Continuous subcutaneous infusion of ketorolac in cancer neuropathic pain unresponsive to opioid and adjuvant drugs. A case report.

PubMed

Ripamonti, C; Ticozzi, C; Zecca, E; Rodriguez, C H; De Conno, F

1996-01-01

Ketorolac is a new non-steroidal anti-inflammatory drug (NSAID) having a potent nonopioid analgesic activity. Administered by continuous subcutaneous infusion (CSI), its analgesic efficacy has been documented in the treatment of somatic and visceral cancer pain whilst it has been shown to be ineffective in the treatment of neuropathic pain. Here is a description of a cancer patient with neuropathic pain unresponsive to anticonvulsant or antidepressant drugs administered in association or not with oral opioids but who was successfully treated with ketorolac alone via CSI. Furthermore, the analgesia lasted over 75 days of treatment without any significant renal and gastric side effects.

The Effect of Preoperative Ketorolac on WBC Response and Pain in Laparoscopic Surgery for Endometriosis

PubMed Central

2005-01-01

Surgical stress causes changes in the composition of white blood cells (WBCs). Ketorolac is believed to have analgesic effects and to reduce the stress response and may therefore improve postoperative outcomes. The aim of this study was to assess the effect of preoperative ketorolac on the WBC subsets in patients who had laparoscopic surgery for endometriosis. Fifty patients who had laparoscopic surgery for endometriosis were randomly assigned to one of two groups: the ketorolac group (n = 25) received ketorolac 0.5 mg/kg before the induction of anesthesia, and the control group (n = 25) received saline. White cell count, differential, and pathology studies were done immediately after surgery, on postoperative day 1, and on postoperative day 3. We compared the baseline values within and between the two groups. We also assessed postoperative pain and side effects. The time that elapsed before the first patient request for analgesia, total meperidine dose and VAS (Visual Analog Scale) for postoperative pain were significantly lower in the ketorolac group than in the control group. Compared to the pre- surgical values, there was an increase in total WBC count and percentage of neutrophils, but a decrease in percentages of lymphocytes, monocytes, eosinophils, basophils, and leucocytes. Total WBC count, neutrophils, monocytes, eosinophils and leucocytes showed significant differences between the two groups. The incidences of postoperative side effects, such as nausea, dizziness, headache, and shoulder pain were not different between the groups. Preoperative ketorolac reduced postoperative pain and influenced the WBC response in laparoscopic surgery for endometriosis. PMID:16385658

Ketorolac administration does not delay early fracture healing in a juvenile rat model: a pilot study.

PubMed

Cappello, Teresa; Nuelle, Julia A V; Katsantonis, Nicolas; Nauer, Rachel K; Lauing, Kristen L; Jagodzinski, Jason E; Callaci, John J

2013-06-01

ketorolac on early juvenile rat fracture healing supports the clinical practice of utilizing NSAIDs for analgesia in children with long bone fractures.

Pharmacokinetics and perioperative efficacy of intravenous ketorolac in dogs.

PubMed

Cagnardi, P; Zonca, A; Gallo, M; Villa, R; Carli, S; Beccaglia, M; Fonda, D; Ravasio, G

2013-12-01

Ketorolac (KET) is a nonsteroidal anti-inflammatory drug approved for the use in humans that possesses a potent analgesic activity, comparable to morphine, and could represent a useful tool to control acute pain also in animals. The clinical efficacy and pharmacokinetic profile of intravenous (IV) ketorolac tromethamine (0.5 mg/kg) were studied in 15 dogs undergoing gonadectomy. Intra-operative cardiorespiratory variables were monitored, and post-operative pain was assessed using a subjective pain score (0-24) in all dogs, whereas the pharmacokinetic profile of the drug was determined in 10 animals. During surgery, mean minimal alveolar concentration of isoflurane was 1.69 ± 0.11%, and normocapnia and spontaneous ventilation were maintained in all animals. During pain assessment, no significant differences between males and females were found, and in no case rescue analgesia was necessary. No adverse effects were reported. Serum samples were purified by solid-phase extraction and analysed by HPLC with UV-Vis detection. A large variability was observed in serum concentrations. The kinetics of ketorolac was described by a noncompartmental analysis. The elimination half-life (t½λz ) and ClB were 10.95 ± 7.06 h and 92.66 ± 84.49 mL/h/kg, respectively, and Vdss and Vz were 1030.09 ± 620.50 mL/kg and 1512.25 ± 799.13 mL/kg, respectively. AUC(0→last) and MRT(0→last) were 6.08 ± 3.28 h × μg/mL and 5.59 ± 2.12 h, respectively. The results indicate that ketorolac possess good post-operative analgesic effects until about 6 h after administration in dogs undergoing moderately painful surgery. © 2013 John Wiley & Sons Ltd.

Pediatric Tonsillectomy and Ketorolac.

PubMed

Phillips-Reed, Lesley D; Austin, Paul N; Rodriguez, Ricardo E

2016-12-01

The use of ketorolac in children undergoing tonsillectomy remains limited because of the concern about postoperative bleeding. A search was performed addressing the question: For patients undergoing a surgical tonsillectomy, does a weight-appropriate single dose of intravenous ketorolac affect the incidence of postoperative hemorrhage? Five systematic reviews met the inclusion criteria. A Cochrane Review included 15 studies with 1,101 pediatric subjects and focused on perioperative bleeding requiring intervention. Many of the systematic reviews appraised the same studies. Subgroup analysis often allowed assessment of the effects of ketorolac administration. There was no consensus on the increased risk of bleeding when nonsteriodal anti-inflammatory drugs such as ketorolac are given to pediatric patients undergoing tonsillectomy. The conclusions varied from ketorolac should not be used to it is safe to use with these patients. The perianesthesia team must carefully weigh the risks and benefits before deciding to use ketorolac with this subset of patients. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial.

PubMed

Isiordia-Espinoza, M-A; Pozos-Guillen, A; Martinez-Rider, R; Perez-Urizar, J

2016-09-01

Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. According to the VAS and UAC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery.

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

Does ketorolac have a preemptive analgesic effect? A randomized, double-blind, control study.

PubMed

Gutta, Rajesh; Koehn, Christopher R; James, Laura E

2013-12-01

To examine the effect of ketorolac used as preemptive analgesia on the intensity of pain and analgesic requirements in the postoperative period. The present study was a randomized, double-blind, control study involving human subjects who underwent extraction of the mandibular third molars under intravenous anesthesia. The study group received 30 mg of intravenous ketorolac preoperatively, and the control group received a placebo. The pain intensity was measured using a visual analog scale. The decrease in postoperative pain was measured as the primary outcome variable. The interval to the first dose of analgesic, total analgesic requirements, and the global assessment were measured as secondary outcomes. The data were analyzed using the Student t test, Wilcoxon rank sum test, and χ(2) test. A total of 85 adult subjects, American Society of Anesthesiologists class I and II, participated in the present study. Randomization was effective, as shown by the absence of differences in the study variables between the 2 groups. Of the 85 patients, 29 were men and 56 were women. The average patient age was 22.6 years in the study group and 24 years in the control group. Those in the ketorolac group recorded lower visual analog scale pain scores at all intervals. However, the difference was statistically significant at the 4-hour interval (P = .01). The median interval to the use of rescue medication in the ketorolac group was 9.5 hours compared with 7 hours in the control group. However, no statistically significant difference was found in the interval to the rescue analgesic between the 2 groups (P = .39). No statistically significant difference was noted in the total amount of postoperative analgesics required in the first 72 hours between the 2 groups (P = .54). Also, no difference was seen in the global assessment between the 2 groups (P = .22). Those who received 30 mg of intravenous ketorolac preoperatively had less pain in the early (8-hour) postoperative period. The

Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomised controlled trial

PubMed Central

Rainer, Timothy H; Jacobs, Philip; Ng, Y C; Cheung, N K; Tam, Michael; Lam, Peggo K W; Wong, Robert; Cocks, Robert A

2000-01-01

Objectives To investigate the cost effectiveness of intravenous ketorolac compared with intravenous morphine in relieving pain after blunt limb injury in an accident and emergency department. Design Double blind, randomised, controlled study and cost consequences analysis. Setting Emergency department of a university hospital in the New Territories of Hong Kong. Participants 148 adult patients with painful isolated limb injuries (limb injuries without other injuries). Main outcome measures Primary outcome measure was a cost consequences analysis comparing the use of ketorolac with morphine; secondary outcome measures were pain relief at rest and with limb movement, adverse events, patients' satisfaction, and time spent in the emergency department. Results No difference was found in the median time taken to achieve pain relief at rest between the group receiving ketorolac and the group receiving morphine, but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour (95% confidence interval 1.05 to 2.02) compared with 0.87 (0.84 to 1.06) in the morphine group (P=0.003). The odds of experiencing adverse events was 144.2 (41.5 to 501.6) times more likely with morphine than with ketorolac. The median time from the initial delivery of analgesia to the participant leaving the department was 20 (4.0 to 39.0) minutes shorter in the ketorolac group than in the morphine group (P=0.02). The mean cost per person was $HK44 (£4; $5.6) in the ketorolac group and $HK229 in the morphine group (P<0.0001). The median score for patients' satisfaction was 6.0 for ketorolac and 5.0 for morphine (P<0.0001). Conclusion Intravenous ketorolac is a more cost effective analgesic than intravenous morphine in the management of isolated limb injury in an emergency department in Hong Kong, and its use may be considered as the dominant strategy. PMID:11082083

Local infiltration analgesia followed by continuous infusion of local anesthetic solution for total hip arthroplasty: a prospective, randomized, double-blind, placebo-controlled study.

PubMed

Solovyova, Olga; Lewis, Courtland G; Abrams, Jonathan H; Grady-Benson, John; Joyce, Michael E; Schutzer, Steven F; Arumugam, Sivasenthil; Caminiti, Stephanie; Sinha, Sanjay K

2013-11-06

We studied the efficacy of local infiltration analgesia in surgical wounds with 0.2% ropivacaine (50 mL), ketorolac (15 mg), and adrenaline (0.5 mg) compared with that of local infiltration analgesia combined with continuous infusion of 0.2% ropivacaine as a method of pain control after total hip arthroplasty. We hypothesized that as a component of multimodal analgesia, local infiltration analgesia followed by continuous infusion of ropivacaine would result in reduced postoperative opioid consumption and lower pain scores compared with infiltration alone, and that both of these techniques would be superior to placebo. In this prospective, double-blind, placebo-controlled study, 105 patients were randomized into three groups: Group I, in which patients received infiltration with ropivacaine, ketorolac, and adrenaline followed by continuous infusion of 0.2% ropivacaine at 5 mL/hr; Group II, in which patients received infiltration with ropivacaine, ketorolac, and adrenaline followed by continuous infusion of saline solution at 5 mL/hr; and Group III, in which patients received infiltration with saline solution followed by continuous infusion of saline solution at 5 mL/hr.All patients received celecoxib, pregabalin, and acetaminophen perioperatively and patient-controlled analgesia; surgery was performed under general anesthesia. Before wound closure, the tissues and periarticular space were infiltrated with ropivacaine, ketorolac, and adrenaline or saline solution and a fenestrated catheter was placed. The catheter was attached to a pump prefilled with either 0.2% ropivacaine or saline solution set to infuse at 5 mL/hr.The primary outcome measure was postoperative opioid consumption and the secondary outcome measures were pain scores, adverse side effects, and patient satisfaction. There were no differences between groups in the administration of opioids in the operating room, in the recovery room, or on the surgical floor. The pain scores on recovery room admission

Ocular pharmacokinetics of 0.45% ketorolac tromethamine

PubMed Central

Attar, Mayssa; Schiffman, Rhett; Borbridge, Lisa; Farnes, Quinn; Welty, Devin

2010-01-01

Purpose A new carboxymethylcellulose (CMC)-containing ophthalmic formulation of 0.45% ketorolac, pH 6.8 (Acuvail®) was recently developed for treatment of inflammation and pain after cataract surgery. This study compared pharmacokinetics of the new formulation with that of a prior formulation, 0.4% ketorolac, pH 7.4 (Acular LS®). Methods Ketorolac formulations were administered bilaterally (35 μL) to female New Zealand White rabbits. Samples from aqueous humor and iris-ciliary body were collected at multiple time points, and ketorolac was quantified using liquid chromatography-tandem mass spectrometry. Results In aqueous humor, the peak concentration (Cmax) and area under the concentration-time curve (AUC0–τ) of ketorolac were, respectively, 389 ng/mL and 939 ng·h/mL following administration of the CMC-containing 0.45% ketorolac, pH 6.8, and 211 ng/mL and 465 ng·hr/mL following administration of the 0.4% ketorolac, pH 7.4. In iris-ciliary body, Cmax and AUC0–τ of ketorolac were, respectively 450 ng/g and 2040 ng·h/g after administration of the CMC-containing 0.45% ketorolac, pH 6.8, and 216 ng/g and 699 ng·h/g after administration of the 0.4% ketorolac, pH 7.4. PK simulations predicted an AUC0–τ of 2910 ng·h/g for twice daily, CMC-containing 0.45% ketorolac, pH 6.8, compared to 725 ng·h/g for 4 times daily, 0.4% ketorolac, pH 7.4. Conclusions The CMC-containing formulation of 0.45% ketorolac, pH 6.8, increased ketorolac bioavailability by 2-fold in aqueous humor and by 3-fold in iris-ciliary body in comparison to the 0.4% ketorolac, pH 7.4, allowing a reduced dosing schedule from 4 times daily to twice daily. PMID:21179226

Ocular pharmacokinetics of 0.45% ketorolac tromethamine.

PubMed

Attar, Mayssa; Schiffman, Rhett; Borbridge, Lisa; Farnes, Quinn; Welty, Devin

2010-12-01

A new carboxymethylcellulose (CMC)-containing ophthalmic formulation of 0.45% ketorolac, pH 6.8 (Acuvail(®)) was recently developed for treatment of inflammation and pain after cataract surgery. This study compared pharmacokinetics of the new formulation with that of a prior formulation, 0.4% ketorolac, pH 7.4 (Acular LS(®)). Ketorolac formulations were administered bilaterally (35 μL) to female New Zealand White rabbits. Samples from aqueous humor and iris-ciliary body were collected at multiple time points, and ketorolac was quantified using liquid chromatography-tandem mass spectrometry. In aqueous humor, the peak concentration (C(max)) and area under the concentration-time curve (AUC(0-τ)) of ketorolac were, respectively, 389 ng/mL and 939 ng·h/mL following administration of the CMC-containing 0.45% ketorolac, pH 6.8, and 211 ng/mL and 465 ng·hr/mL following administration of the 0.4% ketorolac, pH 7.4. In iris-ciliary body, C(max) and AUC(0-τ) of ketorolac were, respectively 450 ng/g and 2040 ng·h/g after administration of the CMC-containing 0.45% ketorolac, pH 6.8, and 216 ng/g and 699 ng·h/g after administration of the 0.4% ketorolac, pH 7.4. PK simulations predicted an AUC(0-τ) of 2910 ng·h/g for twice daily, CMC-containing 0.45% ketorolac, pH 6.8, compared to 725 ng·h/g for 4 times daily, 0.4% ketorolac, pH 7.4. The CMC-containing formulation of 0.45% ketorolac, pH 6.8, increased ketorolac bioavailability by 2-fold in aqueous humor and by 3-fold in iris-ciliary body in comparison to the 0.4% ketorolac, pH 7.4, allowing a reduced dosing schedule from 4 times daily to twice daily.

The Impact of Caesarean Delivery on Paracetamol and Ketorolac Pharmacokinetics: A Paired Analysis

PubMed Central

Kulo, Aida; van Calsteren, Kristel; Verbesselt, Rene; Smits, Anne; Devlieger, Roland; de Hoon, Jan; Allegaert, Karel

2012-01-01

Pharmacokinetics is a first, but essential step to improve population-tailored postoperative analgesia, also after Caesarean delivery. We therefore aimed to quantify the impact of caesarean delivery on the pharmacokinetics of intravenous (iv) paracetamol (2 g, single dose) and iv ketorolac tromethamine (30 mg, single dose) in 2 cohorts eachof 8 women at caesarean delivery and to compare these findings with postpartum to quantify intrapatient changes. We documented a higher median paracetamol clearance at delivery when compared to 10–15 weeks postpartum (11.7 to 6.4 L/h·m2, P < 0.01), even after correction for weight-related changes. Similar conclusions were drawn for ketorolac: median clearance was higher at delivery with a subsequent decrease (2.03 to 1.43 L/h·m2, P < 0.05) in postpartum (17–23 weeks). These differences likely reflect pregnancy- and caesarean-delivery-related changes in drug disposition. Moreover, postpartum paracetamol clearance was significantly lower when compared to estimates published in healthy young volunteers (6.4  versus  9.6 L/h·m2), while this was not the case for ketorolac (1.43  versus  1.48 L/h·m2). This suggests that postpartum is another specific status in young women that merits focused, compound-specific pharmacokinetic evaluation. PMID:22675252

Local infiltration analgesia in knee and hip arthroplasty efficacy and safety.

PubMed

Affas, Fatin

2016-10-01

This is a secondary publication of a PhD thesis. Local infiltration analgesia (LIA) is a new multimodal wound infiltration method for treating postoperative pain after knee and hip arthroplasty. This method is based on systematic infiltration of a mixture of ropivacaine, a long acting local anaesthetic, ketorolac, a cyclooxygenase inhibitor (NSAID), and adrenalin around all structures subject to surgical trauma in knee and hip arthroplasty. Paper I: to assess whether pain relief after LIA in total knee arthroplasty (TKA) is as effective as femoral block. Paper II: to assess whether the plasma concentration of ropivacaine and ketorolac after LIA in TKA reaches levels linked to toxicity. Paper III: to assess whether the plasma concentration of unbound ropivacaine after LIA in THA reaches levels linked to toxicity and if it is higher in THA as compared to TKA. Paper IV: to assess whether the plasma concentration of ketorolac after LIA in THA reaches levels linked to toxicity, and whether administration of ketorolac in LIA is safer as compared to the intramuscular route. Two patient cohorts of 40 patients scheduled for elective total knee arthroplasty (TKA) and 15 patients scheduled for total hip arthroplasty (THA) contributed to this work. In a randomized trial the efficacy of LIA in TKA with regard to pain at rest and upon movement was compared to femoral block. Both methods result in a high quality pain relief and similar morphine consumption during the 24h monitoring period. In the same patient cohort the maximal total plasma concentration of ropivacaine was below the established toxic threshold for most patients. All patients in the THA cohort were subjected to the routine LIA protocol. In these patients both the total and unbound plasma concentration of ropivacaine was determined. The concentration was below the established toxic threshold. As ropivacaine binds to α-1 acid glycoprotein (AAG) we assessed the possibility that increased AAG may decrease the unbound

[Management of ureteric colic with ketorolac and nifedipin vs. ketorolac and tamsulosin in the emergency room].

PubMed

Montiel-Jarquín, Álvaro J; Rocha-Rocha, Valeria M; Solís-Mendoza, Hugo A; Romero-Figueroa, María S; Etchegaray-Morales, Ivet; Alvarado-Ortega, Ivan

2017-01-01

Ureteric colic is the most common symptom of lithiasis. It is caused by the presence of stones accumulated in the renal papillae. These stones often migrate down the ureter, causing a ureteric colic, characterized by a severe pain in the lumbar region. The aim of this study was to compare the use of ketorolac and nifedipine vs. ketorolac and tamsulosin for the medical treatment of pain caused by stones in the lower ureter. Longitudinal study of 150 patients of 21-years or older with stones in the lower third of the ureter. 50% received ketorolac and nifedipine and the other 50%, ketorolac and tamsulosin. The Numeric Pain Rating Scale (NPRS) was used for the assessment of pain at admission and 4 and 12 hours after the treatment was administered. We used descriptive and inferential statistics (Mann-Whitney-Wilcoxon, chi-squared and Poisson regression). Mean age was 38.17 years; 54.7% were male and 45.3% female. NPRS mean was 9.69 (initially), 7.42 (at 4 hours) and 2.05 (at 12 hours). There were no significant differences in the initial measurement of pain between groups (p < 0.005); four and 12 hours later the pain decreased more in patients managed with ketorolac and nifedipine, p = 0.0041. There were no complications nor side effects in both treatments. The use of ketorolac and nifedipine is more effective than the use of ketorolac and tamsulosin for the management of pain caused by lower ureteral colic during the first 12 hours of treatment.

Ketorolac Use and Postoperative Complications in Gastrointestinal Surgery.

