient satisfaction. The incidence of side effects (nausea and vomiting and pruritis) was low in the 2 groups. TAP block and wound infiltration did not significantly differ regarding postoperative fentanyl consumption, pain scores, and patient satisfaction in parturients undergoing cesarean delivery under spinal anesthesia.

Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department.

PubMed

Reynolds, Stacy L; Studnek, Jonathan R; Bryant, Kathleen; VanderHave, Kelly; Grossman, Eric; Moore, Charity G; Young, James; Hogg, Melanie; Runyon, Michael S

2016-09-08

Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage. This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 μg/kg) for analgesia in 80 children aged 4-17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug. This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial. NCT02521415. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

PubMed

Galinkin, J L; Fazi, L M; Cuy, R M; Chiavacci, R M; Kurth, C D; Shah, U K; Jacobs, I N; Watcha, M F

2000-12-01

Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during halothane or sevoflurane anesthesia for BMT is associated with diminished postoperative agitation without an increase in vomiting, hypoxemia, or discharge times.

Epidural Neostigmine versus Fentanyl to Decrease Bupivacaine Use in Patient-controlled Epidural Analgesia during Labor: A Randomized, Double-blind, Controlled Study.

PubMed

Booth, Jessica L; Ross, Vernon H; Nelson, Kenneth E; Harris, Lynnette; Eisenach, James C; Pan, Peter H

2017-07-01

The addition of opioids to epidural local anesthetic reduces local anesthetic consumption by 20% but at the expense of side effects and time spent for regulatory compliance paperwork. Epidural neostigmine also reduces local anesthetic use. The authors hypothesized that epidural bupivacaine with neostigmine would decrease total hourly bupivacaine use compared with epidural bupivacaine with fentanyl for patient-controlled epidural analgesia. A total of 215 American Society of Anesthesiologists physical status II, laboring parturients requesting labor epidural analgesia consented to the study and were randomized to receive 0.125% bupivacaine with the addition of either fentanyl (2 μg/ml) or neostigmine (2, 4, or 8 μg/ml). The primary outcome was total hourly local anesthetic consumption, defined as total patient-controlled epidural analgesia use and top-ups (expressed as milliliters of 0.125% bupivacaine) divided by the infusion duration. A priori analysis determined a group size of 35 was needed to have 80% power at α = 0.05 to detect a 20% difference in the primary outcome. Of 215 subjects consented, 151 patients were evaluable. Demographics, maternal and fetal outcomes, and labor characteristics were similar among groups. Total hourly local anesthetic consumption did not differ among groups (P = 0.55). The total median hourly bupivacaine consumption in the fentanyl group was 16.0 ml/h compared with 15.3, 14.6, and 16.2 ml/h in the 2, 4, and 8 μg/ml neostigmine groups, respectively (P = 0.55). The data do not support any difference in bupivacaine requirements for labor patient-controlled epidural analgesia whether patients receive epidural bupivacaine with 2 to 8 μg/ml neostigmine or epidural bupivacaine with 2 μg/ml fentanyl.

Epidural Analgesia with Amide Local Anesthetics, Bupivacaine, and Ropivacaine in Combination with Fentanyl for Labor Pain Relief: A Meta-Analysis

PubMed Central

Li, Yiyang; Hu, Cong; Fan, Yanyan; Wang, Huixia; Xu, Hongmei

2015-01-01

Background The study compares the effectiveness of bupivacaine and fentanyl (BUPI-FEN) and ropivacaine and fentanyl (ROPI-EFN) in epidural analgesia for labor pain through a meta-analysis of relevant randomized clinical trials. Material/Methods Multiple electronic databases were searched using appropriate MeSH terms and keywords for original English language research papers published between 1990 and March 2014. Meta-analyses results were based on the mean differences between the groups as well as odds ratios where appropriate. Statistical heterogeneity amongst the included studies was tested by I2 index. Results Nine studies that met the inclusion criteria were selected for analysis which consisted of 556 parturient patients. The duration of the second stage of labor was significantly shorter in the BUPI-FEN group by a mean of −6.87 (−10.98, −2.77; P<0.002). On the other hand, the ROPI-FEN group had a significantly lower incidence of motor blockade by a mean of 0.31 (0.18, 0.51; P<0.00001). A positive relationship between the amide local anesthetic concentration and the number of women having motor blockade was observed, but a negative relationship between fentanyl concentration and the number of women experiencing a motor block. Moreover, a positive correlation was found between the concentration of ropivacaine and the incidence of instrumental delivery and between the concentration of bupivacaine and the incidence of cesarean delivery. Conclusions In combination with fentanyl, bupivacaine and ropivacaine exhibit comparable efficacy and safety. However, BUP-FEN analgesia led to a shortened second-stage labor and ROPI-FEN resulted in a significantly lower incidence of motor block. PMID:25816849

Epidural analgesia with amide local anesthetics, bupivacaine, and ropivacaine in combination with fentanyl for labor pain relief: a meta-analysis.

PubMed

Li, Yiyang; Hu, Cong; Fan, Yanyan; Wang, Huixia; Xu, Hongmei

2015-03-29

The study compares the effectiveness of bupivacaine and fentanyl (BUPI-FEN) and ropivacaine and fentanyl (ROPI-EFN) in epidural analgesia for labor pain through a meta-analysis of relevant randomized clinical trials. Multiple electronic databases were searched using appropriate MeSH terms and keywords for original English language research papers published between 1990 and March 2014. Meta-analyses results were based on the mean differences between the groups as well as odds ratios where appropriate. Statistical heterogeneity amongst the included studies was tested by I^2 index. Nine studies that met the inclusion criteria were selected for analysis which consisted of 556 parturient patients. The duration of the second stage of labor was significantly shorter in the BUPI-FEN group by a mean of -6.87 (-10.98, -2.77; P<0.002). On the other hand, the ROPI-FEN group had a significantly lower incidence of motor blockade by a mean of 0.31 (0.18, 0.51; P<0.00001). A positive relationship between the amide local anesthetic concentration and the number of women having motor blockade was observed, but a negative relationship between fentanyl concentration and the number of women experiencing a motor block. Moreover, a positive correlation was found between the concentration of ropivacaine and the incidence of instrumental delivery and between the concentration of bupivacaine and the incidence of cesarean delivery. In combination with fentanyl, bupivacaine and ropivacaine exhibit comparable efficacy and safety. However, BUP-FEN analgesia led to a shortened second-stage labor and ROPI-FEN resulted in a significantly lower incidence of motor block.

Comparison of midazolam with fentanyl-midazolam combination during flexible bronchoscopy: A randomized, double-blind, placebo-controlled study

PubMed Central

Prabhudev, Amithash Marulaiah; Chogtu, Bharti; Magazine, Rahul

2017-01-01

BACKGROUND: Sedation during flexible bronchoscopy is desirable, but the drugs and the dosage protocols that are used vary. OBJECTIVE: To study and compare the effects of midazolam with fentanyl-midazolam combination during flexible bronchoscopy. MATERIALS AND METHODS: The study was conducted on 144 patients, from October 2013 to July 2015. They answered Hospital Anxiety and Depression Scale-Anxiety subscale and a prebronchoscopy questionnaire to assess their expectation toward flexible bronchoscopy. The patients were randomized into three groups: placebo, midazolam, and fentanyl-midazolam. Vitals signs including heart rate, respiratory rate, blood pressure, and oxygen saturation (SpO2) were recorded. Furthermore, Ramsay Sedation Scale was assessed during the procedure. Primary outcome measure was the composite score of patient-reported tolerance and satisfaction (assessed after the procedure). Secondary outcome measures were composite score of physician-reported feasibility of the procedure, hemodynamic changes during bronchoscopy, and side effects. RESULTS: Patient-reported tolerance and satisfaction composite scores (median, interquartile range) for placebo, midazolam, and fentanyl-midazolam groups were 54 (52, 57), 59 (57, 61.5), 62 (58.5, 66), respectively; P < 0.001. Physician-reported feasibility composite scores (median, interquartile range) for the respective groups were 24.5 (20.5, 28), 25 (21, 27), 26 (25, 29); P = 0.004. There was no significant difference between the groups so far as mean heart rate (P = 0.305), mean systolic blood pressure (P = 0.532), mean diastolic blood pressure (P = 0.516), mean respiratory rate (P = 0.131), and mean SpO2 (P = 0.968) were concerned. CONCLUSION: Conscious sedation with fentanyl and midazolam combination can result in better patient and operator satisfaction when compared with midazolam alone. PMID:29326491

Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations*†‡

PubMed Central

Fields, Marcia D.; Abate, Marie A.; Hu, Lan; Long, D. Leann; Blommel, Matthew L.; Haikal, Nabila A.; Kraner, James C.

2016-01-01

Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored. PMID:26223761

Identification of Unique Metabolites of the Designer Opioid Furanyl Fentanyl.

PubMed

Goggin, Melissa M; Nguyen, An; Janis, Gregory C

2017-06-01

The illicit drug market has seen an increase in designer opioids, including fentanyl and methadone analogs, and other structurally unrelated opioid agonists. The designer opioid, furanyl fentanyl, is one of many fentanyl analogs clandestinely synthesized for recreational use and contributing to the fentanyl and opioid crisis. A method has been developed and validated for the analysis of furanyl fentanyl and furanyl norfentanyl in urine specimens from pain management programs. Approximately 10% of samples from a set of 500 presumptive heroin-positive urine specimens were found to contain furanyl fentanyl, with an average concentration of 33.8 ng/mL, and ranging from 0.26 to 390 ng/mL. Little to no furanyl norfentanyl was observed; therefore, the furanyl fentanyl specimens were further analyzed by untargeted high-resolution mass spectrometry to identify other metabolites. Multiple metabolites, including a dihydrodiol metabolite, 4-anilino-N-phenethyl-piperidine (4-ANPP) and a sulfate metabolite were identified. The aim of the presented study was to identify the major metabolite(s) of furanyl fentanyl and estimate their concentrations for the purpose of toxicological monitoring. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Heroin Contaminated with Fentanyl Dramatically Enhances Brain Hypoxia and Induces Brain Hypothermia.

PubMed

Solis, Ernesto; Cameron-Burr, Keaton T; Kiyatkin, Eugene A

2017-01-01

While opioid abuse is an established medical and public health issue, the increased availability of highly potent synthetic opioids, such as fentanyl, has given rise to acute health complications, including a comatose state and death during drug overdose. Since respiratory depression that leads to acute hypoxia is the most dangerous complication of opioid drug use, we examined the effects of intravenous heroin and heroin contaminated with 10% fentanyl on oxygen levels in the nucleus accumbens (NAc) monitored using high-speed amperometry in freely moving rats. Additionally, we examined the effects of heroin, fentanyl, and their mixture on locomotion and temperatures in the NAc, temporal muscle, and skin. Both fentanyl and heroin at human-relevant doses (400 and 40 μg/kg, respectively) induced rapid, strong and transient decreases in NAc oxygen, indicative of brain hypoxia. When the heroin-fentanyl mixture was injected, the NAc hypoxic response was greatly potentiated in its duration, suggesting sustained hypoxia. In contrast to modest, monophasic brain temperature increases caused by heroin alone, the heroin-fentanyl mixture induced a biphasic temperature response, with a prominent postinjection decrease resulting from peripheral vasodilation. This hypothermic effect, albeit much smaller and more transient, was typical of fentanyl injected alone. Our findings indicate that accidental use of fentanyl instead of heroin, or even a relatively minor contamination of "street heroin" with fentanyl, poses great danger for acute health complications, including a comatose state and death.

Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe.

PubMed

Mounteney, Jane; Giraudon, Isabelle; Denissov, Gleb; Griffiths, Paul

2015-07-01

Fentanyl is a synthetic opioid analgesic historically used as a pain reliever and an anaesthetic. Recent concerns have arisen around the illicit use of fentanyl and its analogues in a number of European countries, linked to their high potency and associated risk of fatal overdose. Evidence has been emerging from Estonia for over a decade of entrenched patterns of fentanyl use, including injection of the drug and hundreds of overdose deaths. More recently, reports indicate that both fentanyl and 3-methylfentanyl (TMF) have been marketed as a replacement for heroin in European countries (e.g. Bulgaria, Slovakia) affected by heroin shortages. In addition, Germany, Finland and the United Kingdom, reported new outbreaks of fentanyl-related deaths. This combination of increasing mortality data alongside law enforcement intelligence suggesting both diversion and illicit production of fentanyls, prompted wider investigation using a targeted multi-source data collection exercise and analysis. This identified that in the European context, fentanyls are 'low use but high risk/harm' substances. Evidence shows that Estonia stands out as having an endemic problem, while the use of fentanyls in other European countries appears to be geographically localised. Developments in illicit supply of fentanyls reflect the complexity of Europe's contemporary drug market: manifesting illicit production and use, the diversion and misuse of medicines, and the online sale of non-controlled new psychoactive substances. Likewise effective and integrated responses will need to address fentanyl production, diversion as well as ensuring the availability of harm reduction measures to users. Copyright © 2015 Elsevier B.V. All rights reserved.

21 CFR 524.916 - Fentanyl.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Fentanyl. 524.916 Section 524.916 Food and Drugs..., AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.916 Fentanyl. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) fentanyl. (b) Sponsor. See No. 000986 in...

76 FR 19997 - Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-11

...] Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn From Sale for... Food and Drug Administration (FDA) has determined that FENTORA (fentanyl citrate) buccal tablet, 300... allow FDA to approve abbreviated new drug applications (ANDAs) for fentanyl citrate buccal tablet, 300...

21 CFR 524.916 - Fentanyl.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Fentanyl. 524.916 Section 524.916 Food and Drugs..., AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.916 Fentanyl. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) fentanyl. (b) Sponsor. See No. 050929 in...

Suicide by fentanyl.

PubMed

Sutlović, Davorka; Definis-Gojanović, Marija

2007-09-01

Fentanyl is a potent, short-acting narcotic analgesic widely used as surgical anaesthetic. This article presents a case in which fentanyl was self-injected by a 41-year old nurse, an employee at the hospital emergency department, who was found dead at home. She had no known history of drug and alcohol abuse. Two syringes, one empty and one filled with a clear liquid, were found near the body, while a needle was stuck into her hand. Toxicological analysis showed fentanyl poisoning. Fentanyl overdose was declared the cause of death and the manner of death was classified as suicide. To our knowledge, death due to the intravenous injection of fentanyl has not previously been reported in Croatia.

Fentanyl by continuous subcutaneous infusion for the management of cancer pain: a retrospective study.

PubMed

Watanabe, S; Pereira, J; Hanson, J; Bruera, E

1998-11-01

Twenty-two patients who received fentanyl by continuous subcutaneous infusion for treatment of cancer pain were evaluated retrospectively. No local toxicities were noted. Five patients were switched from transdermal fentanyl due to uncontrolled pain; three achieved stability, accompanied by improvement in visual analogue scores for pain. Seventeen patients were switched from other opioids due to toxicity; 10 achieved stability, with documented improvement in toxicity in seven. The median dose ratio of opioid prior to switchover (mg/day) to fentanyl at stabilization (mg/day) was 85.4 (range 65-112.5) for morphine and 23.0 (range 10.7-29.7) for hydromorphone. Of six stable patients switched from subcutaneous to transdermal fentanyl, four maintained stability. We conclude that fentanyl by continuous subcutaneous infusion is a useful alternative for cancer patients who experience uncontrolled pain while receiving transdermal fentanyl or who experience toxicity on other opioids.

21 CFR 522.800 - Droperidol and fentanyl.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Droperidol and fentanyl. 522.800 Section 522.800... Droperidol and fentanyl. (a) Specifications. Each milliliter of solution contains 20 milligrams (mg) of droperidol and 0.4 mg of fentanyl citrate. (b) Sponsor. See No. 000061 in § 510.600(c) of this chapter. (c...

Solution-state structure and affinities of cyclodextrin: Fentanyl complexes by nuclear magnetic resonance spectroscopy and molecular dynamics simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, Brian P.; Kennedy, Daniel J.; Lau, Edmond Y.

Cyclodextrins (CDs) are investigated for their ability to form inclusion complexes with the analgesic fentanyl and three similar molecules: acetylfentanyl, thiofentanyl, and acetylthiofentanyl. Stoichiometry, binding strength, and complex structure are revealed through nuclear magnetic resonance (NMR) techniques and discussed in terms of molecular dynamics (MD) simulations. It was found that β-cyclodextrin is generally capable of forming the strongest complexes with the fentanyl panel. Two-dimensional NMR data and computational chemical calculations are used to derive solution-state structures of the complexes. Binding of the fentanyls to the CDs occurs at the amide phenyl ring, leaving the majority of the molecule solvated bymore » water, an observation common to all four fentanyls. This finding suggests a universal binding behavior, as the vast majority of previously synthesized fentanyl analogues contain this structural moiety. Furthermore, this baseline study serves as the most complete work on CD:fentanyl complexes to date and provides the insights into strategies for producing future generations of designer cyclodextrins capable of stronger and more selective complexation of fentanyl and its analogues.« less

Solution-state structure and affinities of cyclodextrin: Fentanyl complexes by nuclear magnetic resonance spectroscopy and molecular dynamics simulation

DOE PAGES

Mayer, Brian P.; Kennedy, Daniel J.; Lau, Edmond Y.; ...

2016-02-04

Cyclodextrins (CDs) are investigated for their ability to form inclusion complexes with the analgesic fentanyl and three similar molecules: acetylfentanyl, thiofentanyl, and acetylthiofentanyl. Stoichiometry, binding strength, and complex structure are revealed through nuclear magnetic resonance (NMR) techniques and discussed in terms of molecular dynamics (MD) simulations. It was found that β-cyclodextrin is generally capable of forming the strongest complexes with the fentanyl panel. Two-dimensional NMR data and computational chemical calculations are used to derive solution-state structures of the complexes. Binding of the fentanyls to the CDs occurs at the amide phenyl ring, leaving the majority of the molecule solvated bymore » water, an observation common to all four fentanyls. This finding suggests a universal binding behavior, as the vast majority of previously synthesized fentanyl analogues contain this structural moiety. Furthermore, this baseline study serves as the most complete work on CD:fentanyl complexes to date and provides the insights into strategies for producing future generations of designer cyclodextrins capable of stronger and more selective complexation of fentanyl and its analogues.« less

Effects of fentanyl on pain and motor behaviors following a collagenase-induced intracerebral hemorrhage in rats

PubMed Central

Saine, Laurence; Hélie, Pierre; Vachon, Pascal

2016-01-01

Purpose Intracerebral hemorrhage (IH) and cephalalgia are common consequences of traumatic brain injury. One of the primary obstacles for patient recovery is the paucity of treatments to support an appropriate analgesic protocol. The present study aimed to assess pain and motor behaviors following different doses of fentanyl on a rat model of IH. Methods Twenty-one male Sprague Dawley rats underwent a stereotaxic surgery to produce a collagenase-induced IH in the right caudoputamen nucleus. The control group (n=6) received saline subcutaneously (SC), and experimental groups received either 5 (n=6), 10 (n=6), or 20 (n=3) µg/kg of fentanyl SC, 2 hours following surgery and on 2 subsequent days. Only 3 animals received 20 µg/kg because this dose caused catalepsy for 15–20 minutes following the injection. The rat grimace scale, a neurological examination, balance beam test, and rotarod test were performed for 5 consecutive days postoperatively to evaluate pain and motor performance. At the end of the experimentation, the brains were evaluated to determine hematoma volume, and the number of reactive astrocytes and necrotic neurons. Results When compared to controls, the grimace scale showed that 5 µg/kg fentanyl significantly alleviated pain on day 2 only (P<0.01) and that 10 µg/kg alleviated pain on days 1 (P<0.01), 2 (P<0.001), and 3 (P<0.01). For the rotarod test, only the 10 µg/kg group showed significant decreases in performance on days 5 (P<0.05) and 6 (P<0.02). The neurological examination was not significantly different between the groups, but only the hopping test showed poor recuperation for the 5 and 10 µg/kg fentanyl group when compared to saline (P<0.01). No differences were found between the groups for the balance beam test, the histopathological results. Conclusion Fentanyl, at a dose of 10 µg/kg SC, provides substantial analgesia following a collagenase-induced IH in rats; however, it can alter motor performance following analgesic treatments. PMID:27895509

Population Pharmacokinetics of Fentanyl in the Critically Ill

PubMed Central

Choi, Leena; Ferrell, Benjamin A; Vasilevskis, Eduard E; Pandharipande, Pratik P; Heltsley, Rebecca; Ely, E Wesley; Stein, C Michael; Girard, Timothy D

2016-01-01

Objective To characterize fentanyl population pharmacokinetics in patients with critical illness and identify patient characteristics associated with altered fentanyl concentrations. Design Prospective cohort study. Setting Medical and surgical ICUs in a large tertiary care hospital in the United States. Patients Patients with acute respiratory failure and/or shock who received fentanyl during the first five days of their ICU stay. Measurements and Main Results We collected clinical and hourly drug administration data and measured fentanyl concentrations in plasma collected once daily for up to five days after enrollment. Among 337 patients, the mean duration of infusion was 58 hours at a median rate of 100 µg/hr. Using a nonlinear mixed-effects model implemented by NONMEM, we found fentanyl pharmacokinetics were best described by a two-compartment model in which weight, severe liver disease, and congestive heart failure most affected fentanyl concentrations. For a patient population with a mean weight of 92 kg and no history of severe liver disease or congestive heart failure, the final model, which performed well in repeated 10-fold cross-validation, estimated total clearance (CL), intercompartmental clearance (Q), and volumes of distribution for the central (V1) and peripheral compartments (V2) to be 35 (95% confidence interval: 32 to 39) L/hr, 55 (42 to 68) L/hr, 203 (140 to 266) L, and 523 (428 to 618) L, respectively. Severity of illness was marginally associated with fentanyl pharmacokinetics but did not improve the model fit after liver and heart disease were included. Conclusions In this study, fentanyl pharmacokinetics during critical illness were strongly influenced by severe liver disease, congestive heart failure, and weight, factors that should be considered when dosing fentanyl in the ICU. Future studies are needed to determine if data-driven fentanyl dosing algorithms can improve outcomes for ICU patients. PMID:26491862

Detection of illicit online sales of fentanyls via Twitter.

PubMed

Mackey, Tim K; Kalyanam, Janani

2017-01-01

A counterfeit fentanyl crisis is currently underway in the United States.  Counterfeit versions of commonly abused prescription drugs laced with fentanyl are being manufactured, distributed, and sold globally, leading to an increase in overdose and death in countries like the United States and Canada.  Despite concerns from the U.S. Drug Enforcement Agency regarding covert and overt sale of fentanyls online, no study has examined the role of the Internet and social media on fentanyl illegal marketing and direct-to-consumer access.  In response, this study collected and analyzed five months of Twitter data (from June-November 2015) filtered for the keyword "fentanyl" using Amazon Web Services.  We then analyzed 28,711 fentanyl-related tweets using text filtering and a machine learning approach called a Biterm Topic Model (BTM) to detect underlying latent patterns or "topics" present in the corpus of tweets.  Using this approach we detected a subset of 771 tweets marketing the sale of fentanyls online and then filtered this down to nine unique tweets containing hyperlinks to external websites.  Six hyperlinks were associated with online fentanyl classified ads, 2 with illicit online pharmacies, and 1 could not be classified due to traffic redirection.  Importantly, the one illicit online pharmacy detected was still accessible and offered the sale of fentanyls and other controlled substances direct-to-consumers with no prescription required at the time of publication of this study.   Overall, we detected a relatively small sample of Tweets promoting illegal online sale of fentanyls.  However, the detection of even a few online sellers represents a public health danger and a direct violation of law that demands further study.

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

PubMed

Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

2017-12-01

We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most common side effects of ketamine were bad taste in the mouth (37; 90.2%), dizziness (30; 73.2%), and sleepiness (19; 46.3%). The most common side effects of fentanyl were sleepiness (15; 36.6%), bad taste in the mouth (9; 22%), and itchy nose (9; 22%). No patients experienced respiratory side effects. At 20 minutes, the mean pain scale score reduction was 44 ± 36 for ketamine and 35 ± 29 for fentanyl (mean difference = 9 [95% CI = -4 to 23]). Procedural sedation with ketamine occurred in 28 ketamine patients (65%) and 25 fentanyl patients (57%) prior to completing the study. Intranasal ketamine was associated with more minor side effects than intranasal fentanyl. Pain relief at 20 minutes was similar between groups. Our data support the feasibility of a larger, noninferiority trial to more rigorously evaluate the safety, efficacy, and potential opioid-sparing benefits of intranasal ketamine analgesia for children with acute pain. © 2017 by the Society for Academic Emergency Medicine.

Two Different Epidural Analgesic Combinations: Morphine vs. Fentanyl/Bupivacaine or Fentanyl/Ropivacaine and Their Post Operative Effects

DTIC Science & Technology

2001-10-01

Association for the Study of Pain defines pain as, "the sensory and emotional experiences associated with actual or potential tissue damage," (Taber, 1989...accentuating the pain response (Taber, 1989). In addition to the patients’ perception and experience of pain, the healthcare providers’ beliefs, biases...provide patients with quick recovery and pain-free postoperative experiences is a priority. The goal of this study was to compare the effectiveness

Pain Relievers - Multiple Languages

MedlinePlus

... español (Spanish) Bilingual PDF Health Information Translations Fentanyl - Opioid addiction, part 6 - English PDF Fentanyl - Opioid addiction, part 6 - español (Spanish) PDF Fentanyl - Opioid addiction, ...

Fentanyl produces an anti-hyperalgesic effect through the suppression of sodium channels in mice with painful diabetic neuropathy.

PubMed

Tanaka, Ken-ichiro; Nakanishi, Yuki; Sekino, Shyota; Ikegami, Megumi; Ikeda, Hiroko; Kamei, Junzo

2014-06-15

Diabetic neuropathy is one of the most frequent complications of diabetes mellitus. Therefore, the present study was designed to investigate the anti-hyperalgesic mechanism of fentanyl in a mouse model of streptozotocin-induced diabetic neuropathy. The antinociceptive response was assessed by recording the latency in a tail-flick test. The tail-flick latency in diabetic mice was significantly shorter than that in non-diabetic mice. Fentanyl, at doses of 3 and 10 μg/kg, s.c., produced a dose-dependent increase in the tail-flick latencies in diabetic mice. While fentanyl (3 μg/kg, s.c.) did not produce a significant inhibition of the tail-flick response in non-diabetic mice, it significantly prolonged the tail-flick latency in diabetic mice to the same level as the baseline latency in non-diabetic mice. Although pretreatment with naloxone (3mg/kg, s.c.) completely antagonized fentanyl-induced antinociception in non-diabetic mice, it had no effect on the antinociceptive effect of fentanyl in diabetic mice. Pretreatment with either of the voltage-gated sodium channel openers fenvarelarte and veratridine practically abolished the antinociceptive effects of fentanyl in diabetic mice. However, neither fenvarelate nor veratridine affected the antinociceptive effect of fentanyl in non-diabetic mice. These results suggest that the anti-hyperalgesic effect of fentanyl is mediated through the blockade of sodium channels in diabetic mice, whereas opioid receptors mediate the antinociceptive effect of fentanyl in non-diabetic mice. Copyright © 2014 Elsevier B.V. All rights reserved.

Brain injury and development in preterm infants exposed to fentanyl

PubMed Central

McPherson, Christopher; Haslam, Matthew; Pineda, Roberta; Rogers, Cynthia; Neil, Jeffrey J.; Inder, Terrie E.

2015-01-01

Background Fentanyl is commonly utilized in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl. Objective To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants Methods Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤ 30 weeks gestational age who underwent magnetic resonance imaging at term equivalent age (mean gestational age 26.9 ± 1.8 weeks). Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age. Results Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 μg/kg, interquartile range 1 – 441 μg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (OR 2.1, 95% confidence interval 1.1 – 4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates including the presence of cerebellar hemorrhage (r = 0.461, p = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age. Conclusions Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly utilized analgesic agents in preterm infants. PMID:26369570

Fentanyl related overdose in Indianapolis: Estimating trends using multilevel Bayesian models.

PubMed

Phalen, Peter; Ray, Bradley; Watson, Dennis P; Huynh, Philip; Greene, Marion S

2018-03-20

The opioid epidemic has been largely attributed to changes in prescribing practices over the past 20 years. Although current overdose trends appear driven by the opioid fentanyl, heroin has remained the focus of overdose fatality assessments. We obtained full toxicology screens on lethal overdose cases in a major US city, allowing more accurate assessment of the time-course of fentanyl-related deaths. We used coroner data from Marion County, Indiana comprising 1583 overdose deaths recorded between January 1, 2010 and April 30, 2017. Bayesian multilevel models were fitted to predict likelihood of lethal fentanyl-related overdose using information about the victim's age, race, sex, zip code, and date of death. Three hundred and seventy-seven (23.8%) overdose deaths contained fentanyl across the seven-year period. Rates rose exponentially over time, beginning well below 15% from 2010 through 2013 before rising to approximately 50% by 2017. At the beginning of the study period, rates of fentanyl overdose were lowest among Black persons but increased more rapidly, eventually surpassing Whites. Currently, White females are at particularly low risk of fentanyl overdose whereas Black females are at high risk. Rates were highest for younger and middle-aged groups. Over time, fentanyl was more likely detected without the presence of other opioids. Fentanyl has increasingly been detected in fatal overdose deaths in Marion County. Policy and program responses must focus on education for those at highest risk of fentanyl exposure and death. These responses should also be tailored to meet the unique needs of high-risk demographics. Copyright © 2018 Elsevier Ltd. All rights reserved.

75 FR 37295 - Control of Immediate Precursor Used in the Illicit Manufacture of Fentanyl as a Schedule II...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

... are the most potent opioids available for human and veterinary use. Fentanyl produces opioid effects that are indistinguishable from morphine or heroin, but fentanyl has a greater potency and a shorter duration of action. Fentanyl is approximately 50 to 100 times more potent than morphine and 30 to 50 times...

Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats

PubMed Central

Henderson, Fraser; May, Walter J.; Gruber, Ryan B.; Discala, Joseph F.; Puscovic, Veljko; Young, Alex P.; Baby, Santhosh M.; Lewis, Stephen J.

2015-01-01

This study determined the effects of the peripherally restricted µ-opiate receptor (µ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25 µg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5 mg/kg of NLXmi but was attenuated by a 5.0 mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5 mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5 mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral µ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. PMID:24284037

Hypobaric bupivacaine spinal anesthesia for cystoscopic intervention: the impact of adding fentanyl.

PubMed

Atallah, Mohamed M; Helal, Mostafa A; Shorrab, Ahmed A

2003-10-01

Addition of fentanyl to hyperbaric bupivacaine spinal anesthesia prolonged the duration of sensory block. This study seeks to test the hypothesis that adding fentanyl to small dose hypobaric spinal anesthesia will improve intraoperative patients and surgeon satisfaction without delay in recovery. Patients (n = 80) subjected to minor cystoscopic surgery were randomly assigned to have spinal anesthesia with either 5 mg bupivacaine 0.1% or 5 mg bupivacaine 0.1% mixed with 20 micrograms fentanyl. The main outcome measures included intraoperative patient and endoscopist satisfaction, sedative/analgesic supplementation, postoperative side effects and time to ambulation. Patients in the bupivacaine group needed more analgesic supplementation. Analgesia was more adequate in the bupivacaine-fentanyl group. Pruritus was the main side effect in the bupivacaine fentanyl group. Ambulation and discharge of patients were nearly the same in both groups. Spinal anesthesia with small dose (5 mg) hypobaric (0.1%) bupivacaine mixed with fentanyl (20 micrograms) produced adequate anesthesia for short cystoscopic procedures with minimal side effects and without delay in ambulation.

Fentanyl self-testing outside supervised injection settings to prevent opioid overdose: Do we know enough to promote it?

PubMed

McGowan, Catherine R; Harris, Magdalena; Platt, Lucy; Hope, Vivian; Rhodes, Tim

2018-05-11

Since 2013, North America has experienced a sharp increase in unintentional fatal overdoses: fentanyl, and its analogues, are believed to be primarily responsible. Currently, the most practical means for people who use drugs (PWUD) to avoid or mitigate risk of fentanyl-related overdose is to use drugs in the presence of someone who is in possession of, and experienced using, naloxone. Self-test strips which detect fentanyl, and some of its analogues, have been developed for off-label use allowing PWUD to test their drugs prior to consumption. We review the evidence on the off-label sensitivity and specificity of fentanyl test strips, and query whether the accuracy of fentanyl test strips might be mediated according to situated practices of use. We draw attention to the weak research evidence informing the use of fentanyl self-testing strips. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Notes from the field: increase in fentanyl-related overdose deaths - Rhode Island, November 2013-March 2014.

PubMed

Mercado-Crespo, Melissa C; Sumner, Steven A; Spelke, M Bridget; Sugerman, David E; Stanley, Christina

2014-06-20

During November 2013-March 2014, twice as many all-intent drug overdose deaths were reported in Rhode Island as were reported during the same period in previous years. Most deaths were among injection-drug users, and a large percentage involved fentanyl, a synthetic opioid that is 50-100 times more potent than morphine. Clusters of fentanyl-related deaths have been reported recently in several states. From April 2005 to March 2007, time-limited active surveillance from CDC and the Drug Enforcement Administration identified 1,013 deaths caused by illicit fentanyl use in New Jersey; Maryland; Chicago, Illinois; Detroit, Michigan; and Philadelphia, Pennsylvania. Acetyl fentanyl, an illegally produced fentanyl analog, caused a cluster of overdose deaths in northern Rhode Island in 2013.

Synergistic interaction between fentanyl and bupivacaine given intrathecally for labor analgesia.

PubMed

Ngan Kee, Warwick D; Khaw, Kim S; Ng, Floria F; Ng, Karman K L; So, Rita; Lee, Anna

2014-05-01

Lipophilic opioids and local anesthetics are often given intrathecally in combination for labor analgesia. However, the nature of the pharmacologic interaction between these drugs has not been clearly elucidated in humans. Three hundred nulliparous women randomly received 1 of 30 different combinations of fentanyl and bupivacaine intrathecally using a combined spinal-epidural technique for analgesia in the first stage of labor. Visual analogue scale pain scores were recorded for 30 min. Response was defined by percentage decrease in pain score from baseline at 15 and 30 min. Dose-response curves for individual drugs were fitted to a hyperbolic dose-response model using nonlinear regression. The nature of the drug interaction was determined using dose equivalence methodology to compare observed effects of drug combinations with effects predicted by additivity. The derived dose-response models for individual drugs (doses in micrograms) at 15 min were: Effect = 100 × dose / (13.82 + dose) for fentanyl, and Effect = 100 × dose / (1,590 + dose) for bupivacaine. Combinations of fentanyl and bupivacaine produced greater effects than those predicted by additivity at 15 min (P < 0.001) and 30 min (P = 0.015) (mean differences, 9.1 [95% CI, 4.1-14.1] and 6.4 [95% CI, 1.2-11.5] units of the normalized response, respectively), indicating a synergistic interaction. The pharmacologic interaction between intrathecal fentanyl and bupivacaine is synergistic. Characterization and quantification of this interaction provide a theoretical basis and support for the clinical practice of combining intrathecal opioids and local anesthetics.

Opioid Concentrations in Oral Fluid and Plasma in Cancer Patients With Pain.

PubMed

Heiskanen, Tarja; Langel, Kaarina; Gunnar, Teemu; Lillsunde, Pirjo; Kalso, Eija A

2015-10-01

Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone, or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. A total of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R(2) = 0.628 and 0.700, respectively), but not morphine (R(2) = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL vs. plasma concentrations of oxycodone compared with morphine and fentanyl. OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery.

PubMed

Honca, Mehtap; Dereli, Necla; Kose, Emine Arzu; Honca, Tevfik; Kutuk, Selcen; Unal, Selma Savas; Horasanli, Eyup

2015-01-01

the aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. in this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5 μg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25 μg fentanyl. All the patients remained in the seated position for 5 min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. spinal saddle block using hyperbaric levobupivacaine with both 12.5 μg and 25 μg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery].

PubMed

Honca, Mehtap; Dereli, Necla; Kose, Emine Arzu; Honca, Tevfik; Kutuk, Selcen; Unal, Selma Savas; Horasanli, Eyup

2015-01-01

The aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. In this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5μg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25μg fentanyl. All the patients remained in the seated position for 5min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. Motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. Spinal saddle block using hyperbaric levobupivacaine with both 12.5μg and 25μg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Intranasal Fentanyl Intoxication Leading to Diffuse Alveolar Hemorrhage.

PubMed

Ruzycki, Shannon; Yarema, Mark; Dunham, Michael; Sadrzadeh, Hossein; Tremblay, Alain

2016-06-01

Increasing rates of opioid abuse, particularly fentanyl, may lead to more presentations of unusual effects of opioid toxicity. Diffuse alveolar hemorrhage is a rare complication of fentanyl overdose. A 45-year-old male presented in hypoxic respiratory failure secondary to diffuse alveolar hemorrhage requiring intubation. Comprehensive drug screening detected fentanyl without exposure to cocaine. Further history upon the patient's recovery revealed exposure to snorted fentanyl powder immediately prior to presentation. Diffuse alveolar hemorrhage is a potential, though rare, presentation of opioid intoxication. Recognition of less common complications of opioid abuse such as diffuse alveolar hemorrhage is important in proper management of overdoses.

Fentanyl Sublingual Spray

MedlinePlus

Fentanyl sublingual spray is used to treat breakthrough pain (sudden episodes of pain that occur despite round ... effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic ( ...

Fentanyl Nasal Spray

MedlinePlus

Fentanyl nasal spray is used to treat breakthrough pain (sudden episodes of pain that occur despite round ... effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic ( ...

Prehospital Pain Medication Use by U.S. Forces in Afghanistan

DTIC Science & Technology

2015-03-01

oral transmucosal fentanyl citrate were the most commonly used pain medications during POI care, whereas ketamine and fentanyl predominated during...difference in vital signs on arrival to the hospital between casualties who received no pain medication, morphine, fentanyl , or ketamine during TACEVAC. In...this convenience sample, fentanyl and ketamine were as safe as morphine for prehospital use within the dose ranges administered. Future efforts to

Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats.

PubMed

Richebé, Philippe; Rivalan, Bertrand; Rivat, Cyril; Laulin, Jean-Paul; Janvier, Gérard; Maurette, Pierre; Simonnet, Guy

2009-02-01

Opioids are widely used for anesthesia but paradoxically induce postoperative pain hypersensitivity via N-methyl-D: -aspartate (NMDA) receptor modulation. Sevoflurane effects on opioid-induced hyperalgesia have not been yet evaluated in vivo. Nevertheless, some experimental in vitro studies reported anti-NMDA receptor properties for sevoflurane. The aim of this study was to evaluate sevoflurane effects on fentanyl-induced hyperalgesia in opioid-naive rats and in rats with inflammatory pain. Sevoflurane effects on hyperalgesia were evaluated in Sprague-Dawley rats: opioid-naive rats, rats treated with fentanyl (4 x 60 microg kg(-1)) and rats with inflammatory pain (carrageenan) treated with fentanyl (4 x 60 microg kg(-1)). On day zero, subcutaneous fentanyl injections were administered and inflammatory pain was induced with one carrageenan injection in one hind paw. Rats were exposed to low concentrations of sevoflurane (1.0 or 1.5%) on day zero prior to fentanyl injections and inflammatory pain induction, and for the duration of the fentanyl analgesic effect. The nociceptive threshold (Randall-Selitto test) was evaluated daily for 7 days. On day seven, naloxone was injected and the nociceptive threshold was assessed 5 min later. In rats without inflammatory pain but treated with fentanyl on day zero, sevoflurane 1.0% reversed the early (day zero) and long-lasting (day zero to day three) hyperalgesia classically described after high-doses of fentanyl (P < 0.05). This sevoflurane concentration antagonized the hyperalgesia induced by naloxone on day seven (P = 0.33). In a second experiment in rats with inflammatory pain, exposure to low concentrations of sevoflurane (1.0 and 1.5%) did not reduce fentanyl-induced hyperalgesia (P > 0.05), but nevertheless antagonized the naloxone induced hyperalgesia on day seven (P = 0.061). Relatively low sevoflurane concentrations (1.0%) reverse fentanyl-induced hyperalgesia in rats without inflammatory pain. Nevertheless, the lack of effect of sevoflurane concentrations of 1.0% and 1.5% to oppose hyperalgesia following high-dose fentanyl and inflammatory pain suggests that sevoflurane anti-hyperalgesic properties are weak.

Reduced incidence of laryngospasm with remifentanil-midazolam anaesthesia compared to halothane-fentanyl.

PubMed

Ali, Shahriari

2008-03-01

To compare the incidence of laryngospasm by using halothane-fentanyl anaesthesia and midazolam-remifentanil anaesthesia in paediatric patients undergoing eye surgery. We enrolled 120 ASA physical status I children aged 7-12 years scheduled for eye surgery from March 2004 to February 2006 in this prospective clinical trial study. Children suffering from any medical condition that could affect airway reflexes such as active upper respiratory infection, symptomatic asthma, obesity, patients with predicted difficulty in tracheal intubation were not included in the study. Patients with prolonged or difficult intubation or those who received another drug before extubation were excluded from the study. Using a random numbers table, participants were allocated to two equal groups. After induction of anaesthesia, in one group Halothane 1% was administered for the maintenance of anaesthesia in addition with intravenous fentanyl 1.5 microg kg(-1), and for the patients of the other group midazolam with a dose of 0.1 mg kg(-1) and remifentanil infusion by a dose of 0.1 microg kg(-1) min(-1) was administered. The patients were extubated in a unique plan of anaesthesia, using the sign of swallowing as a clinical indicator for extubation of patients. The incidence of laryngospasm was lower in midazolam-remifentanil group (0%) in comparison with halothane-fentanyl group (6.6%). The results of our study suggest that remifentanil combined with midazolam in children undergoing eye surgery provided a better condition for extubation of the patients.

Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist

PubMed Central

Doi, Seira; Mori, Tomohisa; Uzawa, Naoki; Arima, Takamichi; Takahashi, Tomoyuki; Uchida, Masashi; Yawata, Ayaka; Narita, Michiko; Uezono, Yasuhito; Suzuki, Tsutomu

2016-01-01

Background Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we further investigated the pharmacological profile of methadone compared to those of fentanyl and morphine as measured mainly by the discriminative stimulus effect and in vitro assays for NMDA receptor binding, µ-opioid receptor-internalization, and µ-opioid receptor-mediated β-arrestin recruitment. Results We found that fentanyl substituted for the discriminative stimulus effects of methadone, whereas a relatively high dose of morphine was required to substitute for the discriminative stimulus effects of methadone in rats. Under these conditions, the non-competitive NMDA receptor antagonist MK-801 did not substitute for the discriminative stimulus effects of methadone. In association with its discriminative stimulus effect, methadone failed to displace the receptor binding of MK801 using mouse brain membrane. Methadone and fentanyl, but not morphine, induced potent µ-opioid receptor internalization accompanied by the strong recruitment of β-arrestin-2 in µ-opioid receptor-overexpressing cells. Conclusions These results suggest that methadone may, at least partly, produce its pharmacological effect as a β-arrestin-biased µ-opioid receptor agonist, similar to fentanyl, and NMDA receptor blockade is not the main contributor to the pharmacological profile of methadone. PMID:27317580

Nebulized fentanyl vs intravenous morphine for ED patients with acute abdominal pain: a randomized double-blinded, placebo-controlled clinical trial.

PubMed

Deaton, Travis; Auten, Jonathan D; Darracq, Michael A

2015-06-01

Patients with acute abdominal pain commonly present to emergency departments. The safe and effective relief of discomfort is a concern to patients and physicians. Intravenous opioids are the traditional method used to provide pain relief in this setting, but intravenous access is time consuming and not always achievable. Alternative methods of pain control may therefore be necessary for the acute management of painful conditions without adding to the overall physical or psychological discomfort. The purpose of this study was to evaluate the feasibility of nebulized fentanyl (NF) in the alleviation of acute and undifferentiated abdominal pain. We also sought to compare NF with intravenous morphine (IVM) and to assess patient and provider satisfaction with NF. Nebulized fentanyl (2 μg/kg) was compared to IVM (0.1 mg/kg) at 10, 20, 30, and 40 minutes; and patient and physician satisfaction was recorded. The NF group experienced more rapid pain relief and more sustained and clinically significant pain relief over the 40-minute study interval. There were no adverse effects noted in the NF group. Both patient and physician satisfaction scores were higher in the NF group. Fentanyl citrate at a dose of 2 μg/kg through a breath-actuated nebulizer appears to be a feasible and safe alternative to IVM (0.1 mg/kg) in the treatment of acute abdominal pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiovascular effects of fentanyl in conscious rats.

PubMed

Baechtold, F; Cavadas, C; Gasser, D; Markert, M; Grouzmann, E; Peterson, K L; Waeber, B; Feihl, F

2001-10-01

The polymicrobial sepsis induced by cecal ligation and puncture (CLP) in the rat is widely used in shock research. For ethical reasons, narcotic analgesics are often administered in this model, with the potential risk of confounding effects. In conscious non-septic rats, we investigated the cardiovascular effects of a continuous i.v. infusion of fentanyl (20 microg/kg per h) administered with fluid loading (10 ml/kg per h) for 24 h, a regimen commonly applied in rat CLP. Animals were randomly allocated to receive analgesia with fluid loading (Fentanyl group), or fluid loading alone (Control). All endpoints were assessed after 24 h of infusion. At that time, Control animals had mild respiratory alkalosis, which was essentially abolished by fentanyl. Analgesia mildly elevated the plasma norepinephrine levels [median (interquartile range): Control 232 pg/ml (0-292), Fentanyl 302 pg/ml (234-676), P=0.045] but was devoid of any effect on blood pressure, heart rate, cardiac output (mean +/-SD: Control 388+/-61 ml/kg per min, Fentanyl 382+/-62 ml/kg per min, P=0.87) and indices of left ventricular function derived from high-fidelity recordings of left ventricular pressure (dP/dtmax: Control 11782+/-2324 mmHg/s, Fentanyl 12107+/-2816 mmHg/s, P=0.77). In ex vivo experiments carried out immediately after animal sacrifice, no differences were noted between the Control and Fentanyl groups in the sensitivity of endothelium-intact aortic rings to norepinephrine-induced vasoconstriction (-logEC50: Control 8.78+/-0.28, Fentanyl 8.83+/-0.26, P=0.52) or acetylcholine-induced vasodilatation (-logEC50: Control 7.00+/-0.37, Fentanyl 7.06+/-0.26+/-0.53, P=0.75). In conclusion, the present data provide no contraindication, and even some support for the ethical use of a high dose i.v. infusion of fentanyl in cardiovascular studies of conscious catheterized rats undergoing CLP or other painful procedures.

Qualitative Identification of Fentanyl Analogs and Other Opioids in Postmortem Cases by UHPLC-Ion Trap-MSn.

PubMed

Shoff, Elisa N; Zaney, M Elizabeth; Kahl, Joseph H; Hime, George W; Boland, Diane M

2017-07-01

Since 2013, the Miami-Dade County Medical Examiner Department has experienced an increase in the number of opioid-related deaths. The majority of cases coincided with the introduction of fentanyl into the local heroin supply. From 2014 to 2015, Miami-Dade County experienced a near 600% increase in fentanyl-related deaths, followed by an additional 200% increase in 2016. In 2015, two novel fentanyl analogs were identified in medical examiner cases: beta-hydroxythiofentanyl and acetyl fentanyl. In 2016, four additional fentanyl analogs emerged: para-fluoroisobutyryl fentanyl, butyryl fentanyl, furanyl fentanyl and carfentanil, as well as the synthetic opioid U-47700. In order to address this epidemic, a method was developed and validated to identify 44 opioid-related and analgesic compounds in postmortem samples using ultra high performance liquid chromatography ion trap mass spectrometry with MSn capabilities. The limit of detection for all compounds ranged from 0.1 to 5 ng/mL, with a majority having MS3 spectral fragmentation. Blood, urine, liver or brain specimens from ~500 postmortem cases were submitted for analysis based on case history and/or initial screening results. Of those cases, 375 were positive for illicit fentanyl and/or one or more fentanyl analogs. Due to the potency of these compounds, they were almost always included in the cause of death. Worth emphasizing and extremely alarming is the detection of carfentanil in 134 cases, 104 of which were initially missed by gas chromatography mass spectrometry. By incorporating this sensitive, highly specific, and evolving screening procedure into the workflow, the toxicology laboratory continues to effectively assist the medical examiners in determining the cause and manner of death of decedents in Miami-Dade County. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Detection of illicit online sales of fentanyls via Twitter

PubMed Central

Mackey, Tim K.; Kalyanam, Janani

2017-01-01

A counterfeit fentanyl crisis is currently underway in the United States.  Counterfeit versions of commonly abused prescription drugs laced with fentanyl are being manufactured, distributed, and sold globally, leading to an increase in overdose and death in countries like the United States and Canada.  Despite concerns from the U.S. Drug Enforcement Agency regarding covert and overt sale of fentanyls online, no study has examined the role of the Internet and social media on fentanyl illegal marketing and direct-to-consumer access.  In response, this study collected and analyzed five months of Twitter data (from June-November 2015) filtered for the keyword “fentanyl” using Amazon Web Services.  We then analyzed 28,711 fentanyl-related tweets using text filtering and a machine learning approach called a Biterm Topic Model (BTM) to detect underlying latent patterns or “topics” present in the corpus of tweets.  Using this approach we detected a subset of 771 tweets marketing the sale of fentanyls online and then filtered this down to nine unique tweets containing hyperlinks to external websites.  Six hyperlinks were associated with online fentanyl classified ads, 2 with illicit online pharmacies, and 1 could not be classified due to traffic redirection.  Importantly, the one illicit online pharmacy detected was still accessible and offered the sale of fentanyls and other controlled substances direct-to-consumers with no prescription required at the time of publication of this study.   Overall, we detected a relatively small sample of Tweets promoting illegal online sale of fentanyls.  However, the detection of even a few online sellers represents a public health danger and a direct violation of law that demands further study. PMID:29259769

Beneficial Effects of Adding Ketamine to Intravenous Patient-Controlled Analgesia with Fentanyl after the Nuss Procedure in Pediatric Patients

PubMed Central

Cha, Moon Ho; Eom, Ji Hye; Lee, Yoon Sook; Kim, Woon Young; Park, Young Cheol; Min, Sam Hong

2012-01-01

Purpose The aim of this prospective, double-blind, randomized study was to investigate the analgesic effects of low-dose ketamine on intravenous patient-controlled analgesia (IV-PCA) with fentanyl for pain control in pediatric patients following the Nuss procedure for pectus excavatum. Materials and Methods Sixty pediatric patients undergoing the Nuss procedure were randomly assigned to receive fentanyl (Group F, n=30) or fentanyl plus ketamine (Group FK, n=30). Ten minutes before the end of surgery, following the loading dose of each solution, 0.5 µg/kg/hr of fentanyl or 0.5 µg/kg/hr of fentanyl plus 0.15 mg/kg/hr of ketamine was infused via an IV-PCA pump (basal rate, 1 mL/hr; bolus, 0.5 mL; lock out interval, 30 min). Fentanyl consumption, pain score, ketorolac use, nausea/vomiting, ondansetron use, pruritus, respiratory depression, hallucination, dreaming, and parent satisfaction with pain control were measured throughout the 48 hours following surgery. Results The pain scores, ketorolac use, and fentanyl consumption of Group FK were significantly lower than in Group F (p<0.05). The incidence of nausea/vomiting and ondansetron use in Group FK was significantly lower than in Group F (p<0.05). There were no reports of respiratory depression, hallucination or dreaming. Parent satisfaction with pain control was similar between the two groups. Conclusion We concluded that low-dose ketamine added to IV-PCA with fentanyl after the Nuss procedure in pediatric patients can reduce pain scores, consumption of fentanyl, and incidence of nausea/vomiting without increasing side effects. PMID:22318834

Fentanyl inhibits proliferation and invasion of colorectal cancer via β-catenin

PubMed Central

Zhang, Xiu-Lai; Chen, Min-Li; Zhou, Sheng-Li

2015-01-01

Background and aim: Fentanyl is widely used for relieving pain and narcotizing in cancer patients. However, there are few published reports regarding the effects of fentanyl on tumor control and treatment. Here we investigated the effects of fentanyl on tumor growth and cell invasion in the human colorectal carcinoma (HCT116) cells. Methods: Nude mice xenografts of HCT116 cells were established to assess the inhibition effect on tumor growth by fentanyl. MTT and Transwell were employed to determine the cell survival rate and cell invasion, respectively. MicroRNAs and mRNAs expression were quantified by real-time PCR. β-catenin and matrix metalloproteinases (MMP-2 and MMP-9) expression were assayed by western blotting. β-Catenin-specific small interfering RNA (Si-β-catenin) and miR-182 mimics were transfected in cells to investigate the mechanism underlying the effects of fentanyl on the colorectal tumor and HCT116 cells. Results: Treatment with fentanyl inhibited the tumor growth and HCT116 cells invasion. Fentanyl also downregulated the expression of β-catenin and miR-182 in both xenograft tumors and HCT116 cells, and decreased the protein level of MMP-9 in HCT116 cells. Downregulation of β-Catenin resulted in the decrease of miR-182 expression in colorectal cells. In addition, the overexpression of miR-182 reversed the effect of fentanyl on MMP-9 expression and cell invasion of HCT116 cells. Conclusions: The current study demonstrated that the inhibition of tumor growth and cell invasion in colorectal cancer by fentanyl is probably due to downregulation of miR-182 and MMP-9 expression by β-catenin. PMID:25755709

Evaluation of plasma fentanyl concentrations in infants during cardiopulmonary bypass with low-volume circuits.

PubMed

Kussman, Barry D; Zurakowski, David; Sullivan, Lorna; McGowan, Francis X; Davis, Peter J; Laussen, Peter C

2005-06-01

The purpose of the study was to measure changes in plasma fentanyl concentrations during infant cardiac surgery using a bypass circuit with low priming volume and to examine the relation of plasma fentanyl concentration and temperature to Bispectral Index (BIS) as an index of conscious level during infant cardiac surgery. Prospective cohort study. Tertiary care, academic children's hospital. Fifteen neonates and infants undergoing cardiac surgery with hypothermic cardiopulmonary bypass (CPB). Patients were anesthetized with fentanyl, receiving a 30 microg/kg bolus for induction immediately followed by continuous infusion of 0.3 microg/kg/min until skin closure. Intraoperative data and total plasma fentanyl concentration were measured at preinduction; 30 minutes postinduction; sternotomy; aortic cannulation; at 4, 30, and 60 minutes on CPB; and at 1 and 30 minutes off CPB. At the onset of CPB, fentanyl declined from 15 +/- 6 to 11 +/- 5 ng/mL (p < 0.01), increasing to 16 +/- 5 ng/mL (p < 0.01) at 30 minutes on CPB and maintaining a similar level until 30 minutes off CPB. BIS decreased from 88 +/- 20 to 42 +/- 11 (p = 0.02) with induction, declined further during cooling to 9 +/- 11 at the nadir temperature ( p < 0.001), and increased during rewarming to 29 +/- 9 at 1 minute (p < 0.001) and 35 +/- 10 at 30 minutes off CPB ( p < 0.01). Because of wide individual variation in BIS, there was no significant correlation between fentanyl and BIS and temperature. There was minimal variability in the plasma fentanyl concentration using a low-volume bypass circuit and constant infusion of fentanyl during surgery. There appears to be minimal utility for using BIS during infant cardiac surgery with no relationship between fentanyl concentration, temperature, and BIS established.

A cluster of fentanyl-related deaths among drug addicts in Sweden.

PubMed

Kronstrand, R; Druid, H; Holmgren, P; Rajs, J

1997-08-22

During a 16-month period, nine fatalities occurred among white male drug-addicts, where fentanyl was detected at postmortem toxicological analysis. The street samples associated with these cases confirmed the presence of fentanyl as an additive in low-concentration amphetamine powders with caffeine, phenazone and sugar as cutting agents. In seven of the cases, an acute intoxication by fentanyl was considered to be the immediate cause of death, and in one case, it was likely, but no analysis of fentanyl was performed in blood, and in another case the death was suicide by hanging. This appears to be the first report of a cluster of fentanyl-related deaths outside the United States, and the occurrence of fentanyl in combination with amphetamine has not previously been reported. In addition, in all cases, femoral blood was collected, and samples were handled and analysed according to standardized, quality-controlled procedures. The previous history, circumstances surrounding the death, autopsy findings, histology and toxicology examination of each case are presented. The gas chromatographic-mass spectrometric method for fentanyl is also described. Fentanyl concentrations ranged from 0.5 to 17 ng g-1 blood, and from 5 to 160 ng ml-1 urine. Other drugs found were amphetamine (8 cases), ethanol (5 cases) and benzodiazepines (5 cases). Morphine was found in only one case. The average age of men was 33.9 years (range 22-44); six were found in their own of friend's apartment, two inside buildings (stairways) and one was found outdoors. We conclude that fentanyl is a dangerous substance that should be considered in drug-addict deaths even outside the United States, particularly when the remaining toxicology is unremarkable, and the cause of death cannot be ascertained

Enhanced Analgesic Responses After Preferential Delivery of Morphine and Fentanyl to the Olfactory Epithelium in Rats

PubMed Central

Hoekman, John D.; Ho, Rodney J.Y.

2011-01-01

Background Centrally acting opioid analgesics such as morphine and fentanyl are effective, but their efficacy is often limited by a delayed response or side effects resulting from systemic first-pass before reaching the brain and the central nervous system (CNS). It is generally accepted that drugs applied to the nasal cavity can directly access the brain and the CNS, which could provide therapeutic advantages such as rapid onset and lower systemic exposure. The olfactory region of the nasal cavity has been implicated in facilitating this direct nose-to-CNS transfer. If the fraction of opioid administered to the olfactory region could be improved, there could be a larger fraction of drug directly delivered to the CNS, mediating greater therapeutic benefit. Methods We have developed a pressurized olfactory delivery (POD) device to consistently and non-invasively deposit a majority of drug on the olfactory region of the nasal cavity in Sprague-Dawley rats. Using the tail-flick latency test and analysis of plasma and CNS tissue drug exposure, we compared distribution and efficacy of the opioids morphine and fentanyl administered to the nasal olfactory region with the POD device or the nasal respiratory region with nose drops or systemically via intraperitoneal (IP) injection. Results Compared to nose drop, POD administration of morphine resulted in significantly higher overall therapeutic effect (AUCeffect) without a significant increase in plasma drug exposure (AUCplasma). POD delivery of morphine resulted in a nose-to-CNS direct transport percentage of 38–55%. POD delivery of fentanyl led to a faster (5 min vs. 10 min) and more intense analgesic effect compared to nasal respiratory administration. Unlike IP injection or nose drop administration, both morphine and fentanyl given by the POD device to olfactory nasal epithelium exhibited clockwise [plasma] versus effect hysteresis after nasal POD administration, consistent with direct nose-to-CNS drug transport mechanism. Conclusions Deposition of opioids to the olfactory region within the nasal cavity could have a significant impact on drug distribution and pharmacodynamic effect, and thus should be considered into account in future nasally administered opioid studies. PMID:21709146

Characteristics of Fentanyl Overdose - Massachusetts, 2014-2016.