PubMed

Kotagal, Meera; Hakkarainen, Timo W; Simianu, Vlad V; Beck, Sara J; Alfonso-Cristancho, Rafael; Flum, David R

2016-01-01

To study the association between ketorolac use and postoperative complications. Nonsteroidal anti-inflammatory drugs may impair wound healing and increase the risk of anastomotic leak in colon surgery. Studies to date have been limited by sample size, inability to identify confounding, and a focus limited to colon surgery. Ketorolac use, reinterventions, emergency department (ED) visits, and readmissions in adults (≥ 18 years) undergoing gastrointestinal (GI) operations was assessed in a nationwide cohort using the MarketScan Database (2008-2012). Among 398,752 patients (median age 52, 45% male), 55% underwent colorectal surgery, whereas 45% had noncolorectal GI surgery. Five percent of patients received ketorolac. Adjusting for demographic characteristics, comorbidities, surgery type/indication, and preoperative medications, patients receiving ketorolac had higher odds of reintervention (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08-1.32), ED visit (OR 1.44, 95% CI 1.37-1.51), and readmission within 30 days (OR 1.11, 95% CI 1.05-1.18) compared to those who did not receive ketorolac. Ketorolac use was associated with readmissions related to anastomotic complications (OR 1.20, 95% CI 1.06-1.36). Evaluating only admissions with ≤ 3 days duration to exclude cases where ketorolac might have been used for complication-related pain relief, the odds of complications associated with ketorolac were even greater. Use of intravenous ketorolac was associated with greater odds of reintervention, ED visit, and readmission in both colorectal and noncolorectal GI surgery. Given this confirmatory evaluation of other reports of a negative association and the large size of this cohort, clinicians should exercise caution when using ketorolac in patients undergoing GI surgery.

Enantioselective Tissue Distribution of Ketorolac and its Enantiomers in Rats.

PubMed

Dubey, S K; Anand, A; Saha, R N

2015-08-01

The difference in tissue distribution of Ketorolac and its enantiomers were investigated in wistar rats. Separate high performance liquid chromatographic method was developed and validated for determination of Ketorolac and its enantiomers. Oyster BDS (150 × 4.6 mm id., 5 μm particle size) column was used for determination of concentration of Ketorolac. Ketorolac enantiomers were determined using Chiral-AGP column (100 × 4.0 mm I.D., particle size 5 μ, Chrom tech Ltd, Sweden). Detection was done at wavelength of 322 nm using an ultraviolet detector in the analytical system. Ketorolac enantiomers exhibit difference in their disposition in Wistar rats. In kidney, there was a significant difference in pharmacokinetic parameters. The Cmax was nearly 4 times and AUC 0-∞ was found to be more than double for S (-) Ketorolac than that of R (+) Ketorolac. MRT, Ke and t1/2 differ significantly in kidney. In liver, Cmax was found to be approximately 69% higher for S (-) Ketorolac compared to R (+) Ketorolac. AUC 0-∞ did not differ significantly for the enantiomers in liver. In liver, S (-) Ketorolac eliminated very fast in comparison to R (+) Ketorolac having t1/2 (one third) in comparison to R (+) Ketorolac. In lungs, there was no difference observed for Cmax and other parameters but AUC 0-∞ was found to be marginally higher for S (-) ketorolac. © Georg Thieme Verlag KG Stuttgart · New York.

Ketorolac

MedlinePlus

... heartburn, vomit that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools.Ketorolac may cause kidney failure. Tell your doctor if you have kidney or liver disease, if you have had severe vomiting or diarrhea ...

Ketorolac Use and Postoperative Complications in Gastrointestinal Surgery

PubMed Central

Kotagal, Meera; Hakkarainen, Timo W.; Simianu, Vlad V.; Beck, Sara J.; Alfonso-Cristancho, Rafael; Flum, David R.

2015-01-01

Objective To study the association between ketorolac use and postoperative complications. Background Nonsteroidal anti-inflammatory drugs may impair wound healing and increase the risk of anastomotic leak in colon surgery. Studies to date have been limited by sample size, inability to identify confounding, and a focus limited to colon surgery. Methods Ketorolac use, reinterventions, emergency department (ED) visits, and readmissions in adults (≥18 years) undergoing gastrointestinal (GI) operations was assessed in a nationwide cohort using the MarketScan Database (2008–2012). Results Among 398,752 patients (median age 52, 45% male), 55% underwent colorectal surgery, whereas 45% had noncolorectal GI surgery. Five percent of patients received ketorolac. Adjusting for demographic characteristics, comorbidities, surgery type/indication, and preoperative medications, patients receiving ketorolac had higher odds of reintervention (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08–1.32), ED visit (OR 1.44, 95% CI 1.37–1.51), and readmission within 30 days (OR 1.11, 95% CI 1.05–1.18) compared to those who did not receive ketorolac. Ketorolac use was associated with readmissions related to anastomotic complications (OR 1.20, 95% CI 1.06–1.36). Evaluating only admissions with ≤3 days duration to exclude cases where ketorolac might have been used for complication-related pain relief, the odds of complications associated with ketorolac were even greater. Conclusions Use of intravenous ketorolac was associated with greater odds of reintervention, ED visit, and readmission in both colorectal and noncolorectal GI surgery. Given this confirmatory evaluation of other reports of a negative association and the large size of this cohort, clinicians should exercise caution when using ketorolac in patients undergoing GI surgery. PMID:26106831

Ketorolac after free tissue transfer: a comparative effectiveness study.

PubMed

Schleiffarth, J Robert; Bayon, Rodrigo; Chang, Kristi E; Van Daele, Douglas J; Pagedar, Nitin A

2014-06-01

We sought to compare postoperative pain and complications in patients undergoing free tissue transfer for reconstruction of head and neck defects with and without ketorolac. In this retrospective cohort study, we identified patients who underwent head and neck free tissue transfer procedures at the University of Iowa between July 2010 and December 2012. A subset of patients received ketorolac as an anti-platelet agent. Main outcome measures include postoperative analgesic use, pain scores, and bleeding complications. We identified 138 free tissue transfers, with 42 procedures in the ketorolac cohort. In the first 7 postoperative days, patients in the ketorolac and non-ketorolac cohorts received equivalent narcotic doses (morphine equivalents, 48.9 mg/day vs 46.6 mg/day, P = .72). The ketorolac group reported higher mean pain scores (3.1 vs 2.4, P = .004). Ketorolac use was not associated with need for transfusion (P = .86) or number of days with neck drains (P = .79). Ketorolac did not demonstrate a significant analgesic effect in this group of patients in terms of pain scores and opioid requirements. However, there also was no evidence to suggest a higher likelihood of bleeding complications. Ketorolac may be safely used as an anti-platelet agent, with narcotic requirements unchanged.

Effect size comparison of ketorolac nasal spray and commonly prescribed oral combination opioids for pain relief after third molar extraction surgery.

PubMed

Niebler, Gwendolyn; Dayno, Jeffrey

2016-01-01

Opioids are frequently used for treatment of moderate to severe short-term pain, but concerns exist about this treatment approach. Ketorolac tromethamine nasal spray, a nonsteroidal anti-inflammatory, is indicated for the short-term management of moderate to moderately severe pain requiring analgesia at the opioid level. However, there are no direct comparison studies between ketorolac nasal spray and opioids. The objective of this study was to use an effect size analysis to compare the effectiveness of ketorolac nasal spray with oral combination opioid formulations in treating moderate to severe short-term pain. An effect size analysis of three randomized, double-blind, placebo-controlled studies of third molar extraction surgery compared pain relief with ketorolac nasal spray and commonly prescribed combination opioids including hydrocodone/acetaminophen (APAP), oxycodone/APAP, oxycodone/ibuprofen and tramadol HCl/APAP. Effect size comparisons were made using total pain relief scores (TOTPAR6 or TOTPAR8; the weighted sum of pain relief scores through 6 or 8 h). Pain relief was measured using a five-point categorical rating scale (0 = none; 4 = complete). The effect size equivalent correlation, r, was determined using an online effect size calculator. The treatment effect size r compared with placebo was classified using established criteria (small = 0.20-0.49, moderate = 0.50-0.79 and large = ≥ 0.80). TOTPAR6 data indicated a moderate effect size for ketorolac nasal spray 31.5 mg (0.51) and oxycodone/ibuprofen 5/400 mg (0.64) and a small effect size for hydrocodone/APAP 7.5/500 mg (0.24) and oxycodone/APAP 5/325 mg (0.32). TOTPAR8 data indicated small effect sizes for ketorolac nasal spray (0.48), hydrocodone/APAP 10/650 mg (0.43), tramadol HCl/APAP 75/650 mg (0.35) and tramadol HCl/APAP 37.5/325 mg (0.17). The treatment effect sizes of ketorolac nasal spray were similar to or higher than the opioid comparators after third molar surgery, a well-accepted pain

Ketorolac Ophthalmic

MedlinePlus

... soft contact lenses. You should not use ketorolac eye drops while wearing your soft contact lenses.use caution when driving or operating machinery because your vision may be blurred after you instill the drops.

Ketorolac Injection

MedlinePlus

... such as ketorolac may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may ... if you have or have ever had ulcers, holes, or bleeding in your stomach or intestine, or ...

Ketorolac Administration Attenuates Retinal Ganglion Cell Death After Axonal Injury.

PubMed

Nadal-Nicolás, Francisco M; Rodriguez-Villagra, Esther; Bravo-Osuna, Irene; Sobrado-Calvo, Paloma; Molina-Martínez, Irene; Villegas-Pérez, Maria Paz; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Herrero-Vanrell, Rocío

2016-03-01

To assess the neuroprotective effects of ketorolac administration, in solution or delivered from biodegradable microspheres, on the survival of axotomized retinal ganglion cells (RGCs). Retinas were treated intravitreally with a single injection of tromethamine ketorolac solution and/or with ketorolac-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Ketorolac treatments were administered either 1 week before optic nerve crush (pre-ONC) or right after the ONC (simultaneous). In all cases, animals were euthanized 7 days after the ONC. As control, nonloaded microspheres or vehicle (balanced salt solution, BSS) were administered in parallel groups. All retinas were dissected as flat mounts; RGCs were immunodetected with brain-specific homeobox/POU domain protein 3A (Brn3a), and their number was automatically quantified. The percentage of Brn3a+RGCs was 36% to 41% in all control groups (ONC with or without BSS or nonloaded microparticles). Ketorolac solution administered pre-ONC resulted in 63% survival of RGCs, while simultaneous administration promoted a 53% survival. Ketorolac-loaded microspheres were not as efficient as ketorolac solution (43% and 42% of RGC survival pre-ONC or simultaneous, respectively). The combination of ketorolac solution and ketorolac-loaded microspheres did not have an additive effect (54% and 55% survival pre-ONC and simultaneous delivery, respectively). Treatment with the nonsteroidal anti-inflammatory drug ketorolac delays RGC death triggered by a traumatic axonal insult. Pretreatment seems to elicit a better output than simultaneous administration of ketorolac solution. This may be taken into account when performing procedures resulting in RGC axonal injury.

A Double-Blind Placebo-Controlled Comparison of a Novel Formulation of Intravenous Diclofenac and Ketorolac for Postoperative Third Molar Extraction Pain

PubMed Central

Christensen, Kyle; Daniels, Stephen; Bandy, Donald; Ernst, Cynthia C.; Hamilton, Douglas A.; Mermelstein, Fred H.; Wang, Jianyuan; Carr, Daniel B.

2011-01-01

Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N  =  51 for all groups, except N  =  47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P  =  .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia. PMID:21679043

Biphasic anaphylactic reaction to Ketorolac tromethamine.

PubMed

Novembre, E; Calogero, C; Mori, F; Bernardini, R; Pucci, N; Neri, P; Bonini, M; Vierucci, A; De Martino, M

2006-01-01

Ketorolac tromethamine is a recent injectable non-steroidal anti-inflammatory drug (NSAID) with analgesic properties approved for short-term pain management. In spite of its increasing use both in adults and children, relatively few allergic-like reactions have been reported. Reactions are often severe, and a death occurred following an intramuscular injection of ketorolac.

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

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.

Pharmacokinetics of intravenous ketorolac in cats undergoing gonadectomy.

PubMed

Villa, R; Ravasio, G; Ferraresi, C; Zonca, A; Carli, S; Borghi, L; Cagnardi, P

2015-05-01

To determine the pharmacokinetics of ketorolac tromethamine (0.5 mg/kg) when administered I/V to cats undergoing gonadectomy. Ketorolac was administered to nine female and three male shorthair domestic cats as an I/V bolus of 0.5 mg/kg after intubation, and 20 minutes prior to ovariectomy or orchiectomy. Intra-operative cardiorespiratory variables were monitored and blood samples were collected over 24 hours. Concentrations of ketorolac in serum were determined by high-performance liquid chromatography to establish pharmacokinetic parameters. During surgery, mean end tidal isoflurane concentration was 1.63 (SD 0.24)% and normocapnia and spontaneous ventilation were maintained in all animals. The kinetics of ketorolac was described by a two-compartment model. The distribution and elimination half-lives were 0.09 (SD 0.06) and 4.14 (SD 1.18) hours, respectively. The body clearance was 56.8 (SD 33.1) mL/h/kg. The volume of distribution at steady-state and the mean residence time were 323.9 (SD 115.7) mL/kg and 6.47 (SD 2.86) hours, respectively. On the basis of the results, concentrations of ketorolac in serum in cats were above the human effective concentrations for 5-6 hours postoperatively. However, other studies including a control group are advocated to further investigate the ketorolac kinetics and the analgesic efficacy in this species.

Effects of Acute Administration of Ketorolac on Mammalian Vestibular Sensory Evoked Potentials

PubMed Central

Gaines, G Christopher; Jones, Timothy A

2013-01-01

The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use as a supplemental analgesic during major surgery in anesthetized rodents. The use of ketorolac during surgery is believed to reduce the anesthetic dose required to achieve and maintain an adequate surgical plane, thus improving the physiologic condition and survival of animals during long experimental procedures. Ketorolac has reported side effects that include dizziness, ear pain, hearing loss, tinnitus, and vertigo in humans, but ketorolac has not been reported to affect the vestibular system in animals. To investigate this possibility, we evaluated the acute effects of ketorolac on vestibular compound action potentials in C57BL/6 mice. Linear vestibular sensory-evoked potentials (VsEP) were recorded during the administration of ketorolac at doses 3 to 14 times the effective analgesic dose. VsEP results for ketorolac were compared with those from a control group maintained under anesthesia for the same period. Ketorolac did not significantly affect the temporal profiles of response latencies and amplitudes or the rate of change in response measures over time between controls and ketorolac-treated mice. These findings demonstrate that ketorolac can be used as an analgesic to supplement anesthesia in mice without concerns of modifying the amplitudes and latencies of the linear VsEP. PMID:23562034

Safety Considerations in the Use of Ketorolac for Postoperative Pain.

PubMed

Maslin, Benjamin; Lipana, Lawrence; Roth, Brandon; Kodumudi, Gopal; Vadivelu, Nalini

2017-01-01

Ketorolac use has significantly expanded for postoperative pain management since it first became available in the United States, primarily due to well established effects on patient pain scores and its ability to reduce perioperative opioid requirements. As an inhibitor of cyclooxygenase, ketorolac use has raised clinical concern including particular controversy regarding its potential effects on bone healing, postoperative kidney function and perioperative bleeding. To review the supporting data from clinical studies addressing the safety of ketorolac use for postoperative pain. This review highlights the most up-to-date research from clinical trials as well as from retrospective studies and meta-analyses regarding the effects of perioperative use of ketorolac on bone healing, kidney function and blood loss. Based on the most up-to-date literature, ketorolac in normal doses has been demonstrated to be safe with respect to bone healing. In patients with normal kidney function, numerous studies have established the safety of Ketorolac; however other studies have raised safety concerns in patients with comorbid kidney, heart and liver disease. While there is evidence that ketorolac may cause prolonged bleeding time and may be associated with increased postoperative blood loss after tonsillectomy, large scale prospective randomized controlled trials and subsequent meta-analyses have failed to establish an association of ketorolac use and perioperative blood loss. Perioperative administration of ketorolac has been demonstrated to be safe and effective in healthy patients and is particularly beneficial as an opioid-sparing agent in vulnerable patient groups. However, in certain surgical and medical contexts, proper patient selection based on the multidisciplinary collaboration between perioperative clinician specialists will optimize patient safety and pain management outcomes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Novel Pharmacologic Activity of Ketorolac for Therapeutic Benefit in Ovarian Cancer Patients.

PubMed

Guo, Yuna; Kenney, S Ray; Cook, Linda; Adams, Sarah F; Rutledge, Teresa; Romero, Elsa; Oprea, Tudor I; Sklar, Larry A; Bedrick, Edward; Wiggins, Charles L; Kang, Huining; Lomo, Lesley; Muller, Carolyn Y; Wandinger-Ness, Angela; Hudson, Laurie G

2015-11-15

We previously identified the R-enantiomer of ketorolac as an inhibitor of the Rho-family GTPases Rac1 and Cdc42. Rac1 and Cdc42 regulate cancer-relevant functions, including cytoskeleton remodeling necessary for tumor cell adhesion and migration. This study investigated whether administration of racemic (R,S) ketorolac after ovarian cancer surgery leads to peritoneal distribution of R-ketorolac, target GTPase inhibition in cells retrieved from the peritoneal cavity, and measureable impact on patient outcomes. Eligible patients had suspected advanced-stage ovarian, fallopian tube or primary peritoneal cancer. Secondary eligibility was met when ovarian cancer was confirmed and optimally debulked, an intraperitoneal port was placed, and there were no contraindications for ketorolac administration. R- and S-ketorolac were measured in serum and peritoneal fluid, and GTPase activity was measured in peritoneal cells. A retrospective study correlated perioperative ketorolac and ovarian cancer-specific survival in ovarian cancer cases. Elevated expression and activity of Rac1 and Cdc42 was detected in ovarian cancer patient tissues, confirming target relevance. Ketorolac in peritoneal fluids was enriched in the R-enantiomer and peritoneal cell GTPase activity was inhibited after ketorolac administration when R-ketorolac was at peak levels. After adjusting for age, AJCC stage, completion of chemotherapy, and neoadjuvant therapy, women given perioperative ketorolac had a lower hazard of death (HR, 0.30; 95% confidence interval, 0.11-0.88). Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, potentially contributing to the observed survival benefit in women who received ketorolac. ©2015 American Association for Cancer Research.

A novel pharmacologic activity of ketorolac for therapeutic benefit in ovarian cancer patients

PubMed Central

Guo, Yuna; Kenney, S. Ray; Cook, Linda; Adams, Sarah F.; Rutledge, Teresa; Romero, Elsa; Oprea, Tudor I.; Sklar, Larry A.; Bedrick, Edward; Wiggins, Charles L.; Kang, Huining; Lomo, Lesley; Muller, Carolyn Y.; Wandinger-Ness, Angela; Hudson, Laurie G.

2015-01-01

PURPOSE We previously identified the R-enantiomer of ketorolac as an inhibitor of the Rho-family GTPases Rac1 and Cdc42. Rac1 and Cdc42 regulate cancer-relevant functions including cytoskeleton remodeling necessary for tumor cell adhesion and migration. This study investigated whether administration of racemic (R,S) ketorolac after ovarian cancer surgery leads to peritoneal distribution of R-ketorolac, target GTPase inhibition in cells retrieved from the peritoneal cavity, and measureable impact on patient outcomes. EXPERIMENTAL DESIGN Eligible patients had suspected advanced stage ovarian, fallopian tube or primary peritoneal cancer. Secondary eligibility was met when ovarian cancer was confirmed and optimally debulked, an intraperitoneal port was placed, and there were no contraindications for ketorolac administration. R- and S-ketorolac were measured in serum and peritoneal fluid, and GTPase activity was measured in peritoneal cells. A retrospective study correlated peri-operative ketorolac and ovarian cancer-specific survival in ovarian cancer cases. RESULTS Elevated expression and activity of Rac1 and Cdc42 was detected in ovarian cancer patient tissues, confirming target relevance. Ketorolac in peritoneal fluids was enriched in the R-enantiomer and peritoneal cell GTPase activity was inhibited after ketorolac administration when R-ketorolac was at peak levels. After adjusting for age, AJCC stage, completion of chemotherapy, and neo-adjuvant therapy, women given peri-operative ketorolac had a lower hazard of death (Hazard Ratio=0.30 [95%CI 0.11–0.88]). CONCLUSION Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, potentially contributing to the observed survival benefit in women who received ketorolac. PMID:26071482

Ketorolac inhibits choroidal neovascularization by suppression of retinal VEGF

PubMed Central

Kim, Stephen J.; Toma, Hassanain S.; Barnett, Joshua M.; Penn, John S.

2011-01-01

We assessed the effect of topical ketorolac on laser-induced choroidal neovascularization (CNV), measured retinal PGE2 and VEGF levels after laser treatment, and determined the effect of ketorolac on PGE2 and VEGF production. Six laser burns were placed in eyes of rats which then received topical ketorolac 0.4% or artificial tears four times daily until sacrifice. Fluorescein angiography (FA) was performed at 2 and 3 weeks and retinal pigment epithelium-choroid-sclera flat mounts were prepared. The retina and vitreous were isolated at 1, 3, 5, 7, and 14 days after laser treatment and tested for VEGF and PGE2. Additional animals were lasered and treated with topical ketorolac or artificial tears and tested at 3 and 7 days for retinal and vitreous VEGF and PGE2. Ketorolac reduced CNV on FA by 27% at 2 weeks (P < 0.001) and 25% at 3 weeks (P < 0.001). Baseline retina and vitreous PGE2 levels were 29.4 μg/g and 16.5 μg/g respectively, and reached 51.2 μg/g and 26.9 μg/g respectively, 24 h after laser treatment (P < 0.05). Retinal VEGF level was 781 pg/g 24 h after laser treatment and reached 931 pg/g by 7 days (P < 0.01). Ketorolac reduced retinal PGE2 by 35% at 3 days (P < 0.05) and 29% at 7 days (P < 0.001) and retinal VEGF by 31% at 3 days (P = 0.10) and 19% at 7 days (P < 0.001). Topical ketorolac inhibited CNV and suppressed retinal PGE2 and VEGF production. PMID:20659449

Impact of ester promoieties on transdermal delivery of ketorolac.

PubMed

Liu, Kuo-Sheng; Hsieh, Pei-Wen; Aljuffali, Ibrahim A; Lin, Yin-Ku; Chang, Shu-Hao; Wang, Jhi-Joung; Fang, Jia-You

2014-03-01

Different types of ketorolac ester prodrugs incorporating tert-butyl (KT), benzyl (KB), heptyl (KH), and diketorolac heptyl (DKH) promoieties were synthesized for the comparison of percutaneous penetration. The prodrugs were characterized according to their melting point, capacity factor, lipophilicity, solubility in 30% ethanol/buffer, enzymatic hydrolysis, in vitro skin permeation, hair follicle accumulation, and in vivo skin tolerance. Interactions between the prodrugs and esterases were predicted by molecular docking. Both equimolar suspensions and saturated solutions in 30% ethanol/pH 7.4 buffer were employed as the applied dose. All of the prodrugs exhibited a lower melting point than ketorolac. The lipophilicity increased in the following order: ketorolac < KT < KB < KH < DKH. The prodrugs were rapidly hydrolyzed to the parent drug in esterase medium, skin homogenate, and plasma, with KT and KB exhibiting higher degradation rates. KT exhibited the highest skin permeation, followed by KB. The flux of KT and KB exceeded that of ketorolac by 2.5-fold and twofold, respectively. KH and DKH did not improve ketorolac permeation but exhibited a sustained release behavior. KT and KH revealed selective absorption into follicles and a threefold greater follicular uptake compared with ketorolac. KB, KH, and DKH slightly but significantly increased transepidermal water loss (TEWL) after consecutive administration for 7 days, whereas ketorolac and KT exhibited no influence on TEWL. According to the experimental results, it can be concluded that an optimal balance between lipophilicity and aqueous solubility is important in the design of a successful prodrug. The acceptable skin tolerance for safe application is also an important consideration. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Safety of perioperative ketorolac administration in pediatric appendectomy.

PubMed

Naseem, Hibbut-Ur-Rauf; Dorman, Robert Michael; Ventro, George; Rothstein, David H; Vali, Kaveh

2017-10-01

Recent studies in adults undergoing gastrointestinal surgeries show an increased rate of complications with the use of ketorolac. This calls into question the safety of ketorolac in certain procedures. We sought to evaluate the impact of perioperative ketorolac administration on outcomes in pediatric appendectomy. The Pediatric Health Information System database was queried for patients aged 5-17 y with a primary diagnosis of appendicitis and a primary procedure of appendectomy during the period 2010-2014. Patients with procedures suggesting incidental appendectomy, those records with data quality issues, deaths, and extracorporeal membrane oxygenation were excluded. Variables recorded included age, sex, race, ethnicity, discharge year, complex chronic conditions, geographic region, intensive care unit admission, mechanical ventilation, and whether appendicitis was coded as complicated. The exposure variable was ketorolac administration on the day of or day after operation. The primary outcomes of interest were any surgical complications during the initial encounter, postoperative length of stay (LOS), total cost for the initial visit, any readmission to ambulatory, observation, or inpatient status within 30 d, and readmission with a diagnosis of peritoneal abscess or other postoperative infection or with transabdominal drainage performed. A total of 78,926 patients were included in the analysis cohort. Mean age was 11.4 y (standard deviation 3.3 y), the majority were males (61%), White (70%), and non-Hispanic (65%). Few had a complex chronic condition (3%) or required mechanical ventilation (2%) or an intensive care unit admission (1%). Patients with complicated appendicitis comprised 28% of the cohort. Most (73%) received ketorolac on postoperative day 0-1; those with complicated appendicitis were more likely to receive ketorolac. In all, 2.6% of the cohort had a surgical complication during the index visit, 4.3% were readmitted within 30 d, and 2% had a

The effect of perioperative ketorolac on pain control in pregnancy termination.

PubMed

Roche, Natalie E; Li, Dongchen; James, Denise; Fechner, Adam; Tilak, Vasanti

2012-03-01

The study was conducted to evaluate the effect of perioperative ketorolac on pain associated with first-trimester aspiration abortion. A double-blind, randomized, placebo-controlled trial was performed involving pregnant women up to 14 weeks' gestation who desired pregnancy termination. Subjects were randomized to receive ketorolac 30 mg intravenously (n=31) or placebo (n=45) at the time of induction of anesthesia. Postoperative pain was assessed using a visual analog scale (VAS). The primary outcome was pain control as determined by VAS score. Secondary measures of patient use of supplemental postoperative pain medications and patient satisfaction were assessed. Subjects in the ketorolac group had lower postoperative pain scores on the VAS at all time points compared to the placebo group, but the difference was not statistically significant. The ketorolac group used less postoperative acetaminophen compared to the placebo group (6.5% versus 35.6%), respectively. Subjects in the placebo group and the ketorolac group had similar requirements for postoperative narcotics in the recovery room (22.2% versus 19.4%). Patient satisfaction with pain level was equivalent between the groups at all postoperative end points. There was no observed difference in perioperative blood loss observed between the two groups. Perioperative ketorolac has the same effect on postoperative pain as determined by VAS as placebo. The use of ketorolac at the 30-mg dose cannot be recommended for better pain control for patients undergoing first-trimester pregnancy termination by suction curettage. The only positive effect of the use of ketorolac compared to placebo was a reduction in the use of acetaminophen. Ketorolac use does not appear to change blood loss in the operating room or through postoperative day 1 compared to placebo. Copyright © 2012 Elsevier Inc. All rights reserved.

Use of Ketorolac Is Associated with Decreased Pneumonia Following Rib Fractures

PubMed Central

Yang, Yifan; Young, Jason B.; Schermer, Carol R.; Utter, Garth H.

2015-01-01

Background The effectiveness of the non-steroidal anti-inflammatory drug ketorolac in reducing pulmonary morbidity following rib fractures remains largely unknown. Methods We conducted a retrospective cohort study spanning January, 2003 to June, 2011, comparing pneumonia within 30 days and potential adverse effects of ketorolac among all patients with rib fractures who received ketorolac within four days post-injury to a random sample of those who did not. Results Among 202 patients who received ketorolac and 417 who did not, ketorolac use was associated with decreased pneumonia [odds ratio 0.14 (95% confidence interval 0.04–0.46)] and increased ventilator- and intensive care unit-free days [1.8 (95% confidence interval 1.1–2.5) and 2.1 (95% confidence interval 1.3–3.0) days, respectively] within 30 days. The rates of acute kidney injury, gastrointestinal hemorrhage, and fracture non-union were not different. Conclusions Early administration of ketorolac to patients with rib fractures is associated with a decreased likelihood of pneumonia, without apparent risks. PMID:24112670

Use of ketorolac is associated with decreased pneumonia following rib fractures.

PubMed

Yang, Yifan; Young, Jason B; Schermer, Carol R; Utter, Garth H

2014-04-01

The effectiveness of the nonsteroidal anti-inflammatory drug ketorolac in reducing pulmonary morbidity after rib fractures remains largely unknown. A retrospective cohort study was conducted spanning January 2003 to June 2011 assessing pneumonia within 30 days and potential adverse effects of ketorolac among all patients with rib fractures who received ketorolac <4 days after injury compared with a random sample of those who did not. Among 202 patients who received ketorolac and 417 who did not, ketorolac use was associated with decreased pneumonia (odds ratio, .14; 95% confidence interval, .04 to .46) and increased ventilator-free days (difference, 1.8 days; 95% confidence interval, 1.1 to 2.5) and intensive care unit-free days (difference, 2.1 days; 95% confidence interval, 1.3 to 3.0) within 30 days. The rates of acute kidney injury, gastrointestinal hemorrhage, and fracture nonunion were not different. Early administration of ketorolac to patients with rib fractures is associated with a decreased likelihood of pneumonia, without apparent risks. Copyright © 2014 Elsevier Inc. All rights reserved.

Perioperative ketorolac increases post-tonsillectomy hemorrhage in adults but not children.

PubMed

Chan, Dylan K; Parikh, Sanjay R

2014-08-01

To evaluate the risk of post-tonsillectomy hemorrhage associated with perioperative ketorolac use. Systematic review and meta-analysis of primary articles reporting individual-level post-tonsillectomy hemorrhage rates in subjects receiving perioperative ketorolac and matched controls. Retrospective and prospective studies were both included. PubMed search was performed for "[ketorolac OR toradol] AND tonsillectomy." Articles fulfilling inclusion criteria were subjected to meta-analysis to determine summary relative risk (RR). Adults are at five times increased risk for post-tonsillectomy hemorrhage with ketorolac use (RR: 5.64; 95% confidence interval [CI]: 2.08-15.27; P < .001). In contrast, children under 18 are not at statistically significantly increased risk (RR: 1.39; 95% CI: 0.84-2.30; P = .20). Both retrospective and prospective studies yield consistent findings. There is no association of RR with pre- or postoperative administration of ketorolac. Ketorolac can be used safely in children, but is associated with a five-fold increased bleeding risk in adults. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Intraperitoneal ketorolac for post-cholecystectomy pain: a double-blind randomized-controlled trial.

PubMed

Murdoch, John; Ramsey, Gillian; Day, Andrew G; McMullen, Michael; Orr, Elizabeth; Phelan, Rachel; Jalink, Diederick

2016-06-01

Ketorolac is a parenterally active nonsteroidal anti-inflammatory drug with localized anti-inflammatory properties. We examine the postoperative analgesic efficacy of locally administered intraperitoneal (IP) ketorolac compared with intravenous (IV) ketorolac during laparoscopic cholecystectomy. With institutional ethics approval, 120 patients undergoing elective laparoscopic cholecystectomy were randomized to receive intraoperative 1) IP ketorolac 30 mg + intravenous saline (IP group), 2) intraperitoneal saline + IV ketorolac 30 mg (IV group), or 3) intraperitoneal saline + intravenous saline (Control group) under standardized anesthesia. The primary and secondary outcomes were postoperative fentanyl requirements in the postanesthesia care unit and the time to first analgesic request, respectively. Other outcomes examined included abdominal pain (at rest and with coughing), shoulder pain, nausea, vomiting, and any other postoperative complications. On average, patients receiving IP ketorolac required less (mean difference, 29 μg; 95% confidence interval [CI], 2 to 56; P = 0.04) fentanyl than patients in the Control group but a similar (mean difference, 16 μg; 95% CI, 12 to 43; P = 0.27) amount compared to patients in the IV group. There was an increase in the median (interquartile range [IQR]) time to first request in the IP group (43[30-52] min) compared with the Control group (35 [27-49]min; P = 0.04) but no difference between the IP group compared with the IV group (47 [40-75] min; P = 0.22). Shoulder pain and resting pain were reduced with IP and IV ketorolac compared with Control, but there was no difference between the IP and IV groups. No differences were observed in any other outcomes, side effects, or complications attributable to opioids or ketorolac at any time points. This study did not demonstrate any advantage for the off-label topical intraperitoneal administration of ketorolac in this surgical population. Intraperitoneal and IV ketorolac showed

Ultrasound-guided transversus abdominal plane block with multimodal analgesia for pain management after total abdominal hysterectomy.

PubMed

Gasanova, Irina; Grant, Erica; Way, Megan; Rosero, Eric B; Joshi, Girish P

2013-07-01

Transversus abdominis plane (TAP) block has been shown to provide pain relief after abdominal procedures. However, TAP block combined with multimodal analgesia technique have not been assessed in a randomized controlled trial. This randomized, controlled, observer-blinded study was designed to evaluate the analgesic efficacy of bilateral ultrasound-guided TAP blocks with or without acetaminophen and non-steroidal anti-inflammatory drug (NSAID) combination. Patients undergoing total abdominal hysterectomy were randomized to one of three groups. Group 1 (n = 25) received a TAP block and ketorolac 30 mg, IV at the end of surgery and then ketorolac plus paracetamol 650 mg, orally, every 6 h for 24 h. Group 2 (n = 24) received only TAP block at the end of surgery. Group 3 (n = 25) received ketorolac 30 mg, IV at the end of surgery and then ketorolac plus paracetamol 650 mg, orally, every 6 h for 24 h. All patients received IV-PCA morphine for 24-h, postoperatively. All patients received a standardized general anaesthetic technique and dexamethasone 4 mg and ondansetron 4 mg, IV for antiemetic prophylaxis. There were no statistically significant differences in pain at rest between the groups. However, the pain on coughing (dynamic pain) in Group 1 was significantly less variable, compared with the other two groups (P = 0.012). Opioid consumption and occurrences of nausea, vomiting, and rescue antiemetic were similar in three the groups. The combination of TAP block and acetaminophen and NSAID provided less variability in dynamic pain compared with either treatment alone.

Local Drug Infiltration Analgesia During Knee Surgery to Reduce Postoperative Pain in Rats.

PubMed

Buvanendran, Asokumar; Kroin, Jeffrey S; Della Valle, Craig J; Moric, Mario; Tuman, Kenneth J

2016-01-01

There is increasing interest in local infiltration analgesia (LIA) to reduce postoperative pain with knee surgery. Despite widespread use of LIA, wide variations in drug combinations, infiltration techniques, and the concomitant use of systemic analgesics have made it difficult to determine the optimal drug combination for LIA.Using a previously validated animal knee surgery model, we aimed to determine the optimal combination of medications to reduce postoperative pain, and the best anatomical location and timing for local drug injection during surgery. Knee surgery was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, dexamethasone, and morphine were injected around the knee and compared to saline placebo. Similar medications were injected systemically as a comparator group. Postoperative pain was assessed by measuring spontaneous rearing activity. Injections were given after bone drilling and/or just before wound closure. The 3-drug LIA combination of bupivacaine, ketorolac, and dexamethasone increased rearing (decreased pain) at 2 hours (P = 0.0198) and 24 hours (P = 0.0384) postsurgery compared to saline. The same drugs injected systemically had no effect. The ketorolac/dexamethasone combination for LIA was also effective at 2 hours (P = 0.0006) and 24 hours (P = 0.0279), and ketorolac alone reduced pain at 2 hours (P = 0.0045). Bupivacaine alone was less effective, and the addition of morphine had no effect. The 3-drug combination infiltrated just after creating holes in bone was more effective than when given into the wound just before wound closure. Our animal study suggests that clinical trials with LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid might be useful for reducing postoperative pain after knee surgery, with the nonsteroidal anti-inflammatory drug having the greatest effect.Perioperative physicians should consider delivering LIA

Effects of ketorolac and bupivacaine on recovery after outpatient arthroscopy.

PubMed

Smith, I; Shively, R A; White, P F

1992-08-01

The effects of intraarticular bupivacaine, systemic ketorolac, and a combination of both treatments on postoperative pain and mobilization were evaluated in 60 healthy outpatients undergoing arthroscopic knee surgery under general anesthesia. After induction of anesthesia, patients received 2 mL of either ketorolac (60 mg) or saline solution (1 mL IV and 1 mL IM). On completion of surgery, the patient's knee joint was injected with 30 mL of either 0.5% bupivacaine or saline solution, according to a randomized, double-blind protocol. Only one patient (6%) receiving both medications complained of pain on awakening, compared with seven patients receiving either bupivacaine (37%) or ketorolac (41%) alone. Postoperative fentanyl was required by significantly fewer patients receiving combined therapy (n = 4, 21%) than either bupivacaine (n = 13, 62%) or ketorolac (n = 12, 60%) alone; however, there were no significant differences among the three treatment groups in terms of perioperative pain, nausea, or sedation visual analogue scale scores. Similarly, there were no differences in the times to ambulation or discharge or in analgesic requirements at home. In conclusion, a combination of systemic ketorolac and intraarticular bupivacaine decreased analgesic requirements and pain on awakening after arthroscopic surgery. However, the use of ketorolac alone or in combination with bupivacaine offered no advantage over bupivacaine alone with respect to recovery times after outpatient arthroscopy.

Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials.

PubMed

Gobble, Ryan M; Hoang, Han L T; Kachniarz, Bart; Orgill, Dennis P

2014-03-01

Postoperative pain control is essential for optimal patient outcomes. Ketorolac is an attractive alternative for achieving pain control postoperatively, but concerns over postoperative bleeding have limited its use. Computer searches of the MEDLINE, EMBASE, and Cochrane Library databases were performed. Twenty-seven double-blind, randomized, controlled studies were reviewed by two independent investigators for the incidence of adverse events, including postoperative bleeding. Comprehensive meta-analysis software was used to evaluate the differences between ketorolac and control groups. Twenty-seven studies with 2314 patients were analyzed. Postoperative bleeding occurred in 33 of 1304 patients (2.5 percent) in the ketorolac group compared with 21 of 1010 (2.1 percent) in the control group (OR, 1.1; 95 percent CI, 0.61 to 2.06; p = 0.72). Adverse events were similar in the groups, 31.7 percent in the control group and 27.9 percent in the ketorolac group (OR, 0.64; 95 percent CI, 0.41 to 1.01; p = 0.06). There was a lower incidence of adverse effects with low-dose ketorolac (OR, 0.49; 95 percent CI, 0.27 to 0.91; p = 0.02). Pain control with ketorolac was superior to controls and equivalent to opioids. This is the first meta-analysis of randomized controlled trials examining whether there is increased postoperative bleeding with ketorolac. Postoperative bleeding was not significantly increased with ketorolac compared with controls, and adverse effects were not statistically different between the groups. Pain control was found to be superior with ketorolac compared with controls. Ketorolac should be considered for postoperative pain control, especially to limit the use of opioid pain medications. Therapeutic, II.

The effect of ketorolac on pregnancy rates when used immediately after oocyte retrieval.

PubMed

Mesen, Tolga B; Kacemi-Bourhim, Lamya; Marshburn, Paul B; Usadi, Rebecca S; Matthews, Michelle; Norton, H James; Hurst, Bradley S

2013-09-01

To study the effect of ketorolac, a potent anti-inflammatory medication, on in vitro fertilization (IVF) pregnancy outcomes when used at the time of oocyte retrieval. Retrospective review of 454 patients from 2003-2009. Tertiary hospital-affiliated fertility center. Consecutive subfertile women undergoing their first IVF cycle. Ketorolac administration immediately after oocyte retrieval. Pregnancy, implantation, live-birth, and miscarriage rates, and postsurgical visual analog pain score. Of the 454 patients undergoing their first IVF cycle for all indications, 103 received intravenous ketorolac immediately after oocyte retrieval, based on anesthesiologist preference. Patient and procedural characteristics were similar between both groups. The use of ketorolac had no effect on the rates of implantation, miscarriage, pregnancy, live birth, or multiple pregnancy. The patients receiving ketorolac experienced statistically significantly less pain. This study suggests ketorolac has no apparent detrimental effect on IVF pregnancy outcomes when administered immediately after oocyte retrieval. Ketorolac appears to be a safe and effective analgesic to use at the time of oocyte retrieval. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Ketogal: A Derivative Ketorolac Molecule with Minor Ulcerogenic and Renal Toxicity.

PubMed

Russo, Roberto; De Caro, Carmen; Avallone, Bice; Magliocca, Salvatore; Nieddu, Maria; Boatto, Gianpiero; Troiano, Roberta; Cuomo, Rosario; Cirillo, Carla; Avagliano, Carmen; Cristiano, Claudia; La Rana, Giovanna; Sarnelli, Giovanni; Calignano, Antonio; Rimoli, Maria G

2017-01-01

Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic activity, present on the Italian market since 1991. Despite the excellent therapeutic activity, the chronic use of ketorolac has long been limited owing to the high incidence of gastrointestinal and kidney side events. In our previous study, we demonstrated that ketorolac-galactose conjugate (ketogal), synthesized and tested in a single-dose study, was able to reduce ulcerogenicity, while preserving the high pharmacological efficacy of its parent drug. In this paper, in order to verify the suitability of this compound, for repeated administration, ex vivo experiments on naïve mice were performed. Mice were treated for 5 or 7 days with the highest doses of two drugs (ketorolac 10 mg/kg and ketogal 16.3 mg/kg), and the expression of both gastric COX-1 and PGsyn was evaluated. Results showed that oral ketorolac treatment significantly reduced both enzymes; surprisingly, oral treatment with ketogal did not produce significant variation in the expression of the two constitutive enzymes. Moreover, histological experiments on stomach and kidneys clearly indicated that repeated administration of ketogal induced lower toxicity than ketorolac. At same time, in vivo results clearly showed that both ketorolac and ketogal had a similar therapeutic activity in a model of inflammation and in pain perception. These effects were accompanied by the reduction of enzyme expression such as COX-2 and iNOS, and by the modulation of levels of nuclear NF-κB and cytosolic IκB-α in the inflamed paws. These very encouraging results demonstrate for the first time that ketogal could represent a valid and novel therapeutic alternative to the ketorolac and might pave the way for clinical studies.