PubMed

Somerville, Nicholas J; O'Donnell, Julie; Gladden, R Matthew; Zibbell, Jon E; Green, Traci C; Younkin, Morgan; Ruiz, Sarah; Babakhanlou-Chase, Hermik; Chan, Miranda; Callis, Barry P; Kuramoto-Crawford, Janet; Nields, Henry M; Walley, Alexander Y

2017-04-14

Opioid overdose deaths in Massachusetts increased 150% from 2012 to 2015 (1). The proportion of opioid overdose deaths in the state involving fentanyl, a synthetic, short-acting opioid with 50-100 times the potency of morphine, increased from 32% during 2013-2014 to 74% in the first half of 2016 (1-3). In April 2015, the Drug Enforcement Agency (DEA) and CDC reported an increase in law enforcement fentanyl seizures in Massachusetts, much of which was believed to be illicitly manufactured fentanyl (IMF) (4). To guide overdose prevention and response activities, in April 2016, the Massachusetts Department of Public Health and the Office of the Chief Medical Examiner collaborated with CDC to investigate the characteristics of fentanyl overdose in three Massachusetts counties with high opioid overdose death rates. In these counties, medical examiner charts of opioid overdose decedents who died during October 1, 2014-March 31, 2015 were reviewed, and during April 2016, interviews were conducted with persons who used illicit opioids and witnessed or experienced an opioid overdose. Approximately two thirds of opioid overdose decedents tested positive for fentanyl on postmortem toxicology. Evidence for rapid progression of fentanyl overdose was common among both fatal and nonfatal overdoses. A majority of interview respondents reported successfully using multiple doses of naloxone, the antidote to opioid overdose, to reverse suspected fentanyl overdoses. Expanding and enhancing existing opioid overdose education and prevention programs to include fentanyl-specific messaging and practices could help public health authorities mitigate adverse effects associated with overdoses, especially in communities affected by IMF.

Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats.

PubMed

Henderson, Fraser; May, Walter J; Gruber, Ryan B; Discala, Joseph F; Puskovic, Veljko; Young, Alex P; Baby, Santhosh M; Lewis, Stephen J

2014-01-15

This study determined the effects of the peripherally restricted μ-opiate receptor (μ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25μg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5mg/kg of NLXmi but was attenuated by a 5.0mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral μ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. Copyright © 2013 Elsevier B.V. All rights reserved.

pKa of fentanyl varies with temperature: implications for acid-base management during extremes of body temperature.

PubMed

Thurlkill, Richard L; Cross, David A; Scholtz, J Martin; Pace, C Nick

2005-12-01

The pKa of fentanyl has not been measured previously at varying extremes of body temperature. The goal of this laboratory investigation was to test the hypothesis that the pKa of fentanyl changes with temperature. The investigation involved measuring the pKa values of aqueous fentanyl at varying temperatures. The investigation was conducted in a controlled laboratory environment. No human or animal subjects were involved. Because no live subjects were involved in the investigation, no interventions were necessary. This paper reports the effect of temperature on the pKa of fentanyl. The pKa of aqueous fentanyl was measured at 15 degrees C, 25 degrees C, 37 degrees C, 42 degrees C, and 47.5 degrees C by potentiometric titration in 0.01 mmol/L of potassium chloride after extensive degassing. Data were analyzed using the least squares method with an appropriately fitting equation. The pKa of fentanyl was found to change in a similar manner to the neutral point of water at varying temperatures. This finding has implications for the bioavailability of fentanyl at extremes of body temperature in association with the clinical acid-base management of the patient. Clinical implications for differing methods of intraoperative acid-base management at varying temperatures are discussed.

Laparoscopic cholecystectomy under spinal anesthesia: comparative study between conventional-dose and low-dose hyperbaric bupivacaine

PubMed Central

Imbelloni, Luiz Eduardo; Sant’Anna, Raphael; Fornasari, Marcos; Fialho, José Carlos

2011-01-01

Background Laparoscopic cholecystectomy has the advantages of causing less postoperative pain and requiring a short hospital stay, and therefore is the treatment of choice for cholelithiasis. This study was designed to compare spinal anesthesia using hyperbaric bupivacaine given as a conventional dose by lumbar puncture or as a low-dose by thoracic puncture. Methods A total of 140 patients with symptomatic gallstone disease were randomized to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under spinal anesthesia using either conventional lumbar spinal anesthesia (hyperbaric bupivacaine 15 mg and fentanyl 20 mg) or low-dose thoracic spinal anesthesia (hyperbaric bupivacaine 7.5 mg and fentanyl 20 μg). Intraoperative parameters, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two treatment groups. Results All procedures were completed under spinal anesthesia, with no cases needing conversion to general anesthesia. Values for time for block to reach the T3 dermatomal level, duration of motor and sensory block, and hypotensive events were significantly lower with low-dose bupivacaine. Postoperative pain was higher for low-dose hyperbaric bupivacaine at 6 and 12 hours. All patients were discharged after 24 hours. Follow-up 1 week postoperatively showed all patients to be satisfied and to be keen advocates of spinal anesthesia. Conclusion Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia. A small dose of hyperbaric bupivacaine 7.5 mg and 20 μg fentanyl provides adequate spinal anesthesia for laparoscopy and, in comparison with hyperbaric bupivacaine 15% and fentanyl 20 μg, causes markedly less hypotension. The low-dose strategy may have an advantage in ambulatory patients because of the earlier recovery of motor and sensory function and earlier discharge. PMID:22915892

The analgesic efficacy of oxycodone hydrochloride versus fentanyl during outpatient artificial abortion operation: A randomized trial.

PubMed

Xie, Kangjie; Zhang, Wen; Fang, Wumei; Lian, Yanhong; Lin, Sufeng; Fang, Jun

2017-06-01

Problems like body movement, respiratory depression, and complained of pain are still common phenomenon in outpatient artificial abortion general anesthesia. Oxycodone hydrochloride is a semisynthetic opioid and has a good therapeutic effect on visceral pain. We hypothesize that oxycodone hydrochloride would be superior to fentanyl in outpatient artificial abortion surgery. In this clinical trial 149 American Society of Anesthesiologists (ASA) I or II female outpatients scheduled for elective artificial abortion surgeries under general anesthesia were randomly divided into 3 groups: oxycodone hydrochloride 0.06 mg/kg group (group A), oxycodone hydrochloride 0.08 mg/kg group (group B), and control group fentanyl 2 ug/kg (group C). The primary outcome was level body movement and respiratory depression during the surgery, the second outcome included the visual analogue scale (VAS) score 30 minutes after waking. A total of 120 participants completed the study, n = 40 in each group. There was no significant difference in patients' age, body mass index (BMI), preoperative heart rate, mean arterial blood pressure, consumption dose of propofol, intraoperative body movement type and times, and duration of surgery among the 3 groups (P > .05). Comparing the incidence of intraoperative respiratory depression and SPO2 < 90% among the 3 groups, group C's was significantly higher than those of groups A and B, and the difference was statistically significant (P < .05). Group A had no difference compared with group B. In VAS score 30minutes after waking, group C was the highest, followed by group A, with group B as the lowest. The difference among the 3 groups was statistically significant (P < .05), but a difference delta less than 1 on the VAS scale is not clinically significant. The analgesic effect of oxycodone hydrochloride at 0.06 mg/kg applied to painless artificial abortion surgery is not superior than that of fentanyl, but the incidence of intraoperative respiratory depression and hypoxemia is significantly lower than fentanyl.

[A case of gastric cancer accompanied by disseminated carcinomatosis of bone marrow wherein long-term chemotherapy was enabled by early supportive palliative care].

PubMed

Yamagiwa, Tetsuya; Amakawa, Ryuichi; Takeda, Yasuhiro; Fukuda, Akiko; Ito, Satoko; Nakayama, Shinya; Shiotani, Tomohiro; Watanabe, Go; Kita, Kenkichi; Yamaoka, Yoshio

2014-02-01

Here we report gastric cancer accompanied by bone marrow carcinomatosis in a patient for whom long-term chemotherapy was enabled by early pain-relief therapy. A 45-year-old man was admitted to our hospital because of back pain associated with multiple spinal tumors in June 2011. Blood tests showed a trend toward disseminated intravascular coagulation(DIC) and gastric cancer was suspected as the primary lesion. Because pain was severe, emergency pain relief was provided by flurbiprofen axetil and a continuous subcutaneous infusion of fentanyl citrate. After bone marrow examination gave a diagnosis of poorly differentiated adenocarcinoma, we performed sequential methotrexate(MTX)and 5-fluorouracil(5-FU)therapy. The therapy successfully decreased tumor marker levels, and alkaline phosphatase and lactate dehydrogenase levels normalized. Finally, gastric cancer accompanied by bone marrow carcinomatosis was diagnosed. Because the patient had anxiety and spiritual pain from the time of admission, psychiatric care was also required. In November 2011, the tumor recurred, and we switched therapy to a combination of S-1 and cisplatin. The patient's pain was controlled by combined treatment with a fentanyl patch and etodolac, and he was discharged in December 2011. However, severe pain recurred and pain therapy was continued. DIC developed in February 2012 and transiently resolved after resuming combination therapy with MTX and 5-FU; however, it subsequently recurred, leading to the patient's death in May 2012.

Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray

PubMed Central

Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.

2014-01-01

Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060

Neither xenon nor fentanyl induces neuroapoptosis in the newborn pig brain.

PubMed

Sabir, Hemmen; Bishop, Sarah; Cohen, Nicki; Maes, Elke; Liu, Xun; Dingley, John; Thoresen, Marianne

2013-08-01

Some inhalation anesthetics increase apoptotic cell death in the developing brain. Xenon, an inhalation anesthetic, increases neuroprotection when combined with therapeutic hypothermia after hypoxic-ischemic brain injury in newborn animals. The authors, therefore, examined whether there was any neuroapoptotic effect of breathing 50% xenon with continuous fentanyl sedation for 24 h at normothermia or hypothermia on newborn pigs. Twenty-six healthy pigs (<24-h old) were randomized into four groups: (1) 24  h of 50% inhaled xenon with fentanyl at hypothermia (Trec = 33.5 °C), (2) 24 h of 50% inhaled xenon with fentanyl at normothermia (Trec = 38.5 °C), (3) 24 h of fentanyl at normothermia, or (4) nonventilated juvenile controls at normothermia. Five additional nonrandomized pigs inhaled 2% isoflurane at normothermia for 24 h to verify any proapoptotic effect of inhalation anesthetics in our model. Pathological cells were morphologically assessed in cortex, putamen, hippocampus, thalamus, and white matter. To quantify the findings, immunostained cells (caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphate nick-end labeling) were counted in the same brain regions. For groups (1) to (4), the total number of apoptotic cells was less than 5 per brain region, representing normal developmental neuroapoptosis. After immunostaining and cell counting, regression analysis showed that neither 50% xenon with fentanyl nor fentanyl alone increased neuroapoptosis. Isoflurane caused on average a 5- to 10-fold increase of immunostained cells. At normothermia or hypothermia, neither 24 h of inhaled 50% xenon with fentanyl sedation nor fentanyl alone induces neuroapoptosis in the neonatal pig brain. Breathing 2% isoflurane increases neuroapoptosis in neonatal pigs.

A series of forensic toxicology and drug seizure cases involving illicit fentanyl alone and in combination with heroin, cocaine or heroin and cocaine.

PubMed

Marinetti, Laureen J; Ehlers, Brooke J

2014-10-01

The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Analgesia and sedation in neonatal-pediatric intensive care].

PubMed

Schlünder, C; Houben, F; Hartwig, S; Theisohn, M; Roth, B

1991-01-01

In pediatric intensive care, analgesia and sedation has become increasingly important for newborns as well as prematures in recent years. However, its importance is frequently not well recognized and sedation is confounded with analgesia. In our intensive-care unit (ICU), fentanyl and midazolam have proved to be useful. In newborn and premature infants, fentanyl alone has been sufficient because of its analgesic and sedative action. In a study on 20 newborns and prematures suffering from severe respiratory problems as compared with a historical group that did not receive fentanyl, we could show that in subjects receiving fentanyl, considerably less treatment with sedatives and other analgesics was necessary. Cardiopulmonary tolerance was satisfactory. The highest bilirubin values were reached about 1 day earlier and were slightly higher than those measured in the control group, but oral nutrition could be initiated sooner. In small infants, additional midazolam was given after cardiac surgery. During the first 72 h, we found a correlation between serum levels of midazolam and the depth of sedation; however, after 72 h of medication, the dose had to be raised because of an increase in metabolic clearance. During the concomitant administration of midazolam and fentanyl, significantly less midazolam was needed to achieve appropriate analog-sedation. Prior to the administration of analgesics and sedatives, care should be taken to ensure that circulatory conditions are stable and that there is no hypovolemia, and the drugs must be given slowly during several minutes. Especially in a pediatric ICU, light and noise should be diminished and contact between the parents and the child should be encouraged, even when the child is undergoing mechanical ventilation.

Does nebulized fentanyl relieve dyspnea during exercise in healthy man?

PubMed Central

Kotrach, Houssam G.; Bourbeau, Jean

2015-01-01

Few therapies exist for the relief of dyspnea in restrictive lung disorders. Accumulating evidence suggests that nebulized opioids selective for the mu-receptor subtype may relieve dyspnea by modulating intrapulmonary opioid receptor activity. Our respective primary and secondary objectives were to test the hypothesis that nebulized fentanyl (a mu-opioid receptor agonist) relieves dyspnea during exercise in the presence of abnormal restrictive ventilatory constraints and to identify the physiological mechanisms of this improvement. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of 250 μg nebulized fentanyl, chest wall strapping (CWS), and their interaction on detailed physiological and perceptual responses to constant work rate cycle exercise (85% of maximum incremental work rate) in 14 healthy, fit young men. By design, CWS decreased vital capacity by ∼20% and mimicked the negative consequences of a mild restrictive lung disorder on exercise endurance time and on dyspnea, breathing pattern, dynamic operating lung volumes, and diaphragmatic electromyographic and respiratory muscle function during exercise. Compared with placebo under both unrestricted control and CWS conditions, nebulized fentanyl had no effect on exercise endurance time, integrated physiological response to exercise, sensory intensity, unpleasantness ratings of exertional dyspnea. Our results do not support a role for intrapulmonary opioids in the neuromodulation of exertional dyspnea in health nor do they provide a physiological rationale for the use of nebulized fentanyl in the management of dyspnea due to mild restrictive lung disorders, specifically those arising from abnormalities of the chest wall and not affiliated with airway inflammation. PMID:26031762

Prehospital and En Route Analgesic Use in the Combat Setting: A Prospectively Designed, Multicenter, Observational Study

DTIC Science & Technology

2015-03-01

combat medic has access to both opioid and nonopioid analgesics.3 Morphine and fentanyl are effective opioid analgesics and are commonly used...transmucosal (TM) fentanyl8,9 or parenteral ketamine. YM fentanyl has been shown to be a safe, effective, and easy method of administer- ing analgesics in a...a subsequent different drug, or the same drug via an alternative route). Ketamine was most frequently administered, followed by fentanyl , mor- phine

Stability of Fentanyl Citrate in Polyolefin Bags.

PubMed

Donnelly, Ronald F

2016-01-01

Fentanyl is used to manage pain because it is a potent lipophilic opiate agonist. The stability of fentanyl in polyolefin bags when diluted to either 10 µg/mL or 50 µg/mL with sodium chloride 0.9% has not been studied. The chemical stability of fentanyl 50 µg/mL packaged in polyvinyl chloride bags has been studied, however, the stability in polyolefin bags is lacking. Polyolefin bags were aseptically filled with either 10-µg/mL or 50-µg/mL fentanyl solution. Containers were then stored at either 5°C and protected from light or 22°C and exposed to light for 93 days. Fentanyl peaks were monitored using a stability-indicatin high-performance liquid chromatographic method. Changes to color, clarity, and pH were also monitored. There were no signs of chemical degradation of fentanyl packaged in polyolefin bags at either 5°C or 22°C after storage for 93 days. Over the course of the study, all solutions remained colorless and clear. The pH showed a slight decrease during the 93 days of storage. The stability of both undiluted (50-µg/mL) and diluted (10-µg/mL) fentanyl solutions when packaged in polyolefin bags was 93 days when stored at either 5°C or 22°C. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Comparison of topical oxybuprocaine and intravenous fentanyl in pediatric strabismus surgery

PubMed Central

Yousafzai, Ibrahim; Zahoor, Abdul; Andrey, Butrov; Ahmad, Nauman

2017-01-01

Purpose: To compare the outcomes such as postoperative nausea/vomiting, analgesic requirements, and hospital stay following the use of topical oxybuprocaine hydrochloride 0.4% or intravenous (IV) fentanyl in children undergoing strabismus surgery. Methods: This was a prospective cohort study. Children operated under general anesthesia for strabismus were given topical oxybuprocaine hydrochloride 0.4% (Group T) and IV fentanyl (Group F) before surgery. The episodes of nausea/vomiting, pain score, requirement of additional analgesia during postoperative period, and duration of hospital stay were compared in two groups. Results: There were 47 children in Group T and 59 children in Group F. The median pain score in two groups were 2.38 (25% quartile; 2.0) and 3.00 (25% quartile; 3.00), respectively. The difference was significant (K W P < 0.03). The episodes of nausea/vomiting in two groups were in 2 and 6 children in Group T and Group F, respectively. The median hospital stay of children of Group T and Group F were 242 and 285 min, respectively. The difference was not statistically significant (P = 0.22). Conclusions: Using intraoperative topical oxybuprocaine drops, one can achieve better analgesic outcomes and reduce risk of nausea and vomiting compared to intravenous opioid analgesics and therefore, the hospital stay could also be marginally reduced. PMID:28217057

Comparison of topical oxybuprocaine and intravenous fentanyl in pediatric strabismus surgery.

PubMed

Yousafzai, Ibrahim; Zahoor, Abdul; Andrey, Butrov; Ahmad, Nauman

2017-01-01

To compare the outcomes such as postoperative nausea/vomiting, analgesic requirements, and hospital stay following the use of topical oxybuprocaine hydrochloride 0.4% or intravenous (IV) fentanyl in children undergoing strabismus surgery. This was a prospective cohort study. Children operated under general anesthesia for strabismus were given topical oxybuprocaine hydrochloride 0.4% (Group T) and IV fentanyl (Group F) before surgery. The episodes of nausea/vomiting, pain score, requirement of additional analgesia during postoperative period, and duration of hospital stay were compared in two groups. There were 47 children in Group T and 59 children in Group F. The median pain score in two groups were 2.38 (25% quartile; 2.0) and 3.00 (25% quartile; 3.00), respectively. The difference was significant (K W P < 0.03). The episodes of nausea/vomiting in two groups were in 2 and 6 children in Group T and Group F, respectively. The median hospital stay of children of Group T and Group F were 242 and 285 min, respectively. The difference was not statistically significant ( P = 0.22). Using intraoperative topical oxybuprocaine drops, one can achieve better analgesic outcomes and reduce risk of nausea and vomiting compared to intravenous opioid analgesics and therefore, the hospital stay could also be marginally reduced.

The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision.

PubMed

Smith, C; McEwan, A I; Jhaveri, R; Wilkinson, M; Goodman, D; Smith, L R; Canada, A T; Glass, P S

1994-10-01

We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively), were calculated by logistic regression. There were 56 evaluable patients for calculating the propofol Cp50s and 53 patients for calculating the propofol Cp50i. For propofol alone the Cp50s was 3.3 micrograms/ml and the Cp95s 5.4 microgram/ml. Increasing fentanyl concentrations reduced the Cp50s (P = 0.03), and increasing age decreased the Cp50s (P = 0.04). For propofol alone the Cp50i was 15.2 (95% confidence interval 7.6-22.8) micrograms/ml and the Cp95i 27.4 micrograms/ml. Increasing fentanyl concentrations markedly reduced the Cp50i (P < 0.01), with a 50% reduction in Cp50i produced by 0.63 ng/ml fentanyl. The propofol Cp50i was decreased by 63% with 1 ng/ml fentanyl and 89% by 3 ng/ml fentanyl. At higher fentanyl concentrations the decrease in Cp50i was proportionally less, demonstrating a ceiling effect. We defined the propofol concentration required for loss of consciousness and showed that it is reduced by increasing fentanyl concentration and by increasing age. The propofol concentration (alone) adequate for skin incision is high but is markedly reduced by fentanyl. A ceiling effect in the Cp50i for propofol is seen with fentanyl concentrations greater than 3 ng/ml.

Effects of fentanyl on isoflurane minimum alveolar concentration in New Zealand White rabbits (Oryctolagus cuniculus).

PubMed

Barter, Linda S; Hawkins, Michelle G; Pypendop, Bruno H

2015-02-01

To determine effects of increasing plasma fentanyl concentrations on the minimum alveolar concentration (MAC) of isoflurane in rabbits. 6 adult female New Zealand White rabbits (Oryctolagus cuniculus). Rabbits were anesthetized with isoflurane in oxygen; ventilation was controlled and body temperature maintained between 38.5° and 39.5°C. Fentanyl was administered IV by use of a computer-controlled infusion system to achieve 6 target plasma concentrations. Isoflurane MAC was determined in duplicate by use of the bracketing technique with a supramaximal electrical stimulus. Blood samples were collected for measurement of plasma fentanyl concentration at each MAC determination. The MAC values were analyzed with a repeated-measures ANOVA followed by Holm-Sidak pairwise comparisons. Mean ± SD plasma fentanyl concentrations were 0 ± 0 ng/mL (baseline), 1.2 ± 0.1 ng/mL, 2.2 ± 0.3 ng/mL, 4.4 ± 0.4 ng/mL, 9.2 ± 0.4 ng/mL, 17.5 ± 2.6 ng/mL, and 36.8 ± 2.4 ng/mL. Corresponding mean values for isoflurane MAC were 1.92 ± 0.16%, 1.80 ± 0.16%, 1.60 ± 0.23%, 1.46 ± 0.22%, 1.12 ± 0.19%, 0.89 ± 0.14%, and 0.70 ± 0.15%, respectively. Isoflurane MAC for plasma fentanyl concentrations ≥ 2.2 ng/mL differed significantly from the baseline value. In 3 rabbits, excessive spontaneous movement prevented MAC determination at the highest plasma fentanyl concentration. Fentanyl reduced isoflurane MAC by approximately 60% in New Zealand White rabbits. Further studies will be needed to investigate the cardiorespiratory effects of isoflurane and fentanyl combinations in rabbits; however, fentanyl may prove to be a useful adjunct to inhalation anesthesia in this species.

A Cluster of Fentanyl-Laced Heroin Deaths in 2015 in Melbourne, Australia.

PubMed

Rodda, Luke N; Pilgrim, Jennifer L; Di Rago, Matthew; Crump, Kerryn; Gerostamoulos, Dimitri; Drummer, Olaf H

2017-05-01

The prevalence of opioid use in therapeutic and recreational settings has steadily increased throughout the western world. The addition of fentanyl into heroin products can produce potentially dangerous consequences, even to opioid tolerant individuals who may be unaware of such additions. Following an observed spike of heroin-fentanyl related deaths in Melbourne, Australia, a study was undertaken to determine the prevalence of these cases. All reportable deaths occurring in Victoria during 2015 and submitted to the toxicology laboratory were analysed using LC-MS-MS to confirm the combination of the heroin marker 6-acetylmorphine and/or morphine, and fentanyl. Over 4,000 coronial cases in 2015 underwent toxicological analysis for these drugs, there were nine cases identified that involved fentanyl-laced heroin. There was no specific mention of fentanyl use in any of these cases. All occurred within 2 months and in two distinct locations. The first four deaths occurred within 3 days of each other, in neighboring suburbs. The ages ranged from 25 to 57 years with an average of 40 and median of 37 years, and consisted of eight males and one female. The average and median femoral blood concentration of fentanyl was 18 and 20 ng/mL (range: <1-45 ng/mL), and morphine 140 and 80 ng/mL (range: 20-400 ng/mL), respectively. All nine cases had 6-acetylmorphine detectable in blood. Urine analysis was also performed where available. A syringe, powder and spoon found at the scene of one case were also analysed and found to be positive for both heroin and fentanyl, which supported the likelihood of fentanyl-laced heroin. This is the first reported case series of fatalities involving heroin and fentanyl outside of North America in published literature. These findings may help inform public health and prevention strategies serving to decrease the potential for such fatalities in the future. © Crown copyright 2017.

Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain.

PubMed

Miranda, Hugo F; Noriega, Viviana; Zanetta, Pilar; Prieto, Juan Carlos; Prieto-Rayo, Juan Carlos; Aranda, Nicolás; Sierralta, Fernando

2014-07-15

Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain

PubMed Central

2014-01-01

Background Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. Results The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. Conclusion These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity. PMID:25017386

Postoperative nausea and vomiting (PONV) in outpatient repair of inguinal hernia.

PubMed

Palumbo, Piergaspare; Usai, Sofia; Amatucci, Chiara; Pulli, Valentina Taurisano; Illuminati, Giulio; Vietri, Francesco; Tellan, Guglielmo

2018-01-01

Nausea and vomiting are among the most frequent complications following anesthesia and surgery. Due to anesthesia seems to be primarily responsible for post operative nausea and vomiting (PONV) in Day Surgery facilities, the aim of the study is to evaluate how different methods of anesthesia could modify the onset of postoperative nausea and vomiting in a population of patients undergoing inguinal hernia repair. Ninehundredten patients, aged between 18 and 87 years, underwent open inguinal hernia repair. The PONV risk has been assessed according to Apfel Score. Local anesthetic infiltration, performed by the surgeon in any cases, has been supported by and analgo-sedation with Remifentanil in 740 patients; Fentanyl was used in 96 cases and the last 74 underwent deep sedation with Propofol . Among the 910 patients who underwent inguinal hernia repair, PONV occurred in 68 patients (7.5%). Among patients presenting PONV, 29 received Remifentanil, whereas 39 received Fentanyl. In the group of patients receiving Propofol, no one presented PONV. This difference is statistically significant (p < .01). Moreover, only 50 patients of the total sample received antiemetic prophylaxis, and amongst these, PONV occurred in 3 subjects. Compared to Remifentanil, Fentanyl has a major influence in causing PONV. Nonetheless, an appropriate antiemetic prophylaxis can significantly reduce this undesirable complication. Key words: Day Surgery, Fentanyl, Inguinal, Hernia repair, Nausea, Vomiting.

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception.

PubMed

Saccone, Phillip A; Lindsey, Angela M; Koeppe, Robert A; Zelenock, Kathy A; Shao, Xia; Sherman, Phillip; Quesada, Carole A; Woods, James H; Scott, Peter J H

2016-11-01

The goal of this study was to evaluate the effects of intranasally administered opioids in rhesus monkeys using the tail-withdrawal assay, and to correlate these effects with measures of receptor occupancy using positron emission tomography (PET) imaging. Initial experiments characterized the antinociceptive effects of intranasal (IN) fentanyl and buprenorphine relative to intramuscular (IM) injection. Fentanyl (0.010-0.032 mg/kg) and buprenorphine (0.1-1.0 mg/kg) produced dose-dependent increases in tail-withdrawal latency that did not differ between routes of delivery. The second experiment compared the ability of IN and intravenous (IV) naloxone (NLX) to block the antinociceptive effects IV fentanyl, and to measure receptor occupancy at equipotent doses of NLX using PET imaging. IN and IV NLX (0.0032-0.032 mg/kg) produced dose-dependent decreases in fentanyl-induced antinociception. Again, there was no difference observed in overall potency between routes. PET imaging showed that IV and IN NLX produced similar decreases in receptor occupancy as measured by [ 11 C]carfentanil blocking, although there was a trend for IV NLX to produce marginally greater occupancy changes. This study validated the first procedures to evaluate the IN effects of opioids in rhesus monkeys. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

PubMed

French, J P; Nocera, M

1994-04-01

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p < 0.01), between length of infusion of fentanyl and NAST score (r = .70, p < 0.05), and between chloral hydrate dosage and NAST score (r = .62, p < 0.05). These findings suggest the need for an observation protocol and a possible weaning regimen after fentanyl is discontinued.

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

PubMed

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-12-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P < 0.05). The total steady-state plasma concentrations of fentanyl ranged between 0.1 and 9 ng ml-1, with a median of 1 ng ml-1. The unbound fraction of fentanyl in the plasma ranged from 17.8 to 44.4%, with a median value of 33.6%. Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated (Spearman rho = 0.92, P < 0.05 in each case). Even with standardization for dosage, there was an eightfold variation in total plasma concentrations and 3.5-fold variation in unbound plasma concentrations of fentanyl. 3. There is considerable inter-patient variability in the pharmacokinetics of fentanyl with s.c. infusion in the palliative care setting, which necessitates careful titration of dosage according to individual clinical response.

Inhibition of protein kinase A and GIRK channel reverses fentanyl-induced respiratory depression.

PubMed

Liang, Xiaonan; Yong, Zheng; Su, Ruibin

2018-06-11

Opioid-induced respiratory depression is a major obstacle to improving the clinical management of moderate to severe chronic pain. Opioids inhibit neuronal activity via various pathways, including calcium channels, adenylyl cyclase, and potassium channels. Currently, the underlying molecular pathway of opioid-induced respiratory depression is only partially understood. This study aimed to investigate the mechanisms of opioid-induced respiratory depression in vivo by examining the effects of different pharmacological agents on fentanyl-induced respiratory depression. Respiratory parameters were detected using whole body plethysmography in conscious rats. We show that pre-treatment with the protein kinase A (PKA) inhibitor H89 reversed the fentanyl-related effects on respiratory rate, inspiratory time, and expiratory time. Pre-treatment with the G protein-gated inwardly rectifying potassium (GIRK) channel blocker Tertiapin-Q dose-dependently reversed the fentanyl-related effects on respiratory rate and inspiratory time. A phosphodiesterase 4 (PDE4) inhibitor and cyclic adenosine monophosphate (cAMP) analogs did not affect fentanyl-induced respiratory depression. These findings suggest that PKA and GIRK may be involved in fentanyl-induced respiratory depression and could represent useful therapeutic targets for the treatment of fentanyl-induced ventilatory depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of caudal tramadol versus caudal fentanyl with bupivacaine for prolongation of postoperative analgesia in pediatric patients.

PubMed

Solanki, N M; Engineer, S R; Jansari, D B; Patel, R J

2016-01-01

Caudal block is a common technique for pediatric analgesia for infraumblical surgeries. Because of the short duration of analgesia with bupivacaine alone various additive have been used to prolong the action of bupivacaine. The present study was aimed to evaluate the analgesic effect of tramadol or fentanyl added to bupivacaine for infraumblical surgeries in pediatric patients. We conducted a prospective, randomized, single-blind controlled trial. After written informed consent from parents, 100 patients belonging to American Society of Anesthesiologist physical status I-II, in the age group of 1-12 years, of either sex undergoing infraumblical surgery under general anesthesia were divided into two groups. Group BT received 1 ml/kg of 0.25% bupivacaine with tramadol 2 mg/kg in normal saline and Group BF received 1 ml/kg of 0.25% bupivacaine with fentanyl 2 μg/kg in normal saline with maximum volume of 12 ml in both groups. All patients were assessed intraoperatively for hemodynamic changes, the requirement of sevoflurane concentration, as well as postoperatively for pain by using FLACC (F = Face, L = Leg, A = Activity, C = Cry, C = Consolability), pain score and for sedation by using four point sedation score. The mean duration of analgesia was 10-18 h in Group BT while in Group BF it was 7-11 h. The postoperatively period up to 1½ h, Group BF had higher sedation score up to two as compared to that below one on Group BT. Caudal tramadol significantly prolongs the duration of analgesia as compared to caudal fentanyl without any side effects.

Two Fatal Intoxications Involving Butyryl Fentanyl

PubMed Central

Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Hathaway, Cindie; Arbefeville, Elise; Chrostowski, Leszek; Devers, Kelly; Hair, Laura; Mainland, Mary; Merves, Michele; Pearson, Julia

2016-01-01

We present the case histories, autopsy findings and toxicology findings of two fatal intoxications involving the designer drug, butyryl fentanyl. The quantitative analysis of butyryl fentanyl in postmortem fluids and tissues was performed by an ultrahigh-performance liquid chromatography tandem mass spectrometry method. In the first case, butyryl fentanyl was the only drug detected with concentrations of 99 ng/mL in peripheral blood, 220 ng/mL in heart blood, 32 ng/mL in vitreous humor, 590 ng/mL in gastric contents, 93 ng/g in brain, 41 ng/g in liver, 260 ng/mL in bile and 64 ng/mL in urine. The cause of death was ruled fatal intoxication by butyryl fentanyl. In the second case, butyryl fentanyl was detected along with acetyl fentanyl, alprazolam and ethanol. The butyryl fentanyl concentrations were 3.7 ng/mL in peripheral blood, 9.2 ng/mL in heart blood, 9.8 ng/mL in vitreous humor, 4,000 ng/mL in gastric contents, 63 ng/g in brain, 39 ng/g in liver, 49 ng/mL in bile and 2 ng/mL in urine. The acetyl fentanyl concentrations were 21 ng/mL in peripheral blood, 95 ng/mL in heart blood, 68 ng/mL in vitreous humor, 28,000 ng/mL in gastric contents, 200 ng/g in brain, 160 ng/g in liver, 330 ng/mL in bile and 8 ng/mL in urine. In addition, the alprazolam concentration was 40 ng/mL and the ethanol concentration was 0.11 g/dL, both measured in peripheral blood. The cause of death in the second case was ruled a mixed drug intoxication. In both cases, the manner of death was accident. PMID:27339481

Fentanyl and heroin contained in seized illicit drugs and overdose-related deaths in British Columbia, Canada: An observational analysis.

PubMed

Baldwin, Nicholas; Gray, Roger; Goel, Anirudh; Wood, Evan; Buxton, Jane A; Rieb, Launette Marie

2018-04-01

Due to the alarming rise in opioid-related overdose deaths, a public health emergency was declared in British Columbia (BC). In this study, we examined the relationship between illicit fentanyl and heroin found in seized drugs and illicit overdose deaths in BC. An observational cross-sectional survey was conducted using BC data from Health Canada's Drug Analysis Service, which analyzes drug samples seized by law enforcement agencies, and non-intentional illicit overdoses from the BC Coroner's Service, from 2000 to 2016. Initial scatter plots and subsequent multivariate regression analysis were performed to describe the potential relationship between seized illicit fentanyl samples and overdose deaths and to determine if this differed from seized heroin and overdose deaths. Fentanyl samples were analyzed for other drug content. Fentanyl is increasingly being found combined with other opioid and non-opioid illicit drugs. Strong positive relationships were found between the number of seized fentanyl samples and total overdose deaths (R2 = 0.97) as well as between seized fentanyl and fentanyl-detected overdose deaths (R2 = 0.99). A positive association was found between the number of seized heroin samples and total overdose deaths (R2 = 0.78). This research contributes to the expanding body of evidence implicating illicit fentanyl use (often combined with heroin or other substances) in overdose deaths in BC. Policy makers and healthcare providers are urged to implement drug treatment and harm reduction strategies for people at risk of overdose associated with current trends in illicit opioid use. Copyright © 2018 Elsevier B.V. All rights reserved.

Fentanyl-induced respiratory depression is attenuated in pregnant patients

PubMed Central

Sun, Jie; Yu, Min; Fang, Yin; Ding, Zhengnian

2017-01-01

Background Respiratory depression is a complication of intravenous fentanyl administration. The effect of pregnancy on respiratory depression following opioid administration is unclear. This study investigated the effect of pregnancy on fentanyl-induced respiratory depression. Patients and methods Female patients were divided into three groups (n=20 per group): control group (non-pregnant and scheduled for laparoscopic surgery), early pregnancy group (pregnant for 45–60 days and scheduled for abortion), and postpartum group (5–7 days postpartum scheduled for complete curettage of uterine cavity). All patients received an intravenous infusion of fentanyl 2 μg/kg. Respiratory rate (RR), end-tidal pressure of carbon dioxide (PETCO2), and pulse oxygen saturation (SpO2) were recorded continuously from just before fentanyl infusion to 15 min after commencing infusion. Plasma levels of progesterone were measured. Results SpO2 levels in the early pregnancy and postpartum groups were significantly higher and the levels of RR and PETCO2 were significantly lower than the control group. RR and SpO2 levels were significantly decreased in all groups, whereas PETCO2 was significantly increased after fentanyl infusion. The rates of RR increase and SpO2 decrease were significantly faster in the control group than in the other groups. The lowest SpO2 after intravenous fentanyl administration was significantly positively correlated with plasma progesterone levels. Conclusion Pregnancy improves fentanyl-induced respiratory depression, which may be associated with the increased levels of plasma progesterone. PMID:29200828

76 FR 64945 - Teva Pharmaceutical Industries Ltd. and Cephalon, Inc.; Analysis of Agreement Containing Consent...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... Pharmaceutical, Inc. (``Par'') all of Teva's rights and assets relating to its generic transmucosal fentanyl citrate lozenges (``fentanyl citrate'') and generic extended release cyclobenzaprine hydrochloride..., by lessening competition in the U.S. markets for fentanyl citrate, cyclobenzaprine hydrochloride, and...

Crystallographic and theoretical studies of an inclusion complex of β-cyclodextrin with fentanyl.

PubMed

Ogawa, Noriko; Nagase, Hiromasa; Loftsson, Thorsteinn; Endo, Tomohiro; Takahashi, Chisato; Kawashima, Yoshiaki; Ueda, Haruhisa; Yamamoto, Hiromitsu

2017-10-15

The crystal structure of an inclusion complex of β-cyclodextrin (β-CD) with fentanyl was determined by single crystal X-ray diffraction analysis. The crystal belongs to the triclinic space group P1 and the complex comprises one fentanyl, two β-CD, and several water molecules. β-CD and fentanyl form a host-guest inclusion complex at a ratio of 2:1 and the asymmetric unit of the complex contains two host molecules (β-CDs) in a head-to-head arrangement that form dimers through hydrogen bonds between the secondary hydroxyl groups of β-CD and one guest molecule. Fentanyl is totally contained within the β-CD cavity and the structure of the phenylethyl part of fentanyl inside the dimeric cavity of the complex is disordered. Furthermore, theoretical molecular conformational calculations were conducted to clarify the mobility of the guest molecule in the β-CD cavity using CONFLEX software. Crystal optimization and crystal energy calculations were also conducted. The results of the theoretical calculations confirmed that the conformation of disorder part 1, which was high in occupancy by crystal structure analysis, was more stable. The phenylethyl part of fentanyl existed in several stable conformations. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.

PubMed

Andoh, Tsugunobu; Shinohara, Akira; Kuraishi, Yasushi

2017-02-01

Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

PubMed Central

Valls-i-Soler, Adolfo; Encinas, Esther; Lukas, John C.; Vozmediano, Valvanera; Suárez, Elena

2014-01-01

Background Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Methods Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225–300 min). Also plasma samples for quantification of fentanyl were drawn. Results A “reliable degree of sedation” was observed up to T = 210–240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. Conclusion The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions. PMID:24595018

Cost-effectiveness analysis of oral fentanyl formulations for breakthrough cancer pain treatment

PubMed Central

Cortesi, Paolo Angelo; D’Angiolella, Lucia Sara; Vellucci, Renato; Allegri, Massimo; Casale, Giuseppe; Favaretti, Carlo; Kheiraoui, Flavia; Cesana, Giancarlo; Mantovani, Lorenzo Giovanni

2017-01-01

Breakthrough cancer Pain (BTcP) has a high prevalence in cancer population. Patients with BTcP reported relevant health care costs and poor quality of life. The study assessed the cost-effectiveness of the available Oral Fentanyl Formulations (OFFs) for BTcP in Italy. A decision-analytical model was developed to estimate costs and benefits associated with treatments, from the Italian NHS perspective. Expected reductions in pain intensity per BTcP episodes were translated into, percentage of BTcP reduction, resource use and Quality-Adjusted-Life-Years (QALYs). Relative efficacy, resources used and unit costs data were derived from the literature and validated by clinical experts. Probabilistic and deterministic sensitivity analyses were performed. At base-case analysis, Sublingual Fentanyl Citrate (FCSL) compared to other oral formulations reported a lower patient’s cost (€1,960.8) and a higher efficacy (18.7% of BTcP avoided and 0.0507 QALYs gained). The sensitivity analyses confirmed the main results in all tested scenarios, with the highest impact reported by BTcP duration and health care resources consumption parameters. Between OFFs, FCSL is the cost-effective option due to faster reduction of pain intensity. However, new research is needed to better understand the economic and epidemiologic impact of BTcP, and to collect more robust data on economic and quality of life impact of the different fentanyl formulations. Different fentanyl formulations are available to manage BTcP in cancer population. The study is the first that assesses the different impact in terms of cost and effectiveness of OFFs, providing new information to better allocate the resources available to treat BTcP and highlighting the need of better data. PMID:28654672

[Comparison of blood pressure profiles with flunitrazepam/fentanyl/nitrous oxide vs cervical epidural anesthesia in surgery of the carotid artery].

PubMed

Pluskwa, F; Bonnet, F; Abhay, K; Touboul, C; Rey, B; Marcandoro, J; Becquemin, J B

1989-01-01

A study was carried out to compare the evolution of arterial blood pressure during carotid endarterectomy performed under either general anaesthesia (GA) or cervical epidural anaesthesia (CEA). 20 patients were randomly assigned to two equal groups. In the CEA group, 15 ml of 0.375% bupivacaine and 150 micrograms fentanyl were injected into the epidural space at C7-D1 level. In the GA group, patients were anaesthetized with 0.2 mg.kg-1 flunitrazepam and 5 micrograms.kg-1 fentanyl; intubation was carried out using 0.08 mg.kg-1 vecuronium, and the patients were ventilated with a mixture of nitrous oxide and oxygen (50% of each). Further injections, every 30 min, of 2 micrograms.kg-1 fentanyl were given to the patients in group GA. Blood pressure was monitored continuously, up to 4 h postoperatively, with a radial arterial catheter. Per- or postoperative hypertension was defined as a rise in systolic arterial blood pressure (Pasys) over 180 mmHg for greater than 3 min; this was treated with 20 mg nifedipine intranasally (group CEA) or 100 micrograms fentanyl with 0.5 mg flunitrazepam with or without nifedipine (group GA). Per- or postoperative hypotension was defined as a fall in Pasys below 100 mmHg and or a 30% fall in mean arterial blood pressure for greater than 3 min; this was treated, in both groups, with an intravenous bolus of 3 mg ephedrine. Patients in group CEA experienced more frequent episodes of peroperative hypertension (8/2; p less than 0.02) and postoperative hypotension (5/1) than group GA.(ABSTRACT TRUNCATED AT 250 WORDS)

An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

PubMed

Nalamachu, Srinivas

2013-12-01

Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting <1 h. Thus, optimal relief from breakthrough pain is best attained by administering analgesics with dissolution times and bioavailabilities that closely match the onset and duration of breakthrough pain. The objective of this study was to assess complete disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

Anaesthesia modalities during laser photocoagulation for retinopathy of prematurity: a retrospective, longitudinal study.

PubMed

Jiang, Jing-Bo; Strauss, Randy; Luo, Xian-Qiong; Nie, Chuan; Wang, Yan-Li; Zhang, Jia-Wen; Zhang, Zhi-Wei

2017-01-24

Laser photocoagulation surgery is a routine treatment for threshold retinopathy of prematurity (ROP). However, little is known about which anaesthesia protocols provide efficient pain control while minimising exposure risk to vulnerable infants. In this study, therefore, we assessed the efficacy and tolerability of multiple anaesthesia techniques used on premature infants during laser therapy. Anaesthesia modalities consisted of topical eye drops anaesthesia, general anaesthesia and intravenous fentanyl sedation with mechanical ventilation. Laser treatment efficacy and detailed operative information were retrospectively and consecutively analysed. Cardiorespiratory stability was assessed and compared. The Neonatal Pain Agitation and Sedation Scale (N-PASS) was used to evaluate tolerability in infants that underwent intravenous fentanyl sedation. 97 cases of prematurity were included in this study. In 94/97 (96.9%) cases, vascular proliferation regressed. In the topical anaesthesia groups, the ophthalmologist needed 12-16 min more to complete the treatment. During the 3 postoperative days, topical anaesthesia demonstrated the greatest instability; 4/31 (12.90%) infants in this group suffered from life threatening events requiring resuscitation. The only instability observed in general anaesthesia and fentanyl sedation was attributed to difficulty in extubating within 24 hours after surgery. During laser therapy, the N-PASS score increased to 1.8 in the fentanyl sedation group. Topical anaesthesia was associated with more cardiorespiratory instability during ROP laser treatment. While general anaesthesia and fentanyl sedation had similar postoperative cardiorespiratory results, the latter demonstrated acceptable pain stress control. However, the difficulty of weaning off mechanical ventilation in some cases after surgery needs to be addressed in future studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Heroin and fentanyl overdoses in Kentucky: Epidemiology and surveillance.

PubMed

Slavova, Svetla; Costich, Julia F; Bunn, Terry L; Luu, Huong; Singleton, Michael; Hargrove, Sarah L; Triplett, Jeremy S; Quesinberry, Dana; Ralston, William; Ingram, Van

2017-08-01

The study aims to describe recent changes in Kentucky's drug overdose trends related to increased heroin and fentanyl involvement, and to discuss future directions for improved drug overdose surveillance. The study used multiple data sources (death certificates, postmortem toxicology results, emergency department [ED] records, law enforcement drug submissions, and prescription drug monitoring records) to describe temporal, geographic, and demographic changes in drug overdoses in Kentucky. Fentanyl- and heroin-related overdose death rates increased across all age groups from years 2011 to 2015 with the highest rates consistently among 25-34-year-olds. The majority of the heroin and fentanyl overdose decedents had histories of substantial exposures to legally acquired prescription opioids. Law enforcement drug submission data were strongly correlated with drug overdose ED and mortality data. The 2016 crude rate of heroin-related overdose ED visits was 104/100,000, a 68% increase from 2015 (62/100,000). More fentanyl-related overdose deaths were reported between October, 2015, and September, 2016, than ED visits, in striking contrast with the observed ratio of >10 to 1 heroin-related overdose ED visits to deaths. Many fatal fentanyl overdoses were associated with heroin adulterated with fentanyl; <40% of the heroin overdose ED discharge records listed procedure codes for drug screening. The lack of routine ED drug testing likely resulted in underreporting of non-fatal overdoses involving fentanyl and other synthetic drugs. In order to inform coordinated public health and safety responses, drug overdose surveillance must move from a reactive to a proactive mode, utilizing the infrastructure for electronic health records. Copyright © 2017 Elsevier B.V. All rights reserved.

78 FR 44432 - New Animal Drugs; Change of Sponsor; Fentanyl; Iron Injection

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 522, and 524 [Docket No. FDA-2013-N-0002] New Animal Drugs; Change of Sponsor; Fentanyl; Iron Injection AGENCY..., NADA 141-337 for RECUVYRA (fentanyl) Transdermal Solution to Elanco Animal Health, A Division of Eli...

Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

PubMed Central

Barbosa, Thales C.; Vianna, Lauro C.; Fernandes, Igor A.; Prodel, Eliza; Rocha, Helena N. M.; Garcia, Vinicius P.; Rocha, Natalia G.; Secher, Niels H.

2016-01-01

Key points The increase in blood pressure observed during physical activities is exaggerated in patients with hypertension, exposing them to a higher cardiovascular risk.Neural signals from the skeletal muscles appear to be overactive, resulting in this abnormal response in hypertensive patients.In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity.Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure of hypertensive men during cycling exercise to a level comparable to that of normotensive men.Skeletal muscle afferent overactivity causes the abnormal cardiovascular response to exercise and was reverted in this experimental model, appearing as potential target for treatment. Abstract Hypertensive patients present an exaggerated increase in blood pressure and an elevated cardiovascular risk during exercise. Although controversial, human studies suggest that group III and IV skeletal muscle afferents might contribute to this abnormal response. In the present study, we investigated whether attenuation of the group III and IV muscle afferent signal of hypertensive men eliminates the exaggerated increase in blood pressure occurring during exercise. Eight hypertensive men performed two sessions of 5 min of cycling exercise at 40 W. Between sessions, the subjects were provided with a lumbar intrathecal injection of fentanyl, a μ‐opioid receptor agonist, aiming to attenuate the central projection of opioid‐sensitive group III and IV muscle afferent nerves. The cardiovascular response to exercise of these subjects was compared with that of six normotensive men. During cycling, the hypertensive group demonstrated an exaggerated increase in blood pressure compared to the normotensive group (mean ± SEM: +17 ± 3 vs. +8 ± 1 mmHg, respectively; P < 0.05), whereas the increase in heart rate, stroke volume, cardiac output and vascular conductance was similar (P > 0.05). Fentanyl inhibited the blood pressure response to exercise in the hypertensive group (+11 ± 2 mmHg) to a level comparable to that of the normotensive group (P > 0.05). Moreover, fentanyl increased the responses of vascular conductance and stroke volume to exercise (P < 0.05), whereas the heart rate response was attenuated (P < 0.05) and the cardiac output response was maintained (P > 0.05). The results of the present study show that attenuation of the exercise pressor reflex normalizes the blood pressure response to cycling exercise in hypertensive individuals. PMID:26659384

Comparison of caudal tramadol versus caudal fentanyl with bupivacaine for prolongation of postoperative analgesia in pediatric patients

PubMed Central

Solanki, NM; Engineer, SR; Jansari, DB; Patel, RJ

2016-01-01

Background and Aims: Caudal block is a common technique for pediatric analgesia for infraumblical surgeries. Because of the short duration of analgesia with bupivacaine alone various additive have been used to prolong the action of bupivacaine. The present study was aimed to evaluate the analgesic effect of tramadol or fentanyl added to bupivacaine for infraumblical surgeries in pediatric patients. Materials and Methods: We conducted a prospective, randomized, single-blind controlled trial. After written informed consent from parents, 100 patients belonging to American Society of Anesthesiologist physical status I-II, in the age group of 1-12 years, of either sex undergoing infraumblical surgery under general anesthesia were divided into two groups. Group BT received 1 ml/kg of 0.25% bupivacaine with tramadol 2 mg/kg in normal saline and Group BF received 1 ml/kg of 0.25% bupivacaine with fentanyl 2 μg/kg in normal saline with maximum volume of 12 ml in both groups. All patients were assessed intraoperatively for hemodynamic changes, the requirement of sevoflurane concentration, as well as postoperatively for pain by using FLACC (F = Face, L = Leg, A = Activity, C = Cry, C = Consolability), pain score and for sedation by using four point sedation score. Results: The mean duration of analgesia was 10–18 h in Group BT while in Group BF it was 7-11 h. The postoperatively period up to 1½ h, Group BF had higher sedation score up to two as compared to that below one on Group BT. Conclusion: Caudal tramadol significantly prolongs the duration of analgesia as compared to caudal fentanyl without any side effects. PMID:27051365

Optimal dose of rocuronium bromide undergoing adenotonsillectomy under 5% sevoflurane with fentanyl.

PubMed

Huh, Hyub; Park, Jeong Jun; Kim, Ji Yeong; Kim, Tae Hoon; Yoon, Seung Zhoo; Shin, Hye Won; Lee, Hye-Won; Lim, Hye-Ja; Cho, Jang Eun

2017-10-01

Adenotonsillectomy is a short surgical procedure under general anaesthesia in children. An ideal muscle relaxant for adenotonsillectomy would create an intense neuromuscular block while having a quick recovery time without postoperative morbidity. We compared the effect of different doses of rocuronium for the tracheal intubation in children under 5% sevoflurane and fentanyl. 75 children (aged 3-10 years, ASA I) scheduled for adenotonsillectomy were enrolled. Anaesthesia was induced with propofol 2.5 mg/kg, followed by fentanyl 2 μg/kg. After mask ventilation with 5 vol% sevoflurane in 100% oxygen for 2 min, 2 ml of study drug was administered intravenously, i.e., either normal saline (S Group) or one of two doses (0.15 or 0.3 mg/kg) of rocuronium. We assessed conditions during tracheal intubation and also recorded the surgical condition, the time from discontinuation of sevoflurane to extubation and PAED scale, pain scores in PACU. Rocuronium groups (96% and 100%, respectively; P < 0.01) showed statistically superior clinically acceptable intubating conditions than the saline group (72%). The 0.3 mg/kg rocuronium (80%) treatment clearly resulted in excellent intubating conditions compared with the 0.15 mg/kg group (44%; p = 0.028). There was no significant difference in the time to extubation and surgical condition, and in the postoperative measures of emergence delirium, pain, and recovery time among the three groups. A dose of 0.3 mg/kg rocuronium may provide optimal intubating conditions without delayed recovery in 5% sevoflurane anaesthesia with fentanyl in children undergoing adenotonsillectomy. NCT02467595. Copyright © 2017 Elsevier B.V. All rights reserved.

REMIFENTANIL VS FENTANYL DURING DAY CASE DENTAL SURGERY IN PEOPLE WITH SPECIAL NEEDS: A COMPARATIVE, PILOT STUDY OF THEIR EFFECT ON STRESS RESPONSE AND POSTOPERATIVE PAIN.

PubMed

Sklika, Eirini; Kalimeris, Konstantinos; Perrea, Despina; Stavropoulos, Nikolaos; Kostopanagiotou, Georgia; Matsota, Paraskevi

2016-06-01

People with special needs undergoing dental surgery frequently require general anesthesia. We investigated the effect of remifentanil vs fentanyl on stress response and postoperative pain in people with special needs undergoing day-case dental surgery. Forty-six adult patients with cognitive impairment undergoing day-case dental surgery under general anesthesia were allocated to receive intraoperatively either fentanyl 50 μg iv bolus (group F, n = 23) or continuous infusion of remifentanil 0.5-1 μg/kg/min (group R, n = 23). Iintraoperative hemodynamic parameters were recorded and serum inflammatory mediators [tumor necrosis factor-α, substance-P], stress hormons (melatonin, cortisol) and β-endorphin were measured. Postoperative pain was assessed during the first postoperative 12 hours with the Wong-Baker faces pain-rating scale. Demographics were similar in two groups. The two groups did not differ regarding their effects on inflammatory mediators, stress hormons and postoperative pain scores. However, the use of remifentanil prevented intraoperative increases of arterial blood pressure and heart rate. Remifentanil and fentanyl did not affect differently stress and inflammatory hormones during day-case dental surgery, although remifentanil may render intraoperative management of hemodynamic responses easier. Both opioids are equally efficient for postoperative pain management following dental surgery in people with special needs.

Fentanyl Enhances Hepatotoxicity of Paclitaxel via Inhibition of CYP3A4 and ABCB1 Transport Activity in Mice

PubMed Central

Pan, Jia-Hao; Bi, Bing-Tian; Feng, Kun-Yao; Huang, Wan; Zeng, Wei-An

2015-01-01

Fentanyl, a potent opioid analgesic that is used to treat cancer pain, is commonly administered with paclitaxel in advanced tumors. However, the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanism of action is not well studied. The purpose of this study was to investigate the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanisms of action. Pharmacokinetic parameters of paclitaxel were tested using reversed phase high-performance liquid chromatography (RP-HPLC). Aspartate transaminase (AST), alanine aminotransferase (ALT), and mouse liver histopathology were examined. Moreover, the cytotoxicity of anti-carcinogens was examined using 1-(4, 5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), and the intracellular accumulation of doxorubicin and rhodamine 123 was detected by flow cytometry. Furthermore, the expression of ABCB1 and the activity of ABCB1 ATPase and CYP3A4 were also examined. In this study, the co-administration of fentanyl and paclitaxel prolonged the half-life (t1/2) of paclitaxel from 1.455 hours to 2.344 hours and decreased the clearance (CL) from 10.997 ml/h to 7.014 ml/h in mice. Fentanyl significantly increased the levels of ALT in mice to 88.2 U/L, which is more than 2-fold higher than the level detected in the control group, and it increased the histological damage in mouse livers. Furthermore, fentanyl enhanced the cytotoxicity of anti-carcinogens that are ABCB1 substrates and increased the accumulation of doxorubicin and rhodamine 123. Additionally, fentanyl stimulated ABCB1 ATPase activity and inhibited CYP3A4 activity in the liver microsomes of mice. Our study indicates that the obvious hepatotoxicity during this co-administration was due to the inhibition of CYP3A4 activity and ABCB1 transport activity. These findings suggested that the accumulation-induced hepatotoxicity of paclitaxel when it is combined with fentanyl should be avoided. PMID:26633878

Heroin uncertainties: Exploring users' perceptions of fentanyl-adulterated and -substituted 'heroin'.

PubMed

Ciccarone, Daniel; Ondocsin, Jeff; Mars, Sarah G

2017-08-01

The US is experiencing an unprecedented opioid overdose epidemic fostered in recent years by regional contamination of the heroin supply with the fentanyl family of synthetic opioids. Since 2011 opioid-related overdose deaths in the East Coast state of Massachusetts have more than tripled, with 75% of the 1374 deaths with an available toxicology positive for fentanyl. Fentanyl is 30-50X more potent than heroin and its presence makes heroin use more unpredictable. A rapid ethnographic assessment was undertaken to understand the perceptions and experiences of people who inject drugs sold as 'heroin' and to observe the drugs and their use. A team of ethnographers conducted research in northeast Massachusetts and Nashua, New Hampshire in June 2016, performing (n=38) qualitative interviews with persons who use heroin. (1) The composition and appearance of heroin changed in the last four years; (2) heroin is cheaper and more widely available than before; and (3) heroin 'types' have proliferated with several products being sold as 'heroin'. These consisted of two types of heroin (alone), fentanyl (alone), and heroin-fentanyl combinations. In the absence of available toxicological information on retail-level heroin, our research noted a hierarchy of fentanyl discernment methods, with embodied effects considered most reliable in determining fentanyl's presence, followed by taste, solution appearance and powder color. This paper presents a new 'heroin' typology based on users' reports. Massachusetts' heroin has new appearances and is widely adulterated by fentanyl. Persons who use heroin are trying to discern the substances sold as heroin and their preferences for each form vary. The heroin typology presented is inexact but can be validated by correlating users' discernment with drug toxicological testing. If validated, this typology would be a valuable harm reduction tool. Further research on adaptations to heroin adulteration could reduce risks of using heroin and synthetic opioid combinations. Copyright © 2017 Elsevier B.V. All rights reserved.