Effects of intrathecal ketorolac on human experimental pain

PubMed Central

Eisenach, James C.; Curry, Regina; Tong, Chuanyao; Houle, Timothy T.; Yaksh, Tony L.

2010-01-01

Background Nonsteroidal antiinflammatory drugs, the most commonly used analgesics, reduce pain by inhibiting cyclooxygenase at peripheral sites of inflammation, but potentially also by inhibiting cyclooxygenase in the central nervous system, especially the spinal cord. Animal studies suggest that products of cyclooxygenase in the spinal cord do not alter pain responses to acute noxious stimuli, but reduce pain and sensitization following peripheral inflammation. We used spinal injection of small doses of the cyclooxygenase inhibitor, ketorolac, to survey the role of spinal cyclooxygenase in human experimental pain and hypersensitivity states. Methods Following regulatory agency approval and informed consent, we examined the effect of 2.0 mg intrathecal ketorolac in 41 healthy volunteers to acute noxious thermal stimuli in normal skin and to mechanical stimuli in skin sensitized by topical capsaicin or ultraviolet burn. We also examined the effect of intravenous ketorolac, Results Intrathecal ketorolac reduced hypersensitivity when it was induced by a combination of ultraviolet burn plus intermittent heat and, according to one of two analytical strategies, when it was induced by ultraviolet burn alone. Conclusions These data suggest a more limited role for spinal cord cyclooxygenase in human pain states than predicted by studies in animals. PMID:20395821

Local infiltration analgesia in TKA patients reduces length of stay and postoperative pain scores.

PubMed

Tripuraneni, Krishna R; Woolson, Steven T; Giori, Nicholas J

2011-03-11

Numerous postoperative pain protocols exist for patients undergoing total knee arthroplasty (TKA). We compared the length of stay, early range of motion (ROM), and pain scores of a control group with a femoral nerve block to those of a group with femoral nerve block and local infiltration analgesia following TKA. In a consecutive series of patients undergoing primary TKA at a Veteran's Administration hospital, 40 patients (40 TKAs) who had local infiltration analgesia were compared to a historical group of 43 patients (43 TKAs) who had a long-acting femoral nerve block without local infiltration analgesia. Local infiltration analgesia consisted of intraoperative injection of 150 mL of 300 mg ropivacaine, 30 mg ketorolac, and 500 μg epinephrine using 50 mL into each of 3 areas: (1) posterior capsule, (2) medial and lateral capsule, and (3) anterior capsule and subcutaneous tissues. A 17-gauge intra-articular catheter was used to inject an additional 100 mg of ropivacaine on postoperative day 1. The control group had a single-shot femoral nerve block using 150 mg of ropivacaine with epinephrine. Mean length of stay for the local infiltration analgesia group compared to controls was 3.2±1.4 days vs 3.8±1.6 days, respectively (P=.03). No significant differences existed in average ROM (6 weeks), discharge hematocrit, transfusions, and temperature. Mean pain scores were lower in the local infiltration analgesia group on postoperative day 1 (P=.04), but not on postoperative day 2 or 3. Maximum visual analog scale scores (P<.01) were reduced in the local infiltration analgesia group. Our early experience with local infiltration analgesia demonstrated a significantly reduced length of stay due to decreased postoperative pain. Copyright 2011, SLACK Incorporated.

Local Infiltration Analgesia for Postoperative Pain Control following Total Hip Arthroplasty: A Systematic Review

PubMed Central

McCarthy, Denise; Iohom, Gabriella

2012-01-01

Local infiltration analgesia (LIA) is an analgesic technique that has gained popularity since it was first brought to widespread attention by Kerr and Kohan in 2008. The technique involves the infiltration of a large volume dilute solution of a long-acting local anesthetic agent, often with adjuvants (e.g., epinephrine, ketorolac, an opioid), throughout the wound at the time of surgery. The analgesic effect duration can then be prolonged by the placement of a catheter to the surgical site for postoperative administration of further local anesthetic. The technique has been adopted for use for postoperative analgesia following a range of surgical procedures (orthopedic, general, gynecological, and breast surgeries). The primary objective of this paper was to determine, based on the current evidence, if LIA is superior when compared to no intervention, placebo, and alternative analgesic methods in patients following total hip arthroplasty, in terms of certain outcome measures. The outcomes considered were postoperative analgesia scores, joint function/rehabilitation, and length of hospital stay. Secondary objectives were to review available evidence and current knowledge regarding the pharmacokinetics of local anesthetic and adjuvant drugs when administered in this way and the occurrence of adverse events. PMID:22829813

Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine.

PubMed

Friedman, Benjamin W; Garber, Leonid; Yoon, Andrew; Solorzano, Clemencia; Wollowitz, Andrew; Esses, David; Bijur, Polly E; Gallagher, E John

2014-03-18

We compared the efficacy of IV valproate with metoclopramide and with ketorolac in patients presenting to an emergency department (ED) with acute migraine. This was a double-blind comparative efficacy trial. Patients were randomized to 1,000 mg sodium valproate, 10 mg metoclopramide, or 30 mg ketorolac, each administered as an IV drip over 15 minutes. The primary outcome was improvement in headache by 1 hour, measured on a verbal 0 to 10 scale, at baseline and 60 minutes later. Important secondary outcomes included (1) need for rescue medication in the ED, and (2) sustained headache freedom. Three hundred thirty patients were enrolled over 30 months beginning in October 2010. Baseline characteristics were comparable among the 3 arms. On the primary outcome, patients receiving IV valproate improved by a mean of 2.8 (95% confidence interval [CI]: 2.3, 3.3) on the 0 to 10 scale; those receiving IV metoclopramide improved by 4.7 (95% CI: 4.2, 5.2); and those receiving IV ketorolac improved by 3.9 (95% CI: 3.3, 4.5). On the secondary endpoints, 69% (95% CI: 60%, 78%) of patients receiving valproate required rescue medication, compared with 33% (95% CI: 24%, 42%) of metoclopramide patients and 52% (95% CI: 42%, 63%) of those assigned to ketorolac. Sustained headache freedom was achieved in 4% (95% CI: 0%, 7%) of those randomized to valproate, 11% (95% CI: 5%, 17%) of metoclopramide patients, and 16% (95% CI: 9%, 23%) receiving ketorolac. In the metoclopramide arm, 6% (95% CI: 3%, 12%) of patients reported feeling "very restless" after investigational medication administration. Valproate was less efficacious than either metoclopramide or ketorolac. Metoclopramide demonstrated superiority to ketorolac on several endpoints. This study provides Class I evidence that in ED patients with acute migraine, IV valproate is inferior to metoclopramide or ketorolac in improving headache outcomes.

Ketorolac pharmacokinetics in experimental cirrhosis by bile duct ligation in the rat.

PubMed

Rivera-Espinosa, Liliana; Muriel, Pablo; Ordaz Gallo, Mónica; Pérez-Urizar, José; Palma-Aguirre, Antonio; Castañeda-Hernández, Gilberto

2003-01-01

The purpose of the present work was to study the pharmacokinetics of ketorolac, a poorly metabolized drug, in experimental cirrhosis. Cirrhosis was induced by bile duct ligation (BDL) for four weeks in male Wistar rats. Ketorolac was given intravenously (1 mg/kg ) or orally (3.2 mg/kg) to control (sham-operated) and BDL-rats. Determination of ketorolac in plasma was carried out by HPLC and estimation of pharmacokinetic parameters was performed by non-compartmental analysis. Indicators of liver damage and liver fibrosis were significantly increased (p < 0.05) in BDL compared to control rats. Experimental cirrhosis did not induce any significant alteration in intravenous ketorolac pharmacokinetics. Volume of distribution, clearance, AUC and t1/2 were similar in BDL and control animals. Notwithstanding, oral ketorolac bioavailability was significantly altered in BDL rats. AUC and Cmax were reduced, while tmax was prolonged, suggesting that both, the extent and the rate of ketorolac absorption were decreased. Results show that liver cirrhosis may result in significant pharmacokinetic alterations, even for poorly bio-transformed drugs, but that alterations may vary with the route of administration. In conclusion, uncritical generalizations on the effect of liver damage on drug kinetics should be avoided and systematic studies for every drug and every route of administration are thus recommended.

Comparison of intravenous ketorolac with or without paracetamol in postoperative pain control following ambulatory surgery.

PubMed

Iorno, Vittorio; Landi, Laura; Di Pasquale, Raffaella; Cicenia, Stefano; Moschini, Vincenzo

2013-12-01

The aim of this randomized, patient-blinded study was to compare efficacy and safety of oral paracetamol plus intra-venous (i.v.) ketorolac with i.v. ketorolac alone after ambulatory uterine evacuation. Women were randomly assigned to receive either oral paracetamol (1 g), in a melt-in-the mouth, without-water formulation plus ketorolac (30 mg i.v. once daily (o.d.)) or ketorolac (30 mg i.v. o.d.) as monotherapy. The mean duration of uterine evacuation was 11 minutes in the paracetamol + ketorolac group and 13 minutes in the ketorolac-only group. Paracetamol was administered 15 minutes before surgery, on discharge from hospital (mean 6 hours after surgery) and in the morning the day after surgery, while ketorolac was administered at the end of the surgical intervention. The numeric rating scale (NRS) was used by patients to rate their pain on an 11 point scale. Overall, 60 women received paracetamol plus ketorolac (group 1) and 60 ketorolac alone (group 2). There were significant differences in pain levels (NRS 0.92 and 2.08; p < 0.01) at T0 (when patients left the operating room 30 minutes after the end of surgery). At T1 (before discharge from hospital but before the next administration of paracetamol) there were no significant differences between NRS scores in the two groups (3.7 vs. 3.5, respectively, p = 0.3453). At T2 (in the morning after surgery; data collected by phone interview), following administration of the next dose of paracetamol, significant differences in pain scores were recorded (1.58 vs. 1.98; p = 0.01). Only a case of dizziness was reported in the paracetamol + ketorolac group, and no other unexpected adverse events were recorded. Despite the small sample size and the monocentric nature of the study being taken into account, this study suggests, for the first time to our knowledge, that oral paracetamol t.i.d. in combination with i.v. ketorolac o.d. is effective and well tolerated in the control of postoperative pain after ambulatory uterine

A Randomized Trial of Ketorolac vs Sumatripan vs Placebo Nasal Spray (KSPN) for Acute Migraine

PubMed Central

Rao, Aruna S.; Gelaye, Bizu; Kurth, Tobias; Dash, Paul D.; Nitchie, Haley; Peterlin, B. Lee

2016-01-01

Objective To compare the efficacy of ketorolac nasal spray (NS) vs placebo and sumatriptan NS for the acute treatment of migraine. Methods This was a randomized, double-blind, placebo and active-comparator, crossover study. Adult migraineurs were randomized to ketorolac NS 31.5 mg, sumatriptan NS 20 mg, or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack. Patients seeking headache care at a headache center or in response to community advertisement were recruited. Adult participants with episodic migraine who experienced ≥2 migraine attacks per month were eligible for the Ketorolac vs Sumatriptan vs Placebo Nasal Spray migraine study. Participants were randomized to treatment arms by a research pharmacist, in a 1:1:1 ratio using computer-generated lists. The primary outcome was 2-hour pain relief. Secondary outcomes included 2-hour pain freedom and absence of migraine associated symptoms, and 24-hour sustained pain relief and pain freedom. Results Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks. Both ketorolac NS (72.5%, P < .001) and sumatriptan NS (69.4%, P=.001) were more effective than placebo (38.3%) for 2-hour pain relief and 2-hour pain freedom (ketorolac: 43.1%, P=.004; sumatriptan: 36.7%, P=.046; placebo: 18.4%). Ketorolac NS, but not sumatriptan NS, was more effective than placebo in 2-hour absence of nausea. Both ketorolac NS and sumatriptan NS were more effective than placebo for 24-hour sustained pain relief (ketorolac: 49%, P < .001; sumatriptan: 31%, P=.01, placebo: 20%). Only ketorolac NS was superior to placebo for 24-hour (ketorolac: 35.3%, P=.003; sumatriptan: 22.4%, P=.18, placebo: 12.2%) sustained pain freedom. Nasal burning and dysgeusia were the most common adverse effects for active treatments. Conclusions This study supports that ketorolac NS is superior to placebo and that it

Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Motov, Sergey; Yasavolian, Matthew; Likourezos, Antonios; Pushkar, Illya; Hossain, Rukhsana; Drapkin, Jefferson; Cohen, Victor; Filk, Nicholas; Smith, Andrew; Huang, Felix; Rockoff, Bradley; Homel, Peter; Fromm, Christian

2017-08-01

Nonsteroidal anti-inflammatory drugs are used extensively for the management of acute and chronic pain, with ketorolac tromethamine being one of the most frequently used parenteral analgesics in the emergency department (ED). The drugs may commonly be used at doses above their analgesic ceiling, offering no incremental analgesic advantage while potentially adding risk of harm. We evaluate the analgesic efficacy of 3 doses of intravenous ketorolac in ED patients with acute pain. We conducted a randomized, double-blind trial to assess the analgesic efficacy of 3 doses of intravenous ketorolac (10, 15, and 30 mg) in patients aged 18 to 65 years and presenting to the ED with moderate to severe acute pain, defined by a numeric rating scale score greater than or equal to 5. We excluded patients with peptic ulcer disease, gastrointestinal hemorrhage, renal or hepatic insufficiency, allergies to nonsteroidal anti-inflammatory drugs, pregnancy or breastfeeding, systolic blood pressure less than 90 or greater than 180 mm Hg, and pulse rate less than 50 or greater than 150 beats/min. Primary outcome was pain reduction at 30 minutes. We recorded pain scores at baseline and up to 120 minutes. Intravenous morphine 0.1 mg/kg was administered as a rescue analgesic if subjects still desired additional pain medication at 30 minutes after the study drug was administered. Data analyses included mixed-model regression and ANOVA. We enrolled 240 subjects (80 in each dose group). At 30 minutes, substantial pain reduction was demonstrated without any differences between the groups (95% confidence intervals 4.5 to 5.7 for the 10-mg group, 4.5 to 5.6 for the 15-mg group, and 4.2 to 5.4 for the 30-mg group). The mean numeric rating scale pain scores at baseline were 7.7, 7.5, and 7.8 and improved to 5.1, 5.0, and 4.8, respectively, at 30 minutes. Rates of rescue analgesia were similar, and there were no serious adverse events. Secondary outcomes showed similar rates of adverse effects per

Ketorolac use may increase risk of postoperative pancreatic fistula after pancreaticoduodenectomy.

PubMed

Kowalsky, Stacy J; Zenati, Mazen S; Steve, Jennifer; Lee, Kenneth K; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

2018-01-01

Ketorolac (Toradol), a commonly used nonselective nonsteroidal anti-inflammatory drug (NSAID) in the postoperative period, has been associated with increased risk of anastomotic leak after colon resection. The effect of postoperative NSAID and ketorolac use on postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is unknown. Retrospective review of consecutive PDs at a high-volume pancreas center from 2012 to 2015. POPF was identified and graded using International Study Group on Pancreatic Fistula criteria. Demographics, operative variables and 30-d postoperative NSAID use, dosage, and timing (early = postoperative day [POD] 0-5, late > POD 5) were collected. Univariate and multivariate logistic regressions were used to identify predictors of POPF. Four hundred twenty-three PDs were analyzed (mean age 66 y, 47% female), and 60% received NSAIDs postoperatively. Ketorolac (median POD 0-5 cumulative dose = 90 mg, interquartile range 60-165) was used in 35.7% (n = 151). POPF occurred in 90 patients (21.3%). Early (POD 0-5) ketorolac use was associated with increased POPF, especially grade A (odds ratio [OR] 2.16, P = 0.036). Each 25 mg incremental increase in ketorolac use was associated with a 10% increase in the incidence of POPF (OR 1.10, P = 0.021), whereas a cumulative dose of >150 mg was associated with a 44% increased risk of POPF (OR 1.44, 95% confidence interval 1.03-2.01, P = 0.035). A multivariate regression model identified estimated blood loss, soft gland, pancreatic duct diameter, body mass index, and cumulative ketorolac dose >150 mg as independent predictors of POPF (P < 0.0001, pseudo R 2  = 0.149). Increasing doses of ketorolac in the early postoperative period are associated with increased risk of POPF, whereas a cumulative dose of >150 mg is an independent predictor of POPF after PD. Copyright © 2017 Elsevier Inc. All rights reserved.

A Randomized Trial of Ketorolac vs. Sumatripan vs. Placebo Nasal Spray (KSPN) for Acute Migraine.

PubMed

Rao, Aruna S; Gelaye, Bizu; Kurth, Tobias; Dash, Paul D; Nitchie, Haley; Peterlin, B Lee

2016-02-01

To compare the efficacy of ketorolac nasal spray (NS) vs. placebo and sumatriptan NS for the acute treatment of migraine. This was a randomized, double-blind, placebo and active-comparator, crossover study. Adult migraineurs were randomized to ketorolac NS 31.5 mg, sumatriptan NS 20 mg, or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack. Patients seeking headache care at a headache center or in response to community advertisement were recruited. Adult participants with episodic migraine who experienced ≥2 migraine attacks per month were eligible for the Ketorolac vs. Sumatriptan vs. Placebo Nasal Spray migraine study. Participants were randomized to treatment arms by a research pharmacist, in a 1:1:1 ratio using computer-generated lists. The primary outcome was 2-hour pain relief. Secondary outcomes included 2-hour pain freedom and absence of migraine associated symptoms, and 24-hour sustained pain relief and pain freedom. Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks. Both ketorolac NS (72.5%, P < .001) and sumatriptan NS (69.4%, P = .001) were more effective than placebo (38.3%) for 2-hour pain relief and 2-hour pain freedom (ketorolac: 43.1%, P = .004; sumatriptan: 36.7%, P = .046; placebo: 18.4%). Ketorolac NS, but not sumatriptan NS, was more effective than placebo in 2-hour absence of nausea. Both ketorolac NS and sumatriptan NS were more effective than placebo for 24-hour sustained pain relief (ketorolac: 49%, P < .001; sumatriptan: 31%, P = .01, placebo: 20%). Only ketorolac NS was superior to placebo for 24-hour (ketorolac: 35.3%, P = .003; sumatriptan: 22.4%, P = .18, placebo: 12.2%) sustained pain freedom. Nasal burning and dysgeusia were the most common adverse effects for active treatments. This study supports that ketorolac NS is superior to placebo and

Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer

PubMed Central

Samal, Sabindra K.; Routray, Samapika; Veeramachaneni, Ganesh Kumar; Dash, Rupesh; Botlagunta, Mahendran

2015-01-01

DDX3 belongs to DEAD box RNA helicase family and is involved in the progression of several types of cancer. In this work, we employed a High Throughput Virtual screening approach to identify bioactive compounds against DDX3 from ZINC natural database. Ketorolac salt was selected based on its binding free energy less than or equals to −5 Kcal/mol with reference to existing synthetic DDX3 inhibitors and strong hydrogen bond interactions as similar to crystallized DDX3 protein (2I4I). The anti-cancer activity of Ketorolac salt against DDX3 was tested using oral squamous cell carcinoma (OSCC) cell lines. This compound significantly down regulated the expression of DDX3 in human OSCC line (H357) and the half maximal growth inhibitory concentration (IC50) of Ketorolac salt in H357 cell line is 2.6 µM. Ketorolac salt also inhibited the ATP hydrolysis by directly interacting with DDX3. More importantly, we observed decreased number of neoplastic tongue lesions and reduced lesion severity in Ketorolac salt treated groups in a carcinogen induced tongue tumor mouse model. Taken together, our result demonstrates that Ketorolac salt is a newly discovered bioactive compound against DDX3 and this compound can be used as an ideal drug candidate to treat DDX3 associated oral cancer. PMID:25918862

Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer.

PubMed

Samal, Sabindra K; Routray, Samapika; Veeramachaneni, Ganesh Kumar; Dash, Rupesh; Botlagunta, Mahendran

2015-04-28

DDX3 belongs to DEAD box RNA helicase family and is involved in the progression of several types of cancer. In this work, we employed a High Throughput Virtual screening approach to identify bioactive compounds against DDX3 from ZINC natural database. Ketorolac salt was selected based on its binding free energy less than or equals to -5 Kcal/mol with reference to existing synthetic DDX3 inhibitors and strong hydrogen bond interactions as similar to crystallized DDX3 protein (2I4I). The anti-cancer activity of Ketorolac salt against DDX3 was tested using oral squamous cell carcinoma (OSCC) cell lines. This compound significantly down regulated the expression of DDX3 in human OSCC line (H357) and the half maximal growth inhibitory concentration (IC50) of Ketorolac salt in H357 cell line is 2.6 µM. Ketorolac salt also inhibited the ATP hydrolysis by directly interacting with DDX3. More importantly, we observed decreased number of neoplastic tongue lesions and reduced lesion severity in Ketorolac salt treated groups in a carcinogen induced tongue tumor mouse model. Taken together, our result demonstrates that Ketorolac salt is a newly discovered bioactive compound against DDX3 and this compound can be used as an ideal drug candidate to treat DDX3 associated oral cancer.