[Assessment of the use of racemic ketamine and its S(+) isomer, associated or not with low doses of fentanyl, in balneotherapy for major burn patients].

PubMed

Cantinho, Fernando Antônio de Freitas; Silva, Antonio Carlos Pereira da

2009-01-01

The care of the wounds of major burn patients triggers severe painful stimuli. The objective of this study was to assess the safety and efficacy of different drug combinations in anesthesia for balneotherapy. After approval by the Ethics Commission, 200 procedures of balneotherapy in 87 major burn adult patients were evaluated. Midazolam was used in all cases. The vials of ketamine were numbered and, therefore, at the time of the use, one did not know whether racemic or S(+)ketamine was being used. Each morning it was decided by drawing lots whether fentanyl would be used or not in the procedures of that day. Patients were included in one of four groups: ISO/sf (S(+) isomer without fentanyl), ISO/cf (S(+) isomer with fentanyl), RAC/sf (racemic ketamine without fentanyl), and RAC/cf (racemic ketamine with fentanyl). The initial doses proposed were as follows: midazolam, 0.06 mg.kg-1; ketamine, 1.0 to 1.1 mg.kg-1; and fentanyl, 0.8 (1/4)g.kg1-1; additional doses were administered as needed. Only one patient recalled the pain of balneotherapy. In the group that received S(+)ketamine, the use of fentanyl did not bring additional advantages; however, when associated with racemic ketamine, fentanyl reduced the total dose and the number of ketamine boluses. The extension of body surface burned was the main determinant of the severity of post-procedure pain. Reduced pain severity was the main factor considered by patients when grading their satisfaction with the anesthesia. The four different drug combinations proved to be safe and guaranteed the absence of pain during balneotherapy. Characteristics not directly related to the anesthetics proved to be more important in the incidence of post-procedure pain, which was the main factor considered by major burn patient to define their satisfaction with the anesthesia used.

Two Fatal Intoxications Involving Butyryl Fentanyl.

PubMed

Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Hathaway, Cindie; Arbefeville, Elise; Chrostowski, Leszek; Devers, Kelly; Hair, Laura; Mainland, Mary; Merves, Michele; Pearson, Julia

2016-10-01

We present the case histories, autopsy findings and toxicology findings of two fatal intoxications involving the designer drug, butyryl fentanyl. The quantitative analysis of butyryl fentanyl in postmortem fluids and tissues was performed by an ultrahigh-performance liquid chromatography tandem mass spectrometry method. In the first case, butyryl fentanyl was the only drug detected with concentrations of 99 ng/mL in peripheral blood, 220 ng/mL in heart blood, 32 ng/mL in vitreous humor, 590 ng/mL in gastric contents, 93 ng/g in brain, 41 ng/g in liver, 260 ng/mL in bile and 64 ng/mL in urine. The cause of death was ruled fatal intoxication by butyryl fentanyl. In the second case, butyryl fentanyl was detected along with acetyl fentanyl, alprazolam and ethanol. The butyryl fentanyl concentrations were 3.7 ng/mL in peripheral blood, 9.2 ng/mL in heart blood, 9.8 ng/mL in vitreous humor, 4,000 ng/mL in gastric contents, 63 ng/g in brain, 39 ng/g in liver, 49 ng/mL in bile and 2 ng/mL in urine. The acetyl fentanyl concentrations were 21 ng/mL in peripheral blood, 95 ng/mL in heart blood, 68 ng/mL in vitreous humor, 28,000 ng/mL in gastric contents, 200 ng/g in brain, 160 ng/g in liver, 330 ng/mL in bile and 8 ng/mL in urine. In addition, the alprazolam concentration was 40 ng/mL and the ethanol concentration was 0.11 g/dL, both measured in peripheral blood. The cause of death in the second case was ruled a mixed drug intoxication. In both cases, the manner of death was accident. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A quality improvement project to reduce the intraoperative use of single-dose fentanyl vials across multiple patients in a pediatric institution.

PubMed

Buck, David; Subramanyam, Rajeev; Varughese, Anna

2016-01-01

The use of a single-dose vial across multiple patients presents a risk to sterility and is against CDC guidelines. We initiated a quality improvement (QI) project to reduce the intraoperative use of single-dose vials of fentanyl across multiple patients at Cincinnati Children's Hospital Medical Center (CCHMC). The initial step of the improvement project was the development of a Key Driver Diagram. The diagram has the SMART aim of the project, key drivers inherent to the process we are trying to improve, and specific interventions targeting the key drivers. The number of patients each week receiving an IV dose of fentanyl, from a vial previously accessed for another patient was tracked in a high turnover operating room (OR). The improvement model used was based on the concept of building Plan-Do-Study-Act (PDSA) cycles. Tests of change included provider education, provision of an increased number of fentanyl vials, alternate wasting processes, and provision of single-use fentanyl syringes by the pharmacy. Prior to initiation of this project, it was common for a single fentanyl vial to be accessed for multiple patients. Our data showed an average percentage of failures of just over 50%. During the end of the project, after 7 months, the mean percentage failures had dropped to 5%. Preparation of 20 mcg single-use fentanyl syringes by pharmacy, combined with education of providers on appropriate use, was successful in reducing failures to below our goal of 25%. Appropriately sized fentanyl syringes prepared by pharmacy, education on correct use of single-dose vials, and reminders in the OR, reduced the percentage of patients receiving a dose of fentanyl from a vial previously accessed for another patient in a high-volume otolaryngology room. © 2015 John Wiley & Sons Ltd.

Comparison of pain-relieving effects of fentanyl versus ketorolac after eye amputation surgery.

PubMed

Kim, Jin Hyung; Jang, Sun Young; Kim, Myung Jin; Lee, Sang Yeul; Yoon, Jin Sook

2013-08-01

To investigate the analgesic effect and incidence of postoperative nausea and vomiting (PONV) between the opioid fentanyl and the non-steroidal anti-inflammatory drug ketorolac in patients who underwent eye amputation surgery. Retrospective observational case series. Eighty-two patients underwent evisceration or enucleation surgery by one surgeon over a 2-year period. Fentanyl by intravenous patient-controlled analgesia (IV-PCA) at 20 µg/kg with 12 mg/kg ondansetron or intravenous ketorolac at 2 mg/kg/day was administered to patients at postoperative days 0, 1, and 2. The pain score was measured using an 11-point visual analog scale (VAS). The incidence of severe nausea requiring anti-emetics and the incidence of vomiting were reviewed. The mean postoperative VAS in the fentanyl group was significantly lower than that in the ketorolac group on the day of operation for both types of surgery (p = 0.001 and p = 0.004, respectively). At postoperative days 1 and 2, the mean VAS was not different between the two groups for either surgical type (p > 0.05 for both days). The mean VAS was significantly higher in eviscerated patients than in enucleated patients at postoperative days 0 and 1 in the fentanyl group (p = 0.023 and p = 0.016, respectively). However, this was not observed in the ketorolac group. The incidence of PONV was higher in the fentanyl group than in the ketorolac group, although this was not statistically significant for either surgical type (p > 0.05 for both groups). Fentanyl was more effective as an analgesic than was ketorolac on the day of operation for both surgical types. There was no difference between the two analgesics on postoperative day 1. The analgesic effect of fentanyl in enucleated patients was significantly higher than in eviscerated patients at postoperative days 0 and 1. The use of fentanyl by IV-PCA was associated with greater PONV despite co-administration with anti-emetics, although this finding was not significant.

Comparison of Pain-relieving Effects of Fentanyl versus Ketorolac after Eye Amputation Surgery

PubMed Central

Kim, Jin Hyung; Jang, Sun Young; Kim, Myung Jin; Lee, Sang Yeul

2013-01-01

Purpose To investigate the analgesic effect and incidence of postoperative nausea and vomiting (PONV) between the opioid fentanyl and the non-steroidal anti-inflammatory drug ketorolac in patients who underwent eye amputation surgery. Methods Retrospective observational case series. Eighty-two patients underwent evisceration or enucleation surgery by one surgeon over a 2-year period. Fentanyl by intravenous patient-controlled analgesia (IV-PCA) at 20 µg/kg with 12 mg/kg ondansetron or intravenous ketorolac at 2 mg/kg/day was administered to patients at postoperative days 0, 1, and 2. The pain score was measured using an 11-point visual analog scale (VAS). The incidence of severe nausea requiring anti-emetics and the incidence of vomiting were reviewed. Results The mean postoperative VAS in the fentanyl group was significantly lower than that in the ketorolac group on the day of operation for both types of surgery (p = 0.001 and p = 0.004, respectively). At postoperative days 1 and 2, the mean VAS was not different between the two groups for either surgical type (p > 0.05 for both days). The mean VAS was significantly higher in eviscerated patients than in enucleated patients at postoperative days 0 and 1 in the fentanyl group (p = 0.023 and p = 0.016, respectively). However, this was not observed in the ketorolac group. The incidence of PONV was higher in the fentanyl group than in the ketorolac group, although this was not statistically significant for either surgical type (p > 0.05 for both groups). Conclusions Fentanyl was more effective as an analgesic than was ketorolac on the day of operation for both surgical types. There was no difference between the two analgesics on postoperative day 1. The analgesic effect of fentanyl in enucleated patients was significantly higher than in eviscerated patients at postoperative days 0 and 1. The use of fentanyl by IV-PCA was associated with greater PONV despite co-administration with anti-emetics, although this finding was not significant. PMID:23908567

Psychomotor Functioning: Comparison of Patients Recovering From General Anesthesia With Remifentanil and a Volatile Anesthetic Versus Fentanyl and a Volatile Anesthetic

DTIC Science & Technology

1998-10-01

appears to be more potent. The ED100 dose for loss of righting with remifentanil is 0.020mg/kg/min. 14 and for fentanyl the dose is 0.035 mg/kg/min. (Lozito... Remifentanil and fentanyl cause the same adverse effects to varying degrees which are mediated at the µ-receptor. With rapid infusion of large doses of...the potency of remifentanil in dogs (Westmoreland, et al., 1993a). 16 Fentanyl has a t1/2 of 3 to 3.65 hours at clinically relevant doses . This

Effects of intra-articular levobupivacaine, fentanyl-levobupivacaine and tramadol-levobupivacaine for postoperative pain in arthroscopic knee surgery.

PubMed

Sayın, Pınar; Dobrucalı, Hale; Türk, Hacer Şebnem; Totoz, Tolga; Işıl, Canan Tülay; Hancı, Ayşe

2015-01-01

The aim of this study was to compare the postoperative analgesic efficacy of intra-articularly injected levobupivacaine, levobupivacaine-fentanyl, and levobupivacaine-tramadol combinations. Eighty patients scheduled for elective knee arthroscopy were divided randomly into 4 groups of 20 patients each. Group 1 (the control group) received intra-articular saline, Group 2 received levobupivacaine 2.5 mg/ml, Group 3 received levobupivacaine 2.5 mg/ml + tramadol 50 mg, and Group 4 received levobupivacaine 2.5 mg/ml + fentanyl l50 mcg. All patients were operated on under general anesthesia, and a total of 20 ml study solution was injected: 7 ml subcutaneously before surgery and 13 ml intra-articularly upon completion of surgery. For postoperative, pain visual analogue scale (VAS) was assessed at the 1st, 2nd, 4th, 8th, 12th, and 24th hours postoperatively. Patients with a VAS score over 5 received diclofenac sodium, and the need for rescue analgesics was recorded. At the 1st, 2nd, 4th, 8th, 12th, and 24th postoperative hours, Group 3 and Group 4 had statistically significant lower VAS scores of pain (p<0.01). Postoperative rescue analgesic requirements were different among the groups. The postoperative 1st hour analgesic requirement was statistically significantly lower in Group 3 and Group 4 when compared to the other groups (p<0.01). At the postoperative 2nd and 4th hours, analgesic requirements were statistically significantly lower in Group 3 than in the other groups (p<0.01). Analgesic requirements were statistically significantly lower in Group 3 and Group 4 than in the other groups (p<0.01). Analgesic requirements at the 12th and 24th postoperative hours did not show any statistically significant difference (p>0.05). The results indicated that levobupivacaine combined with either fentanyl or tramadol decreased rescue analgesic requirements when compared to levobupivacaine alone.

Pretreatment with remifentanil, fentanyl, or lidocaine to prevent withdrawal after rocuronium using venous occlusion technique in children and adolescents: a prospective randomized placebo-controlled double-blind study.

PubMed

Abu-Halaweh, S A; Aloweidi, A K; Qudaisat, I Y; Al-Hussami, M O; Al Zaben, K R; Abu-Halaweh, A S

2014-12-01

Pain caused by intravenous injection of the muscle relaxant rocuronium bromide is common in children and adolescents. The cause of this unwanted effect is still unclear, and different pretreatment drugs have been administered in attempts to alleviate this side effect, with varying degrees of success. This study used a 60-s venous occlusion technique to evaluate the effectiveness of pretreatment with lidocaine, fentanyl, or remifentanil in preventing pain-induced withdrawal caused by intravenous injection of rocuronium bromide during the induction of general anesthesia. One hundred and one child and adolescent patients, ASA Ι-II, requiring various surgical procedures under general anesthesia with muscle relaxation and mechanical ventilation, were enrolled. Patients were allocated randomly using computer-generated randomization into one of four pretreatment groups: a remifentanil group (1 µg/kg, n = 25), fentanyl group (1 µg/kg, n = 26), lidocaine 1% group (0.5 mg/kg, n = 25), and normal saline group (n = 25). Drug doses were prepared in normal saline to a total volume of 5 ml. Venous occlusion was applied 10 cm above the venous access site. Pretreatment drugs were injected and retained for 60 s at the site of injection by an anesthetist blinded to group allocation. After release of the tourniquet, rocuronium (0.5 mg/kg) was then injected over 5 s, and withdrawal was recorded by another anesthetist blinded to group allocation. Descriptive statistics, analysis of variance, and a chi-squared test were used to statistically analyze the results as appropriate. Compared to normal saline, all other pretreatment groups scored a significantly lower mean of withdrawal response (P < 0.001). Lidocaine was superior to both remifentanil (P < 0.05) and fentanyl (P < 0.05) in suppressing the withdrawal response to rocuronium injection. Remifentanil was superior to fentanyl in suppressing the withdrawal response caused by rocuronium injection (P < 0.001). Using a venous occlusion technique for 60 s, lidocaine was found to be most effective in preventing the withdrawal effect caused by rocuronium injection in children and adolescents. Lidocaine was superior to remifentanil which, in turn, was more effective than fentanyl.

Subanalgesic doses of dexketoprofen and HCT-2037 (nitrodexketoprofen) enhance fentanyl antinociception in monoarthritic rats.

PubMed

Gaitan, Gema; Herrero, Juan F

2005-02-01

Subanalgesic doses of the non-steroidal antiinflammatory drugs (NSAID) dexketoprofen trometamol and nitroparacetamol (NCX-701) enhance mu-opiate fentanyl effect in acute nociception. It is not known if a similar combination of drugs is effective in situations of spinal cord sensitization. The aim of this study was to assess if the enhancement of fentanyl antinociception can be observed in carrageenan-induced monoarthritis, when combined with dexketoprofen (DKT) or nitrodexketoprofen (HCT-2037). Withdrawal reflexes were recorded as single motor units in male Wistar rats anesthetized with alpha-chloralose. Fentanyl was studied alone and in the presence of 0.4, 0.8 micromol/kg of DKT or 0.3 micromol/kg of HCT-2037. In responses to noxious mechanical stimulation, the ID50 of fentanyl was enhanced twofold by 0.8 micromol/kg DKT and more than fourfold by HCT-2037 and no significant recovery was observed 45 min later. DKT 0.4 micromol/kg was, however, very little effective. The opioid antagonist naloxone did not reverse the effect. Enhancement of fentanyl effect on wind-up was only observed with HCT-2037 but not with DKT. We conclude that the combined administration of subanalgesic doses of dexketoprofen derivatives, specially its nitroderivative, and the mu-opiate fentanyl is an effective antinociceptive therapy in situations of articular inflammation involving a naloxone-independent mechanism of action.

75 FR 37300 - Correction of Code of Federal Regulations: Removal of Temporary Listing of Benzylfentanyl and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

... scheduled fentanyl compounds at the University of Michigan Medical School in Ann Arbor and at the Medical College of Virginia in Richmond. The studies indicated that while most of the fentanyl compounds had abuse... samples with other fentanyl analogues and were most likely unreacted intermediates in the synthesis of the...

Mu/Kappa Opioid Interactions in Rhesus Monkeys: Implications for Analgesia and Abuse Liability

PubMed Central

Negus, S. Stevens; Katrina Schrode, KA; Stevenson, Glenn W.

2008-01-01

Mu opioid receptor agonists are clinically valuable as analgesics; however, their use is limited by high abuse liability. Kappa opioid agonists also produce antinociception, but they do not produce mu agonist-like abuse-related effects, suggesting that they may enhance the antinociceptive effects and/or attenuate the abuse-related effects of mu agonists. To evaluate this hypothesis, the present study examined interactions between the mu agonist fentanyl and the kappa agonist U69,593 in three behavioral assays in rhesus monkeys. In an assay of schedule-controlled responding, monkeys responded under a fixed-ratio 30 (FR 30) schedule of food presentation. Fentanyl and U69,593 each produced rate-decreasing effects when administered alone, and mixtures of 0.22:1, 0.65:1 and 1.96:1 U69,593/fentanyl usually produced subadditive effects. In an assay of thermal nociception, tail withdrawal latencies were measured from water heated to 50°C. Fentanyl and U69,593 each produced dose-dependent antinociception, and effects were additive for all mixtures. In an assay of drug self-administration, rhesus monkeys responded for i.v. drug injection, and both dose and FR values were manipulated. Fentanyl maintained self-administration, whereas U69,593 did not. Addition of U69,593 to fentanyl produced a proportion-dependent decrease in both rates of fentanyl self-administration and behavioral economic measures of the reinforcing efficacy of fentanyl. Taken together, these results suggest that simultaneous activation of mu and kappa receptors, either with a mixture of selective drugs or with a single drug that targets both receptors, may reduce abuse liability without reducing analgesic effects relative to selective mu agonists administered alone. PMID:18837635

Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl.

PubMed

Shoushtarian, Mehrnaz; McGlade, Desmond P; Delacretaz, Louis J; Liley, David T J

2016-12-01

The brain anaesthesia response (BAR) monitor uses a method of EEG analysis, based on a model of brain electrical activity, to monitor the cerebral response to anaesthetic and sedative agents via two indices, composite cortical state (CCS) and cortical input (CI). It was hypothesised that CCS would respond to the hypnotic component of anaesthesia and CI would differentiate between two groups of patients receiving different doses of fentanyl. Twenty-five patients scheduled to undergo elective first-time coronary artery bypass graft surgery were randomised to receive a total fentanyl dose of either 12 μg/kg (fentanyl low dose, FLD) or 24 μg/kg (fentanyl moderate dose, FMD), both administered in two divided doses. Propofol was used for anaesthesia induction and pancuronium for intraoperative paralysis. Hemodynamic management was protocolised using vasoactive drugs. BIS, CCS and CI were simultaneously recorded. Response of the indices (CI, CCS and BIS) to propofol and their differences between the two groups at specific points from anaesthesia induction through to aortic cannulation were investigated. Following propofol induction, CCS and BIS but not CI showed a significant reduction. Following the first dose of fentanyl, CI, CCS and BIS decreased in both groups. Following the second dose of fentanyl, there was a significant reduction in CI in the FLD group but not the FMD group, with no significant change found for BIS or CCS in either group. The BAR monitor demonstrates the potential to monitor the level of hypnosis following anaesthesia induction with propofol via the CCS index and to facilitate the titration of fentanyl as a component of balanced anaesthesia via the CI index.

Direct-injection mass spectrometric method for the rapid identification of fentanyl and norfentanyl in postmortem urine of six drug-overdose cases.

PubMed

Peer, Cody J; Shakleya, Diaa M; Younis, Islam R; Kraner, James C; Callery, Patrick S

2007-10-01

A rapid mass spectrometric method was developed for the identification of fentanyl and its major hepatic metabolite norfentanyl in postmortem urine of six drug-overdose victims involving fentanyl use. To reduce matrix effects or ion suppression, sample preparation consisted of centrifugation and solid-phase extraction. Deuterium-labeled internal standards ((2)H(5)-fentanyl and (2)H(5)-norfentanyl) were used to compensate for instrument variation in signal, analyte recovery during sample preparation, and ion suppression. Structural information for fentanyl and norfentanyl were collected using mass spectrometry (MS) with electrospray ionization (ESI) operated in the positive ion mode. Fentanyl (m/z 337) was found in each of the six overdose cases by the appearance of the MS-MS daughter ion on both an ion trap and a triple-quadrupole MS resulting from the fragmentation pathway of fentanyl (m/z 337 --> 188). Norfentanyl was detected in all six cases by the appearance of the MH(+) ion, m/z 233, with a single-quadrupole MS and confirmed in an ion trap MS. Ion suppression, as determined by the comparison of ion intensities from spiked samples in water with postmortem urine from the cases, ranged from 18% to 98% in three ESI sources. The use of stable isotope-labeled internal standards obviates sample preparation because ratios of analyte/internal standard remain constant in the presence of extensive matrix effects. This MS method provided sufficient sensitivity and selectivity for the rapid identification of fentanyl and norfentanyl in urine at levels >/= 10 ng/mL without prior analyte resolution by chromatography and with a total analysis time of less than 1 h.

Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women.

PubMed

Moisés, Elaine Christine Dantas; de Barros Duarte, Luciana; de Carvalho Cavalli, Ricardo; Lanchote, Vera Lúcia; Duarte, Geraldo; da Cunha, Sérgio Pereira

2005-08-01

Fentanyl is an opioid drug widely used as a co-adjuvant in abdominal delivery, a fact that justifies its pharmacokinetic study under these conditions. Our objective was to investigate the pharmacokinetics and placental transfer of fentanyl in parturients whose pregnancies were resolved by cesarian section with epidural anesthesia. Ten clinically normal parturients who delivered at term received 5 ml of 2% lidocaine hydrochloride without a vasoconstrictor for skin and subcutaneous blockade, followed by epidural injection of 2 ml fentanyl citrate (0.05 mg/ml), 15 ml 0.5% bupivacaine hydrochloride with 1:200,000 epinephrine, and 10 ml 2% lidocaine hydrochloride without a vasoconstrictor. Maternal blood samples were collected at various times after injection (1--840 min), and the fentanyl plasma concentrations were determined by gas chromatography-mass spectrometry. Pharmacokinetic analysis was performed using the bi- or tri-compartmental model. The fetal/maternal ratio of the plasma fentanyl was determined at birth. The values of the pharmacokinetic parameters were: t(1/2)alpha=13.5 min, t(1/2)beta=192.5 min, t(1/2)gamma=620 min, AUC(0-infinity)=137.404 ng.min per milliliter, C(l)/f=464.984 ml/min, V(d)/f=299.974 l, C(l)/f/kg=6.875 ml/min per kilogram, and V(d)/f/kg=4.441 l/kg. The latency between drug administration and birth was 28.5 min, with a maternal and fetal plasma concentration of 0.310 and 0.245 ng/ml, respectively, at a median fetal/maternal ratio of 0.892. The study demonstrated a rapid passage of fentanyl from the epidural space to maternal blood and a significant transplacental transfer of maternal fentanyl of about 90%, which should serve as an alert to obstetricians.

Effect of different surgical procedures on the accuracy of prediction of the plasma concentration of fentanyl: comparison between mastectomy and laparoscopic prostatectomy.

PubMed

Fujita, Yoshihito; Yoshizawa, Saya; Hoshika, Maiko; Inoue, Koichi; Matsushita, Shoko; Oka, Hisao; Sobue, Kazuya

2017-01-01

The accuracy of simulation-predicted fentanyl concentration in different types of surgical procedure is not fully understood. We wished to estimate the effect of different types of surgical procedure on the accuracy of such simulations. Fifty patients who had undergone elective mastectomy or laparoscopic prostatectomy (American Society of Anesthesiologists physical status = I-II) were enrolled. Anesthesia was maintained throughout surgery with sevoflurane and a bolus infusion of fentanyl. A maintenance infusion was administered with 8 mL/kg/h Ringer's acetate solution from the start of anesthesia to completion of blood sampling. An infusion to compensate for blood loss was administered (one to two volumes of hydroxyethyl starch). A blood sample was drawn every 30 min during anesthesia.We measured the plasma concentration of fentanyl in 358 samples from 50 patients. The plasma concentration of fentanyl was correlated significantly with the simulated predicted fentanyl concentration ( r  = 0.734, P  < 0.01) but 36.0% of all samples had a difference greater than ±0.5 ng/mL. Approximately 0.3 ng/mL of a fixed bias was shown throughout mastectomy. During laparoscopic prostatectomy, the fixed bias gradually became negative from ≈0.3 to -0.3 ng/mL as the sampling stage proceeded. The predicted concentration of fentanyl was significantly correlated with the plasma concentration of fentanyl ( r  = 0.734). However, there were different patterns of a fixed bias between mastectomy and laparoscopic prostatectomy groups. We should pay attention to this tendency among different surgical procedures. UMIN000005110.

The effect of variable-dose diazepam on dreaming and emergence phenomena in 400 cases of ketamine-fentanyl anaesthesia.

PubMed

Grace, R F

2003-09-01

This randomised double-blind field study compared 400 anaesthetics using diazepam (0, 0.025, 0.5, 0.1, 0.175 mg.kg-1) with ketamine (1 mg.kg-1) and fentanyl (1 microg.kg-1) in Melanesian patients. Dreams were very common and generally positive in nature. A minimum of 0.1 mg.kg-1 of diazepam was needed to significantly reduce dreaming when compared with water (67.5% vs. 94.6%; p < 0.0001), and to significantly lower median (95% CI) emergence delirium scores (4 (3-4) vs. 6 (5-7)). Gender and age did not affect the rate of dreaming. Increasing the dose of diazepam did not improve the dream experience. Patient satisfaction scores were similar between groups. Increases in blood pressure and heart rate were greater in dreamers than in non-dreamers. All groups had high rate-pressure products but this was highest when diazepam was not used. Higher diazepam doses significantly reduced the increase in blood pressure and heart rate at 3 and 6 min postketamine. When used with ketamine and fentanyl, 0.1 mg.kg-1 of diazepam has favourable psychic and cardiovascular effects. Lower diazepam doses generally had little effect whereas larger doses did not enhance the benefits further.

Inhaled fentanyl citrate improves exercise endurance during high-intensity constant work rate cycle exercise in chronic obstructive pulmonary disease.

PubMed

Jensen, Dennis; Alsuhail, Abdullah; Viola, Raymond; Dudgeon, Deborah J; Webb, Katherine A; O'Donnell, Denis E

2012-04-01

Activity limitation and dyspnea are the dominant symptoms of chronic obstructive pulmonary disease (COPD). Traditionally, efforts to alleviate these symptoms have focused on improving ventilatory mechanics, reducing ventilatory demand, or both of these in combination. Nevertheless, many patients with COPD remain incapacitated by dyspnea and exercise intolerance despite optimal therapy. To determine the effect of single-dose inhalation of nebulized fentanyl citrate (a μ-opioid agonist drug) on exercise tolerance and dyspnea in COPD. In a randomized, double-blind, placebo-controlled, crossover study, 12 stable patients with COPD (mean ± standard error of the mean post-β(2)-agonist forced expiratory volume in one second [FEV(1)] and FEV(1) to forced vital capacity ratio of 69% ± 4% predicted and 49% ± 3%, respectively) received either nebulized fentanyl citrate (50 mcg) or placebo on two separate days. After each treatment, patients performed pulmonary function tests and a symptom-limited constant work rate cycle exercise test at 75% of their maximum incremental work rate. There were no significant postdose differences in spirometric parameters or plethysmographic lung volumes. Neither the intensity nor the unpleasantness of perceived dyspnea was, on average, significantly different at isotime (5.0 ± 0.6 minutes) or at peak exercise after treatment with fentanyl citrate vs. placebo. Compared with placebo, fentanyl citrate was associated with 1) increased exercise endurance time by 1.30 ± 0.43 minutes or 25% ± 8% (P=0.01); 2) small but consistent increases in dynamic inspiratory capacity by ∼0.10 L at isotime and at peak exercise (both P≤0.03); and 3) no concomitant change in ventilatory demand, breathing pattern, pulmonary gas exchange, and/or cardiometabolic function during exercise. The mean rate of increase in dyspnea intensity (1.2 ± 0.3 vs. 2.9 ± 0.8 Borg units/minute, P=0.03) and unpleasantness ratings (0.5 ± 0.2 vs. 2.9 ± 1.3 Borg units/minute, P=0.06) between isotime and peak exercise was less after treatment with fentanyl citrate vs. placebo. Single-dose inhalation of fentanyl citrate was associated with significant and potentially clinically important improvements in exercise tolerance in COPD. These improvements were accompanied by a delay in the onset of intolerable dyspnea during exercise near the limits of tolerance. Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

High Body Mass Index and Use of Fentanyl Iontophoretic Transdermal System in Postoperative Pain Management: Results of a Pooled Analysis of Six Phase 3/3B Trials.

PubMed

Viscusi, Eugene R; Ding, Li; Phipps, J Bradley; Itri, Loretta M; Schauer, Philip R

2017-06-01

Postoperative pain management can be challenging in patients with a high body mass index (BMI) especially as a result of poor venous access and delayed ambulation that can result in serious complications. Fentanyl iontophoretic transdermal system (ITS) is a needle-free, patient-controlled analgesic method available for use in acute postoperative pain. The primary objective of these analyses was to determine if there were any differences between patients with high BMI (>40 kg/m 2 ) and lower BMIs (<30 kg/m 2 and 35-40 kg/m 2 ) in terms of efficacy or safety. Data from three registration, placebo-controlled trials and three active-comparator trials using fentanyl ITS (IONSYS ® , The Medicines Company, Parsippany, NJ) for the management of postoperative pain were analyzed using BMI categories of <35 kg/m 2 , 35-40 kg/m 2 , and >40 kg/m 2 . The majority of patients had lower abdominal or orthopedic surgery. For these analyses, the primary efficacy variables were assessed via patient global assessment of pain control (PGA) at 24 h and investigator global assessment (IGA) at study discharge. PGA and IGA are categorical 4-point scales (excellent, good, fair, or poor) with treatment "success" defined as either excellent or good. Safety was evaluated via treatment emergent adverse events (TEAEs). There were 1403 patients randomly assigned and treated with fentanyl ITS for at least 3 h (BMI <35 kg/m 2 : 1180; 35-40 kg/m 2 : 136, BMI >40 kg/m 2 : 85; and 2 missing). PGA treatment success, which evaluates the method of pain control, at 24 h was consistent in the high and low BMI groups in patients treated with fentanyl ITS (<35 kg/m 2 : 946/1180 [80.2%]; 35-40 kg/m 2 : 103/136 [75.7%]; and >40 kg/m 2 : 65/85 [76.5%]). The IGA results at study discharge were similar to the PGA. Safety appeared similar with fentanyl ITS across the BMI groups. In these analyses, fentanyl ITS was as efficacious, as assessed by the PGA ratings of treatment "success", in patients with high BMI (>40 kg/m 2 ) as it was for those with lower BMIs (<35 kg/m 2 or 35-40 kg/m 2 ) and was generally well tolerated across all BMI categories.

A Review on Pharmacokinetic Modeling and the Effects of Environmental Stressors on Pharmacokinetics for Operational Medicine: Operational Pharmacokinetics

DTIC Science & Technology

2009-09-01

hypercholesterolemia Two-compartment model Ezzet, Krishna et al. 2001 Antilipemics Statins: simvastatin, rosuvastatin, atorvastatin Treatment of...Pharmacokinetic model* & rosuvastatin Scopus 14 3 PubMed 9 3 Pharmacokinetic model* & atorvastatin Scopus 49 4 Pharmacokinetic model* & zaleplon...Fentanyl & pharmacokinetic & heat 9 2 Fentanyl & pharmacokinetic & cold 4 0 Fentanyl & pharmacokinetic & blood loss 19 5 Atorvastatin

Fentanyl reduces desflurane-induced airway irritability following thiopental administration in children.

PubMed

Lee, J; Oh, Y; Kim, C; Kim, S; Park, H; Kim, H

2006-10-01

Airway irritation is a major drawback of desflurane anesthesia. This study was designed to evaluate the effect of intravenous fentanyl given before thiopental induction on airway irritation caused by a stepwise increase in desflurane in children. Eighty children (2-8 years) were enrolled in a randomized, double-blind study. Forty received saline and 40 received 2 microg/kg of fentanyl intravenously; this was followed by thiopental sodium 5 mg/kg in both groups. Patients were assistant-ventilated with desflurane 1%, which was then increased by 1% every six breaths up to 10%. During this period, cough, secretion, excitation and apnea were graded and the desflurane concentration at which airway irritation symptoms first occurred was recorded. The results were analyzed using Pearson's chi-squared test. The incidence of typical airway irritation events was lower with fentanyl than with saline (cough, 2.5% vs. 42.5%; secretion, 27.5% vs. 82.5%; excitation, 10% vs. 82.5%; apnea, 20% vs. 65%; P < 0.05). The mean expired desflurane concentration at which the first airway irritation symptom occurred was greater with fentanyl than with saline (7.3% vs. 5.5%, P < 0.05). Intravenous fentanyl in children reduces airway complications caused by desflurane.

A randomized controlled trial of the effect of combined spinal-epidural analgesia on the success of external cephalic version for breech presentation.

PubMed

Sullivan, J T; Grobman, W A; Bauchat, J R; Scavone, B M; Grouper, S; McCarthy, R J; Wong, C A

2009-10-01

Improving the success of external cephalic version (ECV) for breech presentation may help avoid some cesarean deliveries. The results of randomized trials comparing the success of ECV with neuraxial analgesia compared to control are inconsistent. We hypothesized that combined spinal-epidural (CSE) analgesia would increase the success of ECV when compared with systemic opioid analgesia. Parturients with singleton breech presentation (n=96) were randomized to receive CSE analgesia with bupivacaine 2.5mg and fentanyl 15 microg (CSE group) or intravenous fentanyl 50 microg (SYS group) before ECV attempt. The primary outcome was ECV success. The success rate of ECV was 47% with CSE and 31% in the SYS group (P=0.14). Subsequent vaginal delivery was 36% for CSE and 25% for SYS (P=0.27). Median [IQR] visual analog pain scores (0-100mm scale) were lower with CSE (3 [0-12]) compared to SYS analgesia (36 [16 to 54]) (P<0.005) and patient satisfaction (0-10 scale) was higher (CSE 10 [9 to 10] versus SYS 7 [4 to 9]) (P<0.005). There were no differences in fetal heart rate patterns, but median time to return to fetal heart rate reactivity after analgesia was shorter with CSE (13 [IQR 9-21] min) compared to the SYS group (39 [IQR 23-51] min) (P=0.02). There was no difference in the rate of successful ECV or vaginal delivery with CSE compared to intravenous fentanyl analgesia. Pain scores were lower and satisfaction higher with CSE analgesia, and median time to fetal heart rate reactivity was shorter in the CSE group.

THERMAL SENSITIVITY ACROSS AGES AND DURING CHRONIC FENTANYL ADMINISTRATION IN RATS

PubMed Central

Mitzelfelt, Jeremiah D.; Carter, Christy S.; Morgan, Drake

2013-01-01

Rationale Chronic pain is becoming a more common medical diagnosis and is especially prevalent in older individuals. As such, prescribed use of opioids is on the rise, even though the efficacy for pain management in older individuals is unclear. Objectives Thus the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, 24 months). Methods Animals were tested in a thermal sensitivity procedure known to involve neural circuits implicated in chronic pain in humans. Sensitivity to heat and cold thermal stimulation was assessed during 28 days of fentanyl administration (1.0 mg/kg/day), and 28 days of withdrawal. Results Fentanyl resulted in decreased thermal sensitivity to heat but not cold stimulation indicated by more time spent in the hot compartment relative to time spent in the cold or neutral compartments. Unlike previous findings using a hot-water tail withdrawal procedure, tolerance did not develop to the antinociceptive effects of fentanyl over a 28-day period of drug administration. The oldest animals were least sensitive, and the youngest animals most sensitive to the locomotor-stimulating effects of fentanyl. The effect on the antinociceptive response to fentanyl in the oldest group of rats was difficult to interpret due to profound changes in the behavior of saline-treated animals. Conclusions Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies. PMID:23900640

Physiologically-based pharmacokinetic model for Fentanyl in support of the development of Provisional Advisory Levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shankaran, Harish, E-mail: harish.shankaran@pnnl.gov; Adeshina, Femi; Teeguarden, Justin G.

Provisional Advisory Levels (PALs) are tiered exposure limits for toxic chemicals in air and drinking water that are developed to assist in emergency responses. Physiologically-based pharmacokinetic (PBPK) modeling can support this process by enabling extrapolations across doses, and exposure routes, thereby addressing gaps in the available toxicity data. Here, we describe the development of a PBPK model for Fentanyl – a synthetic opioid used clinically for pain management – to support the establishment of PALs. Starting from an existing model for intravenous Fentanyl, we first optimized distribution and clearance parameters using several additional IV datasets. We then calibrated the modelmore » using pharmacokinetic data for various formulations, and determined the absorbed fraction, F, and time taken for the absorbed amount to reach 90% of its final value, t90. For aerosolized pulmonary Fentanyl, F = 1 and t90 < 1 min indicating complete and rapid absorption. The F value ranged from 0.35 to 0.74 for oral and various transmucosal routes. Oral Fentanyl was absorbed the slowest (t90 ∼ 300 min); the absorption of intranasal Fentanyl was relatively rapid (t90 ∼ 20–40 min); and the various oral transmucosal routes had intermediate absorption rates (t90 ∼ 160–300 min). Based on these results, for inhalation exposures, we assumed that all of the Fentanyl inhaled from the air during each breath directly, and instantaneously enters the arterial circulation. We present model predictions of Fentanyl blood concentrations in oral and inhalation scenarios relevant for PAL development, and provide an analytical expression that can be used to extrapolate between oral and inhalation routes for the derivation of PALs. - Highlights: • We develop a Fentanyl PBPK model for relating external dose to internal levels. • We calibrate the model to oral and inhalation exposures using > 50 human datasets. • Model predictions are in good agreement with the available pharmacokinetic data. • The model can be used for extrapolating across routes, doses and exposure durations. • We illustrate how the model can be used for developing Provisional Advisory Levels.« less

Geographic differences in perioperative opioid administration in children

PubMed Central

Rabbitts, Jennifer A.; Groenewald, Cornelius B.; Räsänen, Jukka

2012-01-01

Objectives To investigate whether geographic differences exist in perioperative opioid administration to children. Aim To investigate whether perioperative fentanyl use for cleft lip and palate surgery varies between children of three different geographic regions. Background Differences have been found in perioperative opioid administration to children of differing ethnicity in the U.S.A. Whether similar differences exist in perioperative opioid administration to children residing in different geographic regions is unknown. Methods/materials We retrospectively reviewed the medical records of ASA I children who underwent surgery under standardized general anesthesia between January 2010 and April 2011 during SMILE Network International mission trips to Africa, India and Central and South America. Perioperative administration of fentanyl was compared between these three locations. Results We analyzed data from 79 children who underwent surgery in Africa, 76 in India and 153 in Central and South America. Children in Central and South America were given less than 50% of the intraoperative amount of fentanyl (2.0 ± 1.2 mcg/kg) administered to children in Africa (4.1 ± 2.4 mcg/kg; p<0.001) and children in India (4.3 ± 2.2 mcg/kg; p < 0.001). Postoperatively, fentanyl was administered in equivalent doses to all groups. Conclusions Children in Central and South America received less opioid intraoperatively than African and Indian children, under standardized anesthesia for cleft surgeries. Further research is necessary to elucidate the mechanisms underlying these group differences. PMID:22324378

A Primer on Heroin and Fentanyl.

PubMed

Worley, Julie

2017-06-01

Heroin and fentanyl use have reached epidemic proportions in the United States and are now blamed for the majority of drug-related overdose deaths. Both drugs are produced primarily in South America and Asia and enter the United States illegally. One result of smoking or injecting heroin or fentanyl is the development of a substance use disorder (SUD), which causes changes in brain chemistry and function. These changes result in negative behaviors and an inability to stop use. Yet, treatments are available and recovery is possible. Nurses have the potential to impact the heroin and fentanyl epidemic through developing therapeutic relationships with patients who are at risk or already have a SUD. Strategies for effective communication include maintaining a supportive, nonjudgmental attitude and incorporating motivational interviewing. All patients should be screened for opioid use and referred for treatment if indicated. It is important for nurses to be knowledgeable about heroin and fentanyl and available treatments. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 16-20.]. Copyright 2017, SLACK Incorporated.

Report of Increasing Overdose Deaths that include Acetyl Fentanyl in Multiple Counties of the Southwestern Region of the Commonwealth of Pennsylvania in 2015-2016.

PubMed

Dwyer, Jessica B; Janssen, Jennifer; Luckasevic, Todd M; Williams, Karl E

2018-01-01

Acetyl fentanyl is a Schedule I controlled synthetic opioid that is becoming an increasingly detected "designer drug." Routine drug screening procedures in local forensic toxicology laboratories identified a total of 41 overdose deaths associated with acetyl fentanyl within multiple counties of the southwestern region of the state of Pennsylvania. The range, median, mean, and standard deviation of blood acetyl fentanyl concentrations for these 41 cases were 0.13-2100 ng/mL, 11 ng/mL, 169.3 ng/mL, and 405.3 ng/mL, respectively. Thirty-six individuals (88%) had a confirmed history of substance abuse, and all but one case (96%) were ruled multiple drug toxicities. This report characterizes this localized trend of overdose deaths associated with acetyl fentanyl and provides further evidence supporting an alarmingly concentrated opiate and opioid epidemic of both traditional and novel drugs within this region of the United States. © 2017 American Academy of Forensic Sciences.

An autopsy case of acetyl fentanyl intoxication caused by insufflation of 'designer drugs'.

PubMed

Takase, Izumi; Koizumi, Takako; Fujimoto, Ihoko; Yanai, Aya; Fujimiya, Tatsuya

2016-07-01

We present a fatal case of intoxication due to insufflation of acetyl fentanyl. His blood concentration of acetyl fentanyl was 270ng/mL, and the manner of death was classified as an accident. This is the first report of an autopsy case of acetyl fentanyl delivered by insufflation, rather than intravenous administration. He had been snoring loudly for at least 12h prior to death, and transport to a hospital during this time and treatment with naloxone may have saved his life. In this sense, it can be said that his death was preventable. This case reemphasizes the risk of death associated with drug overdose and the narrow range of acetyl fentanyl between the effective dose (ED50) and lethal dose (LD50). The case should also raise awareness among medical professionals of the effectiveness of naloxone and the need to establish a comprehensive system for toxicological analysis while keeping the possibility of use of 'designer drugs' in mind. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

U.S. Army War College Key Strategic Issues List 2013-2014

DTIC Science & Technology

2013-09-24

of a fentanyl cocktail by Russian special forces in October 2002 to end a hostage crisis in the Dubrovka Theater by Chechen 47 extremists brought...the crisis. In December 2011, the European Court of Human Rights found the Russian government not-guilty regarding the use of the fentanyl cocktail...and development into fentanyls and other pharmaceuticals by CWC signatory countries. While these chemicals are deemed incapacitants, under certain

Stress, Predictability, and Oral Fentanyl Self-Administration in Female and Male Rats

DTIC Science & Technology

1995-03-09

naloxone. When dissolved in water, fentanyl hydrochloride (Hel) is less bitter-tasting than morphine and it is readily self- administered by rats...and for assessment of the biochemical effects of the stressor. Drugs Fentanyl- hydrochloride (HCI) (NIDA, Baltimore, MD), in a concentration of 50...responses despite lower opioid SA, treatment for men might focus on pharmacologic replacement therapies, such as methadone maintenance programs. The

Syndrome surveillance of fentanyl-laced heroin outbreaks: Utilization of EMS, Medical Examiner and Poison Center databases.

PubMed

Moore, P Quincy; Weber, Joseph; Cina, Steven; Aks, Steven

2017-11-01

Describe surveillance data from three existing surveillance systems during an unexpected fentanyl outbreak in a large metropolitan area. We performed a retrospective analysis of three data sets: Chicago Fire Department EMS, Cook County Medical Examiner, and Illinois Poison Center. Each included data from January 1, 2015 through December 31, 2015. EMS data included all EMS responses in Chicago, Illinois, for suspected opioid overdose in which naloxone was administered and EMS personnel documented other criteria indicative of opioid overdose. Medical Examiner data included all deaths in Cook County, Illinois, related to heroin, fentanyl or both. Illinois Poison Center data included all calls in Chicago, Illinois, related to fentanyl, heroin, and other prescription opioids. Descriptive statistics using Microsoft Excel® were used to analyze the data and create figures. We identified a spike in opioid-related EMS responses during an 11-day period from September 30-October 10, 2015. Medical Examiner data showed an increase in both fentanyl and mixed fentanyl/heroin related deaths during the months of September and October, 2015 (375% and 550% above the median, respectively.) Illinois Poison Center data showed no significant increase in heroin, fentanyl, or other opioid-related calls during September and October 2015. Our data suggests that EMS data is an effective real-time surveillance mechanism for changes in the rate of opioid overdoses. Medical Examiner's data was found to be valuable for confirmation of EMS surveillance data and identification of specific intoxicants. Poison Center data did not correlate with EMS or Medical Examiner data. Copyright © 2017 Elsevier Inc. All rights reserved.

Contribution of Central μ-Receptors to Switching Pulmonary C-Fibers-Mediated Rapid Shallow Breathing into An Apnea by Fentanyl in Anesthetized Rats

PubMed Central

Zhang, Zhenxiong; Zhang, Cancan; Zhuang, Jianguo; Xu, Fadi

2012-01-01

Our previous study has shown that activating peripheral μ-receptors is necessary for switching the bronchopulmonary C-fibers (PCFs)-mediated rapid shallow breathing (RSB) into an apnea by systemic administration of fentanyl. The brainstem nuclei, such as the medial nucleus tractus solitarius (mNTS) and the Pre-Botzinger Complex (PBC), are required for completing the PCF-mediated respiratory reflexes. Moreover, these areas contain abundant μ-receptors and their activation prolongs expiratory duration (TE). Thus, we asked if central μ-receptors, especially those in the mNTS and PBC, are involved in fully expressing this RSB-apnea switch by fentanyl. In anesthetized rats, the cardiorespiratory responses to right atrial injection of phenylbiguanide (PBG, 3–6 μg/kg) were repeated after: 1) fentanyl (iv), a μ-receptor agonist, alone (8 μg/kg, iv); 2) fentanyl following microinjection of naloxone methiodide (NXM, an opioid receptor antagonist) into the cisterna magna (10 μg/4 μl); 3) the bilateral mNTS (10 mM, 20 nl); or 4) PBC (10 mM, 20 nl). Our results showed that PBG shortened TE by 37 ± 6 % (RSB, from 0.41 ± 0.05 to 0.26 ± 0.03 s, P < 0.01), but it markedly prolonged TE by 5.8-fold (an apnea, from 0.50 ± 0.04 s to 2.9 ± 0.57 s, P < 0.01) after fentanyl (iv). Pretreatment with NXM injected into the cisterna magna or the PBC, but not the mNTS, prevented the fentanyl-induced switch. This study, along with our previous results mentioned above, suggests that although peripheral μ-receptors are essential for triggering the fentanyl-induced switch, central μ-receptors, especially those in the PBC, are required to fully exhibit such switch. PMID:22759907

Fatalities Involving Carfentanil and Furanyl Fentanyl: Two Case Reports.

PubMed

Swanson, Dina M; Hair, Laura S; Strauch Rivers, Selly R; Smyth, Brianna C; Brogan, Sara C; Ventoso, Alexis D; Vaccaro, Samantha L; Pearson, Julia M

2017-07-01

Carfentanil is a fentanyl analog frequently used in large animal veterinary medicine. Recently, carfentanil has been discovered in postmortem and antemortem cases throughout the United States in the heroin supply either alone or mixed with heroin and/or other fentanyl analogs. The potency of carfentanil is ~10,000 times greater than morphine and 100 times greater than fentanyl. In two recent cases, carfentanil was identified and ruled to be the cause of death, either alone or in combination with other drugs. Case 1 involved a known heroin user. He was discovered slumped over in a running van blocking the bays of a carwash. Two syringes, a spoon with cotton and residue and a yellow baggie of powder were found in the van. Case 2 involved a man living in a tent in a park with his mother. He was last heard from by a sister via phone who stated he sounded very intoxicated and by his mother who noted him to be "itching all over" and upset over his girlfriend. When the mother returned from work, she discovered him unresponsive with a small baggie of brown powder next to him. Routine drug and volatile screening tests were performed on heart blood using headspace gas chromatography, immunoassay and gas chromatography mass spectrometry methods. Results from initial testing on both cases did not have any significant toxicological findings. However, due to the history, scene photos, toxicological findings in blood and urine and analysis of the drug paraphernalia on one of the cases which identified carfentanil and furanyl fentanyl, fentanyl analogues were suspected. Heart blood was sent to a reference laboratory for carfentanil and furanyl fentanyl analysis. Case 1 had a carfentanil concentration of 1.3 ng/mL and a furanyl fentanyl concentration of 0.34 ng/mL. Case 2 had a carfentanil concentration of 0.12 ng/mL. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mechanism-based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers.

PubMed

Yassen, A; Olofsen, E; Romberg, R; Sarton, E; Teppema, L; Danhof, M; Dahan, A

2007-01-01

The objective of this study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of buprenorphine and fentanyl for the respiratory depressant effect in healthy volunteers. Data on the time course of the ventilatory response at a fixed P(ET)CO(2) of 50 mm Hg and P(ET)O(2) of 110 mm Hg following intravenous administration of buprenorphine and fentanyl were obtained from two phase I studies (50 volunteers received buprenorphine: 0.05-0.6 mg/70 kg and 24 volunteers received fentanyl: 0.075-0.5 mg/70 kg). The PK/PD correlations were analyzed using nonlinear mixed effects modeling. A two- and three-compartment pharmacokinetic model characterized the time course of fentanyl and buprenorphine concentration, respectively. Three structurally different PK/PD models were evaluated for their appropriateness to describe the time course of respiratory depression: (1) a biophase distribution model with a fractional sigmoid E(max) pharmacodynamic model, (2) a receptor association/dissociation model with a linear transduction function, and (3) a combined biophase distribution-receptor association/dissociation model with a linear transduction function. The results show that for fentanyl hysteresis is entirely determined by the biophase distribution kinetics, whereas for buprenorphine hysteresis is caused by a combination of biophase distribution kinetics and receptor association/dissociation kinetics. The half-time values of biophase equilibration (t(1/2, k(eo))) were 16.4 and 75.3 min for fentanyl and buprenorphine, respectively. In addition, for buprenorphine, the value of k(on) was 0.246 ml/ng/min and the value of k(off) was 0.0102 min(-1). The concentration-effect relationship of buprenorphine was characterized by a ceiling effect at higher concentrations (intrinsic activity alpha=0.56, 95% confidence interval (CI): 0.50-0.62), whereas fentanyl displayed full respiratory depressant effect (alpha=0.91, 95% CI: 0.19-1.62).

Analgesic efficacy of low-dose intrathecal neostigmine in combination with fentanyl and bupivacaine for total knee replacement surgery

PubMed Central

Jain, Amit; Jain, Kajal; Bhardawaj, Neerja

2012-01-01

Background and Aim: Intrathecal (IT) neostigmine has been used as an adjunct to spinal anesthesia. The purpose of this study was to determine whether a combination of low-dose neostigmine IT would enhance analgesia of a fixed dose of fentanyl IT, in patients undergoing unilateral total knee replacement (TKR) surgery with spinal anesthesia. Settings and Design: Forty-five patients scheduled for unilateral TKR were randomized to one of the three groups (n = 15) and prospectively studied using placebo-controlled, double-blinded design. Materials and Methods: A 19-G epidural catheter was introduced through the L3–L4 interspace with patient in the sitting position, followed by spinal anesthesia administration through the L3–L4 interspace. Fifteen milligrams of hyperbaric bupivacaine (3 ml) plus the test drug (0.5 ml) was administered IT. The test drug was normal saline (0.5 ml) in group I; fentanyl 20 mcg (0.4 ml) and normal saline (0.1 ml) in group II; and fentanyl 20 mcg (0.4 ml) and neostigmine 1 mcg (0.1 ml) in group III. Characteristics of sensory and motor block, heart rate, and blood pressure were recorded intraoperatively. Postoperatively, pain scores, postoperative nausea and vomiting (PONV) scores, and sedation scores, and postoperative analgesic dose were recorded. Results: Forty-five patients were enrolled in this study and 43 patients were subjected to statistical analysis. Overall 24-h visual analog score in group III was significantly less than in those who received fentanyl alone (P = 0.00). The durations of complete analgesia and effective analgesia were longer for all patients in group III compared with group II (P < 0.05) and group I (P < 0.005) patients. The total number of epidural top ups (rescue analgesia) required was less in group II (P < 0.05) and group III (P < 0.005) patients, compared with the control group. The incidence of nausea and vomiting was not increased in group III patients. Conclusions: The addition of 1 mcg neostigmine IT increased the duration of analgesia and decreased the analgesic consumption in 24 h in TKR. There was no increase in the incidence of adverse effects. PMID:23225930

Factors predisposing to coma and delirium: fentanyl and midazolam exposure; CYP3A5, ABCB1, and ABCG2 genetic polymorphisms; and inflammatory factors.

PubMed

Skrobik, Yoanna; Leger, Caroline; Cossette, Mariève; Michaud, Veronique; Turgeon, Jacques

2013-04-01

Delirium and sedative-induced coma are described as incremental manifestations of cerebral dysfunction. Both may be associated with sedative or opiate doses and pharmacokinetic or pharmacogenetic variables, such as drug plasma levels (exposure), drug metabolism, and/or their transport across the blood-brain barrier. To compare biological and drug treatment characteristics in patients with coma and/or delirium while in the ICU. In 99 patients receiving IV fentanyl, midazolam, or both, we evaluated drug doses, covariates likely to influence drug effects (age, body mass index, and renal and hepatic dysfunction); delirium risk factors; concomitant administration of CYP3A and P-glycoprotein substrates/inhibitors; ABCB1, ABCG2, and CYP3A5 genetic polymorphisms; and fentanyl and midazolam plasma levels. Delirium and coma were evaluated daily. In patients with only coma (n=15), only delirium (n=7), and neither ever (n=14), we measured plasma levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1RA, IL-6, IL-8, IL-10, IL-17,macrophage inflammatory protein-1β, and monocyte chemotactic protein-1. Time to first coma was associated with fentanyl and midazolam doses (p=0.03 and p=0.01, respectively). The number of days in coma was associated with the number of days of coadministration of CYP3A inhibitors (r=0.30; p=0.006). Plasma levels of fentanyl were higher in patients with clinical coma (3.7±4.7 vs. 2.0±1.8 ng/mL, p=0.0001) as were midazolam plasma levels (1050±2232 vs. 168±249 ng/mL, p=0.0001). Delirium occurrence was unrelated to midazolam administration, cumulative doses, or serum levels. Days with delirium were associated with days of coadministration of P-glycoprotein inhibitor (r=0.35; p=0.0004). Delirious patients had higher levels of the inflammatory mediator IL-6 than comatose patients (129.3 vs. 35.0 pg/mL, p=0.05). Coma is associated with fentanyl and midazolam exposure; delirium is unrelated to midazolam and may be linked to inflammatory status. These data suggest that iatrogenic coma and delirium are not mechanistically linked.

The Role of Pituitary Beta-Endorphin in the Attenuation of Nociception

DTIC Science & Technology

1986-08-28

204 X TABLES Table # Title 1 Effects of naloxone, fentanyl , diazepam and placebo on plasma norepinephrine levels (pgjml). 2 Lack of...the clinical CRH study. 4 Experimental design and sampling schedule for the clinical dexamethasone study. 5 Effects of naloxone (NAL), fentanyl ...FEN), diazepam (DZP) and placebo (PLBO) on circulating levels of iB-END. 6 7 8 9 10 11 12 Effects of naloxone (NAL), fentanyl (FEN), diazepam

Development of a conformational search strategy for flexible ligands: A study of the potent μ-selective opioid analgesic fentanyl

NASA Astrophysics Data System (ADS)

Cometta-Morini, Chiara; Loew, Gilda H.

1991-08-01

An extensive conformational search of the potent opioid analgesic, fentanyl, was performed using the semiempirical quantum mechanical method AM1 and the CHARMm potential energy function. A combination of two procedures was used to search the conformational space for fentanyl, which included nested dihedral scans, geometry optimization and molecular dynamics simulation at different temperatures. In addition, the effect of a continuum solvent environment was taken into account by use of appropriate values for the dielectric constant in the CHARMm computations. The results of the conformational search allowed the determination of the probable conformation of fentanyl in polar and nonpolar solvents and of three candidate conformers for its bioactive form.

Fentanyl and methadone used as adjuncts to bupivacaine for lumbosacral epidural analgesia in sheep.

PubMed

DeRossi, R; Pagliosa, R C; de Carvalho, A Q; Macedo, G G; Hermeto, L C

2017-01-28

Six healthy, female, mixed-breed 18-24-month-old sheep weighing 30-48 kg were submitted to lumbosacral epidural bupivacaine in combination with either methadone or fentanyl. Epidural catheters were placed in six sheep that were given three treatments: (Bup) bupivacaine (0.5 mg/kg) alone; (BupMet) bupivacaine (0.25 mg/kg) plus methadone (0.3 mg/kg); and (BupFent) bupivacaine (0.25 mg/kg) plus fentanyl (0.002 mg/kg). Haemodynamic variables, respiratory rate, rectal temperature, analgesia by applying a standard painful stimulus, motor block and sedative scores were compared among the three treatments. These parameters were determined before epidural administration and at 5, 10, 20, 30, 60, 90, 120 minutes after treatment administration, and then every 60 minutes thereafter until the end of analgesic effect. Parametrical data were analysed by proc glimmix (SAS) for repeated measures on time and means tested by ls-means. Non-parametrical data were analysed by Fisher's exact test. Duration of analgesia was longer with BupMet (240 minutes) compared with BupFent (180 minutes; P=0.0127), but BupMet was similar to Bup (240 minutes). Both treatments with opioids produced moderate motor blockade. BupMet and BupFent produced mild sedation. Only treatment with bupivacaine alone induced cardiovascular and respiratory rate changes that stayed within acceptable limits. British Veterinary Association.

The usefulness of interpectoral block as an analgesic technique in breast cancer surgery.

PubMed

Ortiz de la Tabla González, R; Gómez Reja, P; Moreno Rey, D; Pérez Naranjo, C; Sánchez Martín, I; Echevarría Moreno, M

2018-04-01

To compare the analgesic efficacy of continuous interpectoral block (CIPB) compared to intravenous analgesia (IV) after breast surgery. A prospective, comparative and randomised study of women aged from 18-75years, ASAI-III, operated for breast cancer. In group1 (CIPB) after general anaesthetic, an ultrasound-guided interpectoral catheter was placed and 30mL of 0.5% ropivacaine was administered through it. In the event of an increase in heart rate and blood pressure >15% after the surgical incision, intravenous fentanyl 1μg·kg -1 was administered, repeating the dose as necessary. In the postoperative period, perfusion of ropivacaine 0.2% 5mL·h -1 ; with PCA bolus 5mL/30minutes was administered through the catheter for 24hours and rescue analgesia prescribed with 5mg subcutaneous morphine chloride. In group2 (IV), after induction of general anaesthesia, intravenous fentanyl was administered in the same way as in the other group. The patients received metamizole 2g with dexketoprofen 50mg and ondansetron 4mg postoperatively followed by perfusion of metamizole 4%, tramadol 0.2% and ondansetron 0.08% 2ml·h -1 ; with PCA bolus 2mL/20min for 24hours. The same rescue analgesia was prescribed. The principal variables recorded were pain at rest and during movement, according to a simple verbal scale (VAS 0-10) and the rescue analgesia required on discharge from recovery, at 12 and at 24hours. 137 patients were included: 81 in group1 (59.12%) and 56 in group2 (40.87%). No significant differences were observed in the analgesia between either group, but differences were observed in the dose of intraoperative fentanyl (P<.05). Differences that were not significant were observed in the rescue analgesia required on recovery (10% fewer on group1). Both techniques provided effective postoperative analgesia, but the CIPB group required significantly less intraoperative fentanyl. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of fentanyl target-controlled infusions on isoflurane minimum anaesthetic concentration and cardiovascular function in red-tailed hawks (Buteo jamaicensis).

PubMed

Pavez, Juan C; Hawkins, Michelle G; Pascoe, Peter J; Knych, Heather K DiMaio; Kass, Philip H

2011-07-01

To determine the impact of three different target plasma concentrations of fentanyl on the minimum anaesthetic concentration (MAC) for isoflurane in the red-tailed hawk and the effects on the haemodynamic profile. Experimental study. Six healthy adult red-tailed hawks (Buteo jamaicensis) of unknown sex with body weights (mean ± SD) of 1.21 ± 0.15 kg. This study was undertaken in two phases. In the first phase anaesthesia was induced with isoflurane in oxygen via facemask and maintained with isoflurane delivered in oxygen via a Bain circuit. Following instrumentation baseline determination of the MAC for isoflurane was made for each animal using the bracketing method and a supramaximal electrical stimulus. End-tidal isoflurane concentration (E'Iso) was then set at 0.75 × MAC and after an appropriate equilibration period a bolus of fentanyl (20 μg kg(-1)) was administered intravenously (IV) in order to determine the pharmacokinetics of fentanyl in the isoflurane-anaesthetized red-tailed hawk. During the second phase anaesthesia was induced in a similar manner and E'Iso was set at 0.75 × MAC for each individual. Fentanyl was infused IV to achieve target plasma concentrations between 8 and 32 ng mL(-1). At each fentanyl plasma concentration, the MAC for isoflurane and cardiovascular variables were determined. Data were analyzed by use of repeated-measures anova. Mean ± SD fentanyl plasma concentrations and isoflurane MACs were 0 ± 0, 8.51 ± 4, 14.85 ± 4.82 and 29.25 ± 11.52 ng mL(-1), and 2.05 ± 0.45%, 1.42 ± 0.53%, 1.14 ± 0.31% and 0.93 ± 0.32% for the target concentrations of 0, 8, 16 and 32 ng mL(-1), respectively. At these concentrations fentanyl significantly (p = 0.0016) decreased isoflurane MAC by 31%, 44% and 55%, respectively. Dose had no significant effect on heart rate, systolic, diastolic or mean arterial blood pressure. Fentanyl produced a dose-related decrease of isoflurane MAC with minimal effects on measured cardiovascular parameters in red-tailed hawks. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Intravenous Dexmedetomidine Infusion Compared with that of Fentanyl in Patients Undergoing Arthroscopic Shoulder Surgery under General Anesthesia.

PubMed

Abdel Hamid, Mona Hossam Eldin

2017-01-01

Anesthesia for arthroscopic shoulder surgery is challenging due to the need for oligaemic surgical field as well as a good postoperative recovery profile. The present study was prospective, randomized to evaluate the efficacy of dexmdetomidine infusion compared to that of fentanyl in patients undergoing arthroscopic shoulder surgery under general anesthesia. A total of 60 patients aged from thirty to fifty years, American Society of Anesthesiologists Class I/II of either sex for arthroscopic shoulder surgery, were included. The patients were divided into two groups of 30 patients each. Group I received dexmedetomidine loading 1 μg/kg over 10 min followed by maintenance 0.5 μg/kg/h and Group II Fentanyl loading 1 μg/kg followed by maintenance 0.5 μg/kg/h. Hemodynamic readings (Heart rate HR, and mean arterial blood pressure MAP) were recorded after the start of the study drug infusion (T1), after intubation (T2), then every 15 minutes till the end of surgery (T15, T30, T45, T60, T75, T90). In the PACU, MAP, and HR were recorded on arrival, after 30 min, 1 hr, and 2 hrs (R0, R30, R1 hr, R2 hr) Postoperative analgesia was assessed by visual analogue scale (VAS), Modified Observers's Assessment of Alertness and Sedation OAA/S was recorded on arrival to PACU. This study showed that in the dexmedatomidine group there was statistically significant decrease of MAP and HR after drug infusion up to two hours in the recovery period, more sedation, better control of pain and surgeon satisfaction. Iv infusion of dexamedatomidine may be an attractive option during arthroscopic shoulder surgery as it provided a better hypotensive anesthesia by lowering MAP and HR which leads to better surgical field and surgeon satisfaction than iv infusion fentanyl along with a better postoperative VAS.

Development of an Injectable Salmon Fibrinogen-Thrombin Matrix to Enhance Healing of Compound Fractures of Extremities

DTIC Science & Technology

2012-09-01

first responder. Many factors may contribute to non-union of fractures, including nutritional or hormonal status, age of the patient, and presence of...of transdermal 420 fentanyl (100 µg/h) in Yucatan minipigs, plasma fentanyl concentration peaked within 48 hours, 421 with peak concentrations...3rd, Morse BC. 2001. Evaluation of a transdermal fentanyl system in 612 yucatan miniature pigs. Contemp Top Lab Anim Sci 40:12-16. 613 50. Wolfe

Cardiorespiratory effects of epidural administration of morphine and fentanyl in dogs anesthetized with sevoflurane.

PubMed

Naganobu, Kiyokazu; Maeda, Noriaki; Miyamoto, Toru; Hagio, Mitsuyoshi; Nakamura, Tadashi; Takasaki, Mayumi

2004-01-01

To determine the cardiorespiratory effects of epidural administration of morphine alone and in combination with fentanyl in dogs anesthetized with sevoflurane. Prospective study. 6 dogs. Dogs were anesthetized with sevoflurane and allowed to breathe spontaneously. After a stable plane of anesthesia was achieved, morphine (0.1 mg/kg [0.045 mg/lb]) or a combination of morphine and fentanyl (10 microg/kg [4.5 microg/lb]) was administered through an epidural catheter, the tip of which was positioned at the level of L6 or L7. Cardiorespiratory variables were measured for 90 minutes. Epidural administration of morphine alone did not cause any significant changes in cardiorespiratory measurements. However, epidural administration of morphine and fentanyl induced significant decreases in diastolic and mean arterial blood pressures and total peripheral resistance. Stroke volume was unchanged, PaCO2 was significantly increased, and arterial pH and base excess were significantly decreased. Heart rate was significantly lower after epidural administration of morphine and fentanyl than after administration of morphine alone. None of the dogs had any evidence of urine retention, vomiting, or pruritus after recovery from anesthesia. Results suggest that epidural administration of morphine at a dose of 0.1 mg/kg in combination with fentanyl at a dose of 10 microg/kg can cause cardiorespiratory depression in dogs anesthetized with sevoflurane.

Fentanyl

MedlinePlus

... a sublingual (underneath the tongue) tablet (Abstral), a film (Onsolis), and a buccal (between the gum and ... still have pain 30 minutes after using fentanyl films (Onsolis), your doctor may tell you to use ...

Effect of ketamine versus thiopental sodium anesthetic induction and a small dose of fentanyl on emergence agitation after sevoflurane anesthesia in children undergoing brief ophthalmic surgery.

PubMed

Jung, Hyun Ju; Kim, Jong Bun; Im, Kyong Shil; Oh, Seung Hwa; Lee, Jae Myeong

2010-02-01

Emergence agitation (EA) in children after sevoflurane anesthesia is common. The purpose of this study was to compare the incidences of EA between ketamine and thiopental sodium induction in children underwent sevoflurane anesthesia. We also evaluated if a small dose of fentanyl could reduce the incidence of EA. The patients who were scheduled for strabismus or entropion surgery were divided into 4 groups. The patients in Groups 1 and 2 were induced anesthesia with ketamine 1.5 mg/kg; those in Groups 3 and 4 were induced with thiopental sodium 5 mg/kg. The patients in Groups 1 and 3 received an injection of fentanyl 1.5 microg/kg, whereas the patients in Groups 2 and 4 received IV saline of the same volume. Anesthesia was maintained with sevoflurane. The recovery characteristics and EA in recovery room were assessed. The incidence of EA was significantly higher in Groups 2 and 4 and there was no difference between Groups 2 and 4. Group 2 had almost an eleven-fold higher risk of developing EA than did Group 1, and the incidence of EA in Group 4 was sixty-nine-fold higher than that of Group 1. The risk factor for EA was only the kind of medication. Preoperative anxiety had no significant correlation with EA. The incidence of EA after sevoflurane anesthesia is similar between ketamine and thiopental sodium anesthetic induction in children undergoing pediatric ophthalmic surgery. Also, the addition of a small dose of fentanyl after anesthetic induction decreases the incidence of EA.

Evaluation of the advantageous anesthetic properties of dexmedetomidine used as hypotensive agent compared with nitroglycerin in orthognathic surgery.

PubMed

Rummasak, Duangdee; Apipan, Benjamas

2014-12-01

To evaluate the advantageous anesthetic properties, such as the decrease of intraoperative analgesic requirement, time to extubation and recovery, and early postoperative pain, of dexmedetomidine used as hypotensive agent compared with nitroglycerin in orthognathic surgery. The authors implemented a prospective, single-blinded, randomized clinical trial. The sample was composed of healthy patients who were admitted for bimaxillary osteotomies and were assigned to 1 of 2 groups by a computer-generated random number and blinded to the group. Dexmedetomidine or nitroglycerin was used as the hypotensive drug for each group. All patients underwent hypotensive anesthesia and surgery according to standard protocol. Intraoperative amount of fentanyl, time to eye opening, time to follow basic verbal commands, time to extubation, early postoperative pain scores, and analgesics were recorded. Compared means were analyzed using the unpaired Student t test. A 2-sided statistical test was used. A P value less than .05 was considered significant. The sample was composed of 40 participants. The intraoperative fentanyl requirement was significantly lower in the dexmedetomidine group than in the nitroglycerin group (168.75±56.29 and 222.50±96.12 μg, respectively; P=.037). Times to eye opening and following commands were considerably longer in the dexmedetomidine group, but the time to extubation showed no meaningful difference. Early postoperative pain after 30 and 60 minutes and the requirement for meperidine were not meaningfully different between the 2 groups. Dexmedetomidine, used as a hypotensive drug, has anesthetic benefits compared with nitroglycerin. Dexmedetomidine decreases the intraoperative fentanyl requirement and does not meaningfully change the time to extubation, early postoperative pain, and analgesic drug requirement. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of anesthetics on the radiosensitivity of a murine tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheldon, P.W.; Chu, A.M.

The effect of four anesthetics on the single dose of x rays required to locally control 50% of implanted MT tumors was investigated. Compared with unanesthetized animals, no change in radiosensitivity was observed if mice were irradiated under either tribromoethanol or fentanyl-fluanisone-diazepam anesthesia. However, a small but significant degree of radioprotection was observed under chloral hydrate or pentobarbital anesthesia. Hypothermia or increased hypoxia are considered unlikely mechanisms for the protection, a direct chemical action being most probable. The preferred method for immobilizing the mice in order to locally irradiate the tumors was by simple physical restraint (with care taken tomore » minimize physiological stress). However, if anesthesia was a necessity, the present work suggests that for the MT tumor at least the nonprotecting tribromoethanol and fentanyl-fluanisone-diazepam are preferable to the protecting chloral hydrate and pentobarbital. Tribromoethanol is preferable to fetanyl-fluanisone-diazepam in that it produces a smaller drop in temperature. However, it is only a short-acting anesthetic, and prolongation of the state of anesthesia by repeated doses simply prolongs the temperature decline so that there may be no real benefit over fentanyl-fluanisone-diazepam.« less

An Efficient, Optimized Synthesis of Fentanyl and Related Analogs

DOE PAGES

Valdez, Carlos A.; Leif, Roald N.; Mayer, Brian P.; ...

2014-09-18

The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73–78%) along with their more commonly encountered hydrochloride and citric acid salts. In conclusion, the following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids.

An Efficient, Optimized Synthesis of Fentanyl and Related Analogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdez, Carlos A.; Leif, Roald N.; Mayer, Brian P.

The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73–78%) along with their more commonly encountered hydrochloride and citric acid salts. In conclusion, the following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids.

Sex Differences and the Effects of Stress on Subsequent Opioid Consumption in Adult Rats Following Adolescent Nicotine Exposure: A Psychopharmacologic Examination of the Gateway Hypothesis

DTIC Science & Technology

1997-07-18

sign of fentanyl addiction is death by drug overdose (David Hester, personal communication, 1996). The addiction and abuse liability offentanyl is high...rats, not exposed to stress, died of apparent fentanyl overdose . These two rats also had been exposed to 12 mg nicotinelkglday and died despite lower...nicotinelkglday) during adolescence was related to increased, subsequent fentanyl self-administration in non-stressed male rats. Exposure to immobilization stress

Comparison of simultaneous and sequential administration of fentanyl-propofol for surgical abortion: a randomized single-blinded controlled trial.

PubMed

Gao, Wei; Sha, Baoyong; Zhao, Yuan; Fan, Zhe; Liu, Lin; Shen, Xin

2017-08-01

Propofol lipid emulsion (PLE) is a nanosized sedative, and it is used with a combination of salted antalgic prodrug, fentanyl citrate (FC). To illustrate the synergistic effect of mixing, we compared the sedation/analgesia resulting from simultaneous and sequential administration in surgically induced abortion (No. ChiCTR-IPC-15006153). Simultaneous group showed lower bispectral index, blood pressure, and heart rate, when cannula was inserted into the uterus. It also showed less frequency of hypertension, sinus tachycardia, movement, pain at the injection site, and additional FC. Therefore, premixing of PLE and FC enhanced the sedation and analgesia; stabilized the hemodynamics; lessened the incidence of movement and injection pain; and reduced the requirement of drugs.

Analysis of Novel Synthetic Opioids U-47700, U-50488 and Furanyl Fentanyl by LC-MS/MS in Postmortem Casework.

PubMed

Mohr, Amanda L A; Friscia, Melissa; Papsun, Donna; Kacinko, Sherri L; Buzby, David; Logan, Barry K

2016-11-01

Following series of synthetic cannabinoid and synthetic cathinone derivatives, the illicit drug market has begun to see increased incidence of synthetic opioids including fentanyl and its derivatives, and other chemically unrelated opioid agonists including AH-7921 and MT-45. Among the most frequently encountered compounds in postmortem casework have been furanyl fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylfuran-2-carboxamide, Fu-F) and U-47700 (trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide). Both drugs have been reported to be present in the heroin supply and to be gaining popularity among recreational opioid users, but were initially developed by pharmaceutical companies in the 1970s as candidates for development as potential analgesic therapeutic agents. A method was developed and validated for the analysis of U-47700, U-50488 and furanyl fentanyl in blood specimens. A total of 20 postmortem cases, initially believed to be heroin or other opioid-related drug overdoses, were submitted for quantitative analysis. The analytical range for U-47770 and U-50488 was 1-500 and 1-100 ng/mL for furanyl fentanyl. The limit of detection was 0.5 ng/mL for all compounds. Within the scope of the method, U-47700 was the only confirmed drug in 11 of the cases, 5 cases were confirmed for both U-47700 and furanyl fentanyl, and 3 cases were confirmed only for furanyl fentanyl. The mean and median blood concentrations for U-47700 were 253 ng/mL (±150) and 247 ng/mL, respectively, range 17-490 ng/mL. The mean and median blood concentrations for furanyl fentanyl were 26 ng/mL (±28) and 12.9 ng/mL, respectively, range 2.5-76 ng/mL. Given the widespread geographical distribution and increase in prevalence in postmortem casework, toxicology testing should be expanded to include testing for "designer opioids" in cases with histories consistent with opioid overdose but with no traditional opioids present or insufficient quantities to account for death. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Data Overview: Overview of an Epidemic

MedlinePlus

... the Epidemic Commonly Used Terms Prescription Opioids Heroin Fentanyl Data Opioid Data Analysis Drug Overdose Death Data ... Overdose Data Heroin Overdose Data Synthetic Opioid Data Fentanyl Encounters Data Overdose Prevention Improve Opioid Prescribing Prevent ...

Bispectral index monitoring during infant cardiac surgery: relationship of BIS to the stress response and plasma fentanyl levels.

PubMed

Kussman, B D; Gruber, E M; Zurakowski, D; Hansen, D D; Sullivan, L J; Laussen, P C

2001-11-01

We evaluated the relationship of the bispectral index (BIS) to commonly used indices of depth of anaesthesia in 19 infants enrolled in a prospective study of the stress response to hypothermic cardiopulmonary bypass. Group 1 (n=8) received high-dose fentanyl by bolus technique; group 2 (n=6) received high-dose fentanyl by continuous infusion; and group 3 (n=5) received a fentanyl-midazolam infusion. Blood pressure (BP), heart rate (HR) and plasma epinephrine, norepinephrine, cortisol, ACTH, glucose, lactate and fentanyl were analysed 15 min postinduction, 15 min poststernotomy, 15 min on CPB during cooling and during skin closure. Mean BIS (SD) values for all 19 patients were 45.3 (12.3), 40.4 (14.5), 24.4 (12.4) and 47.9 (13.9), at the successive time points. No significant differences were observed in changes in BIS over time between the groups. A significant correlation was found 15 min postinduction between BIS and BP (systolic r=0.51, mean r=0.56) in all groups, but not between BIS and HR. BIS did not correlate with BP or HR at any other time point. There was no significant correlation between BIS and hormonal, biochemical or plasma fentanyl levels for any group at any time point. We were unable to demonstrate a relationship between the BIS and haemodynamic, metabolic or hormonal indices of anaesthetic depth. Further evaluation of the BIS algorithm is required in neonates and infants.

Identification of Chemical Attribution Signatures of Fentanyl Syntheses Using Multivariate Statistical Analysis of Orthogonal Analytical Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, B. P.; Mew, D. A.; DeHope, A.

Attribution of the origin of an illicit drug relies on identification of compounds indicative of its clandestine production and is a key component of many modern forensic investigations. The results of these studies can yield detailed information on method of manufacture, starting material source, and final product - all critical forensic evidence. In the present work, chemical attribution signatures (CAS) associated with the synthesis of the analgesic fentanyl, N-(1-phenylethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Six synthesis methods, all previously published fentanyl synthetic routes or hybrid versions thereof, were studied in an effort to identify and classify route-specific signatures. 160 distinct compounds and inorganicmore » species were identified using gas and liquid chromatographies combined with mass spectrometric methods (GC-MS and LCMS/ MS-TOF) in conjunction with inductively coupled plasma mass spectrometry (ICPMS). The complexity of the resultant data matrix urged the use of multivariate statistical analysis. Using partial least squares discriminant analysis (PLS-DA), 87 route-specific CAS were classified and a statistical model capable of predicting the method of fentanyl synthesis was validated and tested against CAS profiles from crude fentanyl products deposited and later extracted from two operationally relevant surfaces: stainless steel and vinyl tile. This work provides the most detailed fentanyl CAS investigation to date by using orthogonal mass spectral data to identify CAS of forensic significance for illicit drug detection, profiling, and attribution.« less

Effects of chronic fentanyl administration on physical performance of aged rats

PubMed Central

Mitzelfelt, Jeremiah D.; DuPree, Jameson P.; Seo, Dong-oh; Carter, Christy S.; Morgan, Drake

2010-01-01

There is growing concern over the increasing use of opioids to treat chronic pain in the elderly primarily because of the potential increased sensitivity to the adverse side effects. Here, we use a preclinical model (male Brown Norway X F344 rats aged 12, 18, 24, and 30 months) to describe the outcome of chronic fentanyl administration (1.0 mg/kg/day) on various physiological and behavioral measures. Continuous fentanyl administration resulted in an initial decrease in food consumption, followed by the development of tolerance to this effect over a 4-week period and a subsequent increase in food consumption during withdrawal. This change in food consumption was associated with decreases in body weight (predominantly due to a loss of fat mass) that was maintained through early withdrawal. After one month of withdrawal, only the 12-month old animals had fully regained body weight. Fentanyl administration resulted in a decrease in grip strength and an increase in locomotor activity that did not differ across age groups. There was no effect of fentanyl administration on rotarod performance. These results demonstrate that while there is a delayed recovery of body mass with age, the observed changes in behavioral responses are uniform across ages. PMID:20951790

[Evaluation of postoperative pain intensity after ear, nose, and throat surgery--the effect of intraoperative fentanyl use].

PubMed

Mizota, Toshiyuki; Suzuki, Haruyo; Daijo, Hiroki; Tanaka, Tomoharu; Fukuda, Kazuhiko

2014-11-01

This study was designed to determine postoperative pain levels after ear, nose, and throat (ENT) surgery, and also to examine whether intraoperative fentanyl use during ENT surgery enhances the quality of postoperative pain control. The distribution of pain scores and rescue analgesic requirements among 198 patients undergoing ENT surgery were examined. Multivariate logistic regression analysis was performed to identify independent factors associated with moderate to severe postoperative pain (maximal pain score ≥ 5 on the numerical rating scale) and postoperative nausea and vomiting (PONV). 27.8% of patients experienced moderate to severe postoperative pain after ENT surgery. The distribution of postoperative pain levels was similar among procedures performed on different anatomical regions. Intraoperative fentanyl use was not associated with moderate to severe postoperative pain (adjusted odds ratio (95% confidence interval) :1.03 (0.51-2.13))]. On the other hand, intraoperative fentanyl use was independently associated with PONV [3.10 (1.25-8.92); P = 0.0138]. Prevalence of moderate to severe postoperative pain after ENT surgery was approximately 28%. Intraoperative fentanyl use was not associated with a decreased incidence of moderate to severe postoperative pain, but was significantly associated with PONV.

[Analgesic effect of intra-artcular fentanyl in knee arthroscopy to treat patellofemoral lateral hyperpressure syndrome].

PubMed

Gutiérrez-Mendoza, Israel; Pérez-Correa, José J; Serna-Vela, Francisco; Góngora-Ortega, Javier; Vilchis-Huerta, Ventura; Pérez-Guzmán, Carlos; Hernández-Garduño, Eduardo; Vidal-Rodríguez, Francisco Alberto

2009-01-01

During arthroscopy for the treatment of patellofemoral lateral hyper-pressure syndrome (LHS), intra-articular morphine or its derivatives (fentanyl) may reduce postoperative pain when combined with anesthetics. We therefore decided to determine whether adding fentanyl to epinephrine and bupivacaine produced an increased analgesia. We randomly distributed 40 patients into two groups. The experimental group (n=20) was given 0.5% bupivacaine (2 mg/kg), epinephrine (100 microg) and fentanyl (2.5 microg/kg). The control group (n=20) received 0.5% bupivacaine (2 mg/kg) and epinephrine (100 microg). Patients underwent chondroplasty and retinacular release, and we assessed pain, time of analgesia and postoperative range of motion at postoperative hours 6 and 24. The age and the grade of patellofemoral chondromalacia (PFC) were similar in both groups (p > 0.05). No differences were found in pain and ranges of motion intraoperatively and at postoperative hours 6 and 24 (p > 0.05) between both groups. The postoperative analgesia time was similar (p > 0.05). Adding intra-articular fentanyl to the combination of epinephrine plus bupivacaine did not decrease pain, and did not increase neither the analgesia time nor the range of motion in patients with LHS undergoing knee arthroscopy.

77 FR 16262 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... Enforcement Administration (DEA) to be registered as an importer of Fentanyl (9801), a basic class of... import of Fentanyl (9801), the authorization for the import of this basic class of controlled substance...

[Effect of fentanyl on expression of mu-receptor and beta-arrestin 2 in periaqueductal gray of rats tolerant to morphine].

PubMed

Liu, Ruo-shan; Sun, Li; Liu, Xiao-yan; Li, Xuan-ying; Xu, Lei

2009-05-19

To investigate the effect of fentanyl upon the expression of mu-receptor and beta-arrestin 2 in peri-aqueductal gray of morphine-tolerant rats. Forty male SD rats weighing (230 +/- 20) g were randomly divided into 5 groups of eight animals each: group NS, group M, group MF1, group MF2 and group MF3. Rats in group NS received only subcutaneous normal saline 1 ml/kg twice a day for 9 consecutive days; group M received subcutaneous morphine 10 mg/kg followed by NS 1 ml/kg twice a day for 9 consecutive days; In groups MF1, MF2 and MF3, morphine 10 mg x kg(-1) was injected subcutaneously followed by fentanyl 3, 6, 12 microg/kg respectively. All animals were sacrificed at Day 9 after measurement of pain threshold. Periaqueductal gray was removed for determination of the expression of mRNA (RT-PCR) and protein (Western-blot) of mu-receptor and beta-arrestin 2. Compared with group NS, TFL of group M was significantly elevated after the first morphine injection (P < 0.01). But TFL of group M returned to the baseline value after chronic morphine treatment. Compared with group M, TFL increased in groups MF2 and MF3 at Days 7 and 9 (P < 0.05 or 0.01). However, TFL of group MF1 was negative (P > 0.05). The expression of mu-receptor mRNA and protein was significantly lower in group M than in group NS (P < 0.01). Compared with group M, the expressions of mu-receptor mRNA and protein were significantly elevated in group MF2 and MF3 (P < 0.05 or 0.01) but there was no significant change in group MF1 (P > 0.05). The expression of beta-arrestin 2 mRNA and protein significantly decreased in group M as compared with group NS (P < 0.01). Compared with group M, the expressions of beta-arrestin 2 mRNA and protein were significantly elevated in group MF2 and MF3 (P < 0.05 or 0.01), but there was no significant change in group MF1 (P > 0.05). Fentanyl at 6 and 12 microg/kg can partly inhibit morphine tolerance through an increased expression of mu-receptor and beta-arrestin 2 in periaqueductal gray of morphine-tolerant rats.

Fatal Fentanyl: One Pill Can Kill.

PubMed

Sutter, Mark E; Gerona, Roy R; Davis, M Thais; Roche, Bailey M; Colby, Daniel K; Chenoweth, James A; Adams, Axel J; Owen, Kelly P; Ford, Jonathan B; Black, Hugh B; Albertson, Timothy E

2017-01-01

The current national opioid epidemic is a public health emergency. We have identified an outbreak of exaggerated opioid toxicity caused by fentanyl adulterated tablets purchased on the street as hydrocodone/acetaminophen. Over an 8-day period in late March 2016, a total of 18 patients presented to our institution with exaggerated opioid toxicity. The patients provided a similar history: ingesting their "normal dose" of hydrocodone/acetaminophen tablets but with more pronounced symptoms. Toxicology testing and analysis was performed on serum, urine, and surrendered pills. One of the 18 patients died in hospital. Five patients underwent cardiopulmonary resuscitation, one required extracorporeal life support, three required intubation, and two received bag-valve-mask ventilation. One patient had recurrence of toxicity after 8 hours after naloxone discontinuation. Seventeen of 18 patients required boluses of naloxone, and four required prolonged naloxone infusions (26-39 hours). All 18 patients tested positive for fentanyl in the serum. Quantitative assays conducted in 13 of the sera revealed fentanyl concentrations of 7.9 to 162 ng/mL (mean = 52.9 ng/mL). Pill analysis revealed fentanyl amounts of 600-6,900 μg/pill. The pills are virtually indistinguishable from authentic hydrocodone/acetaminophen tablets and are similar in weight. To date, our county has reported 56 cases of fentanyl opioid toxicity, with 15 fatalities. In our institution, the outbreak has stressed the capabilities and resources of the emergency department and intensive care units. A serious outbreak of exaggerated opioid toxicity caused by fentanyl-adulterated tablets purchased on the street as hydrocodone/acetaminophen is under way in California. These patients required higher dosing and prolonged infusions of naloxone. Additionally, observation periods off naloxone were extended due to delayed, recurrent toxicity. The outbreak has serious ramifications for public health and safety, law enforcement, and healthcare facilities and resources. © 2016 by the Society for Academic Emergency Medicine.

Effects of fentanyl administration before induction of anesthesia and placement of the Laryngeal Mask Airway: a randomized, placebo-controlled trial.

PubMed

Joshi, Girish P; Kamali, Amin; Meng, Jin; Rosero, Eric; Gasanova, Irina

2014-03-01

To assess the effects of fentanyl administered before induction of anesthesia on movement and airway responses during desflurane anesthesia via the Laryngeal Mask Airway (LMA). Randomized, double-blinded, controlled trial. Tertiary-care academic center. 100 adult, ASA physical status 1, 2, and 3 patients undergoing ambulatory surgery. Patients were administered fentanyl 1 μg/kg (n=51) or saline (n=49) 3 to 5 minutes before induction with propofol 2-2.5 mg/kg intravenously (IV), followed by LMA placement. Anesthesia was maintained with desflurane titrated to a bispectral index (BIS) of 50-60 and 50% nitrous oxide in oxygen, and fentanyl 25 μg boluses were titrated to respiratory rate. Apnea occurrence and duration of manual ventilation, as well as frequency and severity of movement, coughing, breath holding, and laryngospasm were recorded. Two patients in each group were excluded from analysis. The fentanyl pretreatment group had a higher frequency of apnea (94% vs 64%; P=0.0003) and longer duration of manual ventilation (3 [interquartile range (IQR), 1.5-5] min vs 1 [0-1.5] min; P<0.0001) at induction. In contrast, the fentanyl pretreatment group had a lower frequency of movements (16% vs 51%;P=0.0001). The rates of intraoperative breath holding (6.1% vs 8.5%) and laryngospasm (2% vs 4.3%) in the two groups were similar. All subjects experiencing laryngospasm were smokers. Adjusting for smoking status did not affect the differences noted in apnea, duration of manual ventilation, or movement between groups; however, coughing occurrence was statistically higher in the placebo group (P=0.043). Preinduction fentanyl increased the frequency of apnea at induction and duration of manual ventilation, but reduced the frequency of movements. In addition, it reduced intraoperative coughing in smokers. Copyright © 2014 Elsevier Inc. All rights reserved.

The use of a battery of pain models to detect analgesic properties of compounds: a two‐part four‐way crossover study

PubMed Central

Okkerse, Pieter; van Amerongen, Guido; de Kam, Marieke L.; Stevens, Jasper; Butt, Richard P.; Gurrell, Rachel; Dahan, Albert; van Gerven, Joop M.; Hay, Justin L.

2017-01-01

Aim The aim was to investigate the ability of a battery of pain models to detect analgesic properties of commonly used analgesics in healthy subjects. Methods The battery consisted of tests eliciting electrical, mechanical and thermal (contact heat and cold pressor)‐pain and included a UVB model, the thermal grill illusion and a paradigm of conditioned pain modulation. Subjects were administered fentanyl 3 μg kg–1, phenytoin 300 mg, (S)‐ketamine 10 mg and placebo (part I), or imipramine 100 mg, pregabalin 300 mg, ibuprofen 600 mg and placebo (part II). Pain measurements were performed at baseline and up to 10 h post‐dose. Endpoints were analysed using a mixed model analysis of variance. Results Sixteen subjects (8 female) completed each part. The pain tolerance threshold (PTT) for electrical stimulation was increased (all P < 0.05) compared to placebo for (S)‐ketamine (+10.1%), phenytoin (+8.5%) and pregabalin (+10.8%). The PTT for mechanical pain was increased by pregabalin (+14.1%). The cold pressor PTT was increased by fentanyl (+17.1%) and pregabalin (+46.4%). Normal skin heat pain detection threshold was increased by (S)‐ketamine (+3.3%), fentanyl (+2.8%) and pregabalin (+4.1%). UVB treated skin pain detection threshold was increased by fentanyl (+2.6%) and ibuprofen (+4.0%). No differences in conditioned pain modulation were observed. Conclusion This study shows that these pain models are able to detect changes in pain thresholds after administration of different classes of analgesics in healthy subjects. The analgesic compounds all showed a unique profile in their effects on the pain tasks administered. PMID:27862179

The use of a battery of pain models to detect analgesic properties of compounds: a two-part four-way crossover study.

PubMed

Okkerse, Pieter; van Amerongen, Guido; de Kam, Marieke L; Stevens, Jasper; Butt, Richard P; Gurrell, Rachel; Dahan, Albert; van Gerven, Joop M; Hay, Justin L; Groeneveld, Geert Jan

2017-05-01

The aim was to investigate the ability of a battery of pain models to detect analgesic properties of commonly used analgesics in healthy subjects. The battery consisted of tests eliciting electrical, mechanical and thermal (contact heat and cold pressor)-pain and included a UVB model, the thermal grill illusion and a paradigm of conditioned pain modulation. Subjects were administered fentanyl 3 μg kg -1 , phenytoin 300 mg, (S)-ketamine 10 mg and placebo (part I), or imipramine 100 mg, pregabalin 300 mg, ibuprofen 600 mg and placebo (part II). Pain measurements were performed at baseline and up to 10 h post-dose. Endpoints were analysed using a mixed model analysis of variance. Sixteen subjects (8 female) completed each part. The pain tolerance threshold (PTT) for electrical stimulation was increased (all P < 0.05) compared to placebo for (S)-ketamine (+10.1%), phenytoin (+8.5%) and pregabalin (+10.8%). The PTT for mechanical pain was increased by pregabalin (+14.1%). The cold pressor PTT was increased by fentanyl (+17.1%) and pregabalin (+46.4%). Normal skin heat pain detection threshold was increased by (S)-ketamine (+3.3%), fentanyl (+2.8%) and pregabalin (+4.1%). UVB treated skin pain detection threshold was increased by fentanyl (+2.6%) and ibuprofen (+4.0%). No differences in conditioned pain modulation were observed. This study shows that these pain models are able to detect changes in pain thresholds after administration of different classes of analgesics in healthy subjects. The analgesic compounds all showed a unique profile in their effects on the pain tasks administered. © 2016 The British Pharmacological Society.

Fatality due to fentanyl-cocaine intoxication resulting in a fall.

PubMed

Ferrara, S D; Snenghi, R; Tedeschi, L

1994-01-01

This is the first report of fatal intoxication by fentanyl and cocaine outside the USA. The case involved a fall caused by toxic psychosis. The circumstantial, clinical, anatomical, histopathological and toxicological frame-work is interpreted.

Chemical anesthesia of Northern sea otters (Enhydra lutris): Results of past field studies

USGS Publications Warehouse

Monson, Daniel H.; McCormick, C.; Ballachey, Brenda E.

2001-01-01

Between 1987 and 1997, we chemically immobilized 597 wild sea otters (Enhydra lutris) in Alaska for the collection of biological samples or for surgical instrumentation. One drug-related sea otter fatality occurred during this time. Fentanyl in combination with diazepam produced consistent, smooth inductions with minimal need for supplemental anesthetics during procedures lasting 30-40 min. Antagonism with naltrexone or naloxone was rapid and complete, although we observed narcotic recycling in sea otters treated with naloxone. For surgical procedures, we recommend a fentanyl target dose of 0.33 mg/kg of body mass and diazepam at 0.11 mg/kg. For nonsurgical biological sample collection procedures, we recommend fentanyl at 0.22 mg/kg and diazepam at 0.07 mg/kg. We advise the use of the opioid antagonist naltrexone at a ratio of 2:1 to the total fentanyl administered during processing.

Peripheral opioid analgesia in teeth with symptomatic inflamed pulps.

PubMed Central

Uhle, R. A.; Reader, A.; Nist, R.; Weaver, J.; Beck, M.; Meyers, W. J.

1997-01-01

The purpose of this study was to investigate the ability of low-dose fentanyl to produce analgesia when administered via the periodontal ligament injection in teeth with symptomatic, inflamed pulps. All subjects presented for emergency treatment with moderate to severe pain and had a posterior tooth with a clinical diagnosis of irreversible pulpitis. Twenty subjects randomly received either 10 micrograms fentanyl citrate or saline placebo via the periodontal ligament injection in a double-blind manner. The subjects rated their pain prior to injection and rated pain intensity and pain half gone for 59 min postinjection. Low-dose fentanyl delivered via the periodontal ligament injection in inflamed teeth provided significantly greater analgesia than the saline placebo (P < 0.05). Since the dose of fentanyl used was less than the dose required to provide analgesia by a central mechanism, the results of this study may be consistent with a peripheral opioid mechanism of action. PMID:9481968

Opioid Deaths in Milwaukee County, Wisconsin 2013-2017: The Primacy of Heroin and Fentanyl.

PubMed

Peterson, Brian L; Schreiber, Sara; Fumo, Nicole; Brooke Lerner, E

2018-04-23

Heroin and fentanyl are the overwhelming and increasing cause of opioid deaths in Milwaukee County, Wisconsin. We reviewed all drug and opioid deaths from 2013 to 2017 to delineate the specific opioid drugs involved and changes in their incidence. From 2013 to 2017, 980 deaths were due to opioids, rising from 184 in 2013 to 337 in 2017. In 2017, opioid deaths exceeded combined non-natural deaths from homicide and suicide. Illicit heroin and fentanyl/analogs caused 84% of opioid deaths and 80% of drug deaths, with no increase in deaths due to oral prescription drugs such as oxycodone and hydrocodone. Any approach to decreasing this dramatic increase in opioid deaths should first focus on interdicting the supply and cheap availability of these illicit opioids. Fentanyl and its analogs represent the most deadly opioids and the greatest threat to human life in our population. © 2018 American Academy of Forensic Sciences.

Comparison of propofol with pentobarbital/midazolam/fentanyl sedation for magnetic resonance imaging of the brain in children.

PubMed

Pershad, Jay; Wan, Jim; Anghelescu, Doralina L

2007-09-01

Propofol and pentobarbital, alone or combined with other agents, are frequently used to induce deep sedation in children for MRI. However, we are unaware of a previous comparison of these 2 agents as part of a randomized, controlled trial. We compared the recovery time of children after deep sedation with single-agent propofol with a pentobarbital-based regimen for MRI and considered additional variables of safety and efficacy. This prospective, randomized trial at a tertiary children's hospital enrolled 60 patients 1 to 17 years old who required intravenous sedation for elective cranial MRI. Patients were assigned randomly to receive a loading dose of propofol followed by continuous intravenous infusion of propofol or to receive sequential doses of midazolam, pentobarbital, and fentanyl until a modified Ramsay score of >4 was attained. A nurse who was blind to group assignment assessed discharge readiness (Aldrete score > 8) and administered a follow-up questionnaire. We compared recovery time, time to induction of sedation, total sedation time, quality of imaging, number of repeat-image sequences, adverse events, caregiver satisfaction, and time to return to presedation functional status. The groups were similar in age, gender, race, American Society of Anesthesiology physical status class, and frequency of cognitive impairment. No sedation failure or significant adverse events were observed. Propofol offered significantly shorter sedation induction time, recovery time, total sedation time, and time to return to baseline functional status. Caregiver satisfaction scores were also significantly higher in the patients in the propofol group. Propofol permits faster onset and recovery than, and comparable efficacy to, a pentobarbital/midazolam/fentanyl regimen for sedation of children for MRI.

Propofol-fentanyl anaesthesia at high altitude: anaesthetic requirements and haemodynamic variations when compared with anaesthesia at low altitude.

PubMed

Puri, G D; Jayant, A; Dorje, M; Tashi, M

2008-03-01

There are few published accounts of anaesthesia delivery at high altitude. Natives at high altitude are known to have altered cardiorespiratory reserve. This study seeks to demonstrate the safety of propofol-fentanyl anaesthesia at high altitude titrated to the bispectral index (BIS) (3505 metres above sea level) in native highlanders. It also shows the differential effects of anaesthesia and surgery on the haemodynamics of such individuals as compared with individuals living at low altitude. Fifteen consenting adults scheduled to undergo general surgical/orthopaedic procedures under general anaesthesia using fentanyl, and propofol infusions titrated to the BIS along with nitrous oxide in oxygen after intubation, were recruited in the high-altitude arm. Their anaesthesia record was compared with retrospective data from low altitude with respect to anaesthetic requirements, recovery after anaesthesia and the haemodynamic responses to surgical stress. The high-altitude dwellers required significantly larger doses of propofol at anaesthetic induction (2.31+/-0.64 vs. 1.41+/-0.24 mg/kg, P<0.0001) and thereafter to maintain designated BIS than their low-altitude counterparts (6.22+/-1.14 vs. 4.61+/-1.29 mg/kg/h, P<0.01). They, however, had uneventful and short recovery times. The high-altitude population also had significantly lower baseline heart rates (72+/-9.83 vs. 88+/-12.1, P<0.04) as also the heart rate responses to noxious stimulation such as direct laryngoscopy or skin incision (P<0.04, P<0.005, respectively). High-altitude dwellers require significantly larger amounts of intravenous anaesthetic propofol. Heart rate at rest as also the heart rate responses to surgical stress were significantly attenuated at high altitude.

Midazolam as an active placebo in 3 fentanyl-validated nociceptive pain models.

PubMed

Prosenz, Julian; Gustorff, Burkhard

2017-07-01

The use of inactive placebos in early translational trials of potentially analgesic compounds is discouraged because of the side-effect profiles of centrally acting analgesics. Therefore, benzodiazepines are used, although their use has not been validated in this context. Whether benzodiazepines confound the results of acute pain tests is unknown. Midazolam (0.06 mg/kg) as an active placebo was investigated in 3 nociceptive models that included contact heat, electrical pain, and pressure pain thresholds in 24 healthy volunteers. Fentanyl (1 μg/kg) served as an internal validator in this randomized, placebo (saline) controlled, 3-way cross-over trial. The primary outcome parameter (contact heat pain) was analyzed using a one-way, repeated measures analysis of variance and Tukey's post test. Midazolam did not reduce pain ([numeric rating scale], 0-100) in a statistically significant manner compared with placebo for the contact heat (mean difference -1.7, 95% confidence interval -10.6 to 7.3; P = 0.89) or electrical pain (4.3, -5.1 to 13.7; P = 0.51) test, nor did it raise the pressure pain thresholds (-28 kPa, -122; 64 kPa, P = 0.73). The width of the confidence intervals suggested that there were no clinically meaningful analgesic effects compared with the placebo. In contrast, the analgesic efficacy of fentanyl was effectively demonstrated in all 3 models (P < 0.01 vs midazolam and placebo). The findings of this study show that midazolam can be used as an active placebo in analgesic drug trials. Furthermore, the proposed models were simple to implement and very effective in detecting analgesia. The test battery can be used in translational trials for new compounds and comes with an active placebo and an optional active comparator.

Chemical Attribution of Fentanyl Using Multivariate Statistical Analysis of Orthogonal Mass Spectral Data

DOE PAGES

Mayer, Brian P.; DeHope, Alan J.; Mew, Daniel A.; ...

2016-03-24

Attribution of the origin of an illicit drug relies on identification of compounds indicative of its clandestine production and is a key component of many modern forensic investigations. Here, the results of these studies can yield detailed information on method of manufacture, starting material source, and final product, all critical forensic evidence. In the present work, chemical attribution signatures (CAS) associated with the synthesis of the analgesic fentanyl, N-(1-phenylethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Six synthesis methods, all previously published fentanyl synthetic routes or hybrid versions thereof, were studied in an effort to identify and classify route-specific signatures. A total of 160 distinctmore » compounds and inorganic species were identified using gas and liquid chromatographies combined with mass spectrometric methods (gas chromatography/mass spectrometry (GC/MS) and liquid chromatography–tandem mass spectrometry-time of-flight (LC–MS/MS-TOF)) in conjunction with inductively coupled plasma mass spectrometry (ICPMS). The complexity of the resultant data matrix urged the use of multivariate statistical analysis. Using partial least-squares-discriminant analysis (PLS-DA), 87 route-specific CAS were classified and a statistical model capable of predicting the method of fentanyl synthesis was validated and tested against CAS profiles from crude fentanyl products deposited and later extracted from two operationally relevant surfaces: stainless steel and vinyl tile. Finally, this work provides the most detailed fentanyl CAS investigation to date by using orthogonal mass spectral data to identify CAS of forensic significance for illicit drug detection, profiling, and attribution.« less

Fentanyl, but not haloperidol, entrains persisting circadian activity episodes when administered at 24- and 31-hour intervals

PubMed Central

Leffel, Joseph K.; Kosobud, Ann E; Timberlake, William

2009-01-01

Administration of several drugs of abuse on a 24-hour schedule has been shown to entrain both pre-drug (anticipatory) and post-drug (evoked) circadian activity episodes that persist for several days when the drug is withheld. The present tested the entrainment effects of fentanyl, an opioid agonist with a noted abuse liability, and haloperidol, an antipsychotic dopamine antagonist without apparent abuse liability. Adult female Sprague-Dawley rats housed under constant light in cages with attached running wheels received repeated low, medium, or high doses of either fentanyl or haloperidol on a 24-hour administration schedule followed by a 31-hour schedule (Experiment 1) or solely on a 31-hour schedule (Experiment 2). The results showed that all three doses of fentanyl entrained both pre-drug and post-drug episodes of wheel running when administered every 24░hours, and the combined pre- and post-fentanyl activity episodes persist for at least 3 days when the drug is withheld during test days. On the 31-hour schedule, fentanyl produced an ``ensuing" activity episode approximately 24░hours post-administration, but failed to produce an anticipatory episode 29–31░hours post-administration. In contrast, haloperidol injections failed to produce both pre-drug episodes on the 24-hour schedule and circadian ensuing episodes on the 31-hour schedule, and post-haloperidol suppression of activity appeared to mask the freerunning activity rhythm. Taken together, these results provide additional evidence that drugs of abuse share a common ability to entrain circadian activity episodes. PMID:19595707

Chemical Attribution of Fentanyl Using Multivariate Statistical Analysis of Orthogonal Mass Spectral Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, Brian P.; DeHope, Alan J.; Mew, Daniel A.

Attribution of the origin of an illicit drug relies on identification of compounds indicative of its clandestine production and is a key component of many modern forensic investigations. Here, the results of these studies can yield detailed information on method of manufacture, starting material source, and final product, all critical forensic evidence. In the present work, chemical attribution signatures (CAS) associated with the synthesis of the analgesic fentanyl, N-(1-phenylethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Six synthesis methods, all previously published fentanyl synthetic routes or hybrid versions thereof, were studied in an effort to identify and classify route-specific signatures. A total of 160 distinctmore » compounds and inorganic species were identified using gas and liquid chromatographies combined with mass spectrometric methods (gas chromatography/mass spectrometry (GC/MS) and liquid chromatography–tandem mass spectrometry-time of-flight (LC–MS/MS-TOF)) in conjunction with inductively coupled plasma mass spectrometry (ICPMS). The complexity of the resultant data matrix urged the use of multivariate statistical analysis. Using partial least-squares-discriminant analysis (PLS-DA), 87 route-specific CAS were classified and a statistical model capable of predicting the method of fentanyl synthesis was validated and tested against CAS profiles from crude fentanyl products deposited and later extracted from two operationally relevant surfaces: stainless steel and vinyl tile. Finally, this work provides the most detailed fentanyl CAS investigation to date by using orthogonal mass spectral data to identify CAS of forensic significance for illicit drug detection, profiling, and attribution.« less

Misuse of Novel Synthetic Opioids: A Deadly New Trend

PubMed Central

Prekupec, Matthew P.; Mansky, Peter A.; Baumann, Michael H.

2017-01-01

Novel synthetic opioids (NSOs) include various analogs of fentanyl and newly emerging non-fentanyl compounds. Together with illicitly manufactured fentanyl (IMF), these drugs have caused a recent spike in overdose deaths, whereas deaths from prescription opioids have stabilized. NSOs are used as stand-alone products, as adulterants in heroin, or as constituents of counterfeit prescription medications. During 2015 alone, there were 9580 deaths from synthetic opioids other than methadone. Most of these fatalities were associated with IMF rather than diverted pharmaceutical fentanyl. In opioid overdose cases, where the presence of fentanyl analogs was examined, analogs were implicated in 17% of fatalities. Recent data from law enforcement sources show increasing confiscation of acetylfentanyl, butyrylfentanyl, and furanylfentanyl, in addition to non-fentanyl compounds such as U-47700. Since 2013, deaths from NSOs in the United States were 52 for acetylfentanyl, 40 for butyrylfentanyl, 128 for furanylfentanyl, and 46 for U-47700. All of these substances induce a classic opioid toxidrome, which can be reversed with the competitive antagonist naloxone. However, due to the putative high potency of NSOs and their growing prevalence, it is recommended to forgo the 0.4 mg initial dose of naloxone and start with 2 mg. Because NSOs offer enormous profit potential, and there is strong demand for their use, these drugs are being trafficked by organized crime. NSOs present major challenges for medical professionals, law enforcement agencies, and policymakers. Resources must be distributed equitably to enhance harm reduction though public education, medication-assisted therapies, and improved access to naloxone. PMID:28590391

77 FR 31388 - Importer of Controlled Substances; Notice of Registration; Capricorn Pharma, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... importer of Fentanyl (9801), a basic class of controlled substance listed in schedule II. The company plans... manufactured FDF to foreign markets. In reference to the import of Fentanyl (9801), the authorization for the...

Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids

PubMed Central

Gorlin, Andrew W; Rosenfeld, David M; Maloney, Jillian; Wie, Christopher S; McGarvey, Johnathan; Trentman, Terrence L

2016-01-01

The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted. PMID:27703394

Postoperative pain medication requirements in patients undergoing computer-assisted (“Robotic”) and standard laparoscopic procedures for newly diagnosed endometrial cancer.

PubMed

Leitao, Mario M; Malhotra, Vivek; Briscoe, Gabriel; Suidan, Rudy; Dholakiya, Priyal; Santos, Kevin; Jewell, Elizabeth L; Brown, Carol L; Sonoda, Yukio; Abu-Rustum, Nadeem R; Barakat, Richard R; Gardner, Ginger J

2013-10-01

Laparoscopy (LSC) offers superior patient outcomes compared to laparotomy. Small retrospective/prospective series have suggested robotics offers further reduction in postoperative pain and pain medication use compared to standard LSC. Our objective was to compare postoperative pain in patients undergoing robotically assisted (RBT) versus standard LSC for newly diagnosed endometrial cancer. All preoperative endometrial cancer cases scheduled for RBT and LSC from May 1, 2007 to June 9, 2010 were identified. For this analysis, we only included cases not requiring conversion to laparotomy. All patients were offered intravenous (IV) patient-controlled analgesia (PCA) postoperatively. Intraoperative equivalent fentanyl doses (IEFDs) and pain scores in the postanesthesia care unit (PACU) were assessed. IV PCA was used in 206 RBTs (86 %) and 208 LSCs (88 %). Median IEFD was 425 μg for LSCs and 500 μg for RBTs (P = 0.03). Median pain scores on PACU arrival were similar in both groups. Median highest pain score was 5 for LSCs and 4 for RBTs (P = 0.007). Linear regression demonstrated that the IEFD was not correlated with the highest pain score (R = 0.09; P = 0.07). Fentanyl was used postoperatively in 196 of 206 RBTs (95 %) and 187 of 208 LSCs (90 %). The total fentanyl doses were 242.5 (range 0-2705) μg and 380 (range 0-2625) μg, respectively (P < 0.001). The median hourly fentanyl doses were 16.7 (range 0-122.5) μg and 23.5 (range 0-132.4) μg, respectively (P = 0.005). Simultaneous multiple regression analysis further demonstrated RBT was independently associated with a lower total fentanyl dose compared to LSC (P = 0.02). RBT is independently associated with significantly lower postoperative pain and pain medication requirements compared to LSC. The amount of intraoperative fentanyl analgesia does not appear to correlate with postoperative pain.Endometrial cancer is the most common gynecologic malignancy in the United States, with an estimated 47,130 new cases in 2012.1 An estimated 287,100 women were diagnosed with endometrial cancer worldwide in 2008.2 Surgery is the primary treatment of choice for the majority of these women.3 The standard surgical approach has been total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging via laparotomy. Multiple retrospective series have shown that a less invasive surgical approach via laparoscopy (LSC) is feasible and safe, and also associated with improved perioperative outcomes compared to laparotomy in these patients.4 The Gynecologic Oncology Group (GOG) published results of the largest randomized trial (LAP2) comparing LSC to laparotomy in patients with newly diagnosed endometrial carcinoma in 2009.5,6 This landmark study essentially changed the accepted standard surgical approach in this group. Postoperative complications, median blood loss, and median length of stay (LOS), despite increased operative time, were significantly lower in LSC patients despite 25 % requiring conversion to laparotomy.5 The first 802 eligible patients randomized in LAP2 also participated in a quality-of-life (QOL) study. Within 6 weeks of surgery, patients assigned to LSC reported significantly better QOL on all scales other than fear of recurrence.6 Overall, during this 6-week postoperative period, patients assigned to LSC had superior QOL, fewer physical symptoms, less pain and pain-related interference with functioning, better physical functioning and emotional state, earlier resumption of normal activities, earlier return to work, and better body image compared to those assigned to laparotomy.6 Recurrence-free and overall survivals were the same in both groups.7 Multiple published retrospective series have shown possible benefits, such as reduced postoperative pain, using the robotic (RBT) platform compared to LSC or laparotomy in patients with endometrial cancer.8-11 In a randomized trial, LSC was found to be associated with less postoperative pain compared to vaginal approaches in patients undergoing hysterectomy for benign gynecologic disease.12 A small retrospective series reported further reductions in postoperative pain in patients who had undergone an RBT hysterectomy compared to a standard total LSC hysterectomy for benign indications.13 A recent cost analysis suggested that patients experienced less pain and required less pain medication use after RBT procedures compared to LSC for endometrial cancer.14 Based on these reports, we sought to analyze postoperative pain and the use of pain medication in patients undergoing RBT compared to standard transperitoneal LSC procedures for newly diagnosed endometrial cancer during a concurrent time period. Of note, current RBT surgery is not truly robotic in that it is not autonomous. A more appropriate term is “computer-assisted surgery,” but to satisfy current convention, we refer to it as “robotic surgery” in this manuscript.

Computational design of environmental sensors for the potent opioid fentanyl

DOE PAGES

Bick, Matthew J.; Greisen, Per J.; Morey, Kevin J.; ...

2017-09-19

Here, we describe the computational design of proteins that bind the potent analgesic fentanyl. Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds, followed by design of the surrounding residues to optimize binding affinity. Co-crystal structures of the highest affinity binder reveal a highly preorganized binding site, and an overall architecture and ligand placement in close agreement with the design model. We also use the designs to generate plant sensors for fentanyl by coupling ligand binding to design stability. The method should be generally useful for detecting toxic hydrophobic compounds in the environment.

Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications

PubMed Central

Vardanyan, Ruben S; Hruby, Victor J

2014-01-01

Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure–biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed. PMID:24635521

Computational design of environmental sensors for the potent opioid fentanyl

PubMed Central

Morey, Kevin J; Antunes, Mauricio S; La, David; Sankaran, Banumathi; Reymond, Luc; Johnsson, Kai; Medford, June I

2017-01-01

We describe the computational design of proteins that bind the potent analgesic fentanyl. Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds, followed by design of the surrounding residues to optimize binding affinity. Co-crystal structures of the highest affinity binder reveal a highly preorganized binding site, and an overall architecture and ligand placement in close agreement with the design model. We use the designs to generate plant sensors for fentanyl by coupling ligand binding to design stability. The method should be generally useful for detecting toxic hydrophobic compounds in the environment. PMID:28925919

Computational design of environmental sensors for the potent opioid fentanyl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bick, Matthew J.; Greisen, Per J.; Morey, Kevin J.

Here, we describe the computational design of proteins that bind the potent analgesic fentanyl. Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds, followed by design of the surrounding residues to optimize binding affinity. Co-crystal structures of the highest affinity binder reveal a highly preorganized binding site, and an overall architecture and ligand placement in close agreement with the design model. We also use the designs to generate plant sensors for fentanyl by coupling ligand binding to design stability. The method should be generally useful for detecting toxic hydrophobic compounds in the environment.

Postoperative analgesia in children when using clonidine in addition to fentanyl with bupivacaine given caudally.