Ketorolac therapy for the prevention of acute pseudophakic cystoid macular edema: a systematic review

PubMed Central

Yilmaz, T; Cordero-Coma, M; Gallagher, M J

2012-01-01

To assess the effectiveness of ketorolac vs control for prevention of acute pseudophakic cystoid macular edema (CME). The following databases were searched: Medline (1950–June 11, 2011), The Cochrane Library (Issue 2, 2011), and the TRIP Database (up to 11 June 2011), using no language or other limits. Randomized controlled clinical trials (RCTs) were included that consisted of patients with acute pseudophakic cystoid macular edema, those comparing ketorolac with control, and those having at least a minimum follow-up of 28 days. In the four RCTs evaluating ketorolac vs control, treatment with ketorolac significantly reduced the risk of CME development at the end of treatment (∼4 weeks) compared to control (P=0.008; 95% confidence interval (0.03–0.58)). When analyzed individually, each individual study was statistically nonsignificant in its findings with the exception of one study. When the pooled relative risk was calculated, the large sample size of this systematic review led to overall statistical significance, which is attributable to the review's large sample size and not to the individual studies themselves. In this systematic review of four RCTs, two of which compared ketorolac with no treatment and two of which evaluated ketorolac vs placebo drops, treatment with ketorolac significantly reduced the risk of developing CME at the end of ∼4 weeks of treatment compared with controls. These results, however, should be interpreted with caution considering the paucity of large randomized clinical trials in the literature. PMID:22094296

Synergistic antinociceptive interaction of Syzygium aromaticum or Rosmarinus officinalis coadministered with ketorolac in rats.

PubMed

Beltrán-Villalobos, Karla Lyzet; Déciga-Campos, Myrna; Aguilar-Mariscal, Hidemi; González-Trujano, María Eva; Martínez-Salazar, María Fernanda; Ramírez-Cisneros, María de Los Ángeles; Rios, María Yolanda; López-Muñoz, Francisco Javier

2017-10-01

Syzygium aromaticum (L.) Merr. & L.M. Perry (Mirtaceae) and Rosmarinus officinalis L. (Lamiaceae) are both medicinal plants used for centuries to alleviate pain. The aim of the study was to demonstrate the therapeutic potential utility of herb-drug association of S. aromaticum essential oil or R. officinalis ethanolic extract coadministered with ketorolac. Antinociceptive pharmacological interaction was investigated by an isbolographic study using the formalin test in rats. Both alone and in combination with ketorolac; S. aromaticum and R. officinalis produced a dose-dependent antinociceptive response. To plot the isobologram, we used the effective dose 50 of each one component in a fixed 1:1 ratio. The isobolographic analysis showed that, in both combinations, ketorolac plus essential oil S. aromaticum and ketorolac plus ethanolic extract R. officinalis, the experimental value (Z exp ) was lower than the theoretical value (Z add ). In addition, this study shows that eugenol, a metabolite present in S. aromaticum, and ursolic acid, a metabolite present in R. officinalis, also synergized the antinociceptive effect of ketorolac. While, the oleanolic acid present in both medicinal species did not show a synergistic antinociceptive effect in combination with ketorolac. No adverse effects were observed with these herb-drug interactions. These findings suggest that essential oil S. aromaticum and ethanolic extract R. officinalis could be useful in combination with ketorolac for the treatment of inflammatory pain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Appropriateness of ketorolac use in a trauma hospital].

PubMed

Angeles González-Fernández, M

2009-06-01

To evaluate the suitability of ketorolac and non-steroidal anti-inflamatory drugs (NSAIDs) and other analgesic drugs currently used in the hospital. We have followed the steps to develop a PDCA cycle (plan, do, check, act) or quality improvement cycle. The quality problem was analysed using an Ishikawa diagram. We defined both qualitative quality indicators, those that measure prescription quality, and quantitative ones (defined daily dose, DDD/100BDs), which measure drug consumption, being the objectives to achieve. The study was conducted in all patients admitted to the hospital and who were admitted to orthopaedic and trauma surgery and plastic surgery departments with unit-dose dispensing systems. The strategy used was to give information to physicians through meetings and documentation. Finally, the results were analysed and compared with the initial objectives. The study was performed on 260 patients in the first study period and 292 in the second. Qualitative indicators: intravenous ketorolac use < or =2 days, increased in 25.5% (p<0.001); in patients > or =65 years old at dose < or =60 mg/day it increased 27.7% (p<0.05). Quantitative indicators: in the second study period, ketorolac use decreased (plastic surgery department: 61.8 DDD/100BDs to 14.8), whereas tramadol, ibuprofen and metamizole increased (plastic surgery department: 0 to 14.1 in tramadol, 8.7 to 48.6 in ibuprofen and 50.1 to 71 in metamizole). Appropriateness of ketorolac, NSAIDs and tramadol use has been achieved, thus improving patient safety. Strategies have been effective.

Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery.

PubMed

Solomon, K D; Cheetham, J K; DeGryse, R; Brint, S F; Rosenthal, A

2001-02-01

To compare the efficacy and safety of ketorolac 0.5% ophthalmic solution with its vehicle in the treatment of ocular inflammation after cataract surgery and intraocular lens implantation. Multicenter clinical study. One hundred four patients were prospectively randomized, 52 patients in treatment group, 52 patients in control group. Patients received either ketorolac or vehicle four times daily in the operated eye for 14 days starting the day after surgery in a prospective, double-masked, randomized, parallel group study. Only patients with moderate or greater postoperative inflammation the day after surgery were enrolled. The main outcome measures include inflammation (cell, flare, ciliary flush), intraocular pressure and visual acuity. Ketorolac was significantly more effective than vehicle in reducing the manifestations of postoperative ocular inflammation, including: anterior chamber cells (P: = 0.002) and flare (P: = 0.009), conjunctival erythema (P: = 0.010), ciliary flush (P: = 0.022), photophobia (P: = 0.027), and pain (P: = 0.043). Five times as many patients were dropped from the study for lack of efficacy from the vehicle group (22/52) than from the ketorolac group (4/52; P: = 0.001). Ketorolac was found to be equally as safe as vehicle in terms of adverse events, changes in visual acuity, intraocular pressure, and biomicroscopic and ophthalmoscopic variables. Ketorolac tromethamine 0.5% ophthalmic solution was significantly more effective than vehicle in the treatment of moderate or greater ocular inflammation following routine cataract surgery, while being as safe as vehicle.

Effect of caffeine coadministration and of nitric oxide synthesis inhibition on the antinociceptive action of ketorolac.

PubMed

López-Muñoz, F J; Castañeda-Hernández, G; Flores-Murrieta, F J; Granados-Soto, V

1996-07-25

The effects of caffeine and nitric oxide synthesis inhibition on the antinociceptive action of ketorolac were assessed using the pain-induced functional impairment model in the rat. Nociception was induced by the intra-articular injection of uric acid. Ketorolac, but not caffeine, produced an antinociceptive effect which was reduced by NG nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. Caffeine coadministration potentiated the ketorolac effect. L-NAME induced a dose-dependent reduction of this potentiation. The results suggest the participation of the L-arginine-nitric oxide-cyclic GMP pathway in the caffeine potentiation of ketorolac-induced antinociception.

Ketorolac for Pain Control With Intrauterine Device Placement: A Randomized Controlled Trial

PubMed Central

Ngo, Lynn L.; Ward, Kristy K.; Mody, Sheila K.

2015-01-01

Objective To evaluate intramuscular ketorolac compared to placebo saline injection for pain control with intrauterine device (IUD) placement. Methods We conducted a randomized, double-blind, placebo controlled trial between July 2012 and March 2014. Patients received ketorolac 30mg or placebo saline intramuscular injection 30 minutes prior to IUD placement. The primary outcome was pain with IUD placement on a 10cm visual analog scale (VAS). Sample size was calculated to provide 80% power to show a 2.0cm difference (α=0.05) in the primary outcome. Secondary outcomes included pain with study drug injection, speculum insertion, tenaculum placement, uterine sounding, and at 5 and 15 minutes after IUD placement. Results A total of 67 women participated in the study, 33 in the ketorolac arm and 34 in the placebo arm. There were no differences in baseline demographics including age, BMI, and race. There were no differences in median pain scores for IUD placement in the placebo versus ketorolac groups (5.2cm vs 3.6cm, p=0.99). There was a decrease in median pain scores at 5 minutes (2.2cm vs 0.3cm, p=<0.001) and 15 minutes (1.6cm vs 0.1cm, p=<0.001) after IUD placement but no difference for all other time points. Nulliparous participants (n=16, 8 per arm) had a decrease in pain scores with IUD placement (8.1cm vs 5.4cm, p=0.02). In this study, 22% of participants in the placebo group and 18% in the ketorolac group reported injection pain was as painful as IUD placement. Conclusions Ketorolac does not reduce pain with IUD placement but does reduce pain at 5 and 15 minutes after placement. PMID:26241253

Ketorolac for Pain Control With Intrauterine Device Placement: A Randomized Controlled Trial.

PubMed

Ngo, Lynn L; Ward, Kristy K; Mody, Sheila K

2015-07-01

To evaluate intramuscular ketorolac compared with placebo saline injection for pain control with intrauterine device (IUD) placement. We conducted a randomized, double-blind, placebo-controlled trial between July 2012 and March 2014. Patients received 30 mg ketorolac or placebo saline intramuscular injection 30 minutes before IUD placement. The primary outcome was pain with IUD placement on a 10-cm visual analog scale. Sample size was calculated to provide 80% power to show a 2.0-cm difference (α=0.05) in the primary outcome. Secondary outcomes included pain with study drug injection, speculum insertion, tenaculum placement, uterine sounding, and at 5 and 15 minutes after IUD placement. A total of 67 women participated in the study, 33 in the ketorolac arm and 34 in the placebo arm. There were no differences in baseline demographics including age, body mass index, and race. There were no differences in median pain scores for IUD placement in the placebo compared with ketorolac groups (5.2 compared with 3.6 cm, P=.99). There was a decrease in median pain scores at 5 minutes (2.2 compared with 0.3 cm, P≤.001) and 15 minutes (1.6 compared with 0.1 cm, P≤.001) after IUD placement but no difference for all other time points. Nulliparous participants (n=16, eight per arm) had a decrease in pain scores with IUD placement (8.1 compared with 5.4 cm, P=.02). In this study, 22% of participants in the placebo group and 18% in the ketorolac group reported injection pain was as painful as IUD placement. Ketorolac does not reduce pain with IUD placement but does reduce pain at 5 and 15 minutes after placement. ClinicalTrials.gov; www.clinicaltrials.gov, NCT01664559. I.

Comparative bioavailability of two oral formulations of ketorolac tromethamine: Dolac and Exodol.

PubMed

Flores-Murrieta, F J; Granados-Soto, V; Castañeda-Hernández, G; Herrera, J E; Hong, E

1994-03-01

The bioavailability of ketorolac after administration of two oral formulations containing 10 mg of ketorolac tromethamine, Exodol and Dolac, to 12 healthy Mexican volunteers was compared. Subjects received both formulations according to a randomized crossover design and blood samples were drawn at selected times during 24 h. Ketorolac plasma concentrations were determined by HPLC and individual plasma-concentration-against-time curves were constructed. Maximal plasma concentration and AUC0-24 values were compared by analysis of variance followed by Westlake's confidence interval test. 90% confidence limits ranged from 80 to 125% for Cmax and from 85 to 118% for AUC0-24. It is concluded that the two assayed formulations are bioequivalent.

Paracetamol-codeine compared to ketorolac for pain control in the Emergency Department.

PubMed

Buccelletti, F; Marsiliani, D; Zuccalà, G; Iacomini, P; Proietti, L; Pola, E; Zirio, G; Genitiempo, M; Marrocco, R; Conti, C; Brunetti, C; Rocchi, L; Merendi, G; D'Aurizio, G; Gilardi, E; Franceschi, F

2014-10-01

Paracetamol /codeine has shown a strong analgesic activity in several studies conducted among different kind of subjects, including those with trauma. Nevertheless, its efficacy in patients accessing the Emergency Department (ED) for different kind of pain has never been tested. This is a cross-sectional, observational, prospective, cohort study. Inclusion criteria were patients > 18 year old presenting to the ED for localized traumatic or inflammatory pain involving only extremities. Numeric scale (NRS) was recorded thirty minutes and two hours after the administration of the analgesic therapy, consisting of 15 mg of ketorolac or 1000 mg/60 mg of paracetamol/ codeine, both orally. Two-hundred patients were consecutively enrolled; 87 were treated with paracetamol/codeine and 113 with ketorolac. The combination paracetamol/codeine resulted to be not inferior to ketorolac in non-traumatic pain group and trauma group (p = 0.635 and p = 0.482, respectively). Compared to ketorolac, the combination paracetamol/codeine exerted a significantly higher analgesic activity in patients with fractures and muscular pain (p = 0.044) and was more effective in acute pain (p = 0.002), with a significant effect two hours after the administration (p = 0.029). Paracetamol/codeine is equivalent to ketorolac in non-traumatic pain and post-traumatic pain, but is superior in acute pain and in patients with fractures and muscular pain. Those results play in favor of the use of the combination paracetamol/codeine in patients accessing the ED for non-traumatic or traumatic pain of the extremities.

Development of an enantiomer selective microsampling assay for the quantification of ketorolac suitable for paediatric pharmacokinetic studies.

PubMed

Mohammed, Baba S; Engelhardt, Thomas; Cameron, Gary A; Hawwa, Ahmed F; Helms, Peter J; McLay, James S

2013-10-01

Ketorolac, a potent nonsteroidal anti-inflammatory drug used for pain control in children, exists as a racemate of inactive R (+) and active S (-) enantiomers. To develop a microsampling assay for the enantioselective analysis of ketorolac in children. Ketorolac enantiomers were extracted from 50 μl of plasma by liquid–liquid extraction and separated on a ChiralPak AD-RH. Detection was by a TSQ quantum triple quadrupole mass spectrometer with an electrospray ionisation source operating in a positive ion mode. Five children (age 13.8 (1.6) years, weight 52.7 (7.2) kg), were administered intravenous ketorolac 0.5mg/kg (maximum 10mg) and blood samples were taken at 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h post administration. CL, VD and t1/2 were calculated based on non-compartmental methods. The standard curves for R (+) and S (-) ketorolac were linear in the range 0–2000 ng/ml. The LLOQs of the method were 0.15 ng on column and 0.31 ng on column for R (+) and S (-) ketorolac, respectively. The median (range) VD and CL of R (+) and S (-) ketorolac were 0.12 l/kg (0.07–0.17), 0.017 l/h/kg (0.12–0.29) and 0.17 (0.09–0.31) l/kg, 0.049 (0.02–0.1) l/h/kg, p = 0.043), respectively. The median (range) elimination half-life (t1/2) of the R (+) and S (-) ketorolac was 5.0 h (2.5–5.8) and 3.1 h (1.8–4.4), p = 0.043), respectively. The development of a simple, rapid and reliable ketorolac assay suitable for paediatric PK studies is reported. Copyright © 2013 John Wiley & Sons, Ltd.

Isobolographic Analysis of the Interaction Between Tapentadol and Ketorolac in a Mouse Model of Visceral Pain.

PubMed

Zapata-Morales, Juan R; Aragon-Martinez, Othoniel H; Adriana Soto-Castro, Tely; Alonso-Castro, Ángel J; Castañeda-Santana, Demian I; Isiordia-Espinoza, Mario A

2016-06-01

Preclinical Research The aim of this experimental assay was to assess the antinociceptive interaction between tapentadol and ketorolac in the acetic acid-induced writhing model in mice. Tapentadol (5.62-31.6 mg/kg ip) or ketorolac (5.62-31.6 mg/kg ip) were administered 15 min before the acetic acid administration. The ED50 values of the individual drugs were determined and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in combination in the writhing test. Isobolographic analysis and the interaction index demonstrated an antinociceptive synergistic interaction between tapentadol and ketorolac in all combination. Thus, the experimental ED50 values were lower when compared with their theoretical ED50 values. These data suggest that the tapentadol-ketorolac combination produces an antinociceptive synergistic interaction in the mouse acetic acid-induced writhing model. Drug Dev Res 77 : 187-191, 2016.   © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ketorolac does not reduce effectiveness of pleurodesis in pediatric patients with spontaneous pneumothorax.

PubMed

Lizardo, Radhames E; Langness, Simone; Davenport, Katherine P; Kling, Karen; Fairbanks, Timothy; Bickler, Stephen W; Grabowski, Julia

2015-12-01

Antiinflammatory medications are thought to reduce the effectiveness of pleurodesis performed for the treatment of spontaneous pneumothorax. We reviewed our experience with children undergoing video-assisted thorascopic surgery (VATS) with pleurodesis for pneumothorax to determine if ketorolac administration influences patient outcomes. A retrospective review of patients who underwent VATS pleurodesis for spontaneous pneumothorax from 2009 to 2013 at a pediatric hospital was performed. Length of stay, radiographic pneumothorax resolution prior to discharge, and ipsilateral recurrence rates were compared in patients who did and did not receive perioperative ketorolac. Over a 50-month period, 51 patients underwent VATS with mechanical pleurodesis for spontaneous pneumothorax. The average age was 15.5years, and 76% were male. Ketorolac was administered to 26/51 patients. There were no differences in average length of stay (11.3 vs 10.9days, p=0.36), incidence of residual pneumothorax at discharge (22/41 vs 19/41, p=0.48), or ipsilateral recurrence (5/10 vs 5/10, p=1). Despite the intrinsic antiinflammatory properties of ketorolac, our data suggests that its use for patients undergoing pleurodesis for spontaneous pneumothorax does not detrimentally influence the outcomes of surgery. Therefore, we conclude that ketorolac can be used for pain control in this population. Large-scale studies are warranted to validate these findings. Published by Elsevier Inc.

Antihyperalgesic Effects of Indomethacin, Ketorolac, and Metamizole in Rats: Effects of Metformin.

PubMed

Guzmán-Priego, Crystell Guadalupe; Méndez-Mena, Roberto; Baños-González, Manuel Alfonso; Araiza-Saldaña, Claudia Ivonne; Castañeda-Corral, Gabriela; Torres-López, Jorge Elías

2017-03-01

Preclinical Research Metformin-dependent mechanisms have been implicated in the antinociceptive effect of some non-steroidal anti-inflammatory drugs (NSAIDs). In this study, the effect of local peripheral or systemic administration of metformin on the local peripheral or systemic antinociception induced by indomethacin, ketorolac and metamizole was assessed in the rat carrageenan-induced thermal hyperalgesia model. Rats were injected with carrageenan (1%, 50 µl) into the right hindpaw which reduced paw withdrawal latency, a measure of thermal hyperalgesia. Local peripheral or systemic administration of indomethacin, ketorolac or metamizole dose-dependently reduced carrageenan-induced thermal hyperalgesia. Local peripheral pre-treatment with metformin (800 µg/paw) partially inhibited the anti-hyperalgesic effect of indomethacin (200 µg/paw) and metamizole (200 µg/paw), but not that of ketorolac (200 µg/paw). In contrast, systemic pre-treatment with metformin (200 mg/kg) attenuated the antihyperalgesic effect of metamizole (10 mg/kg), but not that observed with either indomethacin (10 mg/kg) or ketorolac (10 mg/kg). These findings suggest that some but not all NSAIDs have effects mediated by metformin-dependent mechanisms. Drug Dev Res 78 : 98-104, 2017. ©2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Routine perioperative ketorolac administration is not associated with hemorrhage in pediatric neurosurgery patients.