PubMed

Jarraya, Anouar; Elleuch, Sahar; Zouari, Jawhar; Smaoui, Mohamed; Laabidi, Sofiene; Kolsi, Kamel

2016-01-01

The aim of the study was to evaluate the efficacy of clonidine in association with fentanyl as an additive to bupivacaine 0.25% given via single shot caudal epidural in pediatric patients for postoperative pain relief. In the present prospective randomized double blind study, 40 children of ASA-I-II aged 1-5 years scheduled for infraumblical surgical procedures were randomly allocated to two groups to receive either bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg and clonidine 1μg/kg (group I) or bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg (group II). Caudal block was performed after the induction of general anesthesia. Postoperatively patients were observed for analgesia, sedation, hemodynamic parameters, and side effects or complications. Both the groups were similar with respect to patient and various block characteristics. Heart rate and blood pressure were not different in 2 groups. Significantly prolonged duration of post-operative analgesia was observed in group I (P<0.05). Side effects such as respiratory depression, vomiting and bradycardia were similar in both groups. The adjunction of clonidine to fentanyl as additives to bupivacaine in single shot caudal epidural in children may provide better and longer analgesia after infraumblical surgical procedures.

Pharmacokinetics of fentanyl in patients undergoing abdominal aortic surgery.

PubMed

Hudson, R J; Thomson, I R; Cannon, J E; Friesen, R M; Meatherall, R C

1986-03-01

The authors determined the pharmacokinetics of fentanyl 100 micrograms X kg-1 iv in patients undergoing elective abdominal aortic surgery. The mean (+/- SD) age of the ten patients was 67.2 +/- 8.7 yr; their mean weight was 78.5 +/- 13.7 kg. Seven patients had aortic aneurysm repair, and the other three patients had aortobifemoral grafts. Serum fentanyl concentrations were determined from samples drawn at increasing intervals over a 24-h period. A three-compartment pharmacokinetic model was fit to the concentration versus time data. Total drug clearance was 9.8 +/- 1.8 ml X min-1 X kg-1. The volume of distribution at steady-state (Vdss) was 5.4 +/- 1.9 X 1 kg-1. Elimination half-time was 8.7 +/- 2.5 h. There were no significant correlations between these pharmacokinetic parameters and patient's age, duration of aortic cross-clamping, duration of surgery, intraoperative blood loss, or volume of iv fluids given intraoperatively. In healthy volunteers or patients undergoing general surgery, other investigators report mean elimination half-times for fentanyl ranging from 1.7 to 4.4 h. The prolonged elimination half-time in patients having abdominal aortic surgery has important clinical implications. In particular, recovery from large doses will take much longer than would have been anticipated from previously published fentanyl pharmacokinetic data.

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats

PubMed Central

Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang

2018-01-01

BACKGROUND: Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. METHODS: Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1–7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. RESULTS: Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1–4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord. The combination of fentanyl and incision resulted in higher increase of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG. CONCLUSIONS: The surgical plantar incision with or without perioperative fentanyl induced significant mechanical and thermal hyperalgesia, an increased expression of IL-1β, IL-6, TNF-α in the spinal cord and DRG, and activation of microglia in the spinal cord. PMID:29135586

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

PubMed

Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

2018-01-01

Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord. The combination of fentanyl and incision resulted in higher increase of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG. The surgical plantar incision with or without perioperative fentanyl induced significant mechanical and thermal hyperalgesia, an increased expression of IL-1β, IL-6, TNF-α in the spinal cord and DRG, and activation of microglia in the spinal cord.

Intramuscular Fentanyl and Ketorolac Associated with Superior Pain Control After Pediatric Bilateral Myringotomy and Tube Placement Surgery: A Retrospective Cohort Study.

PubMed

Stricker, Paul A; Muhly, Wallis T; Jantzen, Ellen C; Li, Yue; Jawad, Abbas F; Long, Alexander S; Polansky, Marcia; Cook-Sather, Scott D

2017-01-01

Bilateral myringotomy and pressure equalization tube insertion (BMT) is the most common surgery in children. Multiple anesthetic techniques for BMT have been proposed, but that which reliably promotes ideal recovery remains unclear. We sought to assess associations between anesthetic regimens that included single-agent (fentanyl or ketorolac) or dual-agent (fentanyl and ketorolac) analgesic therapy and the primary outcome of maximal postanesthesia care unit (PACU) pain score. Secondary outcomes included in-hospital rescue analgesic administration, recovery time, and emesis incidence. Principal analysis was conducted on a retrospective cohort of 3669 children aged 6 months to <7 years who underwent BMT over a 16-month period and received intraoperative fentanyl and/or ketorolac. Routine anesthetic care included preoperative oral midazolam, general anesthesia via a mask maintained with sevoflurane and N2O or air in O2, and intramuscular analgesic administration. Multivariable analyses were performed examining relationships between analgesic regimen with the following outcomes: maximum PACU Face, Legs, Activity, Cry, and Consolability (FLACC) score = 0 or 7 to 10, oxycodone administration, and time to discharge readiness. Demographic variables, midazolam exposure, and location (main hospital vs ambulatory surgery center) were included in the multivariable analyses as potential confounders. Associations with postoperative vomiting were studied separately in 2725 children from a subsequent, nonoverlapping 12-month period using similar inclusion criteria. Fentanyl and ketorolac dose-response relationships were evaluated for selected outcome variables. Maximum FLACC = 0, maximum FLACC score of 7 to 10, and oxycodone rescue were most strongly associated with dual-agent therapy versus single-agent ketorolac: odds ratios 4.89 (95% confidence interval [CI], 4.04-5.93), 0.13 (95% CI, 0.10-0.16), and 0.11 (98.3% CI, 0.09-0.14), respectively, P < .001 for each). Minor associations were found for age, Hispanic ethnicity, midazolam, and location, and none for sex or race. For subjects managed with higher dose fentanyl (≥1.5 µg/kg) and ketorolac (≥0.75 mg/kg), 90% had no demonstrable pain, agitation, or distress. Mean discharge readiness times were 21 ± 11 minutes (ketorolac), 26 ± 16 minutes (fentanyl), and 24 ± 14 minutes (dual) (P < .0001). Postoperative emesis incidences associated with ketorolac (2.7%) versus dual therapy (4.5%) were not different (P = .08). In this large retrospective pediatric BMT study, combination intramuscular fentanyl/ketorolac was strongly associated with superior PACU analgesia and reduced need for oxycodone rescue without clinically significant increases in recovery time or emesis incidence. Combination fentanyl at 1.5 to 2 µg/kg and 1 mg/kg ketorolac was associated with optimal outcomes. Dual therapy appears similarly effective in children of either European Caucasian or African ancestry or of Hispanic ethnicity.

Opiate self-administration as a measure of chronic nociceptive pain in arthritic rats.

PubMed

Colpaert, F C; Tarayre, J P; Alliaga, M; Bruins Slot, L A; Attal, N; Koek, W

2001-03-01

The study examined the validity of oral fentanyl self-administration (FSA) as a measure of the chronic nociceptive pain that develops in rats with adjuvant arthritis independently of acute noxious challenges. Arthritic rats self-administered more of a 0.008 mg/ml fentanyl solution (up to 3.4 g/rat per day) than non-arthritic controls (0.5 g/rat per day) and did so with a biphasic time course that reached peak during weeks 3 and 4 after inoculation with Mycobacterium butyricum. The time course paralleled both the disease process and the chronic pain. Continuous infusion of dexamethasone during weeks 3 and 4 via subcutaneous osmotic pumps at 0.0025-0.04 mg/rat per day disrupted the arthritic disease and decreased FSA to a level (i.e. by 65%) similar to that observed in non-arthritic rats. Continuous naloxone (2.5 mg/rat per day) decreased FSA (by 55%) in arthritic but not in non-arthritic animals. Continuous, subcutaneous infusion of fentanyl also decreased arthritic FSA in a manner that varied with dose at 0.04-0.16 mg/rat per day doses, but leveled off at 47% of controls with 0.31 mg/rat per day. The effects of continuous fentanyl on arthritic FSA occurred only with those doses and dose-dependent dynamics with which fentanyl also induced dependence in non-arthritic rats. The findings indicate that pain, rather than the rewarding or dependence-inducing action of fentanyl mediates FSA in arthritic rats. Paralleling patient-controlled analgesic drug intake, FSA offers a specific measure allowing the dynamic effects of neurobiological agents to be studied in this unique animal model of persistent nociceptive pain.

Prevalence and correlates of fentanyl-contaminated heroin exposure among young adults who use prescription opioids non-medically.

PubMed

Macmadu, Alexandria; Carroll, Jennifer J; Hadland, Scott E; Green, Traci C; Marshall, Brandon D L

2017-05-01

The rate of overdose deaths caused by fentanyl-contaminated heroin (FCH) use is increasing rapidly in the United States. We examined risk factors for exposure to FCH and experiences with FCH use among young adult non-medical prescription opioids (NMPO) users. We analyzed data from the Rhode Island Young Adult Prescription Drug Study (RAPiDS), which enrolled young adults aged 18 to 29 reporting prior 30day NMPO use between January 2015 and February 2016. Participants completed questionnaires ascertaining drug use patterns and risk behaviors, including FCH exposure. Logistic regression was used to assess factors associated with known or suspected FCH exposure. Of 199 participants, the median age was 25 (IQR: 22, 27), 130 (65.3%) were male, and 122 (61.3%) were of White, non-Hispanic race/ethnicity. In total, 22 (11%) reported known or suspected FCH exposure in the prior six months. Several drug use patterns and risk behaviors were associated with FCH exposure, including: regular heroin and cocaine use; diverted pharmaceutical fentanyl use in the prior six months; NMPO use to avoid withdrawal symptoms; longer duration of NMPO use; regular injection drug use; and prior overdose (all p<0.001). Among participants who reported FCH exposure, 59% were unaware that their heroin was contaminated with fentanyl prior to last use, 59% reported that FCH provides a better high, and all recognized that fentanyl increases overdose risk. Exposure to fentanyl-contaminated heroin is an emerging trend among young adult NMPO users in Rhode Island. Overdose prevention programs addressing FCH use are urgently needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

5-Hydroxytryptamine 1A/7 and 4alpha receptors differentially prevent opioid-induced inhibition of brain stem cardiorespiratory function.

PubMed

Wang, Xin; Dergacheva, Olga; Kamendi, Harriet; Gorini, Christopher; Mendelowitz, David

2007-08-01

Opioids evoke respiratory depression, bradycardia, and reduced respiratory sinus arrhythmia, whereas serotonin (5-HT) agonists stimulate respiration and cardiorespiratory interactions. This study tested whether serotonin agonists can prevent the inhibitory effects of opioids on cardiorespiratory function. Spontaneous and rhythmic inspiratory-related activity and gamma-aminobutyric acid (GABA) neurotransmission to premotor parasympathetic cardioinhibitory neurons in the nucleus ambiguus were recorded simultaneously in an in vitro thick slice preparation. The mu-opioid agonist fentanyl inhibited respiratory frequency. The 5-hydroxytryptamine 1A/7 receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin increased respiratory frequency by itself and also prevented the fentanyl-induced respiratory depression. The 5-hydroxytryptamine 4alpha agonist BIMU-8 did not by itself change inspiratory activity but prevented the mu-opioid-mediated respiratory depression. Both spontaneous and inspiratory-evoked GABAergic neurotransmission to cardiac vagal neurons were inhibited by fentanyl. 8-Hydroxy-2-(di-n-propylamino)tetralin inhibited spontaneous but not inspiratory-evoked GABAergic activity to parasympathetic cardiac neurons. However, 8-hydroxy-2-(di-n-propylamino)tetralin differentially altered the opioid-mediated depression of inspiratory-evoked GABAergic activity but did not change the opioid-induced reduction in spontaneous GABAergic neurotransmission. In contrast, BIMU-8 did not alter GABAergic neurotransmission to cardiac vagal neurons by itself but prevented the fentanyl depression of both spontaneous and inspiratory-elicited GABAergic neurotransmission to cardiac vagal neurons. In the presence of tetrodotoxin, the inhibition of GABAergic inhibitory postsynaptic currents with fentanyl is prevented by coapplication of BIMU-8, indicating that BIMU-8 acts at presynaptic GABAergic terminals to prevent fentanyl-induced depression. These results suggest that activation of 5-hydroxytryptamine receptors, particularly 5-hydroxytryptamine 4alpha agonists, may be a useful therapeutic approach in preventing opioid-evoked cardiorespiratory depression.

Impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl.

PubMed

Perelman, Michael; Fisher, Anthony N; Smith, Alan; Knight, Alastair

2013-05-01

Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety. Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period. A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml). Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.

Ligand-induced μ opioid receptor internalization in enteric neurons following chronic treatment with the opiate fentanyl.

PubMed

Anselmi, Laura; Jaramillo, Ingrid; Palacios, Michelle; Huynh, Jennifer; Sternini, Catia

2013-06-01

Morphine differs from most opiates its poor ability to internalize μ opioid receptors (μORs). However, chronic treatment with morphine produces adaptational changes at the dynamin level, which enhance the efficiency of acute morphine stimulation to promote μOR internalization in enteric neurons. This study tested the effect of chronic treatment with fentanyl, a μOR-internalizing agonist, on ligand-induced endocytosis and the expression of the intracellular trafficking proteins, dynamin and β-arrestin, in enteric neurons using organotypic cultures of the guinea pig ileum. In enteric neurons from guinea pigs chronically treated with fentanyl, μOR immunoreactivity was predominantly at the cell surface after acute exposure to morphine with a low level of μOR translocation, slightly higher than in neurons from naïve animals. This internalization was not due to morphine's direct effect, because it was also observed in neurons exposed to medium alone. By contrast, D-Ala2-N-Me-Phe4-Gly-ol5-enkephalin (DAMGO), a potent μOR-internalizing agonist, induced pronounced and rapid μOR endocytosis in enteric neurons from animals chronically treated with fentanyl or from naïve animals. Chronic fentanyl treatment did not alter dynamin or β-arrestin expression. These findings indicate that prolonged activation of μORs with an internalizing agonist such as fentanyl does not enhance the ability of acute morphine to trigger μOR endocytosis or induce changes in intracellular trafficking proteins, as observed with prolonged activation of μORs with a poorly internalizing agonist such as morphine. Cellular adaptations induced by chronic opiate treatment might be ligand dependent and vary with the agonist efficiency to induce receptor internalization. Copyright © 2013 Wiley Periodicals, Inc.

Efficacy of transverse abdominis plane block in reduction of postoperation pain in laparoscopic cholecystectomy.

PubMed

Saliminia, Alireza; Azimaraghi, Omid; Babayipour, Shiva; Ardavan, Kamelia; Movafegh, Ali

2015-12-01

Transversus abdominis plane (TAP) block is a recently introduced regional anesthesia technique that is used for postoperative pain reduction in some abdominal surgeries. The present study evaluated the efficacy of the TAP block on the post laparoscopic cholecystectomy pain intensity and analgesic consumption. Fifty-four patients were enrolled in three groups: TAP block with normal saline (Group 1, n = 18); TAP block with bupivacaine (Group 2, n = 18); and TAP block with bupivacaine plus sufentanil (Group 3, n = 18). The time to the first fentanyl request, fentanyl consumption in the 24 hours following surgery, and postoperative pain intensity at 30 minutes, 1 hour, 6 hours, 12 hours, and 24 hours following discharge for recovery were measured and recorded. The total amount of 24-hour fentanyl consumption was higher in Group 1 (877.8 ± 338.8 μg) than either Group 2 (566.7 ± 367.8 μg) or Group 3 (555.5 ± 356.8 μg; p = 0.03). Postoperative pain score was higher in Group 1 than intervention groups (p = 0.006); however, there was no significant difference in intervention groups. The time to the first fentanyl request in Group 1 (79.44 ± 42.2) was significantly lower than Group 3 (206.38 ± 112.7; p = 0.001). The present study demonstrated that bilateral TAP block with 0.5% bupivacaine reduces post laparoscopic cholecystectomy pain intensity and fentanyl request and prolongs time to the first analgesic request. Adding sufentanil to the block solution reduced neither pain intensity nor fentanyl further consumption. Copyright © 2015. Published by Elsevier B.V.

Physico-chemical stability of butorphanol-tramadol and butorphanol-fentanyl patient-controlled analgesia infusion solutions over 168 hours.

PubMed

Chen, Fuchao; Fang, Baoxia; Li, Peng; Zhu, Xuesong; Zhou, Benhong

2014-08-01

This study was to investigate the physical and chemical compatibility of butorphanol with tramadol or fentanyl in 0.9% sodium chloride injections for patient controlled analgesia administration. The solutions were prepared in polyvinyl chloride (PVC) infusion bags and stored without protected from light exposure at room temperature (25 degrees C) or refrigerated (4 degrees C). Over a period of 168 hours, stabilities were determined by visual inspection, pH measurement, and high-pressure liquid chromatography (HPLC) assay of drug concentrations. At both temperatures, admixtures of butorphanol-tramadol and butorphanol-fentanyl were clear in appearance, and no color change or precipitation was observed during the study period. The maximum losses obtained were lower than 5% for the three drugs after 168 hours of storage. The results indicate that, at ambient or refrigerated storage conditions, the drug mixtures of butorphanol-tramadol and butorphanol-fentanyl in 0.9% sodium chloride injections were physically and chemically stable for at least 168 hours when stored in PVC syringes.

Supply-side response to declining heroin purity: fentanyl overdose episode in New Jersey.

PubMed

Hempstead, Katherine; Yildirim, Emel O

2014-06-01

The inelastic price demand observations characteristic of illegal drug markets have led to the conclusion that the burden of a negative supply shock would be completely reflected to consumers. This paper argues that the increasing availability of prescription opioids may threaten heroin sellers' profit margin and force them to find alternative methods to compensate buyers in the event of a supply shock. We investigate the 2006 fentanyl overdose episode in New Jersey and argue that the introduction of non-pharmaceutical fentanyl, its spatial distribution, and the timing of overdose deaths may have been related to trends in heroin purity. Using medical examiner data, as well as data from the Drug Enforcement Administration, Office of Diversion Control on retail sales of prescription opioids in a negative binomial specification, we show that month-to-month fluctuations in heroin purity have a significant effect on fentanyl-related overdoses, particularly in those areas where prescription opioids are highly available. Copyright © 2013 John Wiley & Sons, Ltd.

mu-Opioid receptor-independent fashion of the suppression of sodium currents by mu-opioid analgesics in thalamic neurons.

PubMed

Hashimoto, Keisuke; Amano, Taku; Kasakura, Akiko; Uhl, George R; Sora, Ichiro; Sakai, Norio; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

2009-03-27

Most reports in the literature have shown that the effects of opioid analgesics are primarily mediated by mu-opioid receptor (MOR), whereas other potential targets of opioid analgesics have not been thoroughly characterized. In this study, we found that extracellular application of morphine, fentanyl or oxycodone, which are all considered to be MOR agonists, at relatively high concentrations, but not endogenous mu-opioid peptides, produced a concentration-dependent suppression of sodium currents in cultured thalamic neurons. These effects of opioids were not affected by either a MOR antagonist naloxone or a deletion of MOR gene. Among these opioids, fentanyl strongly suppressed sodium currents to the same degree as lidocaine, and both morphine and oxycodone slightly but significantly reduced sodium currents when they were present extracellularly. In contrast, the intracellular application of morphine, but not oxycodone, fentanyl or lidocaine, reduced sodium currents. These results suggest that morphine, fentanyl and oxycodone each produce the MOR-independent suppression of sodium currents by distinct mechanisms in thalamic neurons.

Small-dose hypobaric lidocaine-fentanyl spinal anesthesia for short duration outpatient laparoscopy. I. A randomized comparison with conventional dose hyperbaric lidocaine.

PubMed

Vaghadia, H; McLeod, D H; Mitchell, G W; Merrick, P M; Chilvers, C R

1997-01-01

A randomized, single-blind trial of two spinal anesthetic solutions for outpatient laparoscopy was conducted to compare intraoperative conditions and postoperative recovery. Thirty women (ASA physical status I and II) were assigned to one of two groups. Group I patients received a small-dose hypobaric solution of 1% lidocaine 25 mg made up to 3 mL by the addition of fentanyl 25 micrograms. Group II patients received a conventional-dose hyperbaric solution of 5% lidocaine 75 mg (in 7.5% dextrose) made up to 3 mL by the addition of 1.5 mL 10% dextrose. All patients received 500 mL of crystalloid preloading. Spinal anesthesia was performed at L2-3 or L3-4 with a 27-gauge Quincke point needle. Surgery commenced when the level of sensory anesthesia reached T-6. Intraoperative hypotension requiring treatment with ephedrine occurred in 54% of Group II patients but not in any Group I patients. Median (range) time for full motor recovery was 50 (0-95) min in Group I patients compared to 90 (50-120) min in Group II patients (P = 0.0005). Sensory recovery also occurred faster in Group I patients (100 +/- 22 min) compared with Group II patients (140 +/- 27 min, P = 0.0001). Postoperative headache occurred in 38% of all patients and 70% of these were postural in nature. Oral analgesia was the only treatment required. Spinal anesthesia did not result in a significant incidence of postoperative backache. On follow-up, 96% said they found spinal needle insertion acceptable, 93% found surgery comfortable, and 90% said they would request spinal anesthesia for laparoscopy in future. Overall, this study found spinal anesthesia for outpatient laparoscopy to have high patient acceptance and a comparable complication rate to other studies. The small-dose hypobaric lidocaine-fentanyl technique has advantages over conventional-dose hyperbaric lidocaine of no hypotension and faster recovery.

Psychomotor Functioning: Comparison of Patients Recovering From General Anesthesia With Remifentanil and a Volatile Anesthetic Versus Fentanyl and a Volatile Anesthetic

DTIC Science & Technology

1998-10-01

remifentanil appears to be more potent. The ED100 dose for loss of righting with remifentanil is 0.020mg/kg/min. 14 and for fentanyl the dose is 0.035 mg/kg...and 1/4600th the potency of remifentanil in dogs (Westmoreland, et al., 1993a). 16 Fentanyl has a t1/2 of 3 to 3.65 hours at clinically relevant doses ...This prolonged t1/2 reflects fentanyl’s lipophilicity (Murphy, et al., 1983). Remifentanil has a t1/2 of 10 minutes at clinically relevant doses

A structural study of fentanyl by DFT calculations, NMR and IR spectroscopy

NASA Astrophysics Data System (ADS)

Asadi, Zahra; Esrafili, Mehdi D.; Vessally, Esmail; Asnaashariisfahani, Manzarbanou; Yahyaei, Saeideh; Khani, Ali

2017-01-01

N-(1-(2-phenethyl)-4-piperidinyl-N-phenyl-propanamide (fentanyl) is synthesized and characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The geometry optimization is performed using the B3LYP and M06 density functionals with 6-311 + G(d) and 6-311++G(d,p) basis sets. The complete assignments are performed on the basis of the potential energy distribution (PED) of the all vibrational modes. Almost a nice correlation is found between the calculated 13C chemical shifts and experimental data. The frontier molecular orbitals and molecular electrostatic potential of fentanyl are also obtained.

Combat Trauma Lessons Learned from Military Operations of 2001 - 2013

DTIC Science & Technology

2015-03-09

and fentanyl citrate lozenges as described in the TCCC “triple-option analgesia” plan. - Documentation of care by using TCCC Casualty Cards and TCCC...o Meloxicam/acetaminophen o Oral transmucosal fentanyl citrate o Ketamine  Modified tactical combat casualty care (TCCC) measures to optimize

Comparative Analysis of the Biaxial Mechanical Behavior of Carotid Wall Tissue and Biological and Synthetic Materials Used for Carotid Patch Angioplasty

PubMed Central

Kamenskiy, Alexey V.; Pipinos, Iraklis I.; MacTaggart, Jason N.; Jaffar Kazmi, Syed A.; Dzenis, Yuris A.

2011-01-01

Patch angioplasty is the most common technique used for the performance of carotid endarterectomy. A large number of patching materials are available for use while new materials are being continuously developed. Surprisingly little is known about the mechanical properties of these materials and how these properties compare with those of the carotid artery wall. Mismatch of the mechanical properties can produce mechanical and hemodynamic effects that may compromise the long-term patency of the endarterectomized arterial segment. The aim of this paper was to systematically evaluate and compare the biaxial mechanical behavior of the most commonly used patching materials. We compared PTFE (n = 1), Dacron (n = 2), bovine pericardium (n = 10), autogenous greater saphenous vein (n = 10), and autogenous external jugular vein (n = 9) with the wall of the common carotid artery (n = 18). All patching materials were found to be significantly stiffer than the carotid wall in both the longitudinal and circumferential directions. Synthetic patches demonstrated the most mismatch in stiffness values and vein patches the least mismatch in stiffness values compared to those of the native carotid artery. All biological materials, including the carotid artery, demonstrated substantial nonlinearity, anisotropy, and variability; however, the behavior of biological and biologically-derived patches was both qualitatively and quantitatively different from the behavior of the carotid wall. The majority of carotid arteries tested were stiffer in the circumferential direction, while the opposite anisotropy was observed for all types of vein patches and bovine pericardium. The rates of increase in the nonlinear stiffness over the physiological stress range were also different for the carotid and patching materials. Several carotid wall samples exhibited reverse anisotropy compared to the average behavior of the carotid tissue. A similar characteristic was observed for two of 19 vein patches. The obtained results quantify, for the first time, significant mechanical dissimilarity of the currently available patching materials and the carotid artery. The results can be used as guidance for designing more efficient patches with mechanical properties resembling those of the carotid wall. The presented systematic comparative mechanical analysis of the existing patching materials provides valuable information for patch selection in the daily practice of carotid surgery and can be used in future clinical studies comparing the efficacy of different patches in the performance of carotid endarterectomy. PMID:22168740

The pharmacokinetics of ketoconazole and its effects on the pharmacokinetics of midazolam and fentanyl in dogs.

PubMed

KuKanich, B; Hubin, M

2010-02-01

Ketoconazole inhibits the Cytochrome P450 3A12 (CYP3A12) metabolizing enzyme as well as the p-glycoprotein efflux pump. The extent and clinical consequence of these effects are poorly understood in dogs. The objective was to assess the pharmacokinetics of ketoconazole after single and multiple doses and the effect of multiple doses of ketoconazole on midazolam (a known CYP3A12 substrate) and the opioid fentanyl. Six greyhound dogs were studied. The study consisted of three phases. Phase 1 consisted of i.v. midazolam (0.23 mg/kg base) and fentanyl (15.71 microg/kg base). Phase 2 consisted of a single oral dose of ketoconazole (mean dose 12.34 mg/kg). Phase 3 consisted of i.v. midazolam (0.23 mg/kg) and fentanyl (10 microg/kg) after 5 days of oral ketoconazole (12.25 mg/kg/day). Ketoconazole significantly inhibited its own elimination with the mean residence time (MRT) increasing from 6.24 h in Phase 1 to 12.54 h in Phase 3. Ketoconazole significantly decreased the elimination of midazolam, as expected, with the MRT increasing from 0.81 to 1.49 h. The elimination of fentanyl was not significantly altered by co-administration of ketoconazole with the MRT being 3.90 and 6.35 h. The MRT was the most robust estimate of decreased drug elimination.

Labour analgesia with intrathecal fentanyl decreases maternal stress.

PubMed

Cascio, M; Pygon, B; Bernett, C; Ramanathan, S

1997-06-01

Lumbar epidural analgesia (LEA) decreases maternal stress as measured by maternal circulating plasma catecholamine concentrations. Intrathecal fentanyl (ITF) provides effective labour analgesia but its effect on maternal epinephrine (Epi) and norepinephrine (NE) concentrations is not known. This study assesses whether ITF reduces maternal stress in the same manner as conventional LEA. Twenty-four healthy women in active labour received either 25 micrograms ITF (n = 12) or epidural lidocaine 1.5% (n = 12) for analgesia. Venous blood samples were collected before anaesthesia and at five minute intervals for 30 min following anaesthesia for the measurement of plasma Epi and NE by high performance liquid chromatography. Maternal blood pressure (BP), heart rate (HR), visual analog scores (VAS) to pain and pruritus were recorded at the same time. Both ITF and LEA decreased pain VAS scores, maternal BP, and plasma Epi concentrations with only minimal effects on plasma NE concentrations. Intrathecal fentanyl (ITF) and LEA reduced plasma epi to a similar extent, with ITF reducing the levels slightly faster than LEA. Intrathecal fentanyl(ITF) and LEA reduced plasma Epi concentrations by 52% and 51%, respectively (P value < 0.01). We conclude that ITF is as effective as LEA in producing pain relief in the labouring patient. Intrathecal Fentanyl (ITF) is also capable of reducing maternal plasma epinephrine concentration, thus avoiding the possibly deleterious side effects of excess amounts of this catecholamine during labour.

Antiemetic effects of midazolam added to fentanyl-ropivacaine patient-controlled epidural analgesia after subtotal gastrectomy: A prospective, randomized, double-blind, controlled trial

PubMed Central

Kim, Sioh; Seo, Jeongwon; Jeon, Younghoon

2010-01-01

Background: Nausea and vomiting are frequent adverse effects of patient-controlled epidural analgesia (PCEA) with opioids. Objective: This study was designed to assess the antiemetic effect of midazolam added to fentanyl—ropivacaine PCEA. Methods: In a prospective, randomized, double-blind, controlled trial, smoking patients with gastric cancer undergoing elective subtotal gastrectomy were evenly allocated to 1 of 2 treatment groups to manage postoperative pain: 0.2% ropivacaine mixed with fentanyl 4 μg/mL and midazolam 0.2 mg/mL (test group) or 0.2% ropivacaine mixed with fentanyl 4 μg/mL (control group). The PCEA infusion was set to deliver 4 μL/h of the study solution, with a bolus of 2 mL per demand and a 15-minute lockout time. The incidence of postoperative nausea and vomiting (PONV), pain intensity, sedation score, usage of rescue analgesia and rescue antiemetic, respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, 48, and 72 hours after surgery. Total infused volume of PCEA at 72 hours after surgery was measured. Results: A total of 60 patients were approached and randomized to treatment. No patients were excluded by exclusion criteria and all enrolled patients completed this study. Incidence of nausea (7% vs 33%; P = 0.02) in the test group was significantly lower than in the control group. The overall frequency of PONV in the test group was significantly less than that of the control group (7% vs 40%; P = 0.006). In addition, the mean (SD) infused volume of PCEA in the test group was significantly lower than that in the control group (392.3 [68.9] vs 351.2 [49.8] mL; P = 0.01). However, there were no significant differences in pain intensity, usage of rescue antiemetics and rescue analgesics, and mild pruritus between groups. No patient reported moderate or severe sedation, respiratory depression, or hypoxemia. In addition, there were no severe adverse events. Conclusions: Midazolam added to fentanyl-ropivacaine PCEA was associated with a significant reduction in the incidence of PONV compared with fentanyl-ropivacaine alone, and a significant decrease in the amount of PCEA administered without a significant increase in adverse events in these patients who underwent subtotal gastrectomy. PMID:24688151

In Vitro Screening of Opiod Antagonist Effectiveness

DTIC Science & Technology

2018-04-01

with a co-administration of acrylfentanyl and naloxone. Reversibility of acrylfentanyl was achieved at naloxone concentrations comparable to those of...EC50, EC90, and efficacy values were calculated (Figure 4). These values were compared to those of fentanyl (Table 1). 1 2 3 4 5 6 7 8 9 10 11 12... compare that to the metabolic rate of the reversal agent, itself. Metabolic clearance data, when combined with a potency and competition assay

Mu opioid receptor stimulation activates c-Jun N-terminal kinase 2 by distinct arrestin-dependent and independent mechanisms.

PubMed

Kuhar, Jamie Rose; Bedini, Andrea; Melief, Erica J; Chiu, Yen-Chen; Striegel, Heather N; Chavkin, Charles

2015-09-01

G protein-coupled receptor desensitization is typically mediated by receptor phosphorylation by G protein-coupled receptor kinase (GRK) and subsequent arrestin binding; morphine, however, was previously found to activate a c-Jun N-terminal kinase (JNK)-dependent, GRK/arrestin-independent pathway to produce mu opioid receptor (MOR) inactivation in spinally-mediated, acute anti-nociceptive responses [Melief et al.] [1]. In the current study, we determined that JNK2 was also required for centrally-mediated analgesic tolerance to morphine using the hotplate assay. We compared JNK activation by morphine and fentanyl in JNK1(-/-), JNK2(-/-), JNK3(-/-), and GRK3(-/-) mice and found that both compounds specifically activate JNK2 in vivo; however, fentanyl activation of JNK2 was GRK3-dependent, whereas morphine activation of JNK2 was GRK3-independent. In MOR-GFP expressing HEK293 cells, treatment with either arrestin siRNA, the Src family kinase inhibitor PP2, or the protein kinase C (PKC) inhibitor Gö6976 indicated that morphine activated JNK2 through an arrestin-independent Src- and PKC-dependent mechanism, whereas fentanyl activated JNK2 through a Src-GRK3/arrestin-2-dependent and PKC-independent mechanism. This study resolves distinct ligand-directed mechanisms of JNK activation by mu opioid agonists and understanding ligand-directed signaling at MOR may improve opioid therapeutics. Copyright © 2015 Elsevier Inc. All rights reserved.

Improved microsurgical creation of venous pouch arterial bifurcation aneurysms in rabbits.

PubMed

Sherif, C; Marbacher, S; Erhardt, S; Fandino, J

2011-01-01

The choice of the experimental aneurysm model is essential for valid embolization-device evaluations. So far, the use of the rabbit venous pouch arterial bifurcation aneurysm model has been limited by demanding microsurgery, low aneurysm patency rates, and high mortality. This study aimed to facilitate microsurgery and to reduce mortality by optimized peri-/postoperative management. Aneurysms were created in 16 New Zealand white rabbits under general intravenous anesthesia. Using modified microsurgical techniques, we sutured a jugular vein pouch into a bifurcation created between both CCAs. Aggressive anticoagulation (intraoperative intravenous: 1000-IU heparin, 10-mg acetylsalicylic acid/kg; postoperative subcutaneous: 14 days, 250-IU/kg /day heparin) and prolonged postoperative anesthesia (fentanyl patches: 12.5 μg/h for 72 hours) were applied. Angiographic characteristics of created experimental aneurysms were assessed. The reduced number of interrupted sutures and aggressive anticoagulation caused no intra-/postoperative bleeding, resulting in 0% mortality. Four weeks postoperation, angiography showed patency in 14 of 16 aneurysms (87.5%) and Ohshima type B bifurcation geometry. Mean values of parent-artery diameters (2.3 mm), aneurysm lengths (7.9 mm), and neck widths (4.1 mm) resulted in a mean 1.9 aspect ratio. Compared with historical controls, the use of modified microsurgical techniques, aggressive anticoagulation, and anesthesia resulted in higher aneurysm patency rates and lower mortality rates in the venous pouch arterial bifurcation aneurysm model. Gross morphologic features of these aneurysms were similar to those of most human intracranial aneurysms.

Prolactin response to fentanyl in depression.

PubMed

Frecska, E; Arato, M; Banki, C M; Mohari, K; Perenyi, A; Bagdy, G; Fekete, M I

1989-03-15

Ten unmedicated female inpatients with major depression (DSM-III) and 10 healthy volunteer women were given an intravenous injection of 0.1 mg fentanyl at 9:00 AM and 9:00 PM on different days. The prolactin secretory response to this opioid agonist was investigated for 1 h with serial blood sampling. Repeated measures Analysis of Variance yielded a significant effect of fentanyl administration on prolactin secretion (p less than 0.0001), and there were elevated hormone responses in the evening (p less than 0.005). No group difference was seen between healthy volunteers and depressed patients, but four of the depressives showed the most blunted response, and three of these low responders committed suicide within 1 year.

Dexmedetomidine in the Supratentorial Craniotomy

PubMed Central

Ilhan, Osman; Koruk, Senem; Serin, Gokcen; Erkutlu, Ibrahim; Oner, Unsal

2010-01-01

Objective: In this double-blind prospective clinical study, we investigated the effects of fentanyl and dexmedetomidine as adjuvant agents in supratentorial craniotomies on the following: hemodynamic changes during perioperative and recovery periods, brain edema perioperatively, recovery times and side effects, such as hypertension, shivering, nausea and vomiting. Materials and Methods: Thirty consenting ASA physical status I–II patients undergoing intracranial tumor surgery were randomly divided in two groups. In group D (n=15), dexmedetomidine was infused as a 1 μg/kg bolus dose 10 minutes before induction of anesthesia and maintained with 0.4–0.5 μg/kg/min during the operation. In group F (n=15), animals were given fentanyl 0.02 μg/kg/min as an infusion for anesthesia maintenance. At induction, fentanyl was given as a 2 μg/kg dose in group D and as a 4 μg/kg dose in group F. Hemodynamic changes, recovery times and postoperative side effects were recorded before induction, during the perioperative period and 24 hours postoperatively. Results: In group D; MAP and HR values after intubation, after skull clamp insertion and after extubation were lower than in group F (p<0.05). In group D, cerebral relaxation scores were also significantly lower. Recovery times were found to be shorter in group D as compared to group F; the same trend was observed for the supplemental opioid requirement. During the postoperative period, there was no shivering, nausea or vomiting in group D, but in group F, 3 patients complained of shivering, and 2 patients experienced nausea and vomiting. Conclusion: In our study, we found that dexmedetomidine controlled the hemodynamic changes better than fentanyl perioperatively, after extubation and during the early postoperative period. Our results suggest that that dexmedetomidine is safer and more effective in controlling hemodynamic changes during surgical stimulation than the standard agents used in neuroanesthesia. PMID:25610125

SCI with Brain Injury: Bedside to Bench Modeling for Developing Treatment and Rehabilitation Strategies

DTIC Science & Technology

2013-10-01

LISINOPRIL 1 CHLORHEXIDINE 2 CHLORHEXIDINE 2 METOPROLOL 2 METOPROLOL 2 DEXTROSE 2 DEXTROSE 1 MICONAZOLE 2 MICONAZOLE 1 HEPARIN 1 HEPARIN 3 FENTANYL 1... FENTANYL 2 BACLOFEN 1 BACLOFEN 1 FERROUS  SULFATE 1 FERROUS  SULFATE 1 QUETIAPINE 1 QUETIAPINE 1 Admission  Medications 24 VA Frequency SCVMC

The role of magnesium as an adjuvant during general anaesthesia.

PubMed

Gupta, K; Vohra, V; Sood, J

2006-11-01

Magnesium sulphate is used extensively in the treatment of eclampsia, and is also used to treat refractory arrhythmias, asthma, myocardial ischaemia and acute respiratory failure. We studied the interaction between magnesium sulphate and the anaesthetic agents propofol, rocuronium bromide and fentanyl citrate. This randomised, double blind study was conducted in 50 patients. The magnesium group A (n = 25) received 30 mg x kg(-1) magnesium sulphate before induction of anaesthesia and 10 mg x kg(-1) continuously intra-operatively until the end of surgery. Group B (n = 25) received the same volume of isotonic saline. Propofol, rocuronium and fentanyl infusions were started and the patients lungs' were ventilated with 33% oxygen in nitrous oxide. Anaesthetic depth was maintained at a bispectral index value of between 40 and 60. Muscle relaxation was maintained at a train-of-four count of 1 throughout surgery using neuromuscular monitoring. The fentanyl infusion was titrated to haemodynamic variables: heart rate and blood pressure. We concluded that magnesium sulphate has anaesthetic, analgesic and muscle relaxation effects and significantly reduces the drug requirements of propofol, rocuronium and fentanyl during anaesthesia.

[Efficacy of a fentanyl citrate buccal tablet for esophageal cancer pain management in a patient unable to take oral medication].

PubMed

Fujimura, Yoshinori; Nakahara, Osamu; Ohshima, Shigeki; Baba, Hideo

2015-04-01

We report a case ofa 60-year old male esophageal cancer patient who was unable to take oral medication, but was successfully treated using a fentanyl citrate buccal tablet. The patient survived a suicide attempt as a youth in which he ingested poison, but was left with a stricture of the esophagus. It became difficult for him to take nutrition orally, and he underwent an esophageal bypass operation, although he still required frequent endoscopic esophageal dilation. He subsequently presented with an anastomotic stenosis due to anastomotic leakage, and oral intake became completely impossible. The onset of esophageal cancer presented as corrosive esophagitis. We used oxycodone hydrochloride to treat a sharp pain resulting from cataplectic cancer in the jejunal tube, but this provided only limited pain relief. We therefore used a fentanyl citrate oral mucosa absorption preparation with a rescue agent, which did provide effective pain relief. Thus a fentanyl citrate buccal tablet could effectively relief pain in cancer patients who are unable to receive oral medication.

Propofol dose and incidence of dreaming during sedation.

PubMed

Eer, Audrey Singyi; Padmanabhan, Usha; Leslie, Kate

2009-10-01

Dreaming is commonly reported after propofol-based sedation. We measured the incidence of dreaming and bispectral index (BIS) values in colonoscopy patients sedated with combinations of propofol, midazolam and fentanyl. Two hundred patients presenting for elective outpatient colonoscopy were sedated with combinations of propofol, midazolam and fentanyl. BIS was monitored throughout the procedure. Patients were interviewed immediately after they emerged from sedation. The primary end point was a report of dreaming during sedation. Ninety-seven patients were administered propofol alone, 44 were administered propofol and fentanyl, 16 were administered propofol and midazolam and 43 were administered propofol, midazolam and fentanyl. Dreaming was reported by 19% of patients. Dreamers received higher doses of propofol and had lower BIS values during sedation. Age of 50 years or less, preoperative quality of recovery score of less than 14, higher home dream recall, propofol dose of more than 300 mg and time to Observers' Assessment of Alertness/Sedation score equalling 5 of 8 min or less were independent predictors of dreaming. Dreaming during sedation is associated with higher propofol dose and lower BIS values.

Evaluation of intra-operative tramadol for prevention of catheter-related bladder discomfort: a prospective, randomized, double-blind study.

PubMed

Agarwal, A; Yadav, G; Gupta, D; Singh, P K; Singh, U

2008-10-01

Catheter-related bladder discomfort (CRBD) is defined as an urge to void or discomfort in the supra-pubic region; reported postoperatively in patients who have had urinary catheterization intra-operatively. We have evaluated tramadol, a centrally acting opioid analgesic with muscarinic receptor antagonist properties for prevention of CRBD. Fifty-four adults (18-60 yr), ASA physical status I and II of either sex, undergoing elective percutaneous nephro-lithomy were randomly divided into two groups of 27 each. Control (C) group received normal saline (NS; 2 ml), whereas Tramadol (T) group received tramadol 1.5 mg kg(-1). All medications were diluted in 2 ml NS and administered 30 min before extubation. Intra-operatively, urinary catherization was performed with a 16 Fr Foley's catheter, and the balloon was inflated with 10 ml distilled water. The CRBD was assessed at 0, 1, 2, and 6 h after patient's arrival in the post-anaesthesia care unit along with total postoperative fentanyl requirement. Severity of CRBD was graded as none, mild, moderate and severe. Data were analysed by one-way ANOVA, Z-test, and Fisher's exact test. P<0.05 was considered significant. Incidence and severity of CRBD was reduced in T group compared with C group at all time points (P<0.05). Postoperative pain as assessed by visual analogue scale and total postoperative fentanyl requirement (microg kg(-1)) was also reduced in the T group [176 (SD 26.5)] compared with C group [210 (34.6)] (P<0.05). Tramadol 1.5 mg kg(-1) administered i.v. 30 min before extubation decreases the incidence and severity of CRBD and postoperative fentanyl requirement.

Clonidine versus ketamine to prevent tourniquet pain during intravenous regional anesthesia with lidocaine.

PubMed

Gorgias, N K; Maidatsi, P G; Kyriakidis, A M; Karakoulas, K A; Alvanos, D N; Giala, M M

2001-01-01

Both clonidine and ketamine have been found to prolong the action of local anesthetics through a peripheral mechanism. Our study compares the efficacy of a low dose of clonidine or ketamine separately added to intravenous regional anesthesia (IVRA) with lidocaine to prevent tourniquet pain. We conducted a prospective randomized double-blinded study in 45 patients undergoing hand or forearm surgery, with anticipated duration exceeding 1 hour under IVRA. Proximal cuff inflation of a double tourniquet was followed by administration of 40 mL of lidocaine 0.5% and either saline, 1 microg/kg clonidine, or 0.1 mg/kg ketamine. When anesthesia was established, the inflation of the proximal and distal cuff was interchanged. Thereafter, tourniquet pain was rated on a visual analog scale (VAS) every 10 minutes. Intraoperatively, boluses of 25 microg fentanyl were provided for tourniquet pain treatment when required, and total fentanyl consumption was recorded. Patients receiving plain lidocaine persistently reported the highest pain scores among groups (P <.001) 20 minutes after distal cuff inflation. Differences between the groups with additional treatment were noted 50 minutes after distal cuff inflation and until the end of the observation, with significantly lower VAS ratings (P <.001 to P <.01) in ketamine-treated patients. Total fentanyl consumption was significantly decreased by ketamine (70.00 +/- 25.35 microg) or clonidine (136.67 +/- 39.94 microg) compared with the plain lidocaine group (215.33 +/- 52.33 microg) (P <.001 between all groups). The addition of clonidine 1 microg/kg or ketamine 0.1 mg/kg to lidocaine for IVRA delays the onset of unbearable tourniquet pain and decreases analgesic consumption for tourniquet pain relief, although ketamine has a more potent effect.

Naloxone reversal of an overdose of a novel, long-acting transdermal fentanyl solution in laboratory Beagles.

PubMed

Freise, K J; Newbound, G C; Tudan, C; Clark, T P

2012-08-01

Opioid overdose in dogs is manifested by clinical signs such as excessive sedation, bradycardia, and hypothermia. The ability of two different intramuscular (i.m.) naloxone reversal regimens to reverse the opioid-induced effects of a fivefold overdose of long-acting transdermal fentanyl solution was evaluated in dogs. Twenty-four healthy Beagles were administered a single 13 mg/kg dose (fivefold overdose) of transdermal fentanyl solution and randomized to two naloxone reversal regimen treatment groups, hourly administration for 8 h of 40 (n = 8) or 160 μg/kg i.m. (n = 16). All dogs were sedated and had reduced body temperatures and heart rates (HRs) prior to naloxone administration. Both dosage regimens significantly reduced sedation (P < 0.001), and the 160 μg/kg naloxone regimen resulted in a nearly threefold lower odds of sedation than that of the 40 μg/kg i.m. naloxone regimen (P < 0.05). Additionally, naloxone significantly increased the mean body temperatures and HR (P < 0.001), although the 160 μg/kg regimen increased body temperature and HR more (P < 0.05). However, the narcotic side effects of fentanyl returned within 1-3 h following termination of the naloxone dosage regimens. The opioid-induced effects of an overdose of transdermal fentanyl solution can be safely and effectively reversed by either 40 or 160 μg/kg i.m. naloxone administered at hourly intervals. © 2012 Blackwell Publishing Ltd.

New screening methodology for selection of polymeric materials for transdermal drug delivery devices

NASA Astrophysics Data System (ADS)

Falcone, Roberto P.

As medical advances extend the human lifespan, the level of chronic illnesses will increase and thus straining the needs of the health care system that, as a result, governments will need to balance expenses without upsetting national budgets. Therefore, the selection of a precise and affordable drug delivery technology is seen as the most practical solution for governments, health care professionals, and consumers. Transdermal drug delivery patches (TDDP) are one of the best economical technologies that are favored by pharmaceutical companies and physicians alike because it offers fewer complications when compared to other delivery technologies. TDDP provides increased efficiency, safety and convenience for the patient. The TDDP segment within the US and Global drug delivery markets were valued at 5.6 and 12.7 billion respectively in 2009. TDDP is forecasted to reach $31.5 billion in 2015. The present TDDP technology involves the fabrication of a patch that consists of a drug embedded in a polymeric matrix. The diffusion coefficient is determined from the slope of the cumulative drug release versus time. It is a trial and error method that is time and labor consuming. With all the advantages that TDDPs can offer, the methodology used to achieve the so-called optimum design has resulted in several incidents where the safety and design have been put to question in recent times (e.g. Fentanyl). A more logical screening methodology is needed. This work shows the use of a modified Duda Zielinsky equation (DZE). Experimental release curves from commercial are evaluated. The experimental and theoretical Diffusion Coefficient values are found to be within the limits specified in the patent literature. One interesting finding is that the accuracy of the DZE is closer to experimental values when the type of Molecular Shape and Radius are used. This work shows that the modified DZE could be used as an excellent screening tool to determine the optimal polymeric matrices that will yield the desired Diffusion Coefficient and thus effectively decreasing the amount of time and labor when developing TDDPs.

General anesthesia versus segmental thoracic or conventional lumbar spinal anesthesia for patients undergoing laparoscopic cholecystectomy.

PubMed

Yousef, Gamal T; Lasheen, Ahmed E

2012-01-01

Laparoscopic cholecystectomy became the standard surgery for gallstone disease because of causing less postoperative pain, respiratory compromise and early ambulation. This study was designed to compare spinal anesthesia, (segmental thoracic or conventional lumbar) vs the gold standard general anesthesia as three anesthetic techniques for healthy patients scheduled for elective laparoscopic cholecystectomy, evaluating intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction. A total of 90 patients undergoing elective laparoscopic cholecystectomy, between January 2010 and May 2011, were randomized into three equal groups to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under segmental thoracic (TSA group) or conventional lumbar (LSA group) spinal anesthesia or general anesthesia (GA group). To achieve a T3 sensory level we used (hyperbaric bupivacaine 15 mg, and fentanyl 25 mg at L2/L3) for LSAgroup, and (hyperbaric bupivacaine 7.5 mg, and fentanyl 25 mg at T10/T11) for TSAgroup. Propofol, fentanyl, atracurium, sevoflurane, and tracheal intubation were used for GA group. Intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction were compared between the three groups. All procedures were completed laparoscopically by the allocated method of anesthesia with no anesthetic conversions. The time for the blockade to reach T3 level, intraoperative hypotensive and bradycardic events and vasopressor use were significantly lower in (TSA group) than in (LSA group). Postoperative pain scores as assessed throughout any time, postoperative right shoulder pain and hospital stay was lower for both (TSA group) and (LSA group) compared with (GA group). The higher degree of patients satisfaction scores were recorded in patients under segmental TSA. The present study not only confirmed that both segmental TSA and conventional lumber spinal anesthesia (LSA) are safe and good alternatives to general anesthesia (GA) in healthy patients undergoing laparoscopic cholecystectomy but also showed better postoperative pain control of both spinal techniques when compared with general anesthesia. Segmental TSA provides better hemodynamic stability, lesser vasopressor use and early ambulation and discharge with higher degree of patient satisfaction making it excellent for day case surgery compared with conventional lumbar spinal anesthesia.

Safety of a Brief Emergency Department Observation Protocol for Patients With Presumed Fentanyl Overdose.

PubMed

Scheuermeyer, Frank X; DeWitt, Christopher; Christenson, Jim; Grunau, Brian; Kestler, Andrew; Grafstein, Eric; Buxton, Jane; Barbic, David; Milanovic, Stefan; Torkjari, Reza; Sahota, Indy; Innes, Grant

2018-03-09

Fentanyl overdoses are increasing and few data guide emergency department (ED) management. We evaluate the safety of an ED protocol for patients with presumed fentanyl overdose. At an urban ED, we used administrative data and explicit chart review to identify and describe consecutive patients with uncomplicated presumed fentanyl overdose (no concurrent acute medical issues) from September to December 2016. We linked regional ED and provincial vital statistics databases to ascertain admissions, revisits, and mortality. Primary outcome was a composite of admission and death within 24 hours. Other outcomes included treatment with additional ED naloxone, development of a new medical issue while in the ED, and length of stay. A prespecified subgroup analysis assessed low-risk patients with normal triage vital signs. There were 1,009 uncomplicated presumed fentanyl overdose, mainly by injection. Median age was 34 years, 85% were men, and 82% received out-of-hospital naloxone. One patient was hospitalized and one discharged patient died within 24 hours (combined outcome 0.2%; 95% confidence interval [CI] 0.04% to 0.8%). Sixteen patients received additional ED naloxone (1.6%; 95% CI 1.0% to 2.6%), none developed a new medical issue (0%; 95% CI 0% to 0.5%), and median length of stay was 173 minutes (interquartile range 101 to 267). For 752 low-risk patients, no patients were admitted or developed a new issue, and one died postdischarge; 3 (0.4%; 95% CI 0.01% to 1.3%) received ED naloxone. In our cohort of ED patients with uncomplicated presumed fentanyl overdose-typically after injection-deterioration, admission, mortality, and postdischarge complications appear low; the majority can be discharged after brief observation. Patients with normal triage vital signs are unlikely to require ED naloxone. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Effects of Fentanyl on Emergence Agitation in Children under Sevoflurane Anesthesia: Meta-Analysis of Randomized Controlled Trials

PubMed Central

Xiong, Wei; Zhou, Qin; Yang, Peng; Huang, Xiongqing

2015-01-01

Background and Objectives The goal of this meta-analysis study was to assess the effects of fentanyl on emergence agitation (EA) under sevoflurane anesthesia in children. Subjects and Methods We searched electronic databases (PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials) for articles published until December 2014. Randomized controlled trials (RCTs) that assessed the effects of fentanyl and placebo on EA under sevoflurane anesthesia in children that the outcome were the incidence of EA, postoperative pain, emergence time or adverse effects were included in this meta-analysis. Results A total of 16 studies, including 1362 patients (737 patients for the fentanyl group and 625 for the placebo group), were evaluated in final analysis. We found that administration of fentanyl decreased the incidences of EA (RR = 0.37, 95% CI 0.27~0.49, P<0.00001) and postoperative pain (RR = 0.59, 95% CI 0.41~0.85, P = 0.004) but increased the incidence of postoperative nausea and vomiting (PONV) (RR = 2.23, 95% CI 1.33~3.77, P = 0.003). The extubation time (WMD = 0.71 min, 95% CI 0.12~1.3, P = 0.02), emergence time (WMD = 4.90 min, 95% CI 2.49~7.30, P<0.0001), and time in the postanesthesia care unit (PACU) (WMD = 2.65 min, 95% CI 0.76~4.53, P = 0.006) were slightly increased. There were no significant differences in the time to discharge of day patients (WMD = 3.72 min, 95% CI -2.80~10.24, P = 0.26). Conclusion Our meta-analysis suggests that fentanyl decreases the incidence of EA under sevoflurane anesthesia in children and postoperative pain, but has a higher incidence of PONV. Considering the inherent limitations of the included studies, more RCTs with extensive follow-up should be performed to validate our findings in the future. PMID:26275039

Pain control in patients with hepatocellular carcinoma treated by percutaneous radiofrequency ablation: comparison of the efficacy of one-shot and continuous intravenous fentanyl delivery.

PubMed

Yokoyama, Koichi; Ikeda, Osamu; Kawanaka, Koichi; Nakasone, Yutaka; Inoue, Seijiro; Tamura, Yoshitaka; Yamashita, Yasuyuki

2014-12-01

Hepatic percutaneous radiofrequency ablation (RFA) is usually performed with the patient under deep intravenous (i.v.) sedation or general anesthesia. Nonetheless, many patients report pain during and/or after the procedure. To perform a prospective study of pain control obtained by the i.v. one-shot delivery and the continuous i.v. infusion of fentanyl in patients with hepatocellular carcinoma (HCC) treated by RFA. Between April 2007 and March 2010, 83 patients with 106 HCCs underwent percutaneous RFA. All HCCs were addressed by computed tomography (CT)-guided percutaneous RFA performed within 5 h of embolization of the tumor vessels with iodized oil and gelatin sponges. Standard anesthesia consisted of 10 mL of 1% lidocaine injected locally. For conscious sedation, group one patients (n = 41) were injected i.v. with 100 µg of fentanyl before and 100 µg of fentanyl 30 min after percutaneous RFA. In group two (n = 42) we delivered fentanyl by continuous i.v. infusion at 100 µg/h during RFA. Upon request, patients in both groups also received 5 mg of diazepam i.v. for pain during the RFA procedure. The severity of pain experienced by all patients was evaluated on a visual analogue scale (VAS) and complications elicited by the anesthesia regimens were recorded. We also assessed the effectiveness of the treatment on sequential follow-up CT and/or magnetic resonance imaging (MRI) at 3-month intervals. Percutaneous RFA was technically successful in all 83 patients. Two patients in group one (4.8%) and one patient in group two (2.4%) manifested residual enhancement 3 months post RFA. There was no significant difference in the local recurrence rate between the two groups. At 4.0 ± 1.8 for group one and 3.4 ± 1.9 for group two, the VAS score was not significantly different. Major fentanyl or diazepam toxicity was recorded in 11 patients (24.4%) in group one and two patients (4.8%) in group two; the difference was statistically significant (P < 0.01). The continuous infusion of fentanyl provided effective and safe analgesia in HCC patients undergoing percutaneous RFA. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Prehospital analgesia in New South Wales, Australia.

PubMed

Bendall, Jason C; Simpson, Paul M; Middleton, Paul M

2011-12-01

With at least 20% of ambulance patients reporting pain of moderate to severe intensity, pain management has become a primary function of modern ambulance services. The objective of this study was to describe the use of intravenous morphine, inhaled methoxyflurane, and intranasal fentanyl when administered in the out-of-hospital setting by paramedics within a large Australian ambulance service. A retrospective analysis was conducted using data from ambulance patient health care records (PHCR) for all cases from 01 July 2007 through 30 June 2008 in which an analgesic agent was administered (alone or in combination). During the study period, there were 97,705 patients ≤ 100 years of age who received intravenous (IV) morphine, intranasal (IN) fentanyl, or inhaled methoxyflurane, either alone or in combination. Single-agent analgesia was administered in 87% of cases. Methoxyflurane was the most common agent, being administered in almost 60% of cases. Females were less likely to receive an opiate compared to males (RR = 0.83, 95% CI, 0.82-0.84, p <0.0001). Pediatric patients were less likely to receive opiate analgesia compared to adults (RR = 0.65, 95% CI, 0.63-0.67, p <0.0001). The odds of opiate analgesia (compared to pediatric patients 0-15 years) were 1.47; 2.10; 2.56 for 16-39 years, 40-59 years, and ≥ 60 years, respectively. Pediatric patients were more likely to receive fentanyl than morphine (RR = 1.69, 95% CI, 1.64-1.74, p < 0.0001). In this ambulance service, analgesia most often is provided through the use of a single agent. The majority of patients receive non-opioid analgesia with methoxyflurane, most likely because all levels of paramedics are authorized to administer that analgesic. Females and children are less likely to receive opiate-based analgesia than their male and adult counterparts, respectively. Paramedics appear to favor intranasal opiate delivery over intravenous delivery in children with acute pain.