PubMed

Richardson, Marlin Dustin; Palmeri, Nicholas O; Williams, Sarah A; Torok, Michelle R; O'Neill, Brent R; Handler, Michael H; Hankinson, Todd C

2016-01-01

OBJECT NSAIDs are effective perioperative analgesics. Many surgeons are reluctant to use NSAIDs perioperatively because of a theoretical increase in the risk for bleeding events. The authors assessed the effect of routine perioperative ketorolac use on intracranial hemorrhage in children undergoing a wide range of neurosurgical procedures. METHODS A retrospective single-institution analysis of 1451 neurosurgical cases was performed. Data included demographics, type of surgery, and perioperative ketorolac use. Outcomes included bleeding events requiring return to the operating room, bleeding seen on postoperative imaging, and the development of renal failure or gastrointestinal tract injury. Variables associated with both the exposure and outcomes (p < 0.20) were evaluated as potential confounders for bleeding on postoperative imaging, and multivariable logistic regression was performed. Bivariable analysis was performed for bleeding events. Odds ratios and 95% CIs were estimated. RESULTS Of the 1451 patients, 955 received ketorolac. Multivariate regression analysis demonstrated no significant association between clinically significant bleeding events (OR 0.69; 95% CI 0.15-3.1) or radiographic hemorrhage (OR 0.81; 95% CI 0.43-1.51) and the perioperative administration of ketorolac. Treatment with a medication that creates a known bleeding risk (OR 3.11; 95% CI 1.01-9.57), surgical procedure (OR 2.35; 95% CI 1.11-4.94), and craniotomy/craniectomy (OR 2.43; 95% CI 1.19-4.94) were associated with a significantly elevated risk for radiographically identified hemorrhage. CONCLUSIONS Short-term ketorolac therapy does not appear to be associated with a statistically significant increase in the risk of bleeding documented on postoperative imaging in pediatric neurosurgical patients and may be considered as part of a perioperative analgesic regimen. Although no association was found between ketorolac and clinically significant bleeding events, a larger study needs to be

I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia.

PubMed

Hwang, J-Y; Na, H-S; Jeon, Y-T; Ro, Y-J; Kim, C-S; Do, S-H

2010-01-01

In a randomized, double-blind, prospective study, we have evaluated the effect of i.v. infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements. Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included. After the induction of spinal anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) for 15 min and then 15 mg kg(-1) h(-1) by continuous i.v. infusion until the end of surgery. The saline group (Group S) received the same volume of isotonic saline over the same period. After surgery, a patient-controlled analgesia (PCA) device containing morphine and ketorolac was provided for the patients. Postoperative pain scores, PCA consumption, and the incidences of shivering, postoperative nausea, and vomiting were evaluated immediately after surgery, and at 30 min, 4, 24, and 48 h after surgery. Serum magnesium concentrations were checked before the induction of anaesthesia, immediately after surgery, and at 1 and 24 h after surgery. Postoperative pain scores were significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Postoperative magnesium concentrations were higher in Group M (P<0.05 at 4, 24, and 48 h after surgery), but no side-effects associated with hypermagnesemia were observed. Haemodynamic variables and the incidences of shivering, nausea, and vomiting were similar in the two groups. I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia.

A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients.

PubMed

Wittpenn, John R; Silverstein, Steven; Heier, Jeffrey; Kenyon, Kenneth R; Hunkeler, John D; Earl, Melissa

2008-10-01

To evaluate whether adding perioperative topical ketorolac tromethamine 0.4% improves cataract surgery outcomes relative to topical steroids alone in patients without known risk factors for cystoid macular edema (CME). Prospective, randomized, investigator-masked, multicenter clinical trial. Patients scheduled to undergo phacoemulsification and with no recognized CME risks (diabetic retinopathy, retinal vascular disease, or macular abnormality) were randomized to receive either prednisolone acetate 1% 4 times daily (QID) alone (steroid group; n = 278) or prednisolone 1% QID plus ketorolac 0.4% QID (ketorolac/steroid group; n = 268) for approximately four weeks postoperatively. In the ketorolac/steroid group, patients also received topical ketorolac 0.4% QID for three days preoperatively. In both groups, patients received four doses of ketorolac 0.4% one hour before surgery. Patients with capsular disruption or vitreous loss intraoperatively were exited from the study. Outcome measures included CME incidence, retinal thickness as measured by optical coherence tomography (OCT), best-corrected visual acuity, and contrast sensitivity. No patients in the ketorolac/steroid group and five patients in the steroid group had clinically apparent CME (P = .032). Based on OCT, no ketorolac/steroid patient had definite or probable CME, compared with six steroid patients (2.4%; P = .018). In the ketorolac/steroid group, mean retinal thickening was less (3.9 microm vs 9.6 microm; P = .003), and fewer patients had retinal thickening of more than 10 microm as compared with the steroid group (26% vs 51%; P < .001). This study suggests that adding perioperative ketorolac to postoperative prednisolone significantly reduces the incidences of CME and macular thickening in cataract surgery patients already at low risk for this condition.

Low doses of tizanidine synergize the anti-nociceptive and anti-inflammatory effects of ketorolac or naproxen while reducing of side effects.

PubMed

Patiño-Camacho, Selene I; Déciga Campos, Myrna; Beltrán-Villalobos, Karla; Castro-Vidal, Dalia A; Montiel-Ruiz, Rosa M; Flores-Murrieta, Francisco J

2017-06-15

The aim of the present study was to determine whether tizanidine, an alpha2-adrenoceptor agonist, is able to increase the anti-inflammatory and anti-nociceptive effects of naproxen and ketorolac with a low incidence of gastric injury and spontaneous activity in rats. The anti-inflammatory effect was assayed in a carrageenan test, and oral administration of tizanidine (ED 40 =0.94±0.2mg/kg), naproxen (ED 40 =3.18±0.4mg/kg), and ketorolac (ED 40 =16.4±1.9mg/kg) showed a dose-dependent effect on inflammation. The anti-nociceptive effect was assayed in the formalin test, and administration of tizanidine (ED 40 =0.39±0.06mg/kg, p.o.), naproxen (ED 40 =33.9±3.9mg/kg, p.o.) or ketorolac (ED 40 =6.49±1mg/kg, p.o.) each showed a dose-dependent anti-nociceptive effect. The effects of combinations of tizanidine/naproxen and tizanidine/ketorolac were determined considering their ED 40 at a rate of 1:1. Additionally, the tizanidine/naproxen and tizanidine/ketorolac combinations showed anti-inflammatory and anti-nociceptive effects. The tizanidine/ketorolac combination was more potent than tizanidine/naproxen, in both inflammatory (interaction index=0.03 tizanidine/ketorolac and 0.07 tizanidine/naproxen) and nociceptive (interaction index=0.005 tizanidine/ketorolac and 0.01 tizanidine/naproxen) processes. In both cases, tizanidine improved naproxen and ketorolac gastrointestinal tolerability by 50%. Furthermore, co-administration of tizanidine with naproxen or ketorolac did not modify the spontaneous activity in the same way as individual tizanidine administration. Considering that tizanidine increases the anti-inflammatory and anti-nociceptive effects of naproxen or ketorolac, with an increase in gastric tolerability, tizanidine could provide therapeutic advantages in the clinical treatment of inflammation and pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploring Opioid-Sparing Multimodal Analgesia Options in Trauma: A Nursing Perspective.

PubMed

Sullivan, Denise; Lyons, Mary; Montgomery, Robert; Quinlan-Colwell, Ann

Challenges with opioids (e.g., adverse events, misuse and abuse with long-term administration) have led to a renewed emphasis on opioid-sparing multimodal management of trauma pain. To assess the extent to which currently available evidence supports the efficacy and safety of various nonopioid analgesics and techniques to manage trauma pain, a literature search of recently published references was performed. Additional citations were included on the basis of authors' knowledge of the literature. Effective options for opioid-sparing analgesics include oral and intravenous (IV) acetaminophen; nonsteroidal anti-inflammatory drugs available via multiple routes; and anticonvulsants, which are especially effective for neuropathic pain associated with trauma. Intravenous routes (e.g., IV acetaminophen, IV ketorolac) may be associated with a faster onset of action than oral routes. Additional adjuvants for the treatment of trauma pain are muscle relaxants and alpha-2 adrenergic agonists. Ketamine and regional techniques play an important role in multimodal therapy but require medical and nursing support. Nonpharmacologic treatments (e.g., cryotherapy, distraction techniques, breathing and relaxation, acupuncture) supplement pharmacologic analgesics and can be safe and easy to implement. In conclusion, opioid-sparing multimodal analgesia addresses concerns associated with high doses of opioids, and many pharmacologic and nonpharmacologic options are available to implement this strategy. Nurses play key roles in comprehensive patient assessment; administration of patient-focused, opioid-sparing, multimodal analgesia in trauma; and monitoring for safety concerns.

Effects of Ultrasound-guided intra-articular ketorolac injection with capsular distension.

PubMed

Ahn, Jae Ki; Kim, Jongwoo; Lee, Sang Jae; Park, Yongbum; Bae, Byung; Lee, Woo

2015-01-01

Frozen shoulder is a painful condition with gradual onset and loss of range of motion in the glenohumeral joint. To investigate the efficacy of ultrasound(US)-guided intra-articular (IA) ketorolac injection with capsular distension compared with steroid injection alone in patients with frozen shoulder by assessing pain relief, functional improvements, and range of motion at 1,3 and 6 months after the last injections. Between January 2009 and December 2012, 121 patient were treated with US-guided IA steroid injection or IA ketorolac injection with capsular distension for frozen shoulder. Patients (n= 57) of US-guided IA steroid injection group were administered with a mixture of 0.5% lidocaine (4 ml) plus triamcinolone (40 mg/ml; 1 ml) and patients (n= 64) of US-guided IA ketorolac injection with capsular distension group were administered by using 0.5% lidocaine (19 mL) plus ketorolac (30 mg/ml; 1 mL) for capsular distension. Outcome measurement was assessed by Shoulder Pain and Disability Index (SPADI), Verbal Numeric pain Scale (VNS) and passive range of motion (ROM) before injections and at 1, 3 and 6 months after the last injections. We regarded the outcomes as a success if patients obtained significant pain relief (as measured by > 50% improvement in the VNS score and 20 point improvement in the SPASI) at 1, 3 and 6 months after the last injections. SPADI, VNS and passive ROM were improved 1, 3 and 6 months after the last injections in both groups. The statistical differences were not observed in SPADI, VNS between groups (p< 0.05). Successful treatment rate were not significantly different between the groups as well as in 1, 3 and 6 month outcomes. However, greater improvement was found in a matter of range of motion in patients receiving IA ketorolac injection with capsular distension than participants receiving US-guided IA steroid injection alone. Significant differences in improvement at 3 and 6 months were observed for shoulder passive abduction and

R-ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis

PubMed Central

Guo, Yuna; Kenney, Shelby Ray; Muller, Carolyn Y.; Adams, Sarah; Rutledge, Teresa; Romero, Elsa; Murray-Krezan, Cristina; Prekeris, Rytis; Sklar, Larry A.; Hudson, Laurie G.; Wandinger-Ness, Angela

2015-01-01

Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin substrate 1) are attractive therapeutic targets in ovarian cancer based on established importance in tumor cell migration, adhesion and invasion. Despite a predicted benefit, targeting GTPases has not yet been translated to clinical practice. We previously established that Cdc42 and constitutively active Rac1b are overexpressed in primary ovarian tumor tissues. Through high throughput screening and computational shape homology approaches we identified R-ketorolac as a Cdc42 and Rac1 inhibitor; distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on immortalized human ovarian adenocarcinoma cells (SKOV3ip), and primary, patient-derived ovarian cancer cells show R-ketorolac is a robust inhibitor of growth factor or serum dependent Cdc42 and Rac1 activation with a potency and cellular efficacy similar to small molecule inhibitors of Cdc42 (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R-ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits cell adhesion, migration and invasion. In sum, we provide evidence for R-ketorolac as direct inhibitor of Cdc42 and Rac1 that is capable of modulating downstream GTPase-dependent, physiological responses, which are critical to tumor metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1 GTPases by an FDA approved drug-racemic ketorolac that can be used in humans. PMID:26206334

R-Ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis.

PubMed

Guo, Yuna; Kenney, S Ray; Muller, Carolyn Y; Adams, Sarah; Rutledge, Teresa; Romero, Elsa; Murray-Krezan, Cristina; Prekeris, Rytis; Sklar, Larry A; Hudson, Laurie G; Wandinger-Ness, Angela

2015-10-01

Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin substrate 1) are attractive therapeutic targets in ovarian cancer based on established importance in tumor cell migration, adhesion, and invasion. Despite a predicted benefit, targeting GTPases has not yet been translated to clinical practice. We previously established that Cdc42 and constitutively active Rac1b are overexpressed in primary ovarian tumor tissues. Through high-throughput screening and computational shape homology approaches, we identified R-ketorolac as a Cdc42 and Rac1 inhibitor, distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on immortalized human ovarian adenocarcinoma cells (SKOV3ip) and primary patient-derived ovarian cancer cells show that R-ketorolac is a robust inhibitor of growth factor or serum-dependent Cdc42 and Rac1 activation with a potency and cellular efficacy similar to small-molecule inhibitors of Cdc42 (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R-ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits cell adhesion, migration, and invasion. In summary, we provide evidence for R-ketorolac as a direct inhibitor of Cdc42 and Rac1 that is capable of modulating downstream GTPase-dependent, physiologic responses, which are critical to tumor metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1 GTPases by an FDA-approved drug, racemic ketorolac, that can be used in humans. ©2015 American Association for Cancer Research.

An ex vivo investigation into the transurothelial permeability and bladder wall distribution of the nonsteroidal anti-inflammatory ketorolac.

PubMed

Williams, Nicholas A; Bowen, Jenna L; Al-Jayyoussi, Ghaith; Gumbleton, Mark; Allender, Chris J; Li, Jamie; Harrah, Tim; Raja, Aditya; Joshi, Hrishi B

2014-03-03

Transurothelial drug delivery continues to be an attractive treatment option for a range of urological conditions; however, dosing regimens remain largely empirical. Recently, intravesical delivery of the nonsteroidal anti-inflammatory ketorolac has been shown to significantly reduce ureteral stent-related pain. While this latest development provides an opportunity for advancing the management of stent-related pain, clinical translation will undoubtedly require an understanding of the rate and extent of delivery of ketorolac into the bladder wall. Using an ex vivo porcine model, we evaluate the urothelial permeability and bladder wall distribution of ketorolac. The subsequent application of a pharmacokinetic (PK) model enables prediction of concentrations achieved in vivo. Ketorolac was applied to the urothelium and a transurothelial permeability coefficient (Kp) calculated. Relative drug distribution into the bladder wall after 90 min was determined. Ketorolac was able to permeate the urothelium (Kp = 2.63 × 10(-6) cm s(-1)), and after 90 min average concentrations of 400, 141 and 21 μg g(-1) were achieved in the urothelium, lamina propria and detrusor respectively. An average concentration of 87 μg g(-1) was achieved across the whole bladder wall. PK simulations (STELLA) were then carried out, using ex vivo values for Kp and muscle/saline partition coefficient (providing an estimation of vascular clearance), to predict 90 min in vivo ketorolac tissue concentrations. When dilution of the drug solution with urine and vascular clearance were taken into account, a reduced ketorolac concentration of 37 μg g(-1) across the whole bladder wall was predicted. These studies reveal crucial information about the urothelium's permeability to agents such as ketorolac and the concentrations achievable in the bladder wall. It would appear that levels of ketorolac delivered to the bladder wall intravesically would be sufficient to provide an anti-inflammatory effect. The

Recommendations of the national football league physician society task force on the use of toradol(®) ketorolac in the national football league.

PubMed

Matava, Matthew; Brater, D Craig; Gritter, Nancy; Heyer, Robert; Rollins, Douglas; Schlegel, Theodore; Toto, Robert; Yates, Anthony

2012-09-01

Ketorolac tromethamine (Toradol(®)) is a non-steroidal anti-inflammatory drug that has potent analgesic and anti-inflammatory properties. It can be administered orally, intravenously, intramuscularly, or via a nasal route. Ketorolac injections have been used for several years in the National Football League (NFL), in both the oral and injectable forms, to treat musculoskeletal injuries and to prevent post-game soreness. In an attempt to determine the appropriate use of this medication in NFL players, the NFL Team Physician Society appointed a Task Force to consider the best available evidence as to how ketorolac should be used for pain management in professional football players. These treatment recommendations were established based on the available medical literature taking into consideration the pharmacokinetic properties of ketorolac, its accepted indications and contraindications, and the unique clinical challenges of the NFL. The Task Force recommended that 1) ketorolac should only be administered under the direct supervision and order of a team physician; 2) ketorolac should not be used prophylactically as a means of reducing anticipated pain either during or after participation in NFL games or practices and should be limited to those players diagnosed with an injury or condition and listed on the teams' injury report; 3) ketorolac should be given in the lowest effective therapeutic dose and should not be used in any form for more than 5 days; 4) ketorolac should be given in its oral preparation under typical circumstances; 5) ketorolac should not be taken concurrently with other NSAIDs or by those players with a history of allergic reaction to ketorolac, other NSAIDs or aspirin; and 6) ketorolac should not be used by a player with a history of significant gastrointestinal bleeding, renal compromise, or a past history of complications related to NSAIDs.

Recommendations of the National Football League Physician Society Task Force on the Use of Toradol® Ketorolac in the National Football League

PubMed Central

Matava, Matthew; Brater, D. Craig; Gritter, Nancy; Heyer, Robert; Rollins, Douglas; Schlegel, Theodore; Toto, Robert; Yates, Anthony

2012-01-01

Ketorolac tromethamine (Toradol®) is a non-steroidal anti-inflammatory drug that has potent analgesic and anti-inflammatory properties. It can be administered orally, intravenously, intramuscularly, or via a nasal route. Ketorolac injections have been used for several years in the National Football League (NFL), in both the oral and injectable forms, to treat musculoskeletal injuries and to prevent post-game soreness. In an attempt to determine the appropriate use of this medication in NFL players, the NFL Team Physician Society appointed a Task Force to consider the best available evidence as to how ketorolac should be used for pain management in professional football players. These treatment recommendations were established based on the available medical literature taking into consideration the pharmacokinetic properties of ketorolac, its accepted indications and contraindications, and the unique clinical challenges of the NFL. The Task Force recommended that 1) ketorolac should only be administered under the direct supervision and order of a team physician; 2) ketorolac should not be used prophylactically as a means of reducing anticipated pain either during or after participation in NFL games or practices and should be limited to those players diagnosed with an injury or condition and listed on the teams’ injury report; 3) ketorolac should be given in the lowest effective therapeutic dose and should not be used in any form for more than 5 days; 4) ketorolac should be given in its oral preparation under typical circumstances; 5) ketorolac should not be taken concurrently with other NSAIDs or by those players with a history of allergic reaction to ketorolac, other NSAIDs or aspirin; and 6) ketorolac should not be used by a player with a history of significant gastrointestinal bleeding, renal compromise, or a past history of complications related to NSAIDs. PMID:23016110

Effects of lysine clonixinate and ketorolac tromethamine on prostanoid release from various rat organs incubated ex vivo.

PubMed

Pallapies, D; Salinger, A; Meyer zum Gottesberge, A; Atkins, D J; Rohleder, G; Nagyiványi, P; Peskar, B A

1995-01-01

The release of prostanoids from rat brain, gastric mucosa, lungs and kidneys incubated ex vivo has been investigated for up to 5 h after oral administration of 10 mg/kg lysine clonixinate or 1 mg/kg ketorolac tromethamine. Additionally, 60 min after drug administration, a time point of near-maximal inhibition of prostanoid release, the effects of 2.5, 10 and 30 mg/kg lysine clonixinate and of 0.0225, 0.15 and 1 mg/kg ketorolac tromethamine were compared. In all organs investigated both drugs inhibited fatty acid cyclooxygenase (COX) in a dose-dependent manner, but ketorolac tromethamine was more potent and had a longer-lasting effect than lysine clonixinate. While the ID50 values for lysine clonixinate were in the same order of magnitude for all 4 organs investigated, ketorolac tromethamine exhibited some organ selectivity with a particularly high activity in the kidneys. This effect might be related to the renal toxicity of ketorolac tromethamine. On the other hand, the difference in potency was smallest in brain suggesting that inhibition of central prostanoid biosynthesis could contribute to the rapid and effective inhibition of pain by both drugs. IC50 values for inhibition of purified COX-1 and COX-2 in vitro were slightly lower for lysine clonixinate (2.4 and 24.6 micrograms/ml, respectively) than for ketorolac tromethamine (3.7 and 25.6 micrograms/ml, respectively).

TREATMENT OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION WITH RANIBIZUMAB COMBINED WITH KETOROLAC EYEDROPS OR PHOTODYNAMIC THERAPY.

PubMed

Semeraro, Francesco; Russo, Andrea; Delcassi, Luisa; Romano, Mario R; Rinaldi, Michele; Chiosi, Flavia; Costagliola, Ciro

2015-08-01

To evaluate whether ketorolac eyedrops plus intravitreal ranibizumab (IVR) or verteporfin photodynamic therapy plus IVR provides additional benefit over IVR monotherapy for treatment of choroidal neovascularization in age-related macular degeneration. This was a prospective, randomized, pilot study in 75 patients with naive choroidal neovascularization. Patients were randomized 1:1:1 into 3 groups: ranibizumab monotherapy (RM), ranibizumab plus ketorolac, or ranibizumab plus loading-phase reduced-fluence verteporfin photodynamic therapy (RV) groups. At 12 months, all groups showed significant improvement in both best-corrected visual acuity and central retinal thickness. The mean best-corrected visual acuity change from baseline to 12 months was -0.14 ± 0.52 logMAR (20/73 ± 20/29), -0.25 ± 0.60 logMAR (20/46 ± 20/27), and -0.10 ± 0.30 (20/97 ± 20/40) logMAR in RM, ranibizumab plus ketorolac, and RV groups, respectively. The mean central retinal thickness change from baseline to 12 months was -125 ± 15 μm, -141 ± 21 μm, and -130 ± 15 μm in RM, ranibizumab plus ketorolac, and RV groups, respectively. Both ranibizumab plus ketorolac and RV groups required fewer IVR treatments than RM. Compared with RM and ranibizumab plus verteporfin photodynamic therapy, the combination of 0.45% ketorolac eyedrops 3 times a day and ranibizumab in patients with choroidal neovascularization provided superior best-corrected visual acuity and central retinal thickness outcomes. Both combination regimens required fewer IVR injections than RM during the 12-month follow-up period.

Ocular Penetration and Anti-inflammatory Activity of Ketorolac 0.45% and Bromfenac 0.09% Against Lipopolysaccharide-Induced Inflammation

PubMed Central

Galindo, Danielle; Villanueva, Linda; Nguyen, Cathy; Patel, Milan; Borbridge, Lisa; Attar, Mayssa; Schiffman, Rhett M.; Hollander, David A.

2011-01-01

Abstract Purpose Anti-inflammatory activity of topical nonsteroidal anti-inflammatory drugs is mediated by suppression of cyclooxygenase (COX) isoenzymes. This study compared ocular penetration and inflammation suppression of topical ketorolac 0.45% and bromfenac 0.09% ophthalmic solutions in a rabbit model. Methods At hour 0, 36 rabbits received ketorolac 0.45%, bromfenac 0.09%, or an artificial tear 3 times once every 20 min. Half of the rabbits in each group then received intravenous injections of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)–dextran at hour 1, and the other half at hour 10. Aqueous and iris-ciliary body (ICB) samples were collected in the former group at hour 2 (peak) and in the latter group at hour 11 (trough) An additional group of 6 animals received only FITC-dextran, and samples were collected 1 h later. Peak and trough nonsteroidal anti-inflammatory drug concentrations were compared with previously determined half-maximal inhibitory concentrations (IC50) for COX isoenzymes. Results Peak and trough aqueous and ICB concentrations of ketorolac were at least 7-fold or greater than those of bromfenac. At peak levels, both ketorolac 0.45% and bromfenac 0.09% significantly inhibited LPS-induced aqueous prostaglandin E2 and FITC-dextran elevation (P < 0.01). At trough, both study drugs significantly inhibited LPS-induced aqueous prostaglandin E2 elevation (P < 0.05), but only ketorolac 0.45% significantly reduced LPS-induced aqueous FITC-dextran elevation (P < 0.01). Aqueous and ICB ketorolac concentrations exceeded its IC50 for COX-1 and COX-2 at peak and trough. Aqueous and ICB bromfenac levels exceeded its IC50 for COX-2 at peak and trough, but not for COX-1 at trough aqueous levels and peak and trough ICB levels. Conclusions Both ketorolac 0.45% and bromfenac 0.09% effectively suppressed inflammation at peak. At trough, only ketorolac 0.45% effectively suppressed inflammation as measured by FITC

Intramuscular ketorolac versus oral ibuprofen for pain relief in first-trimester surgical abortion: a randomized clinical trial.

PubMed

Braaten, Kari P; Hurwitz, Shelley; Fortin, Jennifer; Goldberg, Alisa B

2014-02-01

Oral nonsteroidal antiinflammatory medications (NSAIDs) have been shown to reduce pain with first-trimester surgical abortion compared to placebo, but it is unclear if one NSAID is better than another. Some providers administer intramuscular ketorolac, though data regarding its efficacy in abortion are limited. This study was designed to compare oral ibuprofen to intramuscular ketorolac for pain management during first-trimester surgical abortion. This was a randomized, double-blind, controlled trial. Women undergoing first-trimester surgical abortion with local anesthesia were randomized to preprocedural oral ibuprofen, 800 mg given 60-90 min preprocedure, or intramuscular ketorolac, 60 mg given 30-60 min preprocedure. The primary outcome was pain with uterine aspiration on a 21-point, 0-100, numerical rating scale. Secondary outcomes included pain with cervical dilation, postoperative pain and patient satisfaction. Ninety-four women were enrolled; 47 were randomized to ibuprofen and 47 to ketorolac. The groups did not differ with regards to demographics, reproductive history or Depression Anxiety Stress Scale scores. Mean pain scores for suction curettage did not differ between groups (52.3 vs. 56.2, p=.53). There was also no difference in pain with cervical dilation (41.6 vs. 45.4, p=0.48) or postoperative pain (22.3 vs. 15.0 p=.076), though patients in the ketorolac group experienced significantly greater arm pain than those who received a placebo injection (30.4 vs. 15.6, p<.001). Satisfaction with pain control did not differ significantly by group. Intramuscular ketorolac does not offer superior pain control compared to oral ibuprofen for first-trimester surgical abortion. Intramuscular ketorolac does not offer superior pain control over oral ibuprofen during first-trimester surgical abortion, is more expensive and causes patients significant arm discomfort. Its use should therefore be reserved for patients who cannot tolerate oral NSAIDs. © 2014.

Intraarticular vs. extraarticular ropivacaine infusion following high-dose local infiltration analgesia after total knee arthroplasty

PubMed Central

2011-01-01

Background and purpose Ropivacaine infusion following high-volume local infiltration analgesia has been shown to be effective after total knee arthroplasty, but the optimum site of administration of ropivacaine has not been evaluated. We compared the effects of intraarticular and extraarticular adminstration of the local anesthetic for postoperative supplementation of high-volume local infiltration analgesia. Patients and methods In this double-blind study, 36 rheumatic patients aged 51–78 years with physical status ASA 2–3 who were scheduled for total knee arthroplasty were randomized into 2 groups. All patients received wound infiltration at the end of surgery with 300 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 156 mL). A tunneled catheter was randomly placed either extraarticularly or intraarticularly. Continuous infusion of ropivacain (0.5%, 2 mL/h) was started immediately and was maintained during the next 48 h. Pain intensity at rest, on movement, and with mobilization was estimated by the patients and the physiotherapist; rescue morphine consumption was recorded. Results As estimated by the patients, ropivacaine administered intraarticularly did not improve analgesia relative to extraarticular infusion, but improved the first mobilization. The incidence of high intensity of pain (VAS 7–10) was less in the group with intraarticular infusion. Analgesic requirements were similar in the 2 groups (47 mg and 49 mg morphine). No complications of postoperative wound healing were seen and there were no toxic side effects. Interpretation Continuous infusion of ropivacaine intraarticulary did not improve postoperative analgesia at rest relative to extraarticular administration, but it appeared to reduce the incidence of high pain intensity during first exercises, and could therefore be expected to improve mobilization up to 24 h after total knee arthroplasty. PMID:22026413

Participation of the nitric oxide-cyclic GMP-ATP-sensitive K(+) channel pathway in the antinociceptive action of ketorolac.

PubMed

Lázaro-Ibáñez, G G; Torres-López, J E; Granados-Soto, V

2001-08-24

The involvement of nitric oxide (NO), cyclic GMP and ATP-sensitive K(+) channels in the antinociceptive effect of ketorolac was assessed using the formalin test in the rat. Local administration of ketorolac in a formalin-injured paw produced a dose-dependent antinociceptive effect due to a local action, as drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with N(G)-L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) or glibenclamide (an ATP-sensitive K(+) channel blocker) prevented ketorolac-induced antinociception. However, pretreatment with saline or N(G)-D-nitro-arginine methyl ester (D-NAME) did not block antinociception. Local administration of S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) was inactive by itself, but increased the effect of ketorolac. The present results suggest that the antinociceptive effect of ketorolac involves activation of the NO-cyclic GMP pathway, followed by an opening of ATP-sensitive K(+) channels at the peripheral level.

Impact of ketorolac administration around ovarian stimulation on in vivo and in vitro fertilization and subsequent embryo development.

PubMed

Jee, Byung Chul; Youm, Hye Won; Lee, Jae Ho; Kim, Jee Hyun; Suh, Chang Suk; Kim, Seok Hyun

2013-05-01

We performed this study to investigate the effect of ketorolac (a non-steroidal anti-inflammatory drug) administration around ovarian stimulation on in vivo and in vitro fertilization process. Sixty-four female mice (ICR) were injected with ketorolac (0, 7.5, 15 and 30 µg/d) for 3 d starting from the day of eCG treatment. In experiment 1, 41 mice were triggered by hCG and then mated; two-cell embryos were obtained and in vitro development up to blastocyst was observed. In experiment 2, 23 mice were triggered by hCG and mature oocytes were collected; in vitro fertilization rate and subsequent embryo development up to blastocyst was recorded. In experiment 1, the blastocyst-forming rates per in vivo fertilized two-cell embryo showed an inverse relationship with a dosage of ketorolac (97.6%, 64.2%, 35.4% and 25.9%). In experiment 2, degenerated oocytes were frequently observed in a dose-dependent manner (4.3%, 22.9%, 22.4% and 75.0%). Lower fertilization rates were noted in all the three ketorolac-treating groups; blastocyst-forming rate was significantly lower in 30-µg-treating group when compared with the control group. Administration of ketorolac around ovarian stimulation significantly affects the development of in vivo fertilized embryo in a dose-dependent manner. High-dose ketorolac could result in a poor oocyte quality and decreased embryo developmental competence.

Oxidative stress and genotoxicity induced by ketorolac on the common carp Cyprinus carpio.

PubMed

Galar-Martínez, M; García-Medina, S; Gómez-Olivan, L M; Pérez-Coyotl, I; Mendoza-Monroy, D J; Arrazola-Morgain, R E

2016-09-01

The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2-60 µg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 µg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1035-1043, 2016. © 2015 Wiley Periodicals, Inc.

An in vitro evaluation of the anti-inflammatory effects of platelet-rich plasma, ketorolac, and methylprednisolone.

PubMed

Mazzocca, Augustus D; McCarthy, Mary Beth R; Intravia, Jessica; Beitzel, Knut; Apostolakos, John; Cote, Mark P; Bradley, James; Arciero, Robert A

2013-04-01

The purpose of this study was to quantify the extent of the anti-inflammatory effect of platelet-rich plasma (PRP) in a controlled in vitro environment. Through the stimulation of human umbilical vein endothelial cells with inflammatory cytokines (tumor necrosis factor α and interferon γ), cell adhesion molecule expression (E-selectin, vascular cell adhesion molecule, and human leukocyte antigen DR) and PRP's anti-inflammatory effect can be measured. PRP was produced from 3 individuals using a single-spin (PRPLP) process. Treatment groups include negative (unstimulated) controls, positive (stimulated) controls, ketorolac tromethamine, methylprednisolone, PRP, ketorolac-PRP, and methylprednisolone-PRP. A fluorescence assay of the cellular inflammation markers was measured by the BioTek Synergy HT plate reader (BioTek Instruments, Winooski, VT) at 0, 1, 2, and 5 days. At days 2 and 5, methylprednisolone treatment showed a 2.1- to 5.8-fold reduction (P < .05) in inflammation markers over PRP. In addition, PRP and ketorolac showed a 1.4- to 2.5-fold reduction (P < .05) in cellular inflammation markers over the control. There was no statistically significant difference between ketorolac and PRP. Although PRP and ketorolac reduced cellular inflammation markers (E-selectin, vascular cell adhesion molecule, and human leukocyte antigen DR) compared with control, neither caused as great a reduction as methylprednisolone. Although PRP and ketorolac did not produce as significant a reduction in cellular inflammation markers as methylprednisolone, they reduced cellular inflammation compared with the control. These agents may have clinical application as injectable anti-inflammatory medications. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Exploring Opioid-Sparing Multimodal Analgesia Options in Trauma: A Nursing Perspective

PubMed Central

Lyons, Mary; Montgomery, Robert; Quinlan-Colwell, Ann

2016-01-01

Challenges with opioids (e.g., adverse events, misuse and abuse with long-term administration) have led to a renewed emphasis on opioid-sparing multimodal management of trauma pain. To assess the extent to which currently available evidence supports the efficacy and safety of various nonopioid analgesics and techniques to manage trauma pain, a literature search of recently published references was performed. Additional citations were included on the basis of authors' knowledge of the literature. Effective options for opioid-sparing analgesics include oral and intravenous (IV) acetaminophen; nonsteroidal anti-inflammatory drugs available via multiple routes; and anticonvulsants, which are especially effective for neuropathic pain associated with trauma. Intravenous routes (e.g., IV acetaminophen, IV ketorolac) may be associated with a faster onset of action than oral routes. Additional adjuvants for the treatment of trauma pain are muscle relaxants and alpha-2 adrenergic agonists. Ketamine and regional techniques play an important role in multimodal therapy but require medical and nursing support. Nonpharmacologic treatments (e.g., cryotherapy, distraction techniques, breathing and relaxation, acupuncture) supplement pharmacologic analgesics and can be safe and easy to implement. In conclusion, opioid-sparing multimodal analgesia addresses concerns associated with high doses of opioids, and many pharmacologic and nonpharmacologic options are available to implement this strategy. Nurses play key roles in comprehensive patient assessment; administration of patient-focused, opioid-sparing, multimodal analgesia in trauma; and monitoring for safety concerns. PMID:27828892

Treatment of retinopathy of prematurity with topical ketorolac tromethamine: a preliminary study.

PubMed

Avila-Vazquez, Medardo; Maffrand, Roque; Sosa, Mirta; Franco, Maria; De Alvarez, Beatriz Vaca; Cafferata, Maria Luisa; Bergel, Eduardo

2004-08-07

Retinopathy of Prematurity (ROP) is a common retinal neovascular disorder of premature infants. It is of variable severity, usually heals with mild or no sequelae, but may progress to blindness from retinal detachments or severe retinal scar formation. This is a preliminary report of the effectiveness and safety of a new and original use of topical ketorolac in preterm newborn to prevent the progression of ROP to the more severe forms of this disease. From January 2001 to December 2002, all fifty nine preterm newborns with birthweight less than 1250 grams or gestational age less than 30 weeks of gestational age admitted to neonatal intensive care were eligible for treatment with topical ketorolac (0.25 milligrams every 8 hours in each eye). The historical comparison group included all 53 preterm newborns, with the same inclusion criteria, admitted between January 1999 and December 2000. Groups were comparable in terms of weight distribution, Apgar score at 5 minutes, incidence of sepsis, intraventricular hemorrhage and necrotizing enterocolitis. The duration of oxygen therapy was significantly longer in the control group. In the ketorolac group, among 43 children that were alive at discharge, one (2.3%) developed threshold ROP and cryotherapy was necessary. In the comparison group 35 children survived, and six child (17%) needed cryotherapy (Relative Risk 0.14, 95%CI 0.00 to 0.80, p = 0.041). Adjusting by duration of oxygen therapy did not significantly change these results. Adverse effects attributable to ketorolac were not detected. This preliminary report suggests that ketorolac in the form of an ophthalmic solution can reduce the risk of developing severe ROP in very preterm newborns, without producing significant adverse side effects. These results, although promising, should be interpreted with caution because of the weakness of the study design. This is an inexpensive and simple intervention that might ameliorate the progression of a disease with devastating

Ketorolac reduces spinal astrocytic activation and PAR1 expression associated with attenuation of pain after facet joint injury.

PubMed

Dong, Ling; Smith, Jenell R; Winkelstein, Beth A

2013-05-15

Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain.

Ketorolac Reduces Spinal Astrocytic Activation and PAR1 Expression Associated with Attenuation of Pain after Facet Joint Injury

PubMed Central

Dong, Ling; Smith, Jenell R.

2013-01-01

Abstract Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain. PMID:23126437

Pharmacokinetics of ketorolac tromethamine compression-coated tablets for colon delivery.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

2014-08-01

Present research efforts are focused in developing compression-coated ketorolac tromethamine tablets to improve the drug levels in colon by retarding the drug release in the stomach and small intestine. To achieve this objective, core tablets containing ketorolac tromethamine were prepared by direct compression and compression coated with sodium alginate. The developed tablets were evaluated for physical properties, in vitro drug release, X-ray imaging, and pharmacokinetic studies in human volunteers. Based on the in vitro drug release study, the optimized formulation showed very little drug release (6.75 ± 0.49 %) in the initial lag period of 5 h, followed by progressive release up to 97.47 ± 0.93 % within 24 h. The X-ray imaging of tablets in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. From the pharmacokinetic study, the C max of colon-targeted tablets was 3,486.70 ng/ml at T max 10 h, whereas in the case of immediate-release tablets, the C max of 4,506.31 ng/ml at T max 2 h signifies the ability of compression-coated tablets to target the colon. In conclusion, compression-coated tablets are suitable to deliver ketorolac tromethamine to the colon.

Ketorolac as an analgesic agent for infants and children after cardiac surgery: safety profile and appropriate patient selection.

PubMed

Jalkut, Meredith K

2014-01-01

Ketorolac has been used safely as an analgesic agent for children following cardiac surgery in selected populations. Controversy exists among institutions about the risks involved with this medication in this patient group. This article reviews the current literature regarding the safety of ketorolac for postoperative pain management in children after cardiac surgery. Specifically, concerns about renal dysfunction and increased bleeding risk are addressed. Additionally, the article details pharmacokinetics and potential benefits of ketorolac, such as its opioid-sparing effect. The literature reflects that the use of this medication is not well studied in certain pediatric cardiac patients such as neonates and those with single-ventricle physiology, and the safety of this medication in regards to these special populations is reviewed. In conclusion, ketorolac can be used in specific pediatric patients after cardiac surgery with minimal risk of bleeding or renal dysfunction with appropriate dosing and duration of use.

Economic Impact of Ketorolac vs Corticosteroid Intra-Articular Knee Injections for Osteoarthritis: A Randomized, Double-Blind, Prospective Study.

PubMed

Bellamy, Jaime L; Goff, Brandon J; Sayeed, Siraj A

2016-09-01

Knee osteoarthritis is a disabling disease that costs billions of dollars to treat. Corticosteroid gives varying pain relief and costs $12 per injection, whereas ketorolac costs $2 per injection, per institutional costs. The aim of this study was to compare ketorolac with corticosteroid based on pain relief using patient outcome measures and cost data. A total of 35 patients were randomized to ketorolac or corticosteroid intra-articular knee injection in a double-blind, prospective study. Follow-up was 24 weeks. Osteoarthritis was evaluated using Kellgren-Lawrence grading. Visual analog scale (VAS) was the primary outcome measure. A query of the institutional database was performed for International Classification of Diseases, Ninth Revision codes 715.16 and 719.46, and procedure code 20610 over a 3-year period. Two-way, repeated measures analysis of variance and Spearman rank correlation were used for statistical analysis. Mean VAS for ketorolac and corticosteroid decreased significantly from baseline at 2 weeks, 6.3-4.6 and 5.2-3.6, respectively and remained decreased for 24 weeks. There was no correlation between VAS and demographics within treatments. There were 220, 602, and 405 injections performed on patients with the International Classification of Diseases, Ninth Revision codes 715.16 and 719.46 during 2013, 2014, and 2015, respectively. The cost savings per year using ketorolac instead of corticosteroid would be $2259.40, $6182.54, and $4159.35 for 2013, 2014, and 2015, respectively, with a total savings of $12,601.29 over this period. Pain relief was similar between ketorolac and corticosteroid injections. Ketorolac knee injection is safe and effective with a cost savings percentage difference of 143% when compared with corticosteroid. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of Retinopathy of Prematurity with topical ketorolac tromethamine: a preliminary study

PubMed Central

Avila-Vazquez, Medardo; Maffrand, Roque; Sosa, Mirta; Franco, Maria; de Alvarez, Beatriz Vaca; Cafferata, Maria Luisa; Bergel, Eduardo

2004-01-01

Background Retinopathy of Prematurity (ROP) is a common retinal neovascular disorder of premature infants. It is of variable severity, usually heals with mild or no sequelae, but may progress to blindness from retinal detachments or severe retinal scar formation. This is a preliminary report of the effectiveness and safety of a new and original use of topical ketorolac in preterm newborn to prevent the progression of ROP to the more severe forms of this disease. Methods From January 2001 to December 2002, all fifty nine preterm newborns with birthweight less than 1250 grams or gestational age less than 30 weeks of gestational age admitted to neonatal intensive care were eligible for treatment with topical ketorolac (0.25 milligrams every 8 hours in each eye). The historical comparison group included all 53 preterm newborns, with the same inclusion criteria, admitted between January 1999 and December 2000. Results Groups were comparable in terms of weight distribution, Apgar score at 5 minutes, incidence of sepsis, intraventricular hemorrhage and necrotizing enterocolitis. The duration of oxygen therapy was significantly longer in the control group. In the ketorolac group, among 43 children that were alive at discharge, one (2.3%) developed threshold ROP and cryotherapy was necessary. In the comparison group 35 children survived, and six child (17%) needed cryotherapy (Relative Risk 0.14, 95%CI 0.00 to 0.80, p = 0.041). Adjusting by duration of oxygen therapy did not significantly change these results. Adverse effects attributable to ketorolac were not detected. Conclusions This preliminary report suggests that ketorolac in the form of an ophthalmic solution can reduce the risk of developing severe ROP in very preterm newborns, without producing significant adverse side effects. These results, although promising, should be interpreted with caution because of the weakness of the study design. This is an inexpensive and simple intervention that might ameliorate the

Failure of intrathecal ketorolac to reduce remifentanil-induced postinfusion hyperalgesia in humans.