Femoral nerve block versus intravenous fentanyl in adult patients with hip fractures - a systematic review.

PubMed

Hartmann, Flávia Vieira Guimarães; Novaes, Maria Rita Carvalho Garbi; de Carvalho, Marta Rodrigues

Hip fractures configure an important public health issue and are associated with high mortality taxes and lose of functionality. Hip fractures refer to a fracture occurring between the edge of the femoral head and 5cm below the lesser trochanter. They are common in orthopedic emergencies. The number of proximal femoral fractures is likely to increase as the population ages. The average cost of care during the initial hospitalization for hip fracture can be estimated about US$ 7,000 per patient. Femoral fractures are painful and need immediate adequate analgesia. Treating pain femoral fractures is difficult because there are limited numbers of analgesics available, many of which have side effects that can limit their use. Opiates are the most used drugs, but they can bring some complications. In this context, femoral nerve blocks can be a safe alternative. It is a specific regional anesthetic technique used by doctors in emergency medicine to provide anesthesia and analgesia of the affected leg. To compare the analgesic efficacy of intravenous fentanyl versus femoral nerve block before positioning to perform spinal anesthesia in patients with femoral fractures assessed by Pain Scales. A systematic review of scientific literature was conducted. Studies described as randomized controlled trials comparing femoral nerve block and traditional fentanyl are included. Two reviewers (MR and FH) independently assessed potentially eligible trials for inclusion. The methodology assessment was based on the tool developed by the Cochrane Collaboration for assessment of bias for randomized controlled trials. The Cochrane Library, Pubmed, Medline and Lilacs were searched for all articles published, without restriction of language or time. Two studies were included in this review. Nerve blockade seemed to be more effective than intravenous fentanyl for preventing pain in patients suffering from a femoral fracture. It also reduced the use of additional analgesia and made lower the risk for systemic complications. Femoral nerve block reduced the time to perform spinal anesthesia to the patient who will be subjected to surgery and facilitate the sitting position for this. The use of femoral nerve block can reduce the level of pain and the need for additional analgesia. There are less adverse systemic events associated with this and the procedure itself does not offer greater risks. More studies are required for further conclusions. Copyright © 2016. Published by Elsevier Editora Ltda.

[Femoral nerve block versus intravenous fentanyl in adult patients with hip fractures - a systematic review].

PubMed

Hartmann, Flávia Vieira Guimarães; Novaes, Maria Rita Carvalho Garbi; Carvalho, Marta Rodrigues de

Hip fractures configure an important public health issue and are associated with high mortality taxes and lose of functionality. Hip fractures refer to a fracture occurring between the edge of the femoral head and 5cm below the lesser trochanter. They are common in orthopedic emergencies. The number of proximal femoral fractures is likely to increase as the population ages. The average cost of care during the initial hospitalization for hip fracture can be estimated about US$ 7,000 per patient. Femoral fractures are painful and need immediate adequate analgesia. Treating pain femoral fractures is difficult because there are limited numbers of analgesics available, many of which have side effects that can limit their use. Opiates are the most used drugs, but they can bring some complications. In this context, femoral nerve blocks can be a safe alternative. It is a specific regional anesthetic technique used by doctors in emergency medicine to provide anesthesia and analgesia of the affected leg. To compare the analgesic efficacy of intravenous fentanyl versus femoral nerve block before positioning to perform spinal anesthesia in patients with femoral fractures assessed by Pain Scales. A systematic review of scientific literature was conducted. Studies described as randomized controlled trials comparing femoral nerve block and traditional fentanyl are included. Two reviewers (MR and FH) independently assessed potentially eligible trials for inclusion. The methodology assessment was based on the tool developed by the Cochrane Collaboration for assessment of bias for randomized controlled trials. The Cochrane Library, Pubmed, Medline and Lilacs were searched for all articles published, without restriction of language or time. Two studies were included in this review. Nerve blockade seemed to be more effective than intravenous fentanyl for preventing pain in patients suffering from a femoral fracture. It also reduced the use of additional analgesia and made lower the risk for systemic complications. Femoral nerve block reduced the time to perform spinal anesthesia to the patient who will be subjected to surgery and facilitate the sitting position for this. The use of femoral nerve block can reduce the level of pain and the need for additional analgesia. There are less adverse systemic events associated with this and the procedure itself does not offer greater risks. More studies are required for further conclusions. Copyright © 2016. Publicado por Elsevier Editora Ltda.

The Metabolites of Fentanyl and its Derivatives

DTIC Science & Technology

1988-09-01

TECHNIQUES ..... ........... 22 4.1 Stable Isotopes .... ............... .... 22 4.2 Radioisotope Tracers ... ............. .... 23 4.3 Radioimmunoassay...50 (relative to morphine).1 These properties have occasioned its popularity in surgical analgesia, especially when combined with a powerful ...studies by Janssen and coworkers, 5 carfentanil is one of the most powerful , achiral fentanyls. In addition to high potency, cis-3-methylfentanyl,5

A comparison of bleeding patterns and cycle control using two transdermal contraceptive systems: a multicenter, open-label, randomized study.

PubMed

Gruber, D; Skřivánek, A; Serrani, M; Lanius, V; Merz, M

2015-02-01

To investigate the bleeding pattern and cycle control parameters of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a patch containing 0.6 mg EE and 6 mg norelgestromin (NGMN). In this phase III, open-label, randomized, parallel-group trial, healthy women aged 18-35 years (smokers aged 18-30 years) received either the EE/GSD patch (n=200) or the EE/NGMN patch (n=198). Treatment consisted of one patch per week for 3 weeks followed by a 7-day, patch-free interval for seven cycles. Bleeding control was assessed in two 90-day reference periods. In reference period 1, mean number of bleeding/spotting days was comparable across treatment groups (p>0.05). However, in reference period 2, there were fewer bleeding/spotting days in the EE/GSD patch group (15.7 versus 18.4; p<0.0001). Mean number of bleeding/spotting episodes was comparable across groups for both reference periods, but bleeding/spotting episodes were shorter for the EE/GSD patch than the EE/NGMN patch during reference period 1 (5.13 days versus 5.53 days, respectively; p<0.05) and reference period 2 (5.07 versus 5.66; p=0.0001). Both treatment groups showed a similar frequency of withdrawal bleeding episodes; however, across all seven cycles, the length of these episodes was consistently shorter with the EE/GSD patch (p<0.01). There were no notable treatment differences in intracyclic bleeding. Bleeding pattern and cycle control achieved with the EE/GSD patch was similar to that of the EE/NGMN patch. The paper presents data on the bleeding pattern and cycle control parameters of an investigational transdermal contraceptive patch containing EE and GSD compared with an approved contraceptive patch containing EE and NGMN. This descriptive study found that bleeding patterns associated with the EE/GSD patch were similar to those of an EE/NGMN patch providing higher EE exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

A hydrogel pericardial patch.

PubMed

Allder, M A; Guilbeau, E J; Brandon, T A; Walker, A S; Koeneman, J B; Fisk, R L

1990-01-01

Patients undergoing repeat cardiac operations are higher operative risks than those undergoing an initial cardiac procedure because adhesion formation can occur if the native pericardium is not closed. A unique composite patch that may be used to augment the pericardial tissue when primary closure is not possible has been developed. The patch is made of a hydrogel, poly (2-hydroxyethyl methacrylate), reinforced with an ethylene tetrafluoroethylene (ETFE) mesh. The mesh provides the needed mechanical properties, whereas the patch's surface properties are comparable to the hydrogel. Two types of patches were fabricated: one with the mesh weave at a perpendicular orientation and one at 45 degrees to the principle loading direction. The patches were mechanically tested and compared with canine pericardium. Ultimate tensile strength of the patches is not significantly different from canine pericardium (p less than 0.05), are the patch suture strength is nearly twice that of canine pericardium. The perpendicular patch is stiffer than canine pericardium, whereas the 45 degree patch is not (p less than 0.05). The 45 degree patch shows considerable promise as a pericardial substitute because it closely matches the properties native canine pericardium.

Comparison of the Haemodynamic Effects of Three Different Methods at the Induction of Anaesthesia

PubMed Central

Uygur, Mehmet Levent; Ersoy, Ayşın; Altan, Aysel; Ervatan, Zekeriya; Kamalı, Sedat

2014-01-01

Objective Haemodynamic variations are inevitable during induction of anaesthetic drugs. The present study investigates the haemodynamic variations of three different drugs (thiopental, propofol, and etomidate) used for induction of general anaesthesia together with fentanyl. Methods In a randomized, double-blind study, 45 patients were assigned to one of three groups (n=15 each). Fentanyl 1 μg kg−1 was injected over 60 sec followed by propofol 2 mg kg−1 (Group P), thiopentone 6 mg kg−1 (Group T), or etomidate 0.3 mg kg−1 (Group E). Noninvasive measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), and heart rate (HR) was performed on admittance, immediately before the induction of anaesthesia, and 1, 3, and 5 min thereafter. Cardiac output (CO) values were recorded before induction, immediately after the injection of the drug, and at 1 min after the intubation. Results In all groups, during the study period, SAP, DAP, MAP, and CO values decreased with respect to time before induction. Following the administration of the induction dose of propofol (Group P), a significantly greater decrease of systolic and diastolic blood pressure was observed with etomidate (Group E) or thiopentone (Group T). Decrease in CO was also more marked with propofol (Group P) than with etomidate (Group E) or thiopentone (Group T). Conclusion It’s concluded that, in this study, the combination of fentanyl-etomidate is safer than both the groups of fentanyl-propofol and fentanyl-thiopental in terms of providing haemodynamic stability. PMID:27366443

NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction.

PubMed

Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee

2013-04-01

Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.

Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia.

PubMed

Armstrong, Edward P; Malone, Daniel C; McCarberg, Bill; Panarites, Christopher J; Pham, Sissi V

2011-05-01

The purpose of this study was to compare the cost effectiveness of a new 8% capsaicin patch, compared to the current treatments for postherpetic neuralgia (PHN), including tricyclic antidepressants (TCAs), topical lidocaine patches, duloxetine, gabapentin, and pregabalin. A 1-year Markov model was constructed for PHN with monthly cycles, including dose titration and management of adverse events. The perspective of the analysis was from a payer perspective, managed-care organization. Clinical trials were used to determine the proportion of patients achieving at least a 30% improvement in PHN pain, the efficacy parameter. The outcome was cost per quality-adjusted life-year (QALY); second-order probabilistic sensitivity analyses were conducted. The effectiveness results indicated that 8% capsaicin patch and topical lidocaine patch were significantly more effective than the oral PHN products. TCAs were least costly and significantly less costly than duloxetine, pregabalin, topical lidocaine patch, 8% capsaicin patch, but not gabapentin. The incremental cost-effectiveness ratio for the 8% capsaicin patch overlapped with the topical lidocaine patch and was within the accepted threshold of cost per QALY gained compared to TCAs, duloxetine, gabapentin, and pregablin. The frequency of the 8% capsaicin patch retreatment assumption significantly impacts its cost-effectiveness results. There are several limitations to this analysis. Since no head-to-head studies were identified, this model used inputs from multiple clinical trials. Also, a last observation carried forward process was assumed to have continued for the duration of the model. Additionally, the trials with duloxetine may have over-predicted its efficacy in PHN. Although a 30% improvement in pain is often an endpoint in clinical trials, some patients may require greater or less improvement in pain to be considered a clinical success. The effectiveness results demonstrated that 8% capsaicin and topical lidocaine patches had significantly higher effectiveness rates than the oral agents used to treat PHN. In addition, this cost-effectiveness analysis found that the 8% capsaicin patch was similar to topical lidocaine patch and within an accepted cost per QALY gained threshold compared to the oral products.

Cost effectiveness of the Oregon quitline "free patch initiative".

PubMed

Fellows, Jeffrey L; Bush, Terry; McAfee, Tim; Dickerson, John

2007-12-01

We estimated the cost effectiveness of the Oregon tobacco quitline's "free patch initiative" compared to the pre-initiative programme. Using quitline utilisation and cost data from the state, intervention providers and patients, we estimated annual programme use and costs for media promotions and intervention services. We also estimated annual quitline registration calls and the number of quitters and life years saved for the pre-initiative and free patch initiative programmes. Service utilisation and 30-day abstinence at six months were obtained from 959 quitline callers. We compared the cost effectiveness of the free patch initiative (media and intervention costs) to the pre-initiative service offered to insured and uninsured callers. We conducted sensitivity analyses on key programme costs and outcomes by estimating a best case and worst case scenario for each intervention strategy. Compared to the pre-intervention programme, the free patch initiative doubled registered calls, increased quitting fourfold and reduced total costs per quit by $2688. We estimated annual paid media costs were $215 per registered tobacco user for the pre-initiative programme and less than $4 per caller during the free patch initiative. Compared to the pre-initiative programme, incremental quitline promotion and intervention costs for the free patch initiative were $86 (range $22-$353) per life year saved. Compared to the pre-initiative programme, the free patch initiative was a highly cost effective strategy for increasing quitting in the population.

Fatal poisoning in drug addicts in the Nordic countries in 2012.

PubMed

Simonsen, K Wiese; Edvardsen, H M E; Thelander, G; Ojanperä, I; Thordardottir, S; Andersen, L V; Kriikku, P; Vindenes, V; Christoffersen, D; Delaveris, G J M; Frost, J

2015-03-01

This report is a follow-up to a study on fatal poisoning in drug addicts conducted in 2012 by a Nordic working group. Here we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on sex, number of deaths, places of death, age, main intoxicants and other drugs detected in the blood were recorded. National data are presented and compared between the Nordic countries and with data from similar studies conducted in 1991, 1997, 2002 and 2007. The death rates (number of deaths per 100,000 inhabitants) increased in drug addicts in Finland, Iceland and Sweden but decreased in Norway compared to the rates in earlier studies. The death rate was stable in Denmark from 1991 to 2012. The death rate remained highest in Norway (5.79) followed by Denmark (5.19) and Iceland (5.16). The differences between the countries diminished compared to earlier studies, with death rates in Finland (4.61) and Sweden (4.17) approaching the levels in the other countries. Women accounted for 15-27% of the fatal poisonings. The median age of the deceased drug addicts was still highest in Denmark, and deaths of addicts >45 years old increased in all countries. Opioids remained the main cause of death, but medicinal opioids like methadone, buprenorphine, fentanyl and tramadol mainly replaced heroin. Methadone was the main intoxicant in Denmark and Sweden, whereas heroin/morphine caused the most deaths in Norway. Finland differed from the other Nordic countries in that buprenorphine was the main intoxicant with only a few heroin/morphine and methadone deaths. Deaths from methadone, buprenorphine and fentanyl increased immensely in Sweden compared to 2007. Poly-drug use was widespread in all countries. The median number of drugs per case varied from 4 to 5. Heroin/morphine, medicinal opioids, cocaine, amphetamines, benzodiazepines and alcohol were the main abused drugs. However, less widely used drugs, like gamma-hydroxybutyric acid (GHB), methylphenidate, fentanyl and pregabalin, appeared in all countries. New psychotropic substances emerged in all countries, with the largest selection, including MDPV, alpha-PVP and 5-IT, seen in Finland and Sweden. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Invertebrate community response to a shifting mosaic of habitat

USGS Publications Warehouse

Engle, David M.; Fuhlendorf, S.D.; Roper, A.; Leslie, David M.

2008-01-01

Grazing management has focused largely on promoting vegetation homogeneity through uniform distribution of grazing to minimize area in a pasture that is either heavily disturbed or undisturbed. An alternative management model that couples grazing and fire (i.e., patch burning) to promote heterogeneity argues that grazing and fire interact through a series of positive and negative feedbacks to cause a shifting mosaic of vegetation composition and structure across the landscape. We compared patch burning with traditional homogeneity-based management in tallgrass prairie to determine the influence of the two treatments on the aboveground invertebrate community. Patch burning resulted in a temporal flush of invertebrate biomass in patches transitional between unburned and patches burned in the current year. Total invertebrate mass was about 50% greater in these transitional patches within patch-burned pastures as compared to pastures under traditional, homogeneity-based management. Moreover, the mosaic of patches in patch-burned pastures contained a wider range of invertebrate biomass and greater abundance of some invertebrate orders than did the traditionally managed pastures. Patch burning provides habitat that meets requirements for a broad range of invertebrate species, suggesting the potential for patch burning to benefit other native animal assemblages in the food chain.

The fentanyl HCl patient-controlled transdermal system (PCTS): an alternative to intravenous patient-controlled analgesia in the postoperative setting.

PubMed

Sinatra, Raymond

2005-01-01

Inadequate pain control in the postoperative period not only contributes to patient discomfort, but also causes physiological changes that may result in increased risk of myocardial ischaemia, deep vein thrombosis and pulmonary embolism. These events complicate postoperative recovery and may lead to longer hospital stays as well as increased healthcare costs. Patient-controlled analgesia (PCA) has emerged as an effective way for patients to manage their pain, allowing self-administration of small doses of analgesics to maintain a certain level of pain control. PCA is most commonly delivered via an intravenous (IV) or epidural route, and while patient satisfaction is higher with PCA than with conventional methods of analgesic administration, the invasiveness, costs and risk of errors associated with currently available modalities may limit their utility. These systems also require significant healthcare resources, as nurses must manually program the pumps to deliver the correct amount of medication. Several new PCA modalities are being developed to address these limitations. These systems deliver drug through a variety of routes, including nasal transmucosal and transdermal. Most notably, a self-contained, credit card-sized, transdermal PCA system is currently in the final stages of development. The fentanyl HCl patient-controlled transdermal system (PCTS; IONSYS, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) uses an imperceptible, low-intensity direct current to transfer fentanyl on demand across the skin into the systemic circulation. This compact system is patient-activated, can be applied to the patient's upper arm or chest, and is designed to manage moderate-to-severe pain requiring opioid analgesia. The system delivers a preprogrammed amount of fentanyl HCI over 10 minutes, for a total of 80 doses, or for 24 hours, whichever occurs first. The on-demand dosing and pharmacokinetics of this system differentiate it from the passive transdermal formulation of fentanyl designed for the management of chronic pain. Clinical studies have shown that the fentanyl HCl PCTS is effective in the management of acute postoperative pain. These studies have also demonstrated that the system is safe and well tolerated by patients.

Fentanyl Iontophoretic Transdermal System (IONSYS(®)) can be Safely used in the Hospital Environment with X-Rays, Computerized Tomography and Radiofrequency Identification Devices.

PubMed

Lemke, John; Sardariani, Edmond; Phipps, Joseph Bradley; Patel, Niki; Itri, Loretta M; Caravelli, James; Viscusi, Eugene R

2016-09-01

Fentanyl iontophoretic transdermal system (fentanyl ITS, IONSYS(®)) is a patient-controlled analgesia system used for the management of acute postoperative pain, designed to be utilized in a hospital setting. The objective of the two studies was to determine if fentanyl ITS could be safely used with X-rays, computerized tomography (CT) scans and radiofrequency identification (RFID) devices. The ITS system has two components: controller and drug unit; the studies utilized ITS systems without fentanyl, referred to as the ITS Placebo system. The first study evaluated the effect of X-radiation on the operation of an ITS Placebo system. Five ITS Placebo systems were exposed to X-rays (20 and 200 mSv total radiation dose-the 200 mSv radiation dose represents a tenfold higher exposure than in clinical practice) while operating in the Ready Mode and five were exposed while operating in the Dose Mode. The second study evaluated the effect of RFID (worst-case scenario of direct contact with an RFID transmitter) on the operation of an ITS Placebo system. During these tests, observations of the user interface and measurements of output voltage confirmed proper function throughout all operational modes (Ready Mode, Dose Mode, End-of-Use Mode, and End-of-Life Mode). The ITS Placebo system met all specifications and no functional anomalies were observed during and following X-ray exposure at two radiation dose levels or exposure at six different combinations of RFID frequencies and field strengths. The performance of the ITS system was unaffected by X-ray exposure levels well beyond those associated with diagnostic X-rays and CT scans, and by exposure to radiofrequency field strengths typically generated by RFID devices. These results provide added confidence to clinicians that the fentanyl ITS system does not need to be removed during diagnostic X-rays and CT scans and can also be utilized in close proximity to RFID devices. The studies and writing of this manuscript were supported financially by The Medicines Company.

Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study.

PubMed

Merz, M; Kroll, R; Lynen, R; Bangerter, K

2015-02-01

The aim of this study was to investigate the bleeding pattern and cycle control of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a combined oral contraceptive (COC) containing 0.02 mg EE and 0.1 mg levonorgestrel (LNG). In this phase III, randomized, controlled, double-blind, double-dummy, multicenter trial, healthy women aged 18-45 years (smokers aged 18-35 years) received either the EE/GSD patch and a placebo tablet (n=171), or a placebo patch and the COC (n=175) for seven 28-day cycles. Bleeding control was assessed in two 90-day reference periods. Mean number of bleeding/spotting days was comparable across treatment groups in both reference periods (p>.05). Mean number of bleeding/spotting episodes was also comparable in reference period 1; however, there were fewer bleeding/spotting episodes for COC in reference period 2 (3.4 versus 3.1; p=.01). Mean length of bleeding/spotting episodes was comparable across treatment groups for both reference periods (p>.05). Withdrawal bleeding occurred consistently in both groups over the entire treatment period, but its absence was more common in the COC group in cycles 4 and 6 of reference period 2 (p<.01). Intracyclic bleeding was comparable between groups. Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC. The findings suggest that bleeding patterns with the EE/GSD patch are similar to an EE/LNG-containing COC, except for absence of withdrawal bleeding, which was less common in patch users. The EE/GSD patch may constitute an additional contraceptive option for women. Copyright © 2015 Elsevier Inc. All rights reserved.

Oracle Applications Patch Administration Tool (PAT) Beta Version

DOE Office of Scientific and Technical Information (OSTI.GOV)

2002-01-04

PAT is a Patch Administration Tool that provides analysis, tracking, and management of Oracle Application patches. This includes capabilities as outlined below: Patch Analysis & Management Tool Outline of capabilities: Administration Patch Data Maintenance -- track Oracle Application patches applied to what database instance & machine Patch Analysis capture text files (readme.txt and driver files) form comparison detail report comparison detail PL/SQL package comparison detail SQL scripts detail JSP module comparison detail Parse and load the current applptch.txt (10.7) or load patch data from Oracle Application database patch tables (11i) Display Analysis -- Compare patch to be applied with currentmore » Oracle Application installed Appl_top code versions Patch Detail Module comparison detail Analyze and display one Oracle Application module patch. Patch Management -- automatic queue and execution of patches Administration Parameter maintenance -- setting for directory structure of Oracle Application appl_top Validation data maintenance -- machine names and instances to patch Operation Patch Data Maintenance Schedule a patch (queue for later execution) Run a patch (queue for immediate execution) Review the patch logs Patch Management Reports« less

Qualitative evaluation of coronary flow during anesthetic induction using thallium-201 perfusion scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleinman, B.; Henkin, R.E.; Glisson, S.N.

Qualitative distribution of coronary flow using thallium-201 perfusion scans immediately postintubation was studied in 22 patients scheduled for elective coronary artery bypass surgery. Ten patients received a thiopental (4 mg/kg) and halothane induction. Twelve patients received a fentanyl (100 micrograms/kg) induction. Baseline thallium-201 perfusion scans were performed 24 h prior to surgery. These scans were compared with the scans performed postintubation. A thallium-positive scan was accepted as evidence of relative hypoperfusion. Baseline hemodynamic and ECG data were obtained prior to induction of anesthesia. These data were compared with the data obtained postintubation. Ten patients developed postintubation thallium-perfusion scan defects (thallium-positivemore » scan), even though there was no statistical difference between their baseline hemodynamics and hemodynamics at the time of intubation. There was no difference in the incidence of thallium-positive scans between those patients anesthetized by fentanyl and those patients anesthetized with thiopental-halothane. The authors conclude that relative hypoperfusion, and possibly ischemia, occurred in 45% of patients studied, despite stable hemodynamics, and that the incidence of these events was the same with two different anesthetic techniques.« less

The dexmedetomidine concentration required after remifentanil anesthesia is three-fold higher than that after fentanyl anesthesia or that for general sedation in the ICU

PubMed Central

Kunisawa, Takayuki; Fujimoto, Kazuhiro; Kurosawa, Atsushi; Nagashima, Michio; Matsui, Koji; Hayashi, Dai; Yamamoto, Kunihiko; Goto, Yuya; Akutsu, Hiroaki; Iwasaki, Hiroshi

2014-01-01

Purpose The general dexmedetomidine (DEX) concentration required for sedation of intensive care unit patients is considered to be approximately 0.7 ng/mL. However, higher DEX concentrations are considered to be required for sedation and/or pain management after major surgery using remifentanil. We determined the DEX concentration required after major surgery by using a target-controlled infusion (TCI) system for DEX. Methods Fourteen patients undergoing surgery for abdominal aortic aneurysms (AAA) were randomly, double-blindly assigned to two groups and underwent fentanyl- or remifentanil-based anesthetic management. DEX TCI was started at the time of closing the peritoneum and continued for 12 hours after stopping propofol administration (M0); DEX TCI was adjusted according to the sedation score and complaints of pain. The doses and concentrations of all anesthetics and postoperative conditions were investigated. Results Throughout the observation period, the predicted plasma concentration of DEX in the fentanyl group was stable at approximately 0.7 ng/mL. In contrast, the predicted plasma concentration of DEX in the remifentanil group rapidly increased and stabilized at approximately 2 ng/mL. The actual DEX concentration at 540 minutes after M0 showed a similar trend (0.54±0.14 [fentanyl] versus 1.57±0.39 ng/mL [remifentanil]). In the remifentanil group, the dopamine dose required and the duration of intubation decreased, and urine output increased; however, no other outcomes improved. Conclusion The DEX concentration required after AAA surgery with remifentanil was three-fold higher than that required after AAA surgery with fentanyl or the conventional DEX concentration for sedation. High DEX concentration after remifentanil affords some benefits in anesthetic management. PMID:25328395

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

PubMed Central

Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

2015-01-01

Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

Mid-latency auditory evoked potentials and circulatory response to loud sounds.

PubMed

Schwender, D; Haessler, R; Klasing, S; Madler, C; Pöppel, E; Peter, K

1994-03-01

We investigated in 60 patients scheduled for elective aorto-coronary bypass grafting if loud sounds by themselves can induce cardiovascular responses and if these could be related to mid-latency auditory evoked potentials (MLAEP). Anaesthesia was induced in group I (n = 20) with flunitrazepam-fentanyl 0.01 mg kg-1 and maintained with flunitrazepam-fentanyl 1.2 mg h-1. Patients in groups II (n = 20) and III (n = 20) received etomidate 0.25 mg kg-1 and fentanyl 0.005 mg kg-1 for induction and 0.6-1.2 vol% isoflurane and fentanyl 1.2 mg h-1, or propofol 4-8 mg kg-1 h-1 and fentanyl 1.2 mg h-1 for maintenance of general anaesthesia. After preparation of the sternum the operation was stopped for several minutes. Then, as a loud auditory stimulus, the sound of the running sternotomy saw was presented to the patients by putting the saw inverted on the sternum for several seconds. Heart rate (HR), arterial pressure (SAP), pulmonary capillary wedge pressure (PCWP), cardiac index, systemic vascular resistance and MLAEP were measured in the awake state, before and after presentation of the sound. Latencies of the peak V, Na, Pa, Nb and P1 were measured. In group I there were statistically significant increases in HR (63.5-70.2 beat min-1), SAP (123.9-146-5 mm Hg) and PCWP (9.2-11.7 mm Hg) after presentation of the sound. These haemodynamic changes were not observed in patients in groups II and III. In the awake state, AEP had high peak -to-peak amplitudes and a periodic waveform.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaesthetic effects of alfaxalone administered intraperitoneally alone or combined with dexmedetomidine and fentanyl in the rat.

PubMed

Arenillas, Mario; Gomez de Segura, Ignacio A

2018-01-01

Alfaxalone is a neuroactive steroid used as a general anaesthetic in several species including dogs, cats, rabbits and ferrets. It has a wide margin of safety and a similar anaesthetic profile to propofol. To increase its aqueous solubility, a new formulation with cyclodextrins has been marketed recently. The objective of this study was to evaluate the anaesthetic effect of several doses of alfaxalone alone, considering differences between sexes, and alfaxalone combined with dexmedetomidine and fentanyl in the rat administered by the intraperitoneal route. A total of 40 Sprague Dawley rats, involved in three studies, were used. Firstly, 25, 35 and 45 mg kg -1 of alfaxalone alone were tested. In a second study, alfaxalone (25 mg kg -1 , females; 75 mg kg -1 , males) was combined with dexmedetomidine (0.05 mg kg -1 ). Finally, alfaxalone (20 mg kg -1 , females; 60 mg kg -1 , males) was combined with dexmedetomidine (0.05 mg kg -1 ) and fentanyl (0.1 mg kg -1 ). Times of onset and duration of anaesthesia, and analgesia, deemed as losing of withdrawal pedal reflex, were recorded. Alfaxalone alone produced a 2 - to 3-fold longer time of anaesthesia in females, although surgical anaesthesia was not achieved in either sex. The addition of dexmedetomidine and fentanyl to alfaxalone produced a similar time of analgesia as well as increased time of anaesthesia in both sexes. In conclusion, alfaxalone produces light anaesthesia in rats, and males required a higher dose. The combination with other sedatives or analgesics, such as dexmedetomidine or fentanyl, allows a more prolonged anaesthesia with analgesic effects, potentially suitable for invasive procedures.

The effect of a nicotine patch on cigarette craving over the course of the day: results from two randomized clinical trials.

PubMed

Shiffman, Saul; Ferguson, Stuart G

2008-10-01

The objective of this analysis was to assess the efficacy of a 21 mg/24-h nicotine patch for the reduction of craving throughout the waking day, compared both to placebo, and to a 15 mg/16-h patch differing pharmacokinetic profile over the day. The primary end-point was craving during the evening hours, because previous research suggested that smoking relapse was particularly likely at that time. Data were drawn from two similar randomized clinical trials among nicotine-dependent smokers who were quitting smoking: Study 1 compared the 21 mg/24-h patch to a placebo patch, while Study 2 compared the 21 mg/24-h patch to a 15 mg/16-h nicotine patch. In both studies, subjects (Study 1: n = 102; Study 2: n = 244) were prompted by an electronic diary to rate their craving multiple times per day during a 1 week baseline period, and for up to 2 weeks after quitting. For analysis, the day was divided into five blocks: morning (up to 10:59 a.m.), mid-day (11:00 a.m.-1:59 p.m.), afternoon (2:00 p.m.-4:59 p.m.), evening (5:00 p.m.-8:59 p.m.), and late night (9:00 p.m. onwards). The individual craving ratings were divided into three intervals based on time since quitting: Days 1-3, 4-7, and 8-14. The 21 mg/24-h nicotine patch resulted in significantly lower craving during all post-quit intervals, at each time of day, both compared to placebo (Study 1), and compared to the 15 mg/16-h nicotine patch (Study 2). Study 2 saw a significant treatment by interval interaction: in later time intervals, the difference in craving experience between 24- and 16-h patch conditions shrunk--while remaining significantly different--as overall levels of craving experienced by subjects in the two groups dropped. Adverse events reported in both studies tended to be mild and transient, consistent with the well characterized adverse event profile of nicotine patches. Study 1 demonstrated that a 21 mg/24-h patch was effective in reducing craving throughout the day, including the evening period when relapse risk is heightened. A further study comparing the 21 mg/24-h patch to a 15 mg/16-h nicotine patch found that craving was significantly lower at all times of day for smokers using the 21 mg/24-h patch. The studies were limited in that craving was only monitored for the first 2 weeks of quitting (when craving is most prominent), and cannot elucidate the impact of patch use on craving outside of this time. Also, there was substantial attrition of the sample over time, partly due to relapse in all conditions.

Butyrfentanyl overdose resulting in diffuse alveolar hemorrhage.

PubMed

Cole, Jon B; Dunbar, John F; McIntire, Sarah A; Regelmann, Warren E; Slusher, Tina M

2015-03-01

Butyrfentanyl is a potent short-acting opioid and a fentanyl analog with uncertain clinical effects. A review of the literature reveals no human case reports of butyrfentanyl overdose. As the use of analog and synthetic drugs continues to increase, clinicians are often faced with tremendous uncertainty when they encounter patients exposed to these synthetic drugs. We describe, to our knowledge, the first case of a butyrfentanyl overdose that resulted in clinically significant hemoptysis, acute lung injury, hypoxic respiratory failure, and diffuse alveolar hemorrhage. Complicating this case was a false-positive urine drug screen for fentanyl. Clinicians who encounter fentanyl exposures should be aware they may in fact be dealing with butyrfentanyl. As little is known of butyrfentanyl and our patient suffered a significant pulmonary hemorrhage, those who encounter butyrfentanyl exposures should monitor for hemorrhagic complications. Copyright © 2015 by the American Academy of Pediatrics.

[Fentanyl Citrate Sublingual Tablets Were Effective in Relieving Symptoms of Akathisia - A Case Report].

PubMed

Kessoku, Takaomi; Kusakabe, Akihiko; Matsuura, Tetsuya; Honda, Yasushi; Yoshimi, Asuka; Goto, Ayumu; Yoshida, Haruhisa; Sukegawa, Akiko; Hata, Chiaki; Saito, Yukie; Miyashita, Yoko; Yashiro, Ryoko; Komori, Tomoya; Arai, Sachiko; Nakajima, Atsushi; Ichikawa, Yasushi

2018-03-01

Akathisia is a condition wherein sitting calmly and quietly is impossible, with a representative complaint of restless legs. It is generally assumed to be caused by anti-dopamine activity. In severe cases, it has been known to result in suicide attempt. We reported a case of drug-induced akathisia with difficulty in oral intake, in which fentanyl citrate sublingual tablets were found to be effective in relieving symptoms. The patient was a female aged 50's who had a gastric cancer with peritoneal dissemination causing pain and vomiting. Palliative care was requested for management of symptoms. Metoclopramide and haloperidol were administered for vomiting. However, because of the complaints of restless legs, the case was diagnosed as drug-induced akathisia. Fentanyl citrate sublingual tablets were then administered for pain management, resulting in temporary improvement of akathisia symptoms.

Opiate sensitivity test in patients with stereotypic movement disorder and trichotillomania.

PubMed

Frecska, Ede; Arato, Mihaly

2002-06-01

Preliminary data about the therapeutic effect of opiate receptor manipulation in self-injurious behavior (SIB) suggest that endogenous opioid mechanisms may have a pathophysiological role in that condition and their involvement may be dependent on the severity of the SIB. The aim of this study was to use fentanyl-induced prolactin response as an opiate receptor sensitivity test in patients with stereotypic movement disorder (SMD) manifesting SIB (skin picking). Healthy volunteers and trichotillomanic patients were enrolled as comparison subjects. Individuals with trichotillomania (TTM) manifest repetitive, less serious self-mutilation (hair pulling) and are classified under different DSM-IV category than SMD. Therefore, they were considered as patient controls. Ten healthy subjects received 0.05 mg/70 kg and another 10 were given 0.1 mg/70 kg dose of fentanyl intravenously in the AM hours. Five of them had placebo trials. A dose of 0.05 mg/70 kg fentanyl was administered to patients with SMD (n = 10) and TTM (n = 12). Serial blood sampling was performed for prolactin measurements. Fentanyl elevated plasma prolactin in a dose-dependent manner. Patients with skin picking, but not with hair pulling, showed significantly increased responses. This finding supports the involvement of endogenous opioids in the pathomechanism of serious SIB.

Comparing reliabilities of strip and conventional patch testing.

PubMed

Dickel, Heinrich; Geier, Johannes; Kreft, Burkhard; Pfützner, Wolfgang; Kuss, Oliver

2017-06-01

The standardized protocol for performing the strip patch test has proven to be valid, but evidence on its reliability is still missing. To estimate the parallel-test reliability of the strip patch test as compared with the conventional patch test. In this multicentre, prospective, randomized, investigator-blinded reliability study, 132 subjects were enrolled. Simultaneous duplicate strip and conventional patch tests were performed with the Finn Chambers ® on Scanpor ® tape test system and the patch test preparations nickel sulfate 5% pet., potassium dichromate 0.5% pet., and lanolin alcohol 30% pet. Reliability was estimated by the use of Cohen's kappa coefficient. Parallel-test reliability values of the three standard patch test preparations turned out to be acceptable, with slight advantages for the strip patch test. The differences in reliability were 9% (95%CI: -8% to 26%) for nickel sulfate and 23% (95%CI: -16% to 63%) for potassium dichromate, both favouring the strip patch test. The standardized strip patch test method for the detection of allergic contact sensitization in patients with suspected allergic contact dermatitis is reliable. Its application in routine clinical practice can be recommended, especially if the conventional patch test result is presumably false negative. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

General anesthesia versus segmental thoracic or conventional lumbar spinal anesthesia for patients undergoing laparoscopic cholecystectomy

PubMed Central

Yousef, Gamal T.; Lasheen, Ahmed E.

2012-01-01

Background: Laparoscopic cholecystectomy became the standard surgery for gallstone disease because of causing less postoperative pain, respiratory compromise and early ambulation. Objective: This study was designed to compare spinal anesthesia, (segmental thoracic or conventional lumbar) vs the gold standard general anesthesia as three anesthetic techniques for healthy patients scheduled for elective laparoscopic cholecystectomy, evaluating intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction. Materials and Methods: A total of 90 patients undergoing elective laparoscopic cholecystectomy, between January 2010 and May 2011, were randomized into three equal groups to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under segmental thoracic (TSA group) or conventional lumbar (LSA group) spinal anesthesia or general anesthesia (GA group). To achieve a T3 sensory level we used (hyperbaric bupivacaine 15 mg, and fentanyl 25 mg at L2/L3) for LSAgroup, and (hyperbaric bupivacaine 7.5 mg, and fentanyl 25 mg at T10/T11) for TSAgroup. Propofol, fentanyl, atracurium, sevoflurane, and tracheal intubation were used for GA group. Intraoperative parameters, postoperative recovery and analgesia, complications as well as patient and surgeon satisfaction were compared between the three groups. Results: All procedures were completed laparoscopically by the allocated method of anesthesia with no anesthetic conversions. The time for the blockade to reach T3 level, intraoperative hypotensive and bradycardic events and vasopressor use were significantly lower in (TSA group) than in (LSA group). Postoperative pain scores as assessed throughout any time, postoperative right shoulder pain and hospital stay was lower for both (TSA group) and (LSA group) compared with (GA group). The higher degree of patients satisfaction scores were recorded in patients under segmental TSA. Conclusion: The present study not only confirmed that both segmental TSA and conventional lumber spinal anesthesia (LSA) are safe and good alternatives to general anesthesia (GA) in healthy patients undergoing laparoscopic cholecystectomy but also showed better postoperative pain control of both spinal techniques when compared with general anesthesia. Segmental TSA provides better hemodynamic stability, lesser vasopressor use and early ambulation and discharge with higher degree of patient satisfaction making it excellent for day case surgery compared with conventional lumbar spinal anesthesia. PMID:25885611

Prediction of Fatigue Crack Growth of Repaired Al-alloy Structures with Double Sides

NASA Astrophysics Data System (ADS)

Benachour, M.; Benachour, N.; Benguediab, M.; Seriari, F. Z.

During navigation, aircrafts are subject to fatigue damage. In order to rehabilitate damaged structures some techniques are often used to resolve this problem. Efficient repair technique, called composite patch repair, was used to reinforce the damaged structures and stop cracks. In this paper, effect of composite patch repair (Boron/Epoxy) on fatigue crack growth (FCG) was investigated on 2219 T62 Al-alloy. Effects of double patch repair in single notch tensile specimen (SENT) on FCG were studied and compared to single patch repair. Results show beneficial effect of patch repair on fatigue life and FCGR in comparison with the un-patched specimen. In addition, effect of mean stress characterized by stress ratio was highlighted. Fatigue behavior of investigated Al-alloy was compared.

The Efficacy and Safety of the Novel Peripheral Analgesic Isovaline as an Adjuvant to Propofol for General Anesthesia and Conscious Sedation: A Proof-of-Principle Study in Mice.

PubMed

Whitehead, Ryan A; Schwarz, Stephan K W; Asiri, Yahya I; Fung, Timothy; Puil, Ernest; MacLeod, Bernard A

2015-12-01

The combination of propofol and an opioid analgesic is widely used for procedural sedation, as well as total IV anesthesia. However, opioids produce respiratory depression, a primary cause of death due to these agents. We recently reported on the antinociceptive actions of isovaline, a small nonbiogenic amino acid that does not readily cross the blood-brain barrier and acts on peripheral γ-aminobutyric acid type B receptors. Here, we explored the possibility that isovaline may be an effective and safe alternative to opioids as an adjunct to propofol for producing anesthesia. With approval from our Animal Care Committee, we conducted an in vivo study in adult female CD-1 mice using Dixon's "up-and-down" method for dose assessment. Animals received intraperitoneal saline, propofol, isovaline, fentanyl, or coadministration of propofol with isovaline or fentanyl. We assessed hypnosis by a loss of righting reflex and immobility by an absence of motor response to tail clip application. General anesthesia was defined as the presence of both hypnosis and immobility. We assessed conscious sedation as a decrease in time on a rotarod. The maximal dose without respiratory rates of <4 per minute, apnea, or death was defined as the maximal tolerated dose. Either isovaline or fentanyl coadministered with propofol at its half-maximal effective dose (ED50) for hypnosis produced general anesthesia (isovaline ED50, 96 mg/kg [95% confidence interval {CI}, 88-124 mg/kg]; fentanyl ED50, 0.12 mg/kg [95% CI, 0.08-3.5 mg/kg]). Propofol produced hypnosis (ED50, 124 mg/kg [95% CI, 84-3520 mg/kg]) but did not block responses to tail clip application. Neither isovaline nor fentanyl produced hypnosis at doses which produced immobility (isovaline ED50, 350 mg/kg [95% CI, 286-1120 mg/kg]; fentanyl ED50, 0.35 mg/kg [95% CI, 0.23-0.51 mg/kg]). Isovaline at its analgesic ED50, coadministered with a subhypnotic dose of propofol (40 mg/kg), did not exacerbate propofol-induced deficits in rotarod performance. The median maximal tolerated dose of fentanyl coadministered with the hypnotic ED50 of propofol was 11 mg/kg (95% CI, 8-18 mg/kg). Isovaline at a maximal deliverable (soluble) dose of 5000 mg/kg produced no apparent respiratory depression or other adverse effects. The novel analgesic, isovaline, coadministered with propofol, produced general anesthesia and conscious sedation in mice. The margin of safety for propofol-isovaline was considerably higher than that for propofol-fentanyl. This study's results show that propofol-based sedation and general anesthesia can be effectively and safely produced by replacing the conventional opioid component with a brain-impermeant peripherally acting γ-aminobutyric acid type B receptor agonist. The results provide proof of the principle of combining a peripheral analgesic with a centrally acting hypnotic to produce general anesthesia. This principle suggests a novel approach to clinical general anesthesia and conscious sedation.

Comparison of bupivacaine and ropivacaine in combination with fentanyl used for walking epidural anesthesia in labor

PubMed Central

Gündüz, Şükrü; Eriş Yalçın, Serenat; Karakoç, Gökhan; Akkurt, Mehmet Özgür; Yalçın, Yakup; Yavuz, And

2017-01-01

Objective: Effective pain relief during labor is essential to reduce maternal and perinatal morbidity arising due to pain-induced maternal sympathetic activation, and to avoid unnecessary cesarean sections performed due to maternal anxiety. Walking epidural analgesia on labor reveals lower pain scores, leading to higher maternal satisfaction with better cardiovascular and pulmonary physiology. Despite the extensive use and relative safety of bupivacaine, newer drugs such as ropivacaine have been developed as alternative agents to decrease the risk for cardiac and central nervous system toxicity. Materials and Methods: One hundred women who requested epidural analgesia in active labor were randomly allocated into two groups; one group received 20 mL of ropivacaine 0.125% with fentanyl 50 µg and the other received 20 mL of bupivacaine 0.125% with fentanyl 50 µg. The efficacy of analgesia, adverse effects, and obstetric and neonatal outcomes of both groups were compared. Results: There were no differences between the two study groups in the measured obstetric and neonatal outcomes. The onset time, duration of analgesia, and sensory levels were similar between the groups. Visual analog pain scale scores did not differ between the groups before analgesia or at any of the subsequent evaluation periods. Conclusion: Both ropivacaine and bupivacaine provide equivalent labor analgesia with high maternal satisfaction and tolerable adverse effects in the clinically used dose range. No adverse obstetric or neonatal outcomes were observed in either group. Therefore, either drug is a reasonable choice for labor analgesia and can be used without jeopardizing the safety of the mother and fetus. PMID:29085707

Nitrous Oxide 70% for Procedural Analgosedation in a Pediatric Emergency Department With or Without Intranasal Fentanyl?: Analgesic Efficacy and Adverse Events if Combined With Intranasal Fentanyl.

PubMed

Seiler, Michelle; Landolt, Markus A; Staubli, Georg

2017-07-03

Nitrous oxide 70% (N20 70%) is an excellent medication for procedural analgosedation in a pediatric emergency department. However, its analgesic efficacy remains uncertain for painful procedures; therefore, a combination with intranasal fentanyl (INF), an opioid, was suggested. This study aimed at observing and assessing the analgesic efficacy and rate of adverse events using N20 70% with and without INF. Children who received N20 70% in a tertiary children's hospital emergency department from January 1, 2014 to June 30, 2015 were included in this observational study with prospective data collection. Physicians decided individually whether INF was administered. Medical staff documented the child's behavior during the procedure, adverse events, and satisfaction rate. A total of 442 children were included; 206 (46.6%) received INF. Group differences regarding patient behavior were not statistically significant; however, N20 70% application time was longer in the INF group (P = .02). Nausea was the most frequent adverse event with 13.1% in the INF group versus 8.1% without INF. Inadequate procedural analgosedation was documented only in the INF group, affecting 1.8% of all patients (P = .002). In contrast, anxiety was exclusively observed in the group without INF, which was presumably misjudged pain (P = .03); the satisfaction rate in the INF group was 95.6% compared with 98.7% without INF. Because of the study design and limitations, no conclusions about adding INF to N20 70% can be made. Additional research is needed to investigate the effect of combining N20 70% with INF.

[Comparative study between 0.5% bupivacaine, 0.5% enantiomeric mixture of bupivacaine (S75-R25) and 0.75% ropivacaine, all associated to fentanyl, for epidural cesarean section anesthesia.].

PubMed

Côrtes, Carlos Alberto Figueiredo; Oliveira, Amaury Sanchez; Castro, Luis Fernando Lima; Cavalcanti, Franz Schubert; Serafim, Maurício Marsaioli; Taia, César; Taia Filho, Siguero

2003-04-01

Clinical trials with local anesthetic levo-enantiomers have shown higher safety due to lower cardiotoxicity. This study aimed at evaluating quality of anesthesia and maternal/fetal repercussions of 0.5% bupivacaine, enantiomeric 0.5% bupivacaine (S75-R25) and 0.75% ropivacaine, all associated to fentanyl, in epidural cesarean section anesthesia. Participated in this study 90 full-term pregnant women, physical status ASA I, submitted to elective cesarean section under epidural anesthesia, who were divided into tree groups: group I - 23 ml racemic 0.5% bupivacaine with epinephrine; Group II -23 ml enantiomeric 0.5% bupivacaine (S75-R25) with epinephrine; Group III - 23 ml of 0.75% ropivacaine. Fentanyl (2 ml) was associated to local anesthetics in all groups. The following parameters were evaluated: onset, analgesia duration, sensory and motor block degree, time to hysterotomy and delivery, quality of muscle relaxation and anesthesia, maternal hemodynamic and respiratory changes, newborn vitality (evaluated through Apgar score and cord-blood gases analysis), and side-effects. There were no differences among groups, except for anesthesia quality. In groups with predominant levo-enantiomer fraction were clinically worse with the need for anesthetic complementation in three cases. Analgesia duration was longer in the ropivacaine group. Enantiomeric mixture 0.5% bupivacaine (S75-R25) and 0.75% ropivacaine for epidural anesthesia have provided as good conditions as racemic 0.5% bupivacaine for the surgical act. Newborn repercussions have shown that all solutions were equally safe.

Prescription opioid abuse based on representative postmortem toxicology.

PubMed

Häkkinen, Margareeta; Vuori, Erkki; Ojanperä, Ilkka

2014-12-01

Opioids are important medications for pain and opioid maintenance treatment. Increasing use and abuse of prescription opioids has, however, caused worldwide concern. Our aim was to estimate the ratio between prescription opioid abuse and total use, based on representative postmortem toxicology. Our material included all the medico-legally examined deaths in Finland during 2010-2011 involving positive findings involving buprenorphine, codeine, fentanyl, methadone, oxycodone, or tramadol. We studied drug abuse by age group, with "abuse" meaning licit opioids used illicitly as narcotics. Drug-abuse history, drug injecting, or laboratory findings of illicit drugs defined an abuser case. We then compared abuser cases and other opioid-related cases between the opioids with the number of fatal poisonings, accidents, suicides, alcohol findings, concomitant opioid use, and median postmortem blood opioid concentrations. Opioid findings numbered 2499 in 2088 cases. Drug abuse involved 545 opioid-positive cases, which in Finland represented 0.5% of those deceased. The proportion of abuser cases among all opioid-related cases for buprenorphine was 85.5%, for methadone 82.4%, for tramadol 29.4%, for codeine 16.3%, for fentanyl 14.5%, and for oxycodone 6.9%. Abuse in age-groups >60 was rare. Concomitant other opioid findings were more frequent in abuser- than in other cases for codeine, oxycodone, and tramadol, whereas alcohol findings were more frequent in buprenorphine, codeine, and fentanyl abuse. Buprenorphine and methadone were most often related to drug abuse. Every other opioid studied involved some abuse, and especially tramadol. Abuse and fatal poisonings were concentrated in men aged 20-49. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Analgesic opioid dose is an important indicator of postoperative ileus following radical cystectomy with ileal conduit: experience in the robotic surgery era.

PubMed

Koo, Kyo Chul; Yoon, Young Eun; Chung, Byung Ha; Hong, Sung Joon; Rha, Koon Ho

2014-09-01

Postoperative ileus (POI) is common following bowel resection for radical cystectomy with ileal conduit (RCIC). We investigated perioperative factors associated with prolonged POI following RCIC, with specific focus on opioid-based analgesic dosage. From March 2007 to January 2013, 78 open RCICs and 26 robot-assisted RCICs performed for bladder carcinoma were identified with adjustment for age, gender, American Society of Anesthesiologists grade, and body mass index (BMI). Perioperative records including operative time, intraoperative fluid excess, estimated blood loss, lymph node yield, and opioid analgesic dose were obtained to assess their associations with time to passage of flatus, tolerable oral diet, and length of hospital stay (LOS). Prior to general anaesthesia, patients received epidural patient-controlled analgesia (PCA) consisted of fentanyl with its dose adjusted for BMI. Postoperatively, single intravenous injections of tramadol were applied according to patient desire. Multivariate analyses revealed cumulative dosages of both PCA fentanyl and tramadol injections as independent predictors of POI. According to surgical modality, linear regression analyses revealed cumulative dosages of PCA fentanyl and tramadol injections to be positively associated with time to first passage of flatus, tolerable diet, and LOS in the open RCIC group. In the robot-assisted RCIC group, only tramadol dose was associated with time to flatus and tolerable diet. Compared to open RCIC, robot-assisted RCIC yielded shorter days to diet and LOS; however, it failed to shorten days to first flatus. Reducing opioid-based analgesics shortens the duration of POI. The utilization of the robotic system may confer additional benefit.

The efficacy and resource utilization of remifentanil and fentanyl in fast-track coronary artery bypass graft surgery: a prospective randomized, double-blinded controlled, multi-center trial.

PubMed

Cheng, D C; Newman, M F; Duke, P; Wong, D T; Finegan, B; Howie, M; Fitch, J; Bowdle, T A; Hogue, C; Hillel, Z; Pierce, E; Bukenya, D

2001-05-01

We compared (a) the perioperative complications; (b) times to eligibility for, and actual time of the following: extubation, less intense monitoring, intensive care unit (ICU), and hospital discharge; and (c) resource utilization of nursing ratio for patients receiving either a typical fentanyl/isoflurane/propofol regimen or a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in 304 adults by using a prospective randomized, double-blinded, double-dummy trial. There were no differences in demographic data, or perioperative mortality and morbidity between the two study groups. The mini-mental status examination at postoperative Days 1 to 3 were similar between the two groups. The eligible and actual times for extubation, less intense monitoring, ICU discharge, and hospital discharge were not significantly different. Further analyses revealed no differences in times for extubation and resource utilization after stratification by preoperative risk scores, age, and country. The nurse/patient ratio was similar between the remifentanil/isoflurane/propofol and fentanyl/isoflu-rane/propofol groups during the initial ICU phase and less intense monitoring phase. Increasing preoperative risk scores and older age (>70 yr) were associated with longer times until extubation (eligible), ICU discharge (eligible and actual), and hospital discharge (eligible and actual). Times until extubation (eligible and actual) and less intense monitoring (eligible) were significantly shorter in Canadian patients than United States' patients. However, there was no difference in hospital length of stay in Canadian and United States' patients. We conclude that both anesthesia techniques permit early and similar times until tracheal extubation, less intense monitoring, ICU and hospital discharge, and reduced resource utilization after coronary artery bypass graft surgery. An ultra-short opioid technique was compared with a standard fast-track small-dose opioid technique in coronary artery bypass graft patients in a prospective randomized, double-blinded controlled study. The postoperative recovery and resource utilization, including stratification of preoperative risk score, age, and country, were analyzed.

Addition of low-dose ketamine to midazolam and low-dose bupivacaine improves hemodynamics and postoperative analgesia during spinal anesthesia for cesarean section

PubMed Central

Basuni, Ahmed Sobhy

2016-01-01

Background and Aims: Spinal anesthesia for cesarean section (CS) is associated with an incidence of hypotension of 60-94%. This study hypothesizes that intrathecal combination of low-dose ketamine, midazolam, and low-dose bupivacaine improves hemodynamics and postoperative analgesia compared with fentanyl and low-dose bupivacaine during CS. Material and Methods: Fifty parturients undergoing elective CS were randomized equally to receive ketamine (10 mg), midazolam (2 mg) and 0.5% hyperbaric bupivacaine (8 mg) in group ketamine-midazolam-bupivacaine (KMB) or fentanyl (25 μg) and 0.5% hyperbaric bupivacaine (8 mg) in group fentanyl-bupivacaine (FB). Heart rate (HR), mean arterial blood pressure (MAP), oxygen saturation, sensorimotor block characteristics, pain-free period, side-effects including: hypotension, bradycardia, nausea, vomiting, sedation, pruritus, respiratory depression and dissociative manifestations, Apgar score at 1 and 5 min, and patients' satisfaction visual analog scores (VAS) were recorded. Patients in group KMB were followed for 6 months in order to assess any neurological disorder. Results: Group KMB showed higher sensory level (P = 0.006), rapid sensory (P = 0.001) and motor (P = 0.005) onsets, prolonged sensory (P = 0.008) and motor (P = 0.002) blocks, and prolonged pain free period (P = 0.002). Ketamine-midazolam stabilized HR and MAP, and significantly reduced incidence of hypotension (P = 0.002), bradycardia (P = 0.013) and vomiting (P = 0.019). Apgar scores at 1 and 5 min were comparable in both groups (P = 0.699 and 0.646 respectively). Patients' satisfaction VAS scores were significantly higher in group KMB (P = 0.001). No patients in KMB group showed dissociative or neurotoxic manifestations. Conclusion: Intrathecal low-dose ketamine combined with midazolam and low-dose bupivacaine stabilizes hemodynamics and prolongs postoperative analgesia without significant side-effects in parturients undergoing CS. PMID:27006540

Emergency Department Pain Management in Adult Patients With Traumatic Injuries Before and After Implementation of a Nurse-Initiated Pain Treatment Protocol Utilizing Fentanyl for Severe Pain.

PubMed

Ridderikhof, Milan L; Schyns, Frederick J; Schep, Niels W; Lirk, Philipp; Hollmann, Markus W; Goslings, J Carel

2017-04-01

Pain management in the emergency department (ED) remains suboptimal. Nursing staff protocols could improve this, but studies show divergent results. Our aim was to evaluate a nurse-initiated pain-management protocol in adult patients with traumatic injuries in the short and in the long term, utilizing fentanyl for severe pain. In this pre-post implementation study, ED patients were included during three periods. The protocol allowed nurses to administer acetaminophen, non-steroidal anti-inflammatory drugs, or fentanyl autonomously, based on Numeric Rating Scale pain scores. Primary outcome was frequency of analgesic administration at 6 and 18 months after implementation. Secondary outcomes were pain awareness, occurrence of adverse events, and pain treatment after discharge. Five hundred and twelve patients before implementation were compared with 507 and 468 patients at 6 and 18 months after implementation, respectively. Analgesic administration increased significantly at 18 months (from 29% to 36%; p = 0.016), not at 6 months (33%; p = 0.19) after implementation. Pain awareness increased from 30% to 51% (p = 0.00) at 6 months and to 56% (p = 0.00) at 18 months, due to a significant increase in pain assessment: 3% to 30% (p = 0.00) and 32% (p = 0.00), respectively. Post-discharge pain treatment increased significantly at 18 months compared to baseline (from 25% to 33%; p = 0.016) and to 6 months (from 24% to 33%; p = 0.004). No adverse events were recorded. Implementation of a nurse-initiated pain-management protocol only increases analgesic administration in adult patients with traumatic injuries in the long term. Auditing might have promoted adherence. Pain awareness increases significantly in the short and the long term. Copyright © 2016 Elsevier Inc. All rights reserved.

Fentanyl novel derivative-related deaths.