PubMed

Eisenach, James C; Tong, Chuanyao; Curry, Regina S

2015-01-01

In rodents, acute exposure to opioids results in transient antinociception followed by longer lasting hypersensitivity to tactile or thermal stimuli, a phenomenon termed opioid-induced hyperalgesia. This hypersensitivity can be blocked or reversed by intrathecally administered cyclooxygenase inhibitors, including ketorolac, suggesting a role for spinal prostaglandins. In surgical patients, the dose of intraoperative opioid, particularly the short-acting drug, remifentanil, is directly related to increased pain and opioid requirements for many hours postoperatively. In addition, experimentally induced tactile hypersensitivity in humans is exaggerated after cessation of remifentanil infusions. The degree of this experimental opioid-induced hyperalgesia is reduced by systemic treatment with cyclooxygenase inhibitors, and investigators have speculated that this reduction reflects the actions in the central nervous system, most likely in the spinal cord. To test this hypothesis, we measured cerebrospinal fluid prostaglandin E2 concentrations during and after remifentanil infusion in 30 volunteers. These volunteers received intrathecal ketorolac or saline in a random, blinded manner during intravenous remifentanil infusion after generation of hypersensitivity by topical capsaicin. Remifentanil reduced pain to noxious heat stimuli and reduced areas of capsaicin-induced hypersensitivity similarly in those receiving intrathecal ketorolac or saline. The primary outcome measure, area of capsaicin-induced hypersensitivity after stopping remifentanil, showed a similar increase in those receiving ketorolac as in those receiving saline. Cerebrospinal fluid prostaglandin E2 concentrations did not increase during postinfusion hyperalgesia compared with those during infusion, and they were not increased during infusion compared with those in historical controls. These data fail to support the hypothesis that acute opioid-induced hyperalgesia reflects spinal cyclooxygenase activation

Tolerability of ketorolac administered via continuous subcutaneous infusion for cancer pain: a preliminary report.

PubMed

De Conno, F; Zecca, E; Martini, C; Ripamonti, C; Caraceni, A; Saita, L

1994-02-01

We evaluated the local and systemic tolerability of ketorolac administered through continuous subcutaneous infusion in ten cancer patients. The patients were monitored daily for the severity and duration of pain, and the development of other symptoms. The duration of injection site varied from 1 to more than 7 days. No patients complained of local discomfort or pain. Mild local bleeding at the site of drug injection was observed in seven cases. No increase in the intensity of symptoms was observed during the infusion of ketorolac.

Comparison of ketorolac 0.45% versus diclofenac 0.1% for macular thickness and volume after uncomplicated cataract surgery.

PubMed

Lee, Tae Hee; Choi, Won; Ji, Yong Sok; Yoon, Kyung Chul

2016-05-01

To compare the effects of ketorolac 0.45% and diclofenac 0.1% on macular thickness and volume after uncomplicated cataract surgery. A total of 76 eyes of 76 patients who underwent uncomplicated cataract surgery were included. Patients were treated with either diclofenac 0.1% (38 eyes) or ketorolac 0.45% (38 eyes) after surgery. The macular thickness and volume were obtained with optical coherence tomography (OCT). Central subfield thickness (CST, OCT 1 mm zone), total foveal thickness (TFT, OCT 3 mm zone), total macular thickness (TMT, OCT 6 mm zone), average macular thickness (AMT) and total macular volume (TMV) were compared between the two study groups. No significant differences between groups were found in macular thickness or volume 1 month after cataract surgery. Two months after surgery, the ketorolac group had significantly lower CST, TFT, TMT and AMT than the diclofenac group (p < 0.05 for all). Additionally, 1 and 2 months after surgery, changes from preoperative values in CST (both p = 0.04), AMT (p = 0.02 and p < 0.01, respectively) and TMV (both p = 0.04) were significantly less in the ketorolac group than in the diclofenac group. Following uncomplicated cataract surgery, topical ketorolac 0.45% was more effective than diclofenac 0.1% in preventing increases in macular thickness and volume. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Recurrent aseptic meningitis secondary to taking ibuprofen and ketorolac].

PubMed

Cano Vargas-Machuca, E; Mondéjar-Marín, B; Navarro-Muñoz, S; Pérez-Molina, I; Garrido-Robres, J A; Alvarez-Tejerina, A

Aseptic meningitis is a process that is characterised by an inflammatory reaction of the meninges that is not due to any infectious agent. Its aetiology is varied and is most frequently caused by rheumatologic and/or autoimmune processes, chemical or medication-induced meningitis, the most notable drugs involved being antibiotics and non-steroidal anti-inflammatory drugs (NSAI). We report the case of a 70-year-old male, with no relevant history, who was admitted to hospital five times over a period of 16 months because of acute meningitis with polymorphonuclear pleocytosis, high protein levels in cerebrospinal fluid and normal glucose in cerebrospinal fluid. No evidence of an infectious causation, chemical meningitis, carcinomatosis or autoimmune disease was found and the patient was diagnosed with recurrent aseptic meningitis. It was found that the patient had taken ibuprofen or ketorolac on several occasions, a few hours before the appearance of symptoms. These episodes were quickly resolved after withdrawal of this medication. A number of NSAI have been reported as inducers of aseptic meningitis, one of the most notable being ibuprofen. We report the case of a patient who, as a consequence of taking ibuprofen and ketorolac, presented episodes of recurrent aseptic meningitis. To our knowledge this side effect of ketorolac has not been reported before. Its clinical features are impossible to differentiate from those of infectious meningitis. Diagnosis is reached by exclusion and a careful pharmacological study, including over-the-counter drugs like some of the NSAI, must be performed in patients with this condition, since it is a problem that can easily be solved by withdrawing the drug that causes it.

Prostaglandin E2 Levels of Aqueous and Vitreous Humor in Ketorolac 0.4% and Nepafenac 0.1% Administered Healthy Rabbits.

PubMed

Acar, Ugur; Acar, Damla Erginturk; Tanriverdi, Cafer; Acar, Mutlu; Ozdemir, Ozdemir; Erikci, Acelya; Ornek, Firdevs

2017-06-01

To compare the lowering effects of ketorolac 0.4% and nepafenac 0.1% on aqueous and vitreous humor prostaglandin E 2 (PGE 2 ) levels in rabbits. Ketorolac and nepafenac ophthalmic solutions were administered to the right eyes of 24 healthy rabbits after randomized division into two groups. The left eyes of these rabbits were considered as controls for the two groups. On the 4th day of the experiment, the samples were taken from the aqueous and vitreous humors of the rabbits bilaterally, and PGE 2 levels were measured by an enzyme immune assay kit. Ketorolac and nepafenac achieved a statistically significant decrease (p<0.001, for each) in PGE 2 levels in the aqueous (11.75 ± 6.15 and 14.75 ± 7.60 pg/mL, respectively) and the vitreous humor (6.58 ± 4.62 and 9.83 ± 4.55 pg/mL, respectively). Both ketorolac and nepafenac inhibited PGE 2 levels in both the aqueous and vitreous humors of rabbits. Although PGE 2 -lowering effects were similar in the aqueous humor, nepafenac seemed to be more potent than ketorolac in the vitreous humor.

Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia.

PubMed

Ryu, J-H; Kang, M-H; Park, K-S; Do, S-H

2008-03-01

This randomized, double-blind, prospective study was undertaken to evaluate the effects of magnesium sulphate on anaesthetic requirements and postoperative analgesia in patients undergoing total i.v. anaesthesia (TIVA). Fifty patients who underwent gynaecological surgery were randomly divided into two groups. Before induction of anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and then 15 mg kg(-1) h(-1) i.v. by continuous infusion. The control group (Group S) received the same amount of isotonic saline. TIVA (propofol+remifentanil) was administered under bispectral index monitoring during anaesthesia induction and maintenance. Rocuronium was administered before orotracheal intubation and during surgery when the train-of-four count was 2 or more. After operation, patient-controlled analgesia with a solution of ketorolac and morphine was used and the consumption of this solution was recorded. Pain scores at rest and upon movement were evaluated 30 min, 4, 24, and 48 h after surgery. Patients in Group M required less rocuronium than those in Group S [mean (SD) 0.44 (0.09) vs 0.35 (0.07) microg kg(-1) min(-1), P<0.05]. The total amounts of propofol and remifentanil administered were similar in the two groups. Postoperative pain scores, cumulative analgesic consumption, and shivering incidents were significantly lower in Group M (P<0.05). Mean arterial pressure just after intubation and during the immediate postoperative period was also significantly lower in Group M (P<0.05). I.v. magnesium sulphate during TIVA reduced rocuronium requirement and improved the quality of postoperative analgesia.

The Effect of Gabapentin and Ketorolac on Allodynia and Conditioned Place Preference in Antibody-Induced Inflammation

PubMed Central

Park, HJ; Sandor, K; McQueen, J; Woller, SA; Svensson, CI; Corr, MP; Yaksh, TL

2018-01-01

Background Glucose-6-phosphate isomerase and collagen type II antibody induced arthritis models (K/BxN and CAIA, respectively) have an inflammatory and a post-inflammatory phase. Both phases display robust tactile allodynia. In previous work, inflammatory phase allodynia was reversed by gabapentin and ketorolac, whereas in late phase only gabapentin was effective. Here we sought to determine if the effects of these two drugs during the early and late phases of the two arthritis models were observed in the conditioned place preference (CPP) paradigm, indicating a differential drug effect on the aversive state. Methods Male C57BL/6 mice received K/BxN serum intraperitoneally, while male BALB/c mice received collagen type II antibody cocktail intravenously. After onset of inflammation and allodynia, we assessed effects of i.p. gabapentin (100 mg/kg) or ketorolac (15 mg/kg) using a CPP paradigm: 2 days adaptation, 2 days conditioning (vehicle in morning and drug in afternoon), preference testing on day 5. Results Consistent with the effects upon allodynia, both gabapentin and ketorolac produced a preference for the drug-paired compartment in the early phase of the K/BxN model, while gabapentin, but not ketorolac, resulted in a place preference during late phase. In the CAIA model, consistent with differential effects upon allodynia, gabapentin produced a preference in the early phase and a trend in the late phase, whereas ketorolac was ineffective at either time. Conclusions CPP validated the aversive state in the inflammatory and post-inflammatory phases of the K/BxN and CAIA arthritis models and correspondence between the anti-hyperpathic pharmacology as defined by thresholds and CPP. PMID:26517300

The effect of gabapentin and ketorolac on allodynia and conditioned place preference in antibody-induced inflammation.

PubMed

Park, H J; Sandor, K; McQueen, J; Woller, S A; Svensson, C I; Corr, M; Yaksh, T L

2016-07-01

Glucose-6-phosphate isomerase and collagen type II antibody-induced arthritis models (K/BxN and CAIA, respectively) have an inflammatory and a post-inflammatory phase. Both phases display robust tactile allodynia. In previous work, inflammatory phase allodynia was reversed by gabapentin and ketorolac, whereas in late phase only gabapentin was effective. Here, we sought to determine if the effects of these two drugs during the early and late phases of the two arthritis models were observed in the conditioned place preference (CPP) paradigm, indicating a differential drug effect on the aversive state. Male C57BL/6 mice received K/BxN serum intraperitoneally, while male BALB/c mice received collagen type II antibody cocktail intravenously. After onset of inflammation and allodynia, we assessed effects of i.p. gabapentin (100 mg/kg) or ketorolac (15 mg/kg) using a CPP paradigm: 2 days adaptation, 2 days conditioning (vehicle in morning and drug in afternoon), preference testing on day 5. Consistent with the effects upon allodynia, both gabapentin and ketorolac produced a preference for the drug-paired compartment in the early phase of the K/BxN model, while gabapentin, but not ketorolac, resulted in a place preference during late phase. In the CAIA model, consistent with differential effects upon allodynia, gabapentin produced a preference in the early phase and a trend in the late phase, whereas ketorolac was ineffective at either time. CPP validated the aversive state in the inflammatory and post-inflammatory phases of the K/BxN and CAIA arthritis models and correspondence between the anti-hyperpathic pharmacology as defined by thresholds and CPP. © 2015 European Pain Federation - EFIC®

Assessing the effects of ketorolac and acetazolamide on macular thickness by optical coherence tomography following cataract surgery.

PubMed

Turan-Vural, Ece; Halili, Elvin; Serin, Didem

2014-06-01

We aimed to evaluate the efficacy of topical ketorolac 0.5 % solution and oral acetazolamide 250 mg/day delivery during the first month after uneventful phacoemulsification surgery by measuring the macular thickness using optical coherence tomography. Our nonmasked randomized prospective study comprised 87 eyes of 80 patients. Complete follow-up was achieved on 84 eyes of 77 eligible patients. Postoperatively, the patients were divided into three groups. One group received ketorolac 0.5 %, the other group received acetazolamide 250 mg/day, and the control group was given no agent. Macular thickness and volume were measured at 1 week and 1 month after surgery by optical coherence tomography. Foveal thickness, parafoveal thickness, and perifoveal thickness were determined to be significantly elevated at postoperative 1 week and 1 month in the control group. Foveal, perifoveal, and parafoveal volumes were also significantly high at postoperative week 1 and month 1 in the control group. There was no significant difference between the ketorolac and acetazolamide groups. The correlation analysis between best-corrected visual acuity, and volume and thickness revealed a negative correlation in the acetazolamide group. Use of acetazolamide after cataract surgery is as effective as ketorolac on macular thickness and volume.

A randomised controlled trial of ranibizumab with and without ketorolac eyedrops for exudative age-related macular degeneration.

PubMed

Russo, Andrea; Costagliola, Ciro; Delcassi, Luisa; Romano, Mario R; Semeraro, Francesco

2013-10-01

To evaluate whether ketorolac eyedrops and ranibizumab intravitreal injections would provide additional benefit over ranibizumab alone in the treatment of choroidal neovascularisation (CNV). This was a pilot study of eyes with new-onset CNV. A total of 56 patients were enrolled consecutively and randomised in a 1:1 ratio to receive combination treatment with intravitreal ranibizumab and topical ketorolac (group 1) or ranibizumab alone (group 2). All patients received monthly 0.5-mg ranibizumab intravitreal injections for 3 months, after which monthly injections were administered in accordance with the standard of care. Group 1 patients also self-administered one drop of ketorolac three times a day for 6 months. All patients were followed up for 6 months. At 6 months, both groups showed a significant improvement in best-corrected visual acuity (both, p<0.001). The two treatments did not show significant differences in terms of the number of ranibizumab injections required. However, the mean 6-month change in central macular thickness (CMT) in the combination group was -124 µm (-29.7%; p<0.001), while in the ranibizumab-only group, the change was -86.9 µm (-19.5%; p=0.001); thus, the combination treatment resulted in a greater reduction (p=0.003). The combination treatment had no adverse effects. This pilot study is the first to prospectively investigate the efficacy and safety of a combination of 0.45% ketorolac eyedrops three times a day and intravitreal ranibizumab injections in patients with CNV, and suggests that topical ketorolac supplements the activity of intravitreal ranibizumab in reducing CMT in CNV.

Ultrasound guided intra-articular ketorolac versus corticosteroid injection in osteoarthritis of the hip: a retrospective comparative study.

PubMed

Park, Ki Deok; Kim, Tai Kon; Bae, Byung Woo; Ahn, JaeKi; Lee, Woo Yong; Park, Yongbum

2015-09-01

Intra-articular steroid injection has been widely used in the management of symptomatic osteoarthritis; however, its frequent use is avoided since there is an increase in the incidence of articular infection and several mechanical side effects such as cartilage breakdown and loss of elasticity of the articular cartilage. For these reasons, nonsteroidal anti-inflammatory drugs instead of corticosteroids can be considered for intra-articular injection. On this basis, we investigated the effects and safety of ultrasound-guided intra-articular ketorolac versus corticosteroid injection for patients with osteoarthritis of the hip. This retrospective study included 98 patients with diagnoses of hip osteoarthritis who underwent ultrasound-guided intra-articular ketorolac or corticosteroid injection. Fifty patients who received ultrasound-guided intra-articular corticosteroid injection were administered a mixture of 0.5% lidocaine and triamcinolone. Forty-eight patients who received ultrasound-guided intra-articular ketorolac injection were administered 0.5% lidocaine and ketorolac. Outcome measurement was assessed using the Harris hip score and verbal numeric pain scale, which were evaluated before the injections and at 1, 3 and 6 months following the injection. Univariate analysis (using the x (2) test) and multiple logistic regression analysis were performed to evaluate the relationship between the possible outcome predictors (injected medications, patients' age, gender, pain duration and Kellgren-Lawrence classification) and the therapeutic effects. The Harris hip score and verbal numeric pain scale were improved at 1, 3 and 6 months after the injection in both groups. No statistical differences in the Harris hip score and verbal numeric pain scale were observed between the groups. The success rate was also not significantly different among the time periods of 1, 3 and 6 months. Multiple logistic regression and univariate analysis showed that injected medications

Does local infiltration analgesia reduce peri-operative inflammation following total hip arthroplasty? A randomized, double-blind study.

PubMed

Kuchálik, J; Magnuson, A; Tina, E; Gupta, A

2017-05-03

Postoperative inflammation following total hip arthroplasty (THA) can lead to delayed mobilization and return of hip function. Our primary aim was to assess whether local infiltration analgesia (LIA) during surgery can prevent postoperative inflammation. This is a sub-analysis of data from a broader double-blind study where 56 patients received spinal anaesthesia for THA. Additionally, Group FNB (Femoral Nerve Block) received an ultrasound-guided femoral nerve block using 30 mL of ropivacaine 7.5 mg/mL (225 mg), and 151.5 mL of saline peri-articularly intra-operatively. Group LIA received 30 mL saline in the femoral nerve block and ropivacaine 2 mg/mL, 300 mg (150 mL) + ketorolac 30 mg (1 mL) + adrenaline 0.5 mg (0.5 mL) peri-articularly. After 23 h, the LIA mixture (22 mL) was injected via a catheter placed peri-articularly in Group LIA and 22 mL saline in Group FNB. A battery of pro- and anti-inflammatory cytokines was assessed using a commercially available kit preoperatively and after 4 h and 3 days postoperatively. Additionally, CRP, platelet count and white blood count was determined pre- and postoperatively. There was a general trend towards an increase in pro-inflammatory cytokines postoperatively, which returned to normal levels after 3 days. IL-6 concentration was significantly lower 4 h postoperatively in Group LIA compared to Group FNB (p = 0.015). No other significant differences were found between the groups in other cytokines. CRP levels were significantly higher in Group FNB compared to Group LIA 3 days postoperatively (p < 0.001). No other significant differences were seen between the groups. Local infiltration analgesia has a modest but short-lasting effect on postoperative inflammation in patients undergoing total hip arthroplasty. This is likely to be due to local infiltration of ketorolac and/or local anaesthetics in the LIA mixture. Future studies should be directed towards assessing whether the use of LIA

The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis.

PubMed

Mohammed, Baba S; Engelhardt, Thomas; Hawwa, Ahmed F; Cameron, Garry A; McLay, James S

2015-09-01

To describe the effect of age and body size on enantiomer selective pharmacokinetic (PK) of intravenous ketorolac in children using a microanalytical assay. Blood samples were obtained at 0, 15 and 30 min and at 1, 2, 4, 6, 8 and 12 h after a weight-dependent dose of ketorolac. Enantiomer concentration was measured using a liquid chromatography tandem mass spectrometry method. Non-linear mixed-effect modelling was used to assess PK parameters. Data from 11 children (1.7-15.6 years, weight 10.7-67.4 kg) were best described by a two-compartment model for R(+), S(-) and racemic ketorolac. Only weight (WT) significantly improved the goodness of fit. The final population models were CL = 1.5 × (WT/46)(0.75) , V1  = 8.2 × (WT/46), Q = 3.4 × (WT/46)(0.75) , V2  = 7.9 × (WT/46), CL = 2.98 × (WT/46), V1  = 13.2 × (WT/46), Q = 2.8 × (WT/46)(0.75) , V2  = 51.5 × (WT/46), and CL = 1.1 × (WT/46)(0.75) , V1  = 4.9 × (WT/46), Q = 1.7 × (WT/46)(0.75) and V2  = 6.3 × (WT/46)for R(+), S(-) and racemic ketorolac. Only body weight influenced the PK parameters for R(+) and S(-) ketorolac. Using allometric size scaling significantly affected the clearances (CL, Q) and volumes of distribution (V1 , V2 ). © 2015 Royal Pharmaceutical Society.

[Efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema].

PubMed

Razo Blanco-Hernández, Dulce Milagros; Lima-Gómez, Virgilio; Asbun