PubMed

Giorgetti, Arianna; Centola, Carmela; Giorgetti, Raffaele

2017-05-01

Fentanyl (FEN) is a potent, synthetic narcotic used as an anaesthetic and a pain reliever, but also illegally manufactured. For diversion purpose, it is being steadily modified to produce new analogous compounds and derivatives (FENS), categorised as novel psychoactive substances. While potential FEN abuse is already known, even in the absence of a clear lethal dosage, there is still a shortage of data on its derivatives. A literature review of FENS-related deaths was performed, to better understand potential damage and future perspectives of FEN congeners. Epidemiological data, pathological findings, administration routes, average concentrations and lethal doses, toxicological issues, trends in misuses, comparison among FENS, and possible explanation for FENS abuse are reviewed and discussed in depth. This study provides a medical-legal and toxicological assessment of this phenomenon in order to understand the role of illegal fentanyl and its congeners in deaths from FENS overdose. Copyright © 2017 John Wiley & Sons, Ltd.

Pretreatment of pericardial patches with antibiotics does not alter patch healing in vivo.

PubMed

Bai, Hualong; Kuwahara, Go; Wang, Mo; Brownson, Kirstyn E; Foster, Trenton R; Yamamoto, Kota; Xing, Ying; Dardik, Alan

2016-04-01

Pretreatment with antibiotics is commonly performed before surgical implantation of prosthetic materials. We previously showed that pericardial patches are infiltrated by macrophages and arterial stem cells after implantation into an artery. We hypothesized that antibiotic pretreatment would diminish the number of cells infiltrating into the patch, potentially affecting early neointimal formation. Bovine pericardial patches were pretreated with saline, bacitracin (500 U/mL), or cephalexin (10 mg/mL) for 30 minutes before implantation into the Wistar rat infrarenal aorta. Patches were retrieved on day 7 or day 30 and analyzed for histology and cell infiltration. Markers of proliferation, apoptosis, vascular cell identity, and M1 and M2 macrophage subtypes were examined using immunofluorescence and immunohistochemistry. Extracted proteins were analyzed by Western blot. At day 7, pericardial patches pretreated with bacitracin or cephalexin showed similar amounts of neointimal thickening (P = .55) and cellular infiltration (P = .42) compared with control patches. Patches pretreated with antibiotics showed similar proliferation (P = .09) and apoptosis (P = .84) as control patches. The cell composition of the neointima in pretreated patches was similar to control patches, with a thin endothelial layer overlying a thin layer of smooth muscle cells (P = .45), and containing similar numbers of CD34-positive (P = .26) and vascular endothelial growth factor receptor 2-positive (P = .31) cells. Interestingly, within the body of the patch, there were fewer macrophages (P = .0003) and a trend towards fewer endothelial progenitor cells (P = .051). No M1 macrophages were found in or around any of the patches. M2 macrophages were present around the patches, and there was no difference in numbers of M2 macrophages surrounding control patches and patches pretreated with antibiotics (P = .24). There was no difference in neointimal thickness at day 30 between control patches and patches pretreated with antibiotics (P = .52). Pretreatment of bovine pericardial patches with the antibiotics bacitracin or cephalexin has no detrimental effect on early patch healing, with similar neointimal thickness, cellular infiltration, and numbers of M2 macrophages compared with control patches. These results suggest that the host vessel response to patch angioplasty using pericardial patches is adaptive remodeling (eg, arterial healing). Published by Elsevier Inc.

Patch size has no effect on insect visitation rate per unit area in garden-scale flower patches

NASA Astrophysics Data System (ADS)

Garbuzov, Mihail; Madsen, Andy; Ratnieks, Francis L. W.

2015-01-01

Previous studies investigating the effect of flower patch size on insect flower visitation rate have compared relatively large patches (10-1000s m2) and have generally found a negative relationship per unit area or per flower. Here, we investigate the effects of patch size on insect visitation in patches of smaller area (range c. 0.1-3.1 m2), which are of particular relevance to ornamental flower beds in parks and gardens. We studied two common garden plant species in full bloom with 6 patch sizes each: borage (Borago officinalis) and lavender (Lavandula × intermedia 'Grosso'). We quantified flower visitation by insects by making repeated counts of the insects foraging at each patch. On borage, all insects were honey bees (Apis mellifera, n = 5506 counts). On lavender, insects (n = 737 counts) were bumble bees (Bombus spp., 76.9%), flies (Diptera, 22.4%), and butterflies (Lepidoptera, 0.7%). On both plant species we found positive linear effects of patch size on insect numbers. However, there was no effect of patch size on the number of insects per unit area or per flower and, on lavender, for all insects combined or only bumble bees. The results show that it is possible to make unbiased comparisons of the attractiveness of plant species or varieties to flower-visiting insects using patches of different size within the small scale range studied and make possible projects aimed at comparing ornamental plant varieties using existing garden flower patches of variable area.

Rivastigmine Patch in Chinese Patients with Probable Alzheimer's disease: A 24-week, Randomized, Double-Blind Parallel-Group Study Comparing Rivastigmine Patch (9.5 mg/24 h) with Capsule (6 mg Twice Daily).

PubMed

Zhang, Zhen-Xin; Hong, Zhen; Wang, Yan-Ping; He, Li; Wang, Ning; Zhao, Zhong-Xin; Zhao, Gang; Shang, Lan; Weisskopf, Marianne; Callegari, Francesca; Strohmaier, Christine

2016-06-01

To compare the once-daily rivastigmine patch 9.5 mg/24 h (10 cm(2) ) versus twice-daily capsule (12 mg/day) in Chinese patients with probable Alzheimer's disease (AD) (mini-mental state examination [MMSE] scores of 10-20). The primary objective was to demonstrate the noninferiority of patch to capsule in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) change from baseline to 24 week. Secondary endpoints included cognition (MMSE), overall clinical response (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC]), activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]), behavior (Neuropsychiatric Inventory [NPI-12]), and safety. Similar cognitive improvement was observed in both patch (n = 248) and capsule (n = 253) groups. Statistical noninferiority for ADAS-Cog was not established (least-square means difference, 0.1; 95% confidence interval, -1.2; 1.5). Considering all efficacy parameters into account, both treatments showed similar performance at Week 24. Treatment-related adverse events (AEs) were lower for patch (39.7%) compared with capsule (49.8%). Application site pruritus was reported in 10.9% of patients receiving patch; most cases were mild. Gastrointestinal AEs including nausea, vomiting, and diarrhea occurred less frequently in the patch group (15.8% vs. 28.7%). Rivastigmine patch 9.5 mg/24 h is effective and well tolerated in Chinese patients with probable AD. © 2016 John Wiley & Sons Ltd.

Patch-augmented rotator cuff repair: influence of the patch fixation technique on primary biomechanical stability.

PubMed

Jung, Christian; Spreiter, Gregor; Audigé, Laurent; Ferguson, Stephen J; Flury, Matthias

2016-05-01

There is an ongoing debate about the potential of patch augmentation to improve biomechanical stability and healing associated with rotator cuff repair. The biomechanical properties of three different patch-augmented rotator cuff repair techniques were assessed in vitro and compared with a standard repair. Dermal collagen patch augmentation may increase the primary stability and strength of the repaired tendon in vitro, depending on the technique used for patch application. Forty cadaveric sheep shoulders with dissected infraspinatus tendons were randomized into four groups (n = 10/group) for tendon repair using a knotless double-row suture anchor technique. A xenologous dermal extracellular matrix patch was used for augmentation in the three test groups using an "integrated", "cover", or "hybrid" technique. Tendons were preconditioned, cyclically loaded from 10 to 30 N at 1 Hz, and then loaded monotonically to failure. Biomechanical properties and the mode of failure were evaluated. Patch augmentation significantly increased the maximum load at failure by 61 % in the "cover" technique test group (225.8 N) and 51 % in the "hybrid" technique test group (211.4 N) compared with the non-augmented control group (140.2 N) (P ≤ 0.015). For the test group with "integrated" patch augmentation, the load at failure was 28 % lower (101.6 N) compared with the control group (P = 0.043). There was no significant difference in initial and linear stiffness among the four experimental groups. The most common mode of failure was tendon pullout. No anchor dislocation, patch disruption or knot breakage was observed. Additional patch augmentation with a collagen patch influences the biomechanical properties of a rotator cuff repair in a cadaveric sheep model. Primary repair stability can be significantly improved depending on the augmentation technique.

Simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and keto-doxapram in plasma using liquid chromatography - tandem mass spectrometry.

PubMed

Flint, Robert B; Bahmany, Soma; van der Nagel, Bart C H; Koch, Birgit C P

2018-05-16

A simple and specific UPLC-MS/MS method was developed and validated for simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and its active metabolite keto-doxapram. The internal standard was fentanyl-d5 for all analytes. Chromatographic separation was achieved with a reversed phase Acquity UPLC HSS T3 column with a run-time of only 5.0 minutes per injected sample. Gradient elution was performed with a mobile phase consisting of ammonium acetate, formic acid in Milli-Q ultrapure water or in methanol with a total flow rate of 0.4 mL minute -1 . A plasma volume of only 50 μL was required to achieve both adequate accuracy and precision. Calibration curves of all 5 analytes were linear. All analytes were stable for at least 48 hours in the autosampler. The method was validated according to US Food and Drug Administration guidelines. This method allows quantification of fentanyl, sufentanil, cefazolin, doxapram and keto-doxapram, which serves purposes for research, as well as therapeutic drug monitoring, if applicable. The strength of this method is the combination of a small sample volume, a short run-time, a deuterated internal standard, an easy sample preparation method and the ability to simultaneously quantify all analytes in one run. This article is protected by copyright. All rights reserved.

Outbreak of Serratia marcescens postsurgical bloodstream infection due to contaminated intravenous pain control fluids.

PubMed

Chiang, Ping-Cherng; Wu, Tsu-Lan; Kuo, An-Jing; Huang, Yhu-Chering; Chung, Ting-Ying; Lin, Chun-Sui; Leu, Hsieh-Shong; Su, Lin-Hui

2013-09-01

Serratia marcescens is an important nosocomial pathogen causing significant outbreaks. Here we report an outbreak of bloodstream infection caused by S. marcescens at a 3500-bed hospital in Taiwan. The effective cooperative efforts of both laboratory personnel and infection control practitioners (ICPs) jointly contributed to the total control of the outbreak. A sudden increase in the isolation of S. marcescens from blood cultures was noted in the Clinical Microbiology Laboratory. The information was passed to the ICPs and an investigation was initiated. Pulsed-field gel electrophoresis was used to study the relationships among the isolates. Pulsotype A was identified in 43 (82.7%) of the 52 blood isolates studied. They were isolated from 52 patients distributed across 22 wards that were surveyed by seven ICPs. All patients had undergone surgery before the infection, and fentanyl-containing intravenous fluids were used for pain control in 43 of them. Isolates from 42 belonged to pulsotype A. Three S. marcescens isolates, all from fentanyl-containing fluids and demonstrating pulsotype A, were identified from 251 environmental cultures. All fentanyl-containing fluids that were in use were withdrawn and the outbreak was stopped. The outbreak of S. marcescens bloodstream infection apparently occurred through the use of fentanyl-containing fluids contaminated by a pulsotype A S. marcescens. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception.

PubMed

Urdl, Wolfgang; Apter, Dan; Alperstein, Alan; Koll, Peter; Schönian, Siegfried; Bringer, Jacques; Fisher, Alan C; Preik, Michael

2005-08-01

To investigate contraceptive efficacy, compliance and user's satisfaction with transdermal versus oral contraception (OC). Randomized, open-label, parallel-group trial conducted at 65 centers in Europe and South Africa. One thousand four hundred and eighty-nine women received a contraceptive patch (n = 846) or an OC (n = 643) for 6 or 13 cycles. Overall/method-failure Pearl Indices were 0.88/0.66 with the patch and 0.56/0.28 with the OC (p = n.s.). Compliance was higher at all age groups with the patch compared to the OC. Significantly more users were very satisfied with the contraceptive patch than with the OC. The percentage of patch users being very satisfied increased with age whereas it did not in the OC group. Likewise, improvements of premenstrual symptoms as well as emotional and physical well-being increased with age in the patch-group in contrast to the OC group. Ratings of satisfaction with the study medication correlated weakly with emotional (r = 0.33) and physical well-being (r = 0.39) as well as premenstrual symptoms (r = 0.30; p < 0.001). Contraceptive efficacy of the patch is comparable to OC, but compliance is consistently better at all age groups. Higher satisfaction with the patch at increasing age may be attributed to improvements in emotional and physical well-being as well as reduction of premenstrual symptoms.

Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014.

PubMed

Rudd, Rose A; Aleshire, Noah; Zibbell, Jon E; Gladden, R Matthew

2016-01-01

The United States is experiencing an epidemic of drug overdose (poisoning) deaths. Since 2000, the rate of deaths from drug overdoses has increased 137%, including a 200% increase in the rate of overdose deaths involving opioids (opioid pain relievers and heroin). CDC analyzed recent multiple cause-of-death mortality data to examine current trends and characteristics of drug overdose deaths, including the types of opioids associated with drug overdose deaths. During 2014, a total of 47,055 drug overdose deaths occurred in the United States, representing a 1-year increase of 6.5%, from 13.8 per 100,000 persons in 2013 to 14.7 per 100,000 persons in 2014. The rate of drug overdose deaths increased significantly for both sexes, persons aged 25-44 years and ≥55 years, non-Hispanic whites and non-Hispanic blacks, and in the Northeastern, Midwestern, and Southern regions of the United States. Rates of opioid overdose deaths also increased significantly, from 7.9 per 100,000 in 2013 to 9.0 per 100,000 in 2014, a 14% increase. Historically, CDC has programmatically characterized all opioid pain reliever deaths (natural and semisynthetic opioids, methadone, and other synthetic opioids) as "prescription" opioid overdoses (1). Between 2013 and 2014, the age-adjusted rate of death involving methadone remained unchanged; however, the age-adjusted rate of death involving natural and semisynthetic opioid pain relievers, heroin, and synthetic opioids, other than methadone (e.g., fentanyl) increased 9%, 26%, and 80%, respectively. The sharp increase in deaths involving synthetic opioids, other than methadone, in 2014 coincided with law enforcement reports of increased availability of illicitly manufactured fentanyl, a synthetic opioid; however, illicitly manufactured fentanyl cannot be distinguished from prescription fentanyl in death certificate data. These findings indicate that the opioid overdose epidemic is worsening. There is a need for continued action to prevent opioid abuse, dependence, and death, improve treatment capacity for opioid use disorders, and reduce the supply of illicit opioids, particularly heroin and illicit fentanyl.

Protective effects of intravenous anesthetics on kidney tissue in obstructive jaundice

PubMed Central

Hatipoglu, Sinan; Yildiz, Huseyin; Bulbuloglu, Ertan; Coskuner, Ismail; Kurutas, Ergul Belge; Hatipoglu, Filiz; Ciralik, Harun; Berhuni, Mehmet Sait

2014-01-01

AIM: To evaluate the protective effects on kidney tissue of frequently used intravenous anesthetics (ketamine, propofol, thiopental, and fentanyl) in rats with obstructive jaundice. METHODS: There is an increased incidence of postoperative acute renal failure in patients with obstructive jaundice. Thirty-two Wistar-albino rats were randomly divided into four equal groups. Laparatomy was performed on each animal in the four groups and common bile ducts were ligated and severed on day 0. After 7 d, laparotomy was again performed using ketamine, propofol, thiopental, or fentanyl anesthesia whose antioxidative properties are well known in oxidative stress in a rat liver model of obstructive jaundice. After 2 h, the rats were sacrificed. Renal tissue specimens were analyzed for catalase, superoxide dismutase and malondialdehyde enzymes activities. All values are expressed as the mean ± SD. P values less than 0.05 were considered statistically significant. RESULTS: All animals survived without complications until the end of the study. Enlargement in the bile duct and obstructive jaundice were observed in all rats. Catalase was found to be significantly lower in the fentanyl group than in the ketamine (P = 0.039), propofol (P = 0.012), and thiopental (P = 0.001) groups. Superoxide dismutase activities were similar in all groups (P > 0.05). Malondialdehyde was found to be significantly lower in the ketamine group than in the propofol (P = 0.028), thiopental (P = 0.002) and fentanyl (P = 0.005) groups. Malondialdehyde was also lower in the fentanyl group than in the thiopental group (P = 0.001). The results showed that obstructive jaundice sensitizes renal tissue to damage under the different anesthetics. CONCLUSION: Among the agents tested, ketamine and propofol generated the least amount of oxidative stres on renal tissues in this rat model of obstructive jaundice created by common bile duct ligation. The importance of free radical injury in renal tissue in obstructive jaundice under different intravenous anesthetics during hepatobiliary and liver transplant surgery should be considered for prevention of postoperative acute renal failure. PMID:24695809

Clinical Efficacy of Intravenous Lidocaine for Thyroidectomy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Choi, Geun Joo; Kang, Hyun; Ahn, Eun Jin; Oh, Jong In; Baek, Chong Wha; Jung, Yong Hun; Kim, Jin Yun

2016-12-01

Systemic lidocaine has analgesic and anti-inflammatory effects. The purpose of this prospective, randomized, double-blind study was to evaluate the effects of intravenous lidocaine on pain following thyroidectomy. Fifty-eight adult patients scheduled for total thyroidectomy were randomly allocated to receive a 1.5 mg/kg lidocaine bolus followed by a 2 mg/kg/h infusion during surgery, or the same volume of normal saline (control). After thyroidectomy, we evaluated postoperative pain, nausea, fentanyl consumption, frequency of pushing the button (FPB) for patient-controlled analgesia (PCA), High-sensitivity C-reactive protein (hs-CRP) in serum, and patient satisfaction scores regarding the recovery process. Postoperative pain and nausea scores were significantly lower in the lidocaine group for the first 4 h following thyroidectomy, compared to the control group. Fentanyl consumption and FPB for the PCA were also significantly reduced in the lidocaine group for 4 h following thyroidectomy, and hs-CRP was significantly less in the lidocaine group at postoperative days 1 and 3. Furthermore, satisfaction scores were significantly higher in the lidocaine group compared to the control group. Intravenous lidocaine effectively reduced postoperative pain and nausea following thyroidectomy as well as improved the quality of recovery. Clinicaltrials.gov NCT01608360.

Patch Time Allocation and Oviposition Behavior in Response to Patch Quality and the Presence of a Generalist Predator in Meteorus pulchricornis (Hymenoptera: Braconidae)

PubMed Central

Sheng, Sheng; Ling, Meng; Fu-an, Wu; Baoping, Li

2015-01-01

Foraging parasitoids often must estimate local risk of predation just as they must estimate local patch value. Here, we investigate the effects a generalist predator Chlaenius bioculatus (Coleoptera: Carabidae), has on the oviposition behavior and the patch residence decisions of a solitary parasitoid Meteorus pulchricornis (Hymenoptera: Braconidae) in response to the varying host quality of Spodoptera litura (Lepidoptera: Noctuidae) larvae (L2 and L4). M. pulchricornis attacked more L4 than on L2 hosts, with the difference in attack rate varying depending on predation treatments, greater in the presence (either actively feeding or not) of the predator than in the absence of it. The parasitoid attacked fewer L2 and L4 hosts when the predator was actively feeding than when it was not feeding or not present in the patch. M. pulchricornis decreased the patch leaving tendency with increasing rejections of hosts, but increased the tendency in response to the presence of the predator as compared with the absence of it, and furthermore, increased the patch leaving tendency when the predator was actively feeding as compared with when it was not. Our study suggests that M. pulchricornis can exploit high quality patches while minimizing predation risk, by attacking more hosts in high quality patches while reducing total patch time in response to risk of predation. PMID:25943317

Laparoscopic repair of perforated peptic ulcer: patch versus simple closure.

PubMed

Abd Ellatif, M E; Salama, A F; Elezaby, A F; El-Kaffas, H F; Hassan, A; Magdy, A; Abdallah, E; El-Morsy, G

2013-01-01

Laparoscopic correction of perforated peptic ulcer (PPU) has become an accepted way of management. Patch omentoplasty stayed for decades the main method of repair. The goal of the present study was to evaluate whether laparoscopic simple repair of PPU is as safe as patch omentoplasty. Since June 2005, 179 consecutive patients of PPU were treated by laparoscopic repair at our centers. We conducted a retrospective chart review in December 2012. Group I (patch group) included patients who were treated with standard patch omentoplasty. Group II (non-patch group) included patients who received simple repair without patch. From June 2007 to Dec. 2012, 179 consecutive patients of PPU who were treated by laparoscopic repair at our centers were enrolled in this multi-center retrospective study. 108 patients belong to patch group. While 71 patients were treated with laparoscopic simple repair. Operative time was significantly shorter in group II (non patch) (p = 0.01). No patient was converted to laparotomy. There was no difference in age, gender, ASA score, surgical risk (Boey's) score, and incidence of co-morbidities. Both groups were comparable in terms of hospital stay, time to resume oral intake, postoperative complications and surgical outcomes. Laparoscopic simple repair of PPU is a safe procedure compared with the traditional patch omentoplasty in presence of certain selection criteria. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch.

PubMed

Molinuevo, José L; Frölich, Lutz; Grossberg, George T; Galvin, James E; Cummings, Jeffrey L; Krahnke, Tillmann; Strohmaier, Christine

2015-01-01

OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer's disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer's disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48 weeks of double-blind treatment, high-dose patch produced greater functional and cognitive benefits compared with 9.5 mg/24 h patch. Using OPTIMA data, a post-hoc responder analysis was performed to firstly, compare the proportion of patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus 9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of decline. 'Improvers' were patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) by ≥4 points from baseline, and did not decline on the instrumental domain of the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-IADL). 'Non-decliners' were patients who did not decline on either scale. Overall, 265 patients randomized to 13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the intention-to-treat population and were included in the analyses. Significantly more patients were 'improvers' with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10 (3.7%); P = 0.023). A significantly greater proportion of patients were 'non-decliners' with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71 (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of 13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind baseline did not consistently predict effects at Weeks 24 or 48. More patients with mild-to-moderate Alzheimer's disease who are titrated to 13.3 mg/24 h rivastigmine patch at time of decline are 'improvers' or 'non-decliners' i.e. show responses on cognition and activities of daily living compared with patients remaining on 9.5 mg/24 h patch. Clinicaltrials.gov identifier: NCT00506415; registered July 20, 2007.

Comparison of two satellite imaging platforms for evaluating quasi-circular vegetation patch in the Yellow River Delta, China

NASA Astrophysics Data System (ADS)

Liu, Qingsheng; Liang, Li; Liu, Gaohuan; Huang, Chong

2017-09-01

Vegetation often exists as patch in arid and semi-arid region throughout the world. Vegetation patch can be effectively monitored by remote sensing images. However, not all satellite platforms are suitable to study quasi-circular vegetation patch. This study compares fine (GF-1) and coarse (CBERS-04) resolution platforms, specifically focusing on the quasicircular vegetation patches in the Yellow River Delta (YRD), China. Vegetation patch features (area, shape) were extracted from GF-1 and CBERS-04 imagery using unsupervised classifier (K-Means) and object-oriented approach (Example-based feature extraction with SVM classifier) in order to analyze vegetation patterns. These features were then compared using vector overlay and differencing, and the Root Mean Squared Error (RMSE) was used to determine if the mapped vegetation patches were significantly different. Regardless of K-Means or Example-based feature extraction with SVM classification, it was found that the area of quasi-circular vegetation patches from visual interpretation from QuickBird image (ground truth data) was greater than that from both of GF-1 and CBERS-04, and the number of patches detected from GF-1 data was more than that of CBERS-04 image. It was seen that without expert's experience and professional training on object-oriented approach, K-Means was better than example-based feature extraction with SVM for detecting the patch. It indicated that CBERS-04 could be used to detect the patch with area of more than 300 m2, but GF-1 data was a sufficient source for patch detection in the YRD. However, in the future, finer resolution platforms such as Worldview are needed to gain more detailed insight on patch structures and components and formation mechanism.

Patch use in time and space for a meso-predator in a risky world.

PubMed

Mukherjee, Shomen; Zelcer, Michal; Kotler, Burt P

2009-03-01

Predator-prey studies often assume a three trophic level system where predators forage free from any risk of predation. Since meso-predators themselves are also prospective prey, they too need to trade-off between food and safety. We applied foraging theory to study patch use and habitat selection by a meso-predator, the red fox. We present evidence that foxes use a quitting harvest rate rule when deciding whether or not to abandon a foraging patch, and experience diminishing returns when foraging from a depletable food patch. Furthermore, our data suggest that patch use decisions of red foxes are influenced not just by the availability of food, but also by their perceived risk of predation. Fox behavior was affected by moonlight, with foxes depleting food resources more thoroughly (lower giving-up density) on darker nights compared to moonlit nights. Foxes reduced risk from hyenas by being more active where and when hyena activity was low. While hyenas were least active during moon, and most active during full moon nights, the reverse was true for foxes. Foxes showed twice as much activity during new moon compared to full moon nights, suggesting different costs of predation. Interestingly, resources in patches with cues of another predator (scat of wolf) were depleted to significantly lower levels compared to patches without. Our results emphasize the need for considering risk of predation for intermediate predators, and also shows how patch use theory and experimental food patches can be used for a predator. Taken together, these results may help us better understand trophic interactions.

An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch.

PubMed

Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li

2017-01-01

We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet ® ) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration ( C max ), extended time to reach the C max and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration-time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.

SCI with Brain Injury: Bedside-to-Bench Modeling for Developing Treatment and Rehabilitation Strategies

DTIC Science & Technology

2012-10-01

GLUCONATE 1 SIMVASTATIN 2 SIMVASTATIN 1 METOPROLOL 1 METOPROLOL 1 Discharge  Medications Note that the length of stay in rehabilitation is shorter in SCVMC...ENOXAPARIN 3 ENOXAPARIN 3 GABAPENTIN 3 GABAPENTIN 2 DOXYCYCLINE 3 DOXYCYCLINE 1 LISINOPRIL 3 LISINOPRIL 1 CHLORHEXIDINE 2 CHLORHEXIDINE 2 METOPROLOL 2... METOPROLOL 2 DEXTROSE 2 DEXTROSE 1 MICONAZOLE 2 MICONAZOLE 1 HEPARIN 1 HEPARIN 3 FENTANYL 1 FENTANYL 2 BACLOFEN 1 BACLOFEN 1 FERROUS  SULFATE 1 FERROUS

Saving Lives on the Battlefield (Part II) - One Year Later: A Joint Theater Trauma System and Joint Trauma System Review of Prehospital Trauma Care in Combined Joint Operations Area-Afghanistan (CJOA-A)

DTIC Science & Technology

2015-01-01

medics’ aid bags? 8% 92% N/A TCCC Pain Management Are you using TCCC guidelines pain medications?4 42% 12% 46% Fentanyl 69% 31% N/A Ketamine 50% 50% N...A Wound (Combat) Pill Pack 4% 96% N/A What pain medication do your medics carry? Morphine5 92% 8% N/A Fentanyl 35% 65% N/A Ketamine 12% 88% N/A TCCC

Linezolid Is Associated with Serotonin Syndrome in a Patient Receiving Amitriptyline, and Fentanyl: A Case Report and Review of the Literature

PubMed Central

Savvari, Paraskevi; Kontogiannis, Sofoklis

2013-01-01

We report a unique case of an adverse interaction between the oxazolidinone antibiotic linezolid, the tricyclic antidepressant amitriptyline and the opioid analgesic fentanyl in a 68-year-old woman with advanced ischemic peripheral arterial disease and sepsis, under empirical antibiotic treatment. We also summarize the current relevant literature as identified via PubMed, EMBASE, and PsycINFO as well as reference sections of selected articles. PMID:23533900

Effects of Dexmedotomidine in the Coronary Artery Bypass Graft (CABG) Patient: A Pilot Study

DTIC Science & Technology

2006-04-14

diabetes, gross obesity, ejection fraction of< 30%, drug overdose , and any other condition or factor that the investigator felt might increase risk to the...addition of DEX to a post-op pain relief regimen has decreased the amount of morphine administered, as well as fentanyl .4’ 15’ 16 Studies have also...and pre-operative fentanyl . British Journal of Anaesthesia. 1992;68:126-131. 7. Jalonen, J., Hynynen, M., Kuitunen, A., Heikkila, H., Perttila, J

Offensive Use of Chemical Technologies by US Special Operations Forces in the Global War on Terrorism: The Nonlethal Option (Maxwell Paper, Number 37)

DTIC Science & Technology

2006-07-01

their application in the October 2002 Moscow 9 theater hostage crisis, where Russian special forces used the analgesic fentanyl to subdue occupying...devices throughout the theater. Female terrorists strapped explosive suicide devices to their bodies and positioned themselves among the hostages as...Federal’naia sluzhba bezopasnosti [FSBI, referred to hereafter as FSB) Al’fa, pumped fentanyl , a nonlethal incapacitating agent, into the theater to subdue

Analgesic Opioid Dose Is an Important Indicator of Postoperative Ileus Following Radical Cystectomy with Ileal Conduit: Experience in the Robotic Surgery Era

PubMed Central

Koo, Kyo Chul; Yoon, Young Eun; Chung, Byung Ha; Hong, Sung Joon

2014-01-01

Purpose Postoperative ileus (POI) is common following bowel resection for radical cystectomy with ileal conduit (RCIC). We investigated perioperative factors associated with prolonged POI following RCIC, with specific focus on opioid-based analgesic dosage. Materials and Methods From March 2007 to January 2013, 78 open RCICs and 26 robot-assisted RCICs performed for bladder carcinoma were identified with adjustment for age, gender, American Society of Anesthesiologists grade, and body mass index (BMI). Perioperative records including operative time, intraoperative fluid excess, estimated blood loss, lymph node yield, and opioid analgesic dose were obtained to assess their associations with time to passage of flatus, tolerable oral diet, and length of hospital stay (LOS). Prior to general anaesthesia, patients received epidural patient-controlled analgesia (PCA) consisted of fentanyl with its dose adjusted for BMI. Postoperatively, single intravenous injections of tramadol were applied according to patient desire. Results Multivariate analyses revealed cumulative dosages of both PCA fentanyl and tramadol injections as independent predictors of POI. According to surgical modality, linear regression analyses revealed cumulative dosages of PCA fentanyl and tramadol injections to be positively associated with time to first passage of flatus, tolerable diet, and LOS in the open RCIC group. In the robot-assisted RCIC group, only tramadol dose was associated with time to flatus and tolerable diet. Compared to open RCIC, robot-assisted RCIC yielded shorter days to diet and LOS; however, it failed to shorten days to first flatus. Conclusion Reducing opioid-based analgesics shortens the duration of POI. The utilization of the robotic system may confer additional benefit. PMID:25048497

Spinal anaesthesia with gamma hydroxybutyrate. A study in a rat model.

PubMed

Chanimov, M; Bahar, M; Cohen, M L; Brenner, R; Koifman, I; Grinshpon, Y

1999-05-01

Gamma hydroxybutyric acid, a central inhibitory neurotransmitter and a cerebral metabolite of gamma-aminobutyric acid, is present in high concentrations in the mammalian hypothalamus and basal ganglia. Its sodium salt gamma hydroxybutyrate has been effectively used as an intravenous anaesthetic agent, and as an oral sedative, and in the management of the alcohol withdrawal syndrome. In an animal model, using 72 Wistar strain rats allocated to one of six groups of 12 animals each, with implanted lumbar intrathecal catheters, we examined whether gamma hydroxybutyrate, 20% 40 microL (32 mg kg-1) administered alone or combined with fentanyl, gamma hydroxybutyrate 20% 20 microL (16 mg kg-1), fentanyl 0.005% 20 microL (4 mg kg-1) as an intrathecal bolus, provides intraoperative anaesthesia, comparable with that produced by intrathecal lignocaine. We demonstrated that gamma hydroxybutyrate, given by an intrathecal bolus in the rat model, produced reversible segmental antinociception, together with muscular relaxation of the abdominal wall and rear limbs. This is accompanied by moderate sedation without haemodynamic or respiratory depression. This agent may thus be promising for use as a spinal anaesthetic drug.

Rifampicin Lipid-Polymer hybrid nanoparticles (LIPOMER) for enhanced Peyer's patch uptake.

PubMed

Bachhav, Sagar S; Dighe, Vikas D; Kotak, Darsheen; Devarajan, Padma V

2017-10-30

The oral uptake of intact nanocarriers through Peyer's patches is an important uptake pathway. We report Rifampicin Lipid-Polymer hybrid nanoparticles (RIF-LIPOMER) using glyceryl monostearate as lipid and the mucoadhesive polymer, Gantrez, with the objective of balancing hydrophobicity and mucoadhesion for enhanced Peyer's patch uptake. RIF-LIPOMER was optimized for size, hydrophobicity, and mucoadhesion using Box-Behnken. Designed RIF-LIPOMER (RIF-LIPO-120) exhibited average particle size in the range 300-400nm with drug loading >12%. DSC and XRD confirmed complete amorphization. Contact angle and mucoadhesion force revealed that RIF-LIPO-120 exhibited greater hydrophobicity and lower mucoadhesion compared to Gantrez nanoparticles (RIF-GzNP). Comparative uptake of fluorescent labelled RIF-LIPO-120 and RIF-GzNP, through Peyer's patch following intraduodenal administration in rats, revealed the high accumulation of RIF-GzNP at the villi border, and high Peyer's patch uptake of RIF-LIPO-120. Furthermore, lower accumulation of RIF-LIPO-120 in the liver, compared to RIF-GzNP, suggested bypass of the portal circulation and lymphatic uptake through Peyer's patches. Significantly higher lung: plasma concentration ratio exhibited by RIF-LIPO-120 compared to RIF-GzNP confirmed the same (p<0.05). Our study demonstrated that optimization of hydrophobicity and mucoadhesion of nanoparticles could favor Peyer's patch uptake, which in turn could enable enhanced drug accumulation in the lungs with advantage in the therapy of pulmonary afflictions. Copyright © 2017 Elsevier B.V. All rights reserved.

Exhaustive comparison and classification of ligand-binding surfaces in proteins

PubMed Central

Murakami, Yoichi; Kinoshita, Kengo; Kinjo, Akira R; Nakamura, Haruki

2013-01-01

Many proteins function by interacting with other small molecules (ligands). Identification of ligand-binding sites (LBS) in proteins can therefore help to infer their molecular functions. A comprehensive comparison among local structures of LBSs was previously performed, in order to understand their relationships and to classify their structural motifs. However, similar exhaustive comparison among local surfaces of LBSs (patches) has never been performed, due to computational complexity. To enhance our understanding of LBSs, it is worth performing such comparisons among patches and classifying them based on similarities of their surface configurations and electrostatic potentials. In this study, we first developed a rapid method to compare two patches. We then clustered patches corresponding to the same PDB chemical component identifier for a ligand, and selected a representative patch from each cluster. We subsequently exhaustively as compared the representative patches and clustered them using similarity score, PatSim. Finally, the resultant PatSim scores were compared with similarities of atomic structures of the LBSs and those of the ligand-binding protein sequences and functions. Consequently, we classified the patches into ∼2000 well-characterized clusters. We found that about 63% of these clusters are used in identical protein folds, although about 25% of the clusters are conserved in distantly related proteins and even in proteins with cross-fold similarity. Furthermore, we showed that patches with higher PatSim score have potential to be involved in similar biological processes. PMID:23934772

Assessing the Potential Cost-Effectiveness of Microneedle Patches in Childhood Measles Vaccination Programs: The Case for Further Research and Development.

PubMed

Adhikari, Bishwa B; Goodson, James L; Chu, Susan Y; Rota, Paul A; Meltzer, Martin I

2016-12-01

Currently available measles vaccines are administered by subcutaneous injections and require reconstitution with a diluent and a cold chain, which is resource intensive and challenging to maintain. To overcome these challenges and potentially increase vaccination coverage, microneedle patches are being developed to deliver the measles vaccine. This study compares the cost-effectiveness of using microneedle patches with traditional vaccine delivery by syringe-and-needle (subcutaneous vaccination) in children's measles vaccination programs. We built a simple spreadsheet model to compute the vaccination costs for using microneedle patch and syringe-and-needle technologies. We assumed that microneedle vaccines will be, compared with current vaccines, more heat stable and require less expensive cool chains when used in the field. We used historical data on the incidence of measles among communities with low measles vaccination rates. The cost of microneedle vaccination was estimated at US$0.95 (range US$0.71-US$1.18) for the first dose, compared with US$1.65 (range US$1.24-US$2.06) for the first dose delivered by subcutaneous vaccination. At 95 % vaccination coverage, microneedle patch vaccination was estimated to cost US$1.66 per measles case averted (range US$1.24-US$2.07) compared with an estimated cost of US$2.64 per case averted (range US$1.98-US$3.30) using subcutaneous vaccination. Use of microneedle patches may reduce costs; however, the cost-effectiveness of patches would depend on the vaccine recipients' acceptability and vaccine effectiveness of the patches relative to the existing conventional vaccine-delivery method. This study emphasizes the need to continue research and development of this vaccine-delivery method that could boost measles elimination efforts through improved access to vaccines and increased vaccination coverage.

Monitoring cocaine use in substance-abuse-treatment patients by sweat and urine testing.

PubMed

Preston, K L; Huestis, M A; Wong, C J; Umbricht, A; Goldberger, B A; Cone, E J

1999-09-01

Sweat and urine specimens were collected from 44 methadone-maintenance patients to evaluate the use of sweat testing to monitor cocaine use. Paired sweat patches that were applied and removed weekly (on Tuesdays) were compared with 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays. All patches (N = 930) were extracted in 2.5 mL of solvent and analyzed by ELISA immunoassay (cutoff concentration 10 ng/mL); a subset of patches (N = 591) was also analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine, benzoylecgonine (BZE), and ecgonine methyl ester (EME) (cutoff concentration 5 ng/mL). Urine specimens were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL) and subsets were analyzed by TDx (semiquantitative, LOD 30 ng/mL) and by GC-MS for cocaine (LOD 5 ng/mL). Results were evaluated to (1) determine the relative amounts of cocaine and its metabolites in sweat; (2) assess replicability in duplicate patches; (3) compare ELISA and GC-MS results for cocaine in sweat; and (4) compare the detection of cocaine use by sweat and urine testing. Cocaine was detected by GC-MS in 99% of ELISA-positive sweat patches; median concentrations of cocaine, BZE, and EME were 378, 78.7, and 74 ng/mL, respectively. Agreement in duplicate patches was approximately 90% by ELISA analysis. The sensitivity, specificity, and efficiency of sweat ELISA cocaine results as compared with sweat GC-MS results were 93.6%, 91.3%, and 93.2%, respectively. The sensitivity, specificity, and efficiency between ELISA sweat patch and EMIT urine results were 97.6%, 60.5%, and 77.7%, respectively. These results support the use of sweat patches for monitoring cocaine use, though further evaluation is needed.

Membrane and functional characterization of lymphoid and macrophage populations of Peyer's patches from adult and aged mice.

PubMed Central

Vĕtvicka, V; Tlaskalová-Hogenová, H; Fornůsek, L; Ríhová, B; Holán, V

1987-01-01

Properties of macrophages isolated from Peyer's patches were compared with properties of peritoneal macrophages. We found a very low expression of all types of Fc receptors as well as a low expression of Ia antigens on Peyer's patch macrophages. No substantial changes in the levels of FcR and Ia antigen expression were found during the process of ageing. The investigation of phagocytic activity showed the activated state of Peyer's patch macrophages. Comparing the surface markers of lymphocytes obtained from Peyer's patches of mice of different ages, we found no differences in the numbers of sIg+, Thy-+ or L3T4+ lymphocytes. The numbers of FcR+ and Lyt 2.2+ lymphocytes decreased markedly with age. PMID:3477526

Electromagnetic Scattering From a Polygonal Thin Metallic Plate Using Quadrilateral Meshing

NASA Technical Reports Server (NTRS)

Deshpande, Manohar D.

2003-01-01

The problem of electromagnetic (EM) scattering from irregularly shaped, thin, metallic flat plates in free space is solved using the electric field integral equation (EFIE) approach in conjunction with the method of moments (MoM) with quadrilateral meshing. An irregularly shaped thin plate is discretized into quadrilateral patches and the unknown electric surface current over the plate is expressed in terms of proper basis functions over these patches. The basis functions for the electric surface current density that satisfy the proper boundary conditions on these quadrilateral patches are derived. The unknown surface current density on these quadrilateral patches is determined by setting up and solving the electric field integral equation by the application of the MoM. From the knowledge of the surface current density, the EM scattering from various irregularly shaped plates is determined and compared with the earlier published results. The novelty in the present approach is the use of quadrilateral patches instead of well known and often used triangular patches. The numerical results obtained using the quadrilateral patches compare favorably with measured results.

Current usage and future directions for the bovine pericardial patch.

PubMed

Li, Xin; Guo, Yuanyuan; Ziegler, Kenneth R; Model, Lynn S; Eghbalieh, Sammy D D; Brenes, Robert A; Kim, Susun T; Shu, Chang; Dardik, Alan

2011-05-01

Bovine pericardium (BP) is widely used in surgery and is commonly used as a patch after arteriotomy in cardiovascular surgery. BP patches have several advantages compared with prosthetic patches, including superior biocompatability, easy handling, less suture line bleeding, and possibly reduced rates of infection. These advantages of BP have led to its common use during carotid endarterectomy (CEA). However, long-term clinical results reported after CEA have suggested several issues that may be related to the patch, including restenosis, pseudoaneurysm formation, infection, fibrosis, calcification, and thrombosis. These complications may diminish the long-term efficacy of CEA and suggest potential areas for improvement of surgical patches. Understanding the mechanisms by which BP heals after patch angioplasty may lead to next generation tissue-engineered patches. Published by Elsevier Inc.

Current usage and future directions for the bovine pericardial patch

PubMed Central

Li, Xin; Guo, Yuanyuan; Ziegler, Kenneth; Model, Lynn; Eghbalieh, Sammy D. D.; Brenes, Robert; Kim, Susun; Shu, Chang; Dardik, Alan

2010-01-01

Bovine pericardium is widely used in surgery and is commonly used for a patch after arteriotomy during cardiovascular surgery. Bovine pericardial patches have several advantages compared to prosthetic patches, including superior biocompatability, easy handling, less suture line bleeding and possibly reduced rates of infection. These advantages of bovine pericardium have led to its common use during carotid endarterectomy. However, long-term clinical results reported after carotid endarterectomy have suggested several issues that may be related to the patch including restenosis, pseudoaneurysm formation, infection, fibrosis, calcification and thrombosis. These complications may diminish the long-term efficacy of carotid endarterectomy and suggest potential areas for improvement of surgical patches. Understanding the mechanisms by which bovine pericardium heals after patch angioplasty may lead to next generation tissue engineered patches. PMID:21276709

Reversal of overdose on fentanyl being illicitly sold as heroin with naloxone nasal spray: A case report.

PubMed

Fareed, Ayman; Buchanan-Cummings, Ann Marie; Crampton, Kelli; Grant, Angela; Drexler, Karen

2015-08-01

This is a case report describing a reversal of fentanyl overdose with naloxone nasal spray. The patient was not aware that he overdosed on fentanyl being sold as heroin. The Veterans Health Administration (VHA) has implemented an initiative to provide education for veterans, their families, friends and significant others about opioid overdose and use of naloxone reversal kits. The Atlanta VA Medical Center adopted this program to reduce the risk of opioid overdose in high risk patients. Over the past year, we provided educational sessions for 63 veterans and their families. We also prescribed 41 naloxone kits. We have received three reports of opioid overdose reversal with use of naloxone kits prescribed by the Atlanta VA Medical Center. The authors recommend that public health administrators and policy makers advocate for the implementation of these programs to reduce the rising number of overdose death in the United States and worldwide. © American Academy of Addiction Psychiatry.

Effects of acupuncture and transcutaneous stimulation analgesia on plasma hormone levels during and after major abdominal surgery.

PubMed

Kho, H G; Kloppenborg, P W; van Egmond, J

1993-05-01

The effects of acupuncture and transcutaneous electrical stimulation (TES) on plasma adrenaline (A) and noradrenaline (NA), adrenocorticotropic hormone (ACTH), beta-endorphin (beta E), anti-diuretic hormone (ADH) and hydrocortisone (cortisol) were evaluated during and, for four days after surgery in 42 male patients submitted to a standardized major abdominal operation in a comparative study of three different anaesthetic techniques. Group 1 received acupuncture and transcutaneous stimulation as the main non-pharmacological analgesic during surgery. Group 2 received moderate-dose fentanyl (initial bolus of 10 micrograms kg-1 followed by continuous infusion of 5 micrograms kg-1 h-1 for the first hour, and then 4 micrograms kg-1 h-1. Group 3 received a combination of both methods. In all three groups analgesia was supplemented, if necessary, by small bolus injections of 50 micrograms fentanyl. Anaesthesia was induced in all groups with thiopentone 5 mg kg-1 and vecuronium 0.1 mg kg-1 and patients were ventilated (N2O:O2 = 2:1) to achieve normocapnia without the use of a halogenated agent. Pre-operatively acupuncture plus TES in Groups 1 and 3 led to a rise in beta E (P < 0.05) without changes of haemodynamics. After intubation beta E did not increase further. Intubation in Group 2 led to an increase of beta E (P < 0.05) also, and to a rise in pulse rate and blood pressure (P < 0.05) in all three groups. Per-operatively acupuncture plus TES in Group 1 showed a response of circulating NA and cortisol similar to that in Groups 2 and 3, whereas the responses of the circulating A, ACTH, beta E and ADH in Group 1 were more pronounced (P < 0.01). Post-operatively no differences in the hormonal profiles could be discerned between the groups with or without acupuncture plus TES (Group 2 vs. Group 3) nor between those with or without moderate-dose fentanyl anaesthesia (Group 1 vs. Group 3). It is concluded that acupuncture and TES have no effect on the cardiovascular response to laryngoscopy and intubation. They can replace moderate-dose fentanyl anaesthesia in major abdominal surgery at the cost of a more enhanced per-operative neuroendocrine stress response, which does not, however, influence the postoperative hormonal profiles nor the rapidity of return to pre-operative values.

Incidence of delayed hair re-growth, pruritus, and urinary retention after epidural anaesthesia in dogs.

PubMed

Kalchofner Guerrero, K S; Guerrero, T G; Schweizer-Kölliker, M; Ringer, S K; Hässig, M; Bettschart-Wolfensberger, R

2014-04-16

Delayed hair re-growth, pruritus and urinary retention are known complications after epidural anaesthesia in dogs. The aim of this study was to prospectively evaluate the effect of epidurally administered drugs on the occurrence of these complications in dogs. Ninety dogs were included in this study. Eighty client-owned dogs undergoing surgery were randomly assigned to one of three epidural treatment groups: either morphine and bupivacaine (MB), bupivacaine (B), or saline solution 0.9% (S) was administered epidurally to these patients. Ten dogs were only clipped in the lumbosacral area (C). Follow-up started 4 weeks after clipping and was performed every 4-5 weeks in cases of delayed hair re-growth or pruritus. Hair re-growth in the lumbosacral area was observed and compared to hair re-growth in the surgical field and the fentanyl patch area. Cytological analysis and a trichogram were performed if hair re-growth was delayed after 6 months. Time interval to first urination postoperatively was recorded (n = 80). Hair re-growth was delayed in 11 dogs (12.2%; B: n = 7, S: n = 2, MB: n = 1, C: n = 1) with no differences between groups. Pruritus was evident in two dogs (2.2%; MB: n = 1, S: n = 1). After 6 months, hair had started to re-grow in all but one dog (B). After 10 months the coat of this dog had re-grown. Time to first urination did not differ between groups. No direct correlation between the particular drugs injected epidurally and delayed hair re-growth, pruritus and urinary retention could be shown. Dog owners should be informed that hair re-growth after epidural anaesthesia could be markedly delayed.

Rotator cuff repair with a tendon-fibrocartilage-bone composite bridging patch.

PubMed

Ji, Xiaoxi; Chen, Qingshan; Thoreson, Andrew R; Qu, Jin; An, Kai-Nan; Amadio, Peter C; Steinmann, Scott P; Zhao, Chunfeng

2015-11-01

To compare the mechanical performance of a rotator cuff repaired with a novel tendon-fibrocartilage-bone composite bridging patch vs the traditional Mason-Allen repair in an in vitro canine model. Twenty shoulders and 10 bridging patches from patellar tendon were harvested. The patches were trimmed and sliced into 2 layers. An infraspinatus tendon tear was created in each shoulder. Modified Mason-Allen sutures were used to repair the infraspinatus tendon to the greater tuberosity, with or without the bridging patch (bridging patch group and controls, respectively). Shoulders were loaded to failure under displacement control at a rate of 0.5mm/s. The ultimate tensile load was significantly higher in the bridging patch group than control (mean [SD], 365.46 [36.45] vs 272.79 [48.88] N; P<.001). Stiffness at the greater tuberosity repair site and the patch-infraspinatus tendon repair site was significantly higher than the control repair site (93.96 [27.72] vs 42.62 [17.48] N/mm P<.001; 65.94 [24.51] vs 42.62 [17.48] N/mm P=.02, respectively). The tendon-fibrocartilage-bone composite bridging patch achieved higher ultimate tensile load and stiffness at the patch-greater tuberosity repair site compared with traditional repair in a canine model. This composite tissue transforms the traditional tendon-to-bone healing interface (with dissimilar tissues) into a pair of bone-to-bone and tendon-to-tendon interfaces, which may improve healing quality and reduce retear rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Patch time allocation and oviposition behavior in response to patch quality and the presence of a generalist predator in Meteorus pulchricornis (Hymenoptera: Braconidae).

PubMed

Sheng, Sheng; Ling, Meng; Fu-An, Wu; Baoping, Li

2015-01-01

Foraging parasitoids often must estimate local risk of predation just as they must estimate local patch value. Here, we investigate the effects a generalist predator Chlaenius bioculatus (Coleoptera: Carabidae), has on the oviposition behavior and the patch residence decisions of a solitary parasitoid Meteorus pulchricornis (Hymenoptera: Braconidae) in response to the varying host quality of Spodoptera litura (Lepidoptera: Noctuidae) larvae (L2 and L4). M. pulchricornis attacked more L4 than on L2 hosts, with the difference in attack rate varying depending on predation treatments, greater in the presence (either actively feeding or not) of the predator than in the absence of it. The parasitoid attacked fewer L2 and L4 hosts when the predator was actively feeding than when it was not feeding or not present in the patch. M. pulchricornis decreased the patch leaving tendency with increasing rejections of hosts, but increased the tendency in response to the presence of the predator as compared with the absence of it, and furthermore, increased the patch leaving tendency when the predator was actively feeding as compared with when it was not. Our study suggests that M. pulchricornis can exploit high quality patches while minimizing predation risk, by attacking more hosts in high quality patches while reducing total patch time in response to risk of predation. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Effect of exposure to fentanyl aerosol in mice on breathing pattern and respiratory variables.

PubMed

Manral, Laxmi; Muniappan, Natrajan; Gupta, Pradeep K; Ganesan, Kumaran; Malhotra, Ramesh Chandra; Vijayaraghavan, Rajagopalan

2009-01-01

The breathing pattern of mice that were exposed to fentanyl aerosol was studied (2.7, 5.7, 6.0, 10.0, and 23.6 microg/m(3); for 1 hour), using dimethyl sulfoxide as a vehicle. This study was conducted in a head-only exposure assembly. Body plethysmographs connected to a volumetric pressure transducer were used to capture the respiratory signals, and an on-line computer program capable of recognizing the changes in the breathing pattern was used for monitoring the respiratory pattern. The response of mice to fentanyl exposure was found to be concentration dependent. A lower concentration (2.7 microg/m(3)) showed fast recovery and no mortality, while 100% mortality was observed at a higher concentration (23.6 microg/m(3)). No sensory, pulmonary irritation, and airway limitation in mice was observed, and death occurred probably due to respiratory depression. The concentration that decreased 50% of the respiratory frequency (RD(50)) was estimated to be 6.4 microg/m(3). The extrapolated human threshold limit value, calculated from the RD(50) value, was found to be 0.192 microg/m(3). The concentration that caused 50% mortality in exposed mice (LC(50)) was estimated to be 8.8 microg/m(3). This study shows that aerosolized fentanyl does not cause sensory and pulmonary irritation, and since the RD(50) and LC(50) are very close with a low safety margin, this type of sedative should not be used as an incapacitating agent.

Complications associated with intravenous midazolam and fentanyl sedation in patients undergoing minor oral surgery

PubMed Central

2017-01-01

Background Anxiety control remains an important concern in dental practice. We evaluated the incidence, nature, and sequelae of complications during and after minor oral surgeries performed under intravenous midazolam and fentanyl sedation using the titration technique. Methods The medical records of patients who had undergone minor oral surgeries under moderate intravenous midazolam and fentanyl sedation at our institution between January 1, 2015 and December 31, 2015 were retrospectively evaluated. Age, sex, body mass index, medical history, American Society of Anesthesiologists (ASA) classification, indications for sedation, amount of sedative used, surgical duration, and recovery time were evaluated for all patients. Results In total, 107 patients aged 9–84 years were included. ASA class I and class II were observed for 56.1% and 43.9% patients, respectively. Complications associated with sedation occurred in 11 (10.2%) patients. There were no serious adverse events. Oxygen saturation reached 95% during the procedure in six patients; this was successfully managed by stimulating the patients to take a deep breath. Two patients exhibited deep sedation and one exhibited paradoxical excitement. After the procedure, one patient experienced nausea without vomiting and one exhibited a prolonged recovery time. The surgical procedures were completed in all patients. Obesity was found to be significantly associated with sedation-related complications. Conclusions Our results suggest that complications associated with intravenous midazolam and fentanyl sedation using the titration technique for minor oral surgeries are mostly minor and can be successfully managed with no prolonged sequelae. PMID:29090250

Validation of a novel epicutaneous delivery system for patch testing of house dust mite-hypersensitive dogs.

PubMed

Olivry, Thierry; Linder, Keith E; Paps, Judy S; Bizikova, Petra; Dunston, Stan; Donne, Nathalie; Mondoulet, Lucie

2012-12-01

Patch tests with allergens are used for the evaluation of cellular hypersensitivity to food and environmental allergens in dogs and humans with atopic dermatitis. Viaskin is a novel allergen epicutaneous delivery system that enhances epidermal allergen capture by immune cells. To compare the use of Viaskin and Finn chamber patch tests in dogs hypersensitive to mite allergens. Empty control or Dermatophagoides farinae house dust mite-containing Viaskin or Finn chamber patches were applied to the thoracic skin of six mite-hypersensitive Maltese-beagle crossbred atopic dogs. Lesions were graded 49 and 72 h after patch test application, and skin biopsies were collected after 72 h. Overall microscopic inflammation, eosinophil and T-lymphocyte infiltrations were scored. Positive macroscopic patch test reactions developed at five of six Viaskin application sites and four of six Finn chamber application sites. Median microscopic epidermal and dermal inflammation, as well as eosinophil and CD3 T-lymphocyte dermal scores were always higher in biopsies collected at Viaskin than at Finn chamber sites. Microscopic inflammation scores were significantly higher after mite allergen-containing Viaskin compared with empty patches, but this was not the case for mite-containing Finn chambers compared with control chambers. Scores obtained using Viaskin were not significantly different from those obtained using Finn chambers. Macroscopic and microscopic scores were significantly correlated. In mite-allergic dogs, Viaskin epicutaneous delivery systems appear to induce stronger allergen-specific inflammation than currently used Finn chamber patch tests. Consequently, Viaskin patches might offer a better alternative for screening cellular hypersensitivity to food and environmental allergens. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

An extended patch-dynamic framework for food chains in fragmented landscapes

PubMed Central

Liao, Jinbao; Chen, Jiehong; Ying, Zhixia; Hiebeler, David E.; Nijs, Ivan

2016-01-01

Habitat destruction, a key determinant of species loss, can be characterized by two components, patch loss and patch fragmentation, where the former refers to the reduction in patch availability, and the latter to the division of the remaining patches. Classical metacommunity models have recently explored how food web dynamics respond to patch loss, but the effects of patch fragmentation have largely been overlooked. Here we develop an extended patch-dynamic model that tracks the patch occupancy of the various trophic links subject to colonization-extinction-predation dynamics by incorporating species dispersal with patch connectivity. We found that, in a simple food chain, species at higher trophic level become extinct sooner with increasing patch loss and fragmentation due to the constraint in resource availability, confirming the trophic rank hypothesis. Yet, effects of fragmentation on species occupancy are largely determined by patch loss, with maximal fragmentation effects occurring at intermediate patch loss. Compared to the spatially explicit simulations that we also performed, the current model with pair approximation generates similar community patterns especially in spatially clustered landscapes. Overall, our extended framework can be applied to model more complex food webs in fragmented landscapes, broadening the scope of existing metacommunity theory. PMID:27608823

Spatial and temporal variation in sponge spicule patches at Station M, northeast Pacific.

PubMed

Laguionie-Marchais, C; Kuhnz, L A; Huffard, C L; Ruhl, H A; Smith, K L

Changes in habitat-forming organisms can have complex consequences for associated species. Sessile epibenthic glass "plate" sponges (Porifera: Hexactinellida) are conspicuous inhabitants of soft-sediment abyssal areas and their siliceous spicules create persistent spicule patches on the seafloor. Sponge spicule patch density, spatial dispersion, and percent cover were examined over a seven-year period (2006-2013) using remotely operated vehicle videos from Station M in the abyssal northeast Pacific (50˚00N, 123˚00W, ~4,000 m depth). There was an apparent large increase in newly dead plate sponges in February 2007 compared with December 2006, with this trend continuing through June 2007 (mean 0.03 % cover increasing to 0.33 %). A second increase in mean percent cover of dead plate sponges occurred from May 2011 (0.24 %) through June 2012 (0.60 %). Among the 28 megafaunal taxa occurring in association with the patches, the distributions of three taxa [two sponge taxa (Porifera) and brittle stars (Ophiuroidea)] suggested selectivity for the sponge spicule patches. The community structure of visible megafauna within sponge spicule patches was different when compared with that outside the patches suggesting that the sponges, after death, provide preferred habitat patches for certain benthic megafauna. These findings indicate that sponge spicule patches contribute to habitat heterogeneity in space and time.

Palliative Care Development in Kyrgyzstan.

PubMed

Mukambetov, Aibek; Sabyrbekova, Taalaigul; Asanalieva, Lola; Sadykov, Ilim; Connor, Stephen R

2018-02-01

Palliative care began in Kyrgyzstan in 2005 as a pilot home-based care program in Osh Cancer Center and was supported by a small group of nurses and one physician from Scotland. In 2010, the Soros Foundation-Kyrgyzstan and the Open Society Foundation's International Palliative Care Initiative began supporting work on palliative care policy, legislation, essential medicine availability, education, advocacy, and implementation. A Ministry of Health working group was established to lead this initiative, and technical assistance was provided by an international palliative care consultant. Work began with a national needs assessment, which identified the existing barriers to the provision of quality palliative care, and recommendations were made to the working group to address these challenges. Today, palliative care is included in many national health care policies and laws, a national palliative care association has been established, undergraduate medical and nursing education include elements of palliative care, oral morphine and fentanyl patches are now available in parts of the country, inpatient services exist in the National Cancer Center in Osh and Bishkek, two tuberculosis hospitals with multidrug resistant/extensively drug resistant, and home care services in Osh and Bishkek. Public information campaigns and advocacy activities continue to increase public awareness about palliative care and press government action. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Probe-fed semi circular microstrip antenna vis-à-vis circular microstrip antenna: a necessary revisit

NASA Astrophysics Data System (ADS)

Ghosh, S. K.; Varshney, S. K.; Chakraborty, S.; Singh, L. L. K.; Chattopadhyay, S.

2018-03-01

Microstrip patch antenna of semicircular geometry has been investigated in view of miniaturization of conventional circular geometry. The precise operating frequency of the semicircular microstrip patch antenna is the most significant parameter to be determined in order to design such antenna system to achieve the optimum performance. In the present investigation an improved formulation is presented for accurate determination of the resonant frequency of semicircular patch. Also, the radiation property of such patch is thoroughly investigated. Through comparisons are documented amongst the circular and semicircular patches. It is revealed that, the semicircular patch offers more better radiation performance compared to circular.

Long-term effectiveness of rivastigmine patch or capsule for mild-to-severe Alzheimer's disease: a meta-analysis.

PubMed

Su, Jiangli; Liu, Yang; Liu, Yu; Ren, Liqun

2015-01-01

To evaluate the long-term effectiveness of rivastigmine patch or capsule on mild to severe Alzheimer's disease (AD). We performed a meta-analysis of 17 studies regarding the treatment effectiveness of rivastigmine patch or capsule on mild-to-severe AD. Significant difference exists between treatment with rivastigmine patch or capsule and placebo groups (p-value < 0.001). In the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score evaluation, a negative weighted mean difference (WMD) was observed in overall and mild-moderate groups after rivastigmine treatment. And in ADAS-ADL score evaluation, a positive WMD was observed in overall groups after rivastigmine treatment. Moreover, WMD value is lower in patch administration subgroup compared to that of capsule administration subgroup. Rivastigmine treatment shows a positive result of improving the condition of patients with mild-to-severe AD. Patch administration shows a stronger effect on decreasing ADAS-Cog score compared to capsule administration.

Plasma concentrations of lidocaine in dogs following lidocaine patch application over an incision compared to intact skin.

PubMed

Joudrey, S D; Robinson, D A; Kearney, M T; Papich, M G; da Cunha, A F

2015-12-01

The objective was to compare plasma lidocaine concentrations when a commercially available 5% lidocaine patch was placed on intact skin vs. an incision. Our hypothesis was that greater absorption of lidocaine would occur from the incision site compared to intact skin. Ten dogs were used in a crossover design. A patch was placed over an incision, and then after a washout period, a patch was placed over intact skin. Plasma lidocaine concentrations were measured at patch placement; 20, 40 and 60 min; and 2, 4, 6, 12, 24, 36, 48, 72 and 96 h after patch placement. After patch removal, the skin was graded using a subjective skin reaction system. No dogs required rescue analgesia, and no toxicity or skin reaction was noted. Mean ± SD AUC and CMAX were 3054.29 ± 1095.93 ng·h/mL and 54.1 ± 15.84 ng/mL in the Incision Group, and 2269.9 ± 1037.08 ng·h/mL and 44.5 ± 16.34 ng/mL in the No-Incision Group, respectively. The AUC was significantly higher in the Incision Group. The results of the study demonstrate that the actual body exposure to lidocaine was significantly higher when an incision was present compared to intact skin. No adverse effects were observed from either treatment. Efficacy was not evaluated. © 2015 John Wiley & Sons Ltd.

The safety and effectiveness of a long-acting transdermal fentanyl solution compared with oxymorphone for the control of postoperative pain in dogs: a randomized, multicentered clinical study

PubMed Central

Martinez, S A; Wilson, M G; Linton, D D; Newbound, G C; Freise, K J; Lin, T-L; Clark, T P

2014-01-01

A prospective, double-blinded, positive-controlled, multicenter, noninferiority study was conducted to evaluate the safety and effectiveness of transdermal fentanyl solution (TFS) compared with oxymorphone for the control of postoperative pain in dogs. Five hundred and two (502) client-owned dogs were assigned to a single dose of TFS (2.7 mg/kg) applied 2–4 h prior to surgery or oxymorphone hydrochloride (0.22 mg/kg) administered subcutaneously 2–4 h prior to surgery and q6h through 90 h. Pain was evaluated over 4 days by blinded observers using a modified Glasgow composite pain scale, and the a priori criteria for treatment failure was a pain score ≥8 or adverse event necessitating withdrawal. Four TFS- and eight oxymorphone-treated dogs were withdrawn due to lack of pain control. Eighteen oxymorphone-treated, but no TFS-treated dogs were withdrawn due to severe adverse events. The one-sided upper 95% confidence interval of the difference between TFS and oxymorphone treatment failure rates was −5.3%. Adverse events associated with oxymorphone were greater in number and severity compared with TFS. It was concluded that a single administration of TFS was safe and noninferior to repeated injections of oxymorphone for the control of postoperative pain over 4 days at the dose rates of both formulations used in this study. PMID:24344787

Delta-Selective Glycopeptides Related to Enkephalin Produce Profound Analgesia with Reduced Side Effects in Mice

DTIC Science & Technology

2004-09-01

depression or the risk of overdose is particularly appealing. Further research needs to be completed in order to quantify the effects of the... fentanyl and other morphine-like analgesics on the warm water-induced tail- withdrawal reflex in rats. Jannsen, P.A.J.; Niemegeers, C.J.E.; Dorg, J.G.H...the delta opioid agonist BW373U86 and the mu opioid agonist fentanyl in mice. O’Neill, S.J.; Collins, M.A.; Pettit, H.O.; McNutt, R.W.; Chang, K.J. J

Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: a multicentre, randomized, assessor-blinded study.

PubMed

Jensen, T S; Høye, K; Fricová, J; Vanelderen, P; Ernault, E; Siciliano, T; Marques, S

2014-10-01

Application of the capsaicin 8% patch is associated with treatment-related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream is recommended; however, this may be uncomfortable and time consuming. We conducted a multicentre, randomized (1:1), assessor-blinded study in patients with peripheral neuropathic pain to assess tolerability of the capsaicin patch following topical lidocaine (4%) or oral tramadol (50 mg) pretreatment. The primary endpoint was the proportion of patients tolerating capsaicin patch application (ability to receive ≥90% of a 60-min application). Numeric Pain Rating Scale (NPRS) scores were assessed before, during and after treatment. Overall, 122 patients were included (61 per arm). The capsaicin patch was tolerated by 121 patients. Tolerability of the capsaicin patch was similar following pretreatment with lidocaine and tramadol. Following patch application, pain levels increased up to 55 min (change from baseline of 1.3 for lidocaine and 1.4 for tramadol). After patch removal, tramadol-treated patients experienced greater pain relief up to the end of day 1; in the evening, mean changes in NPRS scores from baseline were 0 for lidocaine and -1 for tramadol. Proportions of patients reporting increases of ≥2 NPRS points or >33% from baseline at one or more time point(s) on the day of treatment were similar between arms. Adverse event incidence was comparable between arms. Capsaicin 8% patch tolerability was similar in the two arms, with comparable results for most secondary endpoints. Tramadol given 30 min before patch application should be considered as an alternative pretreatment option in patients receiving capsaicin patch treatment. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Low-dose levonorgestrel and ethinyl estradiol patch and pill: a randomized controlled trial.

PubMed

Kaunitz, Andrew M; Portman, David; Westhoff, Carolyn L; Archer, David F; Mishell, Daniel R; Rubin, Arkady; Foegh, Marie

2014-02-01

To compare a new low-dose levonorgestrel and ethinyl estradiol contraceptive patch (Patch) with a combination oral contraceptive (Pill; 100 micrograms levonorgestrel, 20 micrograms ethinyl estradiol) regarding efficacy, safety, compliance, and unscheduled uterine bleeding. Women (17-40 years; body mass index 16-60) were randomized in a 3:1 ratio to one of two groups: Patch only (13 cycles) or Pill (six cycles) followed by Patch (seven cycles). Investigators evaluated adverse events during cycles 2, 4, 6, 9, and 13. Participants recorded drug administration and uterine bleeding on daily diary cards. Compliance was assessed by measuring levonorgestrel and ethinyl estradiol plasma levels. Pearl Index (pregnancies per 100 woman-years) was calculated to evaluate efficacy. Participants (N=1,504) were randomized to Patch (n=1,129) or Pill (n=375). Approximately 30% were obese, more than 40% were racial or ethnic minorities, and more than 55% were new users of hormonal contraceptives. Laboratory-verified noncompliance (undetectable plasma drug levels) was 11% of Patch and 12.6% of Pill users at cycle 6. Pearl Indices (95% confidence intervals) for the intention-to-treat population (cycles 1-6) were 4.45 (2.34-6.57) for Patch and 4.02 (0.50-7.53) for Pill; excluding laboratory-verified noncompliant participants, Pearl Indices were 2.82 (0.98-4.67) for Patch and 3.80 (0.08-7.52) for Pill (differences not statistically significant). Incidence of unscheduled bleeding and incidence and severity of adverse events were similar for both contraceptives (no statistically significant difference). Efficacy and safety of the new contraceptive Patch are comparable to those of a Pill. Laboratory-verified noncompliance and bleeding profile are similar between the two treatments. The Patch was well tolerated. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01181479. I.

The anesthetic effects on vasopressor modulation of cerebral blood flow in an immature swine model.

PubMed

Bruins, Benjamin; Kilbaugh, Todd J; Margulies, Susan S; Friess, Stuart H

2013-04-01

The effect of various sedatives and anesthetics on vasopressor modulation of cerebral blood flow (CBF) in children is unclear. In adults, isoflurane has been described to decrease CBF to a lesser extent than fentanyl and midazolam. Most large-animal models of neurocritical care use inhaled anesthetics for anesthesia. Investigations involving modulations of CBF would have improved translatability within a model that more closely approximates the current practice in the pediatric intensive care unit. Fifteen 4-week-old piglets were given 1 of 2 anesthetic protocols: total IV anesthesia (TIVA) (midazolam 1 mg/kg/h and fentanyl 100 μg/kg/h, n = 8) or ISO (isoflurane 1.5%-2% and fentanyl 100 μg/kg/h, n = 7). Mean arterial blood pressure, intracranial pressure (ICP), CBF, and brain tissue oxygen tension were measured continuously as piglets were exposed to escalating doses of arginine vasopressin, norepinephrine (NE), and phenylephrine (PE). Baseline CBF was similar in the 2 groups (ISO 38 ± 10 vs TIVA 35 ± 26 mL/100 g/min) despite lower baseline cerebral perfusion pressure in the ISO group (45 ± 11 vs 71 ± 11 mm Hg; P < 0.0005). Piglets in the ISO group displayed increases in ICP with PE and NE (11 ± 4 vs 16 ± 4 mm Hg and 11 ± 8 vs 18 ± 5 mm Hg; P < 0.05), but in the TIVA group, only exposure to PE resulted in increases in ICP when comparing maximal dose values with baseline data (11 ± 4 vs 15 ± 5 mm Hg; P < 0.05). Normalized CBF displayed statistically significant increases regarding anesthetic group and vasopressor dose when piglets were exposed to NE and PE (P < 0.05), suggesting an impairment of autoregulation within ISO, but not TIVA. The vasopressor effect on CBF was limited when using a narcotic-benzodiazepine-based anesthetic protocol compared with volatile anesthetics, consistent with a preservation of autoregulation. Selection of anesthetic drugs is critical to investigate mechanisms of cerebrovascular hemodynamics, and in translating critical care investigations between the laboratory and bedside.

Development and validation of a highly sensitive gas chromatographic-mass spectrometric screening method for the simultaneous determination of nanogram levels of fentanyl, sufentanil and alfentanil in air and surface contamination wipes.

PubMed

Van Nimmen, Nadine F J; Veulemans, Hendrik A F

2004-05-07

A highly sensitive gas chromatographic-mass spectrometric (GC-MS) analytical method for the determination of the opioid narcotics fentanyl, alfentanil, and sufentanil in industrial hygiene personal air samples and surface contamination wipes was developed and comprehensively validated. Sample preparation involved a single step extraction of the samples with methanol, fortified with a fixed amount of the penta-deuterated analogues of the opioid narcotics as internal standard. The GC-MS analytical procedure using selected ion monitoring (SIM) was shown to be highly selective. Linearity was shown for levels of extracted wipe and air samples corresponding to at least 0.1-2 times their surface contamination limit (SCL) and accordingly to 0.1-2 times their time weighted average occupational exposure limit (OEL-TWA) based on a full shift 9601 air sample. Extraction recoveries were determined for spiked air samples and surface wipes and were found to be quantitative for both sampling media in the entire range studied. The air sampling method's limit of detection (LOD) was determined to be 0.4 ng per sample for fentanyl and sufentanil and 1.6 ng per sample for alfentanil, corresponding to less than 1% of their individual OEL for a full shift air sample (9601). The limit of quantification (LOQ) was found to be 1.4, 1.2, and 5.0 ng per filter for fentanyl, sufentanil, and alfentanil, respectively. The wipe sampling method had LODs of 4 ng per wipe for fentanyl and sufentanil and 16 ng per wipe for alfentanil and LOQs of respectively, 14, 12, and 50 ng per wipe. The analytical intra-assay precision of the air sampling and wipe sampling method, defined as the coefficient of variation on the analytical result of six replicate spiked media was below 10 and 5%, respectively, for all opioids at all spike levels. Accuracy expressed as relative error was determined to be below 10%, except for alfentanil at the lowest spike level (-13.1%). The stability of the opioids during simulated air sampling was investigated. For fentanyl and sufentanil a quantitative recovery was observed at all spike levels, while for alfentanil recoveries ranged from 60.3 to 85.4%. When spiked air samples were stored at ambient temperature and at -15 degrees C quantitative recovery was found for fentanyl and sufentanil after 7 and 14 days. For alfentanil a slight loss seemed to occur upon storage during 7 days, being more explicit after 14 days. Ambient storage of spiked wipes seemed to lead to significant losses of all opioids studied, yielding recoveries of 37.7-88.3%. Upon storage of similar wipes at -15 degrees C a significantly higher recovery was found ranging from 77.3 to 88.3%. The developed analytical and sampling procedures have been recently applied in an explorative field study of which the results of surface contamination wipe sampling are presented in this paper. To our knowledge, this is the first study addressing the development and validation of analytical procedures for the assessment of external occupational exposure to potent opioid narcotics.

Rotator Cuff Repair with a Tendon-Fibrocartilage-Bone Composite Bridging Patch

PubMed Central

Ji, Xiaoxi; Chen, Qingshan; Thoreson, Andrew R.; Qu, Jin; An, Kai-Nan; Amadio, Peter C.; Steinmann, Scott P.; Zhao, Chunfeng

2015-01-01

Background To compare the mechanical performance of a rotator cuff repaired with a novel tendon-fibrocartilage-bone composite bridging patch vs the traditional Mason-Allen repair in an in vitro canine model. Methods Twenty shoulders and 10 bridging patches from patellar tendon were harvested. The patches were trimmed and sliced into 2 layers. An infraspinatus tendon tear was created in each shoulder. Modified Mason-Allen sutures were used to repair the infraspinatus tendon to the greater tuberosity, with or without the bridging patch (bridging patch group and controls, respectively). Shoulders were loaded to failure under displacement control at a rate of 0.5mm/sec. Findings The ultimate tensile load was significantly higher in the bridging patch group than control (mean [SD], 365.46 [36.45] vs 272.79 [48.88] N; P<.001). Stiffness at the greater tuberosity repair site and the patch-infraspinatus tendon repair site was significantly higher than the control repair site (93.96 [27.72] vs 42.62 [17.48] N/mm P<.001; 65.94 [24.51] vs 42.62 [17.48] N/mm P=.02, respectively). Interpretation The tendon-fibrocartilage-bone composite bridging patch achieved higher ultimate tensile load and stiffness at the patch–greater tuberosity repair site compared with traditional repair in a canine model. This composite tissue transforms the traditional tendon-to-bone healing interface (with dissimilar tissues) into a pair of bone-to-bone and tendon-to-tendon interfaces, which may improve healing quality and reduce retear rate. PMID:26190097

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist

PubMed Central

Mifflin, Steve W.

2017-01-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N-methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO2/pH chemosensitivity. PMID:28202437

Determinants of Fentanyl and other Potent μ Opioid Agonist Misuse in Opioid-Dependent Individuals

PubMed Central

Cicero, Theodore J.; Ellis, Matthew S.; Paradis, Alethea; Ortbal, Zachary

2010-01-01

Purpose Based on preclinical and clinical abuse liability assessments, fentanyl and other potent μ opioid agonists (e.g. hydromorphone and morphine) should be the most misused opioids if accessibility in the real world were not an issue. Since the latter is seldom true, we postulated that there would be a significant mismatch between actual and predicted rates of misuse. Methods We recruited 1,818 prescription-opioid dependent patients entering drug treatment programs to complete an anonymous survey, covering drug use and health related issues. Results Hydrocodone and oxycodone products were the drugs of choice in 75% of patients, whereas potent μ opioid agonists (fentanyl, hydromorphone and morphine), with the greatest predicted abuse potential, were very rarely chosen (<5% each). Most unexpectedly, the rank order of the actual drug of choice and the preferred drug in an ideal world were highly correlated. The reason most commonly given for the failure to endorse fentanyl, for example, as an actual or preferred drug, was fear of toxicity and overdose. We found few differences in drug use patterns between a subset of high-risk, impaired health care professionals (N=196) and all other patients other than source of drug, (forged prescriptions and doctors more common and dealers much less common in the HC sample). Conclusions These results indicate that it should not be assumed- particularly for new drug formulations- that a high potential for abuse will result in actual abuse; and, most importantly, that the hesitancy to use potent opioids because of fears of abuse may be misguided. PMID:20597128

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

PubMed

Lalley, Peter M; Mifflin, Steve W

2017-05-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N -methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO 2 /pH chemosensitivity. Copyright © 2017 the American Physiological Society.

Efficacy of split hours part-time patching versus continuous hours part-time patching for treatment of anisometropic amblyopia in children: a pilot study.

PubMed

Sachdeva, Virender; Mittal, Vaibhev; Kekunnaya, Ramesh; Gupta, Amit; Rao, Harsha L; Mollah, Joseph; Sontha, Anand; Gunturu, Rekha; Rao, B Venkateshwar

2013-07-01

To compare efficacy of 'split hours part-time patching' and 'continuous hours part-time patching' for the treatment of anisometropic amblyopia. We designed a prospective, interventional, non-randomised, comparative pilot study involving children between 4 and 11 years of age with anisometropic amblyopia who were treated with either continuous wear (Group A) or split hours part-time patching (Group B) as per parents wish, after appropriate discussion with the parents. Children were followed-up for the improvement in visual acuity and the compliance at each follow-up visit. 44 and 24 children were recruited in Group A and Group B, respectively (mean ± SD baseline BCVA of the amblyopic eye: 0.99 ± 0.32 and 0.95 ± 0.23 logMAR, respectively). BCVA (adjusted for baseline BCVA and age) at 3 months in Group A (0.59 ± 0.24) was comparable (p=0.08) with that in Group B (0.71 ± 0.24). This was same even at 6 months (0.51 ± 0.25 in Group A and 0.59 ± 0.25 in Group B, p=0.25). The improvement in BCVA at 3 months was also comparable (p=0.06) in Group A (0.39 ± 0.23) and Group B (0.26 ± 0.23). The improvement in BCVA at 6 months was also comparable (p=0.14) in Group A (0.47 ± 0.26) and Group B (0.37 ± 0.26). Both patching regimens lead to significant and comparable improvement in BCVA in anisometropic amblyopia up to 6 months of follow-up.

Comparison of diagnostic value using a small, single channel, P-wave centric sternal ECG monitoring patch with a standard 3-lead Holter system over 24 hours.

PubMed

Smith, Warren M; Riddell, Fiona; Madon, Morag; Gleva, Marye J

2017-03-01

To compare simultaneous recordings from an external patch system specifically designed to ensure better P-wave recordings and standard Holter monitor to determine diagnostic efficacy. Holter monitors are a mainstay of clinical practice, but are cumbersome to access and wear and P-wave signal quality is frequently inadequate. This study compared the diagnostic efficacy of the P-wave centric electrocardiogram (ECG) patch (Carnation Ambulatory Monitor) to standard 3-channel (leads V1, II, and V5) Holter monitor (Northeast Monitoring, Maynard, MA). Patients were referred to a hospital Holter clinic for standard clinical indications. Each patient wore both devices simultaneously and served as their own control. Holter and Patch reports were read in a blinded fashion by experienced electrophysiologists unaware of the findings in the other corresponding ECG recording. All patients, technicians, and physicians completed a questionnaire on comfort and ease of use, and potential complications. In all 50 patients, the P-wave centric patch recording system identified rhythms in 23 patients (46%) that altered management, compared to 6 Holter patients (12%), P<.001. The patch ECG intervals PR, QRS and QT correlated well with the Holter ECG intervals having correlation coefficients of 0.93, 0.86, and 0.94, respectively. Finally, 48 patients (96%) preferred wearing the patch monitor. A single-channel ambulatory patch ECG monitor, designed specifically to ensure that the P-wave component of the ECG be visible, resulted in a significantly improved rhythm diagnosis and avoided inaccurate diagnoses made by the standard 3-channel Holter monitor. Copyright © 2016 Elsevier Inc. All rights reserved.

Skin patch and vaginal ring versus combined oral contraceptives for contraception.

PubMed

Lopez, Laureen M; Grimes, David A; Gallo, Maria F; Stockton, Laurie L; Schulz, Kenneth F

2013-04-30

The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance. To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs). Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials. We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC. Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We also assessed the quality of evidence for this review. We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less likely to have missed days of therapy (OR 0.36; 95% CI 0.25 to 0.51). Of four vaginal ring trials, one found ring users had more noncompliance (OR 3.99; 95% CI 1.87 to 8.52), while another showed more compliance with the regimen (OR 1.67; 95% CI 1.04 to 2.68).More patch users discontinued early than COC users. ORs from two meta-analyses were 1.59 (95% CI 1.26 to 2.00) and 1.56 (95% CI 1.18 to 2.06) and another trial showed OR 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events than COC users. Users of the norelgestromin-containing patch reported more breast discomfort, dysmenorrhea, nausea, and vomiting. In the levonorgestrel-containing patch trial, patch users reported less vomiting, headaches, and fatigue.Of 11 ring trials with discontinuation data, two showed the ring group discontinued less than the COC group: OR 0.32 (95% CI 0.16 to 0.66) and OR 0.52 (95% CI 0.31 to 0.88). Ring users were less likely to discontinue due to adverse events in one study (OR 0.32; 95% CI 0.15 to 0.70). Compared to the COC users, ring users had more vaginitis and leukorrhea but less vaginal dryness. Ring users also reported less nausea, acne, irritability, depression, and emotional lability than COC users.For cycle control, only one trial study showed a significant difference. Women in the patch group were less likely to have breakthrough bleeding and spotting. Seven ring studies had bleeding data; four trials showed the ring group generally had better cycle control than the COC group. Effectiveness was not significantly different for the methods compared. Pregnancy data were available from half of the patch trials but two-thirds of ring trials. The patch could lead to more discontinuation than the COC. The patch group had better compliance than the COC group. Compliance data came from half of the patch studies and one-third of the ring trials. Patch users had more side effects than the COC group. Ring users generally had fewer adverse events than COC users but more vaginal irritation and discharge.The quality of the evidence for this review was considered low for the patch and moderate for the ring. The main reasons for downgrading were lack of information on the randomization sequence generation or allocation concealment, the outcome assessment methods, high losses to follow up, and exclusions after randomization.

Polyurethanes as self adhesive matrix for the transdermal drug delivery of testosterone.

PubMed

Gansen, P; Dittgen, M

2012-05-01

The new technology to manufacture transdermal active patches without solvents or increased temperatures described here is based on polyol and isocyanate reacting to polyurethane (PU) in the presence of the drug. The technology was proven using testosterone (T) as the drug and N,N-Diethyl-m-toluamide (DEET) and Limonene (L) as enhancers for skin permeation. The experimental patches varied in drug content and enhancer concentration. The patches were evaluated regarding adhesion to stainless steel or leather, in vitro drug release and T permeation across human cadaver skin using Franz cell. Comparing the results with those of a parallel investigation of the commercial product, Testopatch(®), adhesion to leather and in vitro drug release of the experimental patches were found to be higher. The steady-state flux (J(SS)) of T from the experimental patches was found lower than Testopatch(®). The flux of the experimental patch P3, which had the highest concentration of DEET and a low concentration of L was comparable to J(SS) of the commercial product, Testopatch(®).

Rapid establishment of a regular distribution of adult tropical Drosophila parasitoids in a multi-patch environment by patch defence behaviour.

PubMed

de Jong, Peter W; Hemerik, Lia; Gort, Gerrit; van Alphen, Jacques J M

2011-01-01

Females of the larval parasitoid of Drosophila, Asobara citri, from sub-Saharan Africa, defend patches with hosts by fighting and chasing conspecific females upon encounter. Females of the closely related, palearctic species Asobara tabida do not defend patches and often search simultaneously in the same patch. The effect of patch defence by A. citri females on their distribution in a multi-patch environment was investigated, and their distributions were compared with those of A. tabida. For both species 20 females were released from two release-points in replicate experiments. Females of A. citri quickly reached a regular distribution across 16 patches, with a small variance/mean ratio per patch. Conversely, A. tabida females initially showed a clumped distribution, and after gradual dispersion, a more Poisson-like distribution across patches resulted (variance/mean ratio was closer to 1 and higher than for A. citri). The dispersion of A. tabida was most probably an effect of exploitation: these parasitoids increasingly made shorter visits to already exploited patches. We briefly discuss hypotheses on the adaptive significance of patch defence behaviour or its absence in the light of differences in the natural history of both parasitoid species, notably the spatial distribution of their hosts.

Comparison of estrus synchronization by controlled internal drug release device (CIDR) and adhesive transdermal progestin patch in postpartum beef cows.

PubMed

Kajaysri, Jatuporn; Chumchoung, Chaiwat; Wutthiwitthayaphong, Supphathat; Suthikrai, Wanvipa; Sangkamanee, Praphai

2017-09-15

Estrous synchronization with progesterone based protocols has been essentially used in cattle industry. Although intravaginal devices have been commonly used, this technique may induce vaginitis. This study aimed at examining the efficiency of novel transdermal progestin patch on follicle development and comparing the progestin patch versus CIDR device on estrous synchronization, complication at treated site and pregnancy in beef cattle. In experiment 1, seven beef cows were treated with an adhesive transdermal progestin patch on the ventral surface of the proximal part of the tail for 7 days. The cows were daily examined the follicular development using ultrasonography starting on Day 0 till 3 days after hormone removal. Experiment 2, forty beef cows were divided into two equal groups (20 cows per group). The cows randomly allocated to received either vaginal insertion of CIDR (n = 20) or treated with an adhesive transdermal progestin patch (n = 20). The levels of plasma progesterone during the experiment and the numbers of standing estrous cows were recorded. Timed artificial inseminated (TAI) was performed at 60 h after CIDR or patch termination. Pregnancy rates were determined at 60 days after TAI. Experiment 1 revealed that the novel transdermal progestin patch could efficiently control follicular growth. All the seven treated cows had dominant follicle upon dermal patch removal indicating the effectiveness of the progestin patch. In experiment 2, the percentages of cows exhibited standing estrus were similar between transdermal patch (72.22%) and CIDR (70.00%). The levels of plasma progesterone during CIDR treatment were significantly higher (4.06 ± 1.65 ng/mL on Day 1 and 3.62 ± 1.60 ng/mL on Day 7) compared with transdermal patch (2.60 ± 1.43 ng/mL on Day 1 and 1.81 ± 1.57 ng/mL on Day 7). Three cows treated with CIDR (15%) developed vaginitis while none of cows had physically dermal reaction at adhesive site. Cows synchronized with these two protocols had similar pregnancy rates (50.00%) following fixed time artificial insemination. It is concluded that transdermal progestin patch was equally effective in estrus synchronization as compared with traditional CIDR. However, the transdermal patch demonstrated less complication. This device should therefore be considered as an alternative method for estrus synchronization in postpartum beef cattle. Copyright © 2017 Elsevier Inc. All rights reserved.

Mass spectrometer with a membrane interface for intraoperative monitoring the elimination of inhalation anesthetic and CO2 through the skin

NASA Astrophysics Data System (ADS)

Elizarov, A. Yu.; Ershov, T. D.; Levshankov, A. I.; Cherebillo, V. Yu.

2016-11-01

A new method is implemented in order to measure the concentration of CO2 and inhalation anesthetic sevoflurane eliminated through the skin during surgery. The concentration of inhalation anesthetic has been measured during general combined anesthesia (sevoflurane, fentanyl) and total intravenous anesthesia (propofol, fentanyl). The dependence of the concentration of CO2 and the inhalation anesthetic from the relaxation of smooth muscles in the walls of blood vessels under the effect of sevoflurane and propofol and on the stress response to surgical injury has been revealed for the first time.

The Effect of Neodymium: Yttrium Aluminum Garnet and Fractional Carbon Dioxide Lasers on Alopecia Areata: A Prospective Controlled Clinical Trial.

PubMed

Yalici-Armagan, Basak; Elcin, Gonca

2016-04-01

Effective treatment options for alopecia areata (AA) are missing. Whether lasers might be effective is a topic of debate. We aimed to evaluate whether neodymium: yttrium aluminum garnet (Nd:YAG) or fractional carbon dioxide lasers might stimulate the development of new hair. Thirty-two patients who had long-standing and treatment refractory diseases were recruited for the study. Three different patches on the scalp were selected, 1 of which served as control. The mean outcome measure was the hair count, which was calculated with the digital phototrichogram. Response was defined as at least 25% increase in the mean hair count at the treated patch compared with the control patch. At the end of the study, there was no statistically significant difference in the mean hair count for the 3 patches. In 7 of 32 patients (22%), an increase in the mean hair count was observed on the whole scalp including the control patch, which resulted in an improved Severity of Alopecia Tool (SALT) score. We have observed that Nd:YAG or fractional carbon dioxide lasers did not increase the mean hair count on the treated AA patches when compared with the control patch. However, an SALT score improvement in 22% of the patients suggested spontaneous remission.

High-density collagen patch prevents stricture after endoscopic circumferential submucosal dissection of the esophagus: a porcine model.

PubMed

Aoki, Shigehisa; Sakata, Yasuhisa; Shimoda, Ryo; Takezawa, Toshiaki; Oshikata-Miyazaki, Ayumi; Kimura, Hiromi; Yamamoto, Mihoko; Iwakiri, Ryuichi; Fujimoto, Kazuma; Toda, Shuji

2017-05-01

Extensive excision of the esophageal mucosa by endoscopic submucosal dissection (ESD) frequently evokes a luminal stricture. This study aimed to determine the efficacy of a high-density collagen patch for the prevention of esophageal stricture in extensive ESD. Six pigs underwent circumferential esophageal ESD under general anesthesia. In 3 pigs, artificial ulcers were covered by 2 collagen patches. The other 3 pigs underwent circumferential ESD only. The 2 collagen patches were settled onto the ulcer surface using a general endoscope and instruments. The collagen patch-treated group showed significantly better patency rates on both the oral and anal sides of the wound area compared with the control group at day 14. The mucosal re-epithelization ratio was significantly promoted, and the extent of mucosal inflammation and fibrosis was significantly decreased with the collagen patch treatment in the wound area. The frequency of cells positive α-smooth muscle actin was significantly reduced in the collagen patch-treated group compared with the control group. We have established a high-density collagen device that can reduce the esophageal stricture associated with extensive ESD. This easy-to-handle device would be useful during superficial esophageal cancer treatment by ESD. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch

PubMed Central

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M. L.; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G.

2015-01-01

Introduction Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. Methods hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. Results SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Conclusions Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment created by an aligned nanofiber patch. In this environment, these cells better approximate normal cardiac tissue compared with cells cultured on flat surface and can serve as the basis for bioengineering of an implantable cardiac patch. PMID:25993466

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch.

PubMed

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M L; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G

2015-01-01

Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment created by an aligned nanofiber patch. In this environment, these cells better approximate normal cardiac tissue compared with cells cultured on flat surface and can serve as the basis for bioengineering of an implantable cardiac patch.

Topical ketoprofen TDS patch versus diclofenac gel: efficacy and tolerability in benign sport related soft‐tissue injuries

PubMed Central

Esparza, Francisco; Cobián, César; Jiménez, José Fernando; García‐Cota, Juan José; Sánchez, Carlos; SETRADE, Antonio Maestro and the working group for the acute pain study of

2007-01-01

Objective To compare the ketoprofen TDS patch with diclofenac gel in the treatment of traumatic acute pain in benign sport‐related soft‐tissue injuries. Design 7–14 treatment days, prospective, randomised, open study. Patients Outpatients aged 18–70 years diagnosed for painful benign sport‐related soft‐tissue injury (sprains, strains and contusions within the prior 48 h), randomised to either ketoprofen patch 100 mg once daily (n = 114) or diclofenac gel 2–4 g three times daily (n = 109). Intervention 7–14 days of topical non‐steroidal anti‐inflammatory drugs treatment to assess the pain intensity changes (daily activities and spontaneous at rest) in a daily diary (100‐mm Visual Analogue Scale (VAS)). Main outcome measurement Pain intensity (VAS). Results The ketoprofen patch was not inferior to diclofenac gel in reducing the baseline pain during daily activities (difference of –1.17 mm in favour of ketoprofen patch, 95% CI (–5.86 to 3.52), reducing to the baseline VAS 79%. Ketoprofen patch presented also a higher cure rate (64%) than diclofenac gel (46%) at day 7 (p = 0.004). Patient opinions about the treatment comfort (pharmaceutical shape, application and dosage) were also statistically higher for the ketoprofen patch (>80% of the patients rated as good or excellent the patch removal and skin adherence). Conclusion Ketoprofen patches are effective and safe pain relievers for the treatment of sports injury pain with advantages compared with diclofenac gel. PMID:17138642

Patch-test reaction patterns in patients with a predisposition to atopic dermatitis.

PubMed

Brasch, Jochen; Schnuch, Axel; Uter, Wolfgang

2003-10-01

Patients with a predisposition to atopic dermatitis often need to be patch tested in order to detect possible contact sensitization. However, it is unknown whether immunologic or other peculiarities of atopic skin are related to altered patch-test reaction patterns. Our study was aimed at answering this question, because patch-test reaction patterns are of considerable practical importance in the reading and interpretation of patch tests. Therefore, we compared patterns of patch-test reactions in patients with a predisposition to atopic dermatitis and in control patients matched for sex, age, reason for testing and test centre. Patch-test results from 9 centres (2322 patients with a disposition to atopic dermatitis and 2126 matched controls) were evaluated retrospectively. All patients were tested with nickel sulfate, fragrance mix, potassium dichromate, lanolin alcohol, formaldehyde and mercury ammonium chloride. Patch tests applied for 1 day with readings on days 1, 2 and 3 were evaluated in order to cover the early phase of the reactions. Not unexpectedly, we found that, compared to the matched controls, patients with a predisposition to atopic dermatitis tended to have more doubtful and irritant reactions on day 1. As a new observation, it turned out that they had less reactions of crescendo pattern and more strong reactions on day 3. All these differences were slight/insignificant. A higher skin irritability in patients with a predisposition to atopic dermatitis is a likely explanation. In conclusion, standard methods for patch testing can be applied in patients with a predisposition to atopic dermatitis, but minor differences in reaction patterns should be considered.

Grassland Fire and Cattle Grazing Regulate Reptile and Amphibian Assembly Among Patches

NASA Astrophysics Data System (ADS)

Larson, Danelle M.

2014-12-01

Fire and grazing are common management schemes of grasslands globally and are potential drivers of reptilian and amphibian (herpetofauna) metacommunity dynamics. Few studies have assessed the impacts of fire and cattle grazing on herpetofauna assemblages in grasslands. A patch-burn grazing study at Osage Prairie, MO, USA in 2011-2012 created landscape patches with treatments of grazing, fire, and such legacies. Response variables were measured before and after the application of treatments, and I used robust-design occupancy modeling to estimate patch occupancy and detection rate within patches, and recolonization and extinction (i.e., dispersal) across patches. I conducted redundancy analysis and a permuted multivariate analysis of variance to determine if patch type and the associated environmental factors explained herpetofauna assemblage. Estimates for reptiles indicate that occupancy was seasonally constant in Control patches ( ψ ~ 0.5), but declined to ψ ~ 0.15 in patches following the applications of fire and grazing. Local extinctions for reptiles were higher in patches with fire or light grazing ( ɛ ~ 0.7) compared to the controls. For the riparian herpetofaunal community, patch type and grass height were important predictors of abundance; further, the turtles, lizards, snakes, and adult amphibians used different patch types. The aquatic amphibian community was predicted by watershed and in-stream characteristics, irrespective of fire or grazing. The varying responses from taxonomic groups demonstrate habitat partitioning across multiple patch types undergoing fire, cattle grazing, and legacy effects. Prairies will need an array of patch types to accommodate multiple herpetofauna species.

Selective versus routine patch metal allergy testing to select bar material for the Nuss procedure in 932 patients over 10years.

PubMed

Obermeyer, Robert J; Gaffar, Sheema; Kelly, Robert E; Kuhn, M Ann; Frantz, Frazier W; McGuire, Margaret M; Paulson, James F; Kelly, Cynthia S

2018-02-01

The aim of the study was to determine the role of patch metal allergy testing to select bar material for the Nuss procedure. An IRB-approved (11-04-WC-0098) single institution retrospective, cohort study comparing selective versus routine patch metal allergy testing to select stainless steel or titanium bars for Nuss repair was performed. In Cohort A (9/2004-1/2011), selective patch testing was performed based on clinical risk factors. In Cohort B (2/2011-9/2014), all patients were patch tested. The cohorts were compared for incidence of bar allergy and resultant premature bar loss. Risk factors for stainless steel allergy or positive patch test were evaluated. Cohort A had 628 patients with 63 (10.0%) selected for patch testing, while all 304 patients in Cohort B were tested. Over 10years, 15 (1.8%) of the 842 stainless steel Nuss repairs resulted in a bar allergy, and 5 had a negative preoperative patch test. The incidence of stainless steel bar allergy (1.8% vs 1.7%, p=0.57) and resultant bar loss (0.5% vs 1.3%, p=0.23) was not statistically different between cohorts. An allergic reaction to a stainless steel bar or a positive patch test was more common in females (OR=2.3, p<0.001) and patients with a personal (OR=24.8, p<0.001) or family history (OR=3.1, p<0.001) of metal sensitivity. Stainless steel bar allergies occur at a low incidence with either routine or selective patch metal allergy testing. If selective testing is performed, it is advisable in females and patients with a personal or family history of metal sensitivity. A negative preoperative patch metal allergy test does not preclude the possibility of a postoperative stainless steel bar allergy. Level III Treatment Study and Study of Diagnostic Test. Copyright © 2017 Elsevier Inc. All rights reserved.

Response to rivastigmine transdermal patch or memantine plus rivastigmine patch is affected by apolipoprotein E genotype in Alzheimer patients.

PubMed

Han, Hyun Jeong; Kim, Byeong C; Lee, Jun-Young; Ryu, Seung-Ho; Na, Hae Ri; Yoon, Soo Jin; Park, Hyun Young; Shin, Joon Hyun; Cho, Soo-Jin; Yi, Hyon-Ah; Choi, Mun Seong; Heo, Jae-Hyeok; Park, Kyung Won; Kim, Kwang K; Choi, Seong Hye

2012-01-01

The apolipoprotein E (APOE) genotype in response to pharmacological treatments in patients with Alzheimer's disease (AD) remains a matter of controversy. This analysis investigated the effect of the APOE genotype on the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine patch in patients with mild to moderate AD. Two hundred and six (n = 206) patients with probable AD and Mini-Mental State Examination (MMSE) scores of 10-20 were randomized to rivastigmine patch monotherapy or memantine plus rivastigmine patch for 24 weeks. Of the 206 patients with probable AD, 146 patients who consented to genetic testing for APOE were included and assessed for this subgroup study. There were no significant differences on MMSE, NPI, ADAS-cog, ADCS-ADL, CDR-SB, NPI and FAB between rivastigmine patch monotherapy and memantine plus rivastigmine patch according to the APOE genotype. However, patients with moderately severe AD (MMSE ≤15) who were APOE ε4 carriers showed higher responder rates on ADCS-ADL with memantine plus rivastigmine patch compared to rivastigmine patch monotherapy. Moderately severe AD patients with the APOE ε4 allele may respond more favorably to memantine plus rivastigmine patch than ε4 noncarriers. Copyright © 2012 S. Karger AG, Basel.

Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine.

PubMed

Kress, Hans G

2009-03-01

Buprenorphine was not used widely in clinical practice over many years, mainly due to analgesic potency and clinical safety concerns based on misinterpreted animal data. Contrary to previous concerns, however, no analgesic ceiling effect and no antagonism of combined pure mu-opioid receptor agonists is seen within the therapeutic dose range. In recent studies, buprenorphine could be effectively and safely combined with full mu-agonists, and switching between buprenorphine and another opioid provided comparable pain relief based on equianalgesic doses. Moreover, buprenorphine exerts an antihyperalgesic effect, which is due -- at least in part -- to antagonistic activity at kappa-opioid receptors. Buprenorphine pharmacokinetics are not altered by advanced age or renal dysfunction. In addition, the risk of respiratory depression is lower than with other opioids including morphine, hydromorphone, methadone and fentanyl. Unlike morphine and fentanyl, there is no immunosuppressive activity with buprenorphine at therapeutic analgesic doses. Transdermal buprenorphine has significantly improved the clinical use of the drug, providing continuous buprenorphine release for up to 96 h. In clinical trials, patients receiving transdermal buprenorphine experienced significantly greater pain relief, better sleep, and a reduced need for rescue therapy, compared to placebo. Large-scale post-marketing studies have confirmed the effectiveness of transdermal buprenorphine in treating moderate-to-severe cancer and non-cancer pain including neuropathic syndromes. Finally, the comparably low incidence of CNS adverse events and constipation, and the possibility of use in severe renal dysfunction without a need for dose adjustment make buprenorphine well suited for chronic pain management in at-risk patients, such as diabetics, elderly or renally impaired individuals including those requiring haemodialysis.

Preferences among four combination nicotine treatments.

PubMed

Schneider, Nina G; Koury, Margaret A; Cortner, Chris; Olmstead, Richard E; Hartman, Neil; Kleinman, Leonard; Kim, Andrew; Chaya, Craig; Leaf, David

2006-09-01

Acute nicotine replacement treatments (NRTs) are disliked or misused, leading to insufficient nicotine intake and poor outcome. Patches provide steady nicotine but are slow and passive. Combining systems may improve efficacy with acute NRTs tailored for compliance. To test initial reactions to and use preferences among combinations of NRTs. Smokers (n=27) tested four combination NRTs in a 5-day crossover trial: 2/4-mg gum + 15-mg patch (G/P), 2/4-mg lozenges + 15-mg patch (L/P), inhaler + 15-mg patch (I/P), and 10 mg + 15-mg patches (P/P). Subjects rated an NRT combination each day after 5-6 h of use and ranked among the NRTs after testing all treatments. Double-patches (P/P) were ranked highest for "ease of use", "safety", and "use in public". However, for "help to quit", 70% preferred some form of acute-patch combination (A/P) compared to 30% choosing P/P. For "use under stress" (an immediate need), 93% preferred A/P systems compared to 7% choosing P/P. L/P ranked lowest for "ease of use", I/P and L/P were lowest on "safety", and I/P ranked lowest for "use in public". Expectations of NRTs changed with test experience for patches (better) and lozenges (worse). In brief testing, all combinations were acceptable. P/P was favored for ease, safety, and public use, but a majority chose A/P systems for help in quitting and use under stress. Combined use is viable and needs to be made known and accessible to smokers.

Dynamics of prey moving through a predator field: a model of migrating juvenile salmon

USGS Publications Warehouse

Petersen, J.H.; DeAngelis, D.L.

2000-01-01

The migration of a patch of prey through a field of relatively stationary predators is a situation that occurs frequently in nature. Making quantitative predictions concerning such phenomena may be difficult, however, because factors such as the number of the prey in the patch, the spatial length and velocity of the patch, and the feeding rate and satiation of the predators all interact in a complex way. However, such problems are of great practical importance in many management situations; e.g., calculating the mortality of juvenile salmon (smolts) swimming down a river or reservoir containing many predators. Salmon smolts often move downstream in patches short compared with the length of the reservoir. To take into account the spatial dependence of the interaction, we used a spatially-explicit, individual-based modeling approach. We found that the mortality of prey depends strongly on the number of prey in the patch, the downstream velocity of prey in the patch, and the dispersion or spread of the patch in size through time. Some counterintuitive phenomena are predicted, such as predators downstrean capturing more prey per predator than those upstream, even though the number of prey may be greatly depleted by the time the prey patch reaches the downstream predators. Individual-based models may be necessary for complex spatial situations, such as salmonid migration, where processes such as schooling occur at fine scales and affect system predictions. We compare some results to predictions from other salmonid models. (C) 2000 Elsevier Science Inc.

Steady-state plasma concentration profile of transdermal rotigotine: an integrated analysis of three, open-label, randomized, phase I multiple dose studies.

PubMed

Elshoff, Jan-Peer; Braun, Marina; Andreas, Jens-Otto; Middle, Michelle; Cawello, Willi

2012-04-01

The dopamine agonist rotigotine is formulated in a transdermal delivery system (patch) for once-daily application. It has been reported as efficacious in the treatment of idiopathic Parkinson's disease (PD) and restless legs syndrome. This article summarizes the results of 3 clinical studies conducted to characterize the 24-hour pharmacokinetic profile of rotigotine in steady state and the effect of different patch application sites on this profile. In addition, the relative bioavailability of a single, large patch versus 2 smaller patches was assessed. One Phase I study (SP871) assessed the steady-state pharmacokinetic properties at different application sites at a rotigotine maintenance dose of 3 mg/24 hours in healthy participants. Due to tolerability issues, the steady-state pharmacokinetic properties of rotigotine at higher doses (8 mg/24 hours) was assessed in 2 Phase I studies (SP630, SP651) in early-stage PD patients. Relative rotigotine bioavailability from a 40 cm(2) patch versus 2 × 20 cm(2) patches (SP651) and from a 15 cm(2) patch versus 1 × 5 cm(2) + 1 × 10 cm(2) patches (SP871) was also evaluated. Rotigotine concentrations in plasma were analyzed using a validated LC-MS/MS method. The pharmacokinetic variables were calculated using standard noncompartmental analysis. Release of rotigotine to the skin was 31% to 62% of total drug content in the patch. Variability of rotigotine exposure was low within participants (15%) compared with the variability observed between participants (54%). Rotigotine exposure increased proportionally in the therapeutic dose range of 2 mg/24 hours to 8 mg/24 hours. Plasma concentrations at steady state were stable over the 24-hour patch-on period. Delivery via a single, large patch compared with a combination of smaller patches did not appear to influence exposure to rotigotine. Bioavailability showed some variability depending on patch application site (hip, shoulder, abdomen, flank, thigh, upper arm); the respective mean ratios for AUC ranged between 0.87 (abdomen vs flank) and 1.46 (shoulder vs thigh). Continuous rotigotine delivery via a once-daily transdermal patch generated stable mean steady-state 24-hour plasma concentrations in healthy participants as well as patients with early-stage PD. Doses were achieved either by application of 1 large patch or a combination of smaller patches, resulting in the same total surface area. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Cost analysis of once-daily ISMN versus twice-daily ISMN or transdermal patch for nitrate prophylaxis.

PubMed

Brown, R E; Kendall, M J; Halpern, M T

1997-02-01

To compare the costs and outcomes of treating exercise-induced angina with once- or twice-daily isosorbide mononitrate (ISMN) or transdermal patch. A decision-analytic model was designed based on published literature showing compliance and increasing symptoms and estimates from physicians on treatment patterns and worsening symptoms. Data show that patients are more compliant with once-daily ISMN (Imdur, Astra Hässle, Mölndal, Sweden) and patch regimens than with twice-daily dose. Based upon the assumption that more compliant patients are better controlled, the model found that fewer medical care resources were consumed by patients treated with the once-daily and the patch regimens. The unit cost of the twice-daily ISMN regimen is 40% of the unit cost of the once-daily. Annual costs of treating an exercise-induced angina patient are 248 pounds for Imdur compared to 250 pounds for the twice-daily ISMN and 299 pounds for the transdermal patch. Unit prices alone are not good indicators for estimating medical management costs.

Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment.

PubMed

Mehta, Nilesh M; Halwick, David R; Dodson, Brenda L; Thompson, John E; Arnold, John H

2007-06-01

Using an ex vivo simulation model we set out to estimate the amount of drug lost due to sequestration within the extracorporeal circuit over time. Simulated closed-loop extracorporeal membrane oxygenation (ECMO) circuits were prepared using a 1.5-m2 silicone membrane oxygenator. Group A consisted of heparin, dopamine, ampicillin, vancomycin, phenobarbital and fentanyl. Group B consisted of epinephrine, cefazolin, hydrocortisone, fosphenytoin and morphine. Drugs were tested in crystalloid and blood-primed circuits. After administration of a one-time dose of drugs in the priming fluid, baseline drug concentrations were obtained (P0). A simultaneous specimen was stored for stability testing at 24 h (P4). Serial post-membrane drug concentrations were then obtained at 30 min (P1), 3 h (P2) and 24 h (P3) from circuit fluid. One hundred and one samples were analyzed. At the end of 24 h in crystalloid-primed circuits, 71.8% of ampicillin, 96.7% of epinephrine, 17.6% of fosphenytoin, 33.3% of heparin, 17.5% of morphine and 87% of fentanyl was lost. At the end of 24 h in blood-primed extracorporeal circuits, 15.4% of ampicillin, 21% of cefazolin, 71% of voriconazole, 31.4% of fosphenytoin, 53.3% of heparin and 100% of fentanyl was lost. There was a significant decrease in overall drug concentrations from 30 min to 24 h for both crystalloid-primed circuits (p = 0.023) and blood-primed circuits (p = 0.04). Our ex vivo study demonstrates serial losses of several drugs commonly used during ECMO therapy. Therapeutic concentrations of fentanyl, voriconazole, antimicrobials and heparin cannot be guaranteed in patients on ECMO.

EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine-Controlled, Crossover, Phase II Trial.

PubMed

Simon, Steffen T; Kloke, Marianne; Alt-Epping, Bernd; Gärtner, Jan; Hellmich, Martin; Hein, Rebecca; Piel, Maren; Cornely, Oliver A; Nauck, Friedemann; Voltz, Raymond

2016-11-01

Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited. To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial. Copyright © 2016. Published by Elsevier Inc.

Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans

PubMed Central

Manini, Alex F.; Yiannoulos, Georgia; Bergamaschi, Mateus M.; Hernandez, Stephanie; Olmedo, Ruben; Barnes, Allan J.; Winkel, Gary; Sinha, Rajita; Jutras-Aswad, Didier; Huestis, Marilyn A.; Hurd, Yasmin L.

2015-01-01

Objectives Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions. Conclusions CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse. PMID:25748562

Pediatric emergency department triage-based pain guideline utilizing intranasal fentanyl: Effect of implementation.

PubMed

Schoolman-Anderson, Kristin; Lane, Roni D; Schunk, Jeff E; Mecham, Nancy; Thomas, Richard; Adelgais, Kathleen

2018-01-16

Pain management guidelines in the emergency department (ED) may reduce time to analgesia administration (TTA). Intranasal fentanyl (INF) is a safe and effective alternative to intravenous opiates. The effect of an ED pain management guideline providing standing orders for nurse-initiated administration of intranasal fentanyl (INF) is not known. The objective of this study was to determine the impact of a pediatric ED triage-based pain protocol utilizing intranasal fentanyl (INF) on time to analgesia administration (TTA) and patient and parent satisfaction. This was a prospective study of patients 3-17 years with an isolated orthopedic injury presenting to a pediatric ED before and after instituting a triage-based pain guideline allowing for administration of INF by triage nurses. Our primary outcome was median TTA and secondary outcomes included the proportion of patients who received INF for pain, had unnecessary IV placement, and patient and parent satisfaction. We enrolled 132 patients; 72 pre-guideline, 60 post-guideline. Demographics were similar between groups. Median TTA was not different between groups (34.5 min vs. 33 min, p = .7). Utilization of INF increased from 41% pre-guideline to 60% post-guideline (p = .01) and unnecessary IV placement decreased from 24% to 0% (p = .002). Patients and parents preferred the IN route for analgesia administration. A triage-based pain protocol utilizing INF did not reduce TTA, but did result in increased INF use, decreased unnecessary IV placement, and was preferred by patients and parents to IV medication. INF is a viable analgesia alternative for children with isolated extremity injuries. Copyright © 2018. Published by Elsevier Inc.

Sedoanalgesia With Midazolam and Fentanyl Citrate Controls Probe Pain During Prostate Biopsy by Transrectal Ultrasound

PubMed Central

Tsuji, Fábio Hissachi; Chambó, Renato Caretta; Agostinho, Aparecido Donizeti; Trindade Filho, José Carlos Souza

2014-01-01

Purpose To assess the pain intensity of patients administered midazolam and fentanyl citrate before undergoing transrectal ultrasound-guided prostate biopsy. Materials and Methods This was a study in patients with different indications for prostate biopsy in whom 5 mg of midazolam and 50 µg of fentanyl citrate was administered intravenously 3 minutes before the procedure. After biopsy, pain was assessed by use of a visual analogue scale (VAS) in three stages: VAS 1, during probe introduction; VAS 2, during needle penetration into prostate tissue; and VAS 3, in the weeks following the exam. Pain intensity at these different times was tested with stratification by age, race, education, prostate volume, rebiopsy, and anxiety before biopsy. Pain was ranked according to the following scores: 0 (no pain), 1-3 (mild pain), 4-7 (moderate pain), and 8-10 (severe pain). Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon two-tailed tests with a significance of 5%. Results Pain intensity was not influenced by any risk factors. The mean VAS 1 score was 1.95±1.98, the mean VAS 2 score was 2.73±2.55, and the mean VAS 3 score was 0.3±0.9, showing greater pain at the time of needle penetration than in other situations (VAS 2>VAS 1>VAS 3, p=0.0013, p=0.0001, respectively). Seventy-five percent of patients reported a VAS pain scale of less than 3.1 or mild pain. Conclusions Intravenous sedation and analgesia with midazolam and fentanyl citrate is a good method for reducing pain caused by prostate biopsy, even during probe insertion. PMID:24578806

The effects of intravenous anesthetics on QT interval during anesthetic induction with sevoflurane.

PubMed

Terao, Yoshiaki; Higashijima, Ushio; Toyoda, Tomomi; Ichinomiya, Taiga; Fukusaki, Makoto; Hara, Tetsuya

2016-12-01

Sevoflurane is known to prolong the QT interval. This study aimed to determine the effect of the interaction between intravenous anesthetics and sevoflurane on the QT interval. The study included 48 patients who underwent lumbar spine surgery. Patients received 3 μg/kg fentanyl and were then randomly allocated to either Group T, in which they received 5 mg/kg thiamylal, or Group P, in which they received 1.5 mg/kg propofol, at 2 min after administration of fentanyl injection for anesthetic induction. Vecuronium (1.5 mg/kg) and sevoflurane (3 % inhaled concentration) were administered immediately after loss of consciousness and tracheal intubation was performed 3 min after vecuronium injection. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and the heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram were recorded immediately before fentanyl administration (T1), 2 min after fentanyl injection (T2), immediately before intubation (T3), and 2 min after intubation (T4). There were no significant differences between the two groups in baseline patient characteristics. BIS and MAP significantly decreased after anesthesia induction in both groups. At T3, MAP in Group T was higher than in Group P, while HR had reduced in both groups. The QTc interval was prolonged after anesthesia induction in Group T, but did not change at any time point in Group P. The QTc interval after anesthesia induction in Group T was longer than in Group P. We concluded that an injection of propofol could counteract QTc interval prolongation associated with sevoflurane anesthesia induction.

Opioid analgesia on the battlefield: a retrospective review of data from Operation HERRICK.

PubMed

Lewis, Pip; Wright, C; Hooper, C

2018-04-06

Acute pain secondary to trauma is commonly encountered on the battlefield. The use of morphine to manage pain during combat has been well established since the 19th century. Despite this, there is relatively little research on analgesia use in this environment. This study aims to review the use and complications of morphine and other opioids during Operation HERRICK. A database search of the Joint Theatre Trauma Registry was completed looking for all incidences of morphine, fentanyl or naloxone use from February 2007 to September 2014. Microsoft Excel was used to analyse the results. Opioid analgesia was administered to 5801 casualties. Morphine was administered 6742 times to 3808 patients. Fentanyl was administered 9672 times to 4318 patients. Naloxone was used 18 times on 14 patients, giving a complication rate of 0.24%. Opioid doses prior to naloxone administration range from 0 to 72 mg of morphine and from 0 to 100 mcg of fentanyl. Four casualties (two local civilians and two coalition forces) received naloxone despite no recorded opioids being administered. Opium abuse was prevalent among the local population in Afghanistan, and this could explain the rationale behind two local national casualties receiving naloxone without any documented opioids being given. The use of opioids in a battlefield environment is extremely safe. Complication rates are similar to previously published data which is reassuring. The efficacy of different opioids was not covered by this study, and further analysis is required, particularly following the introduction of oral transmucosal fentanyl citrate and the availability of novel non-opioid analgesics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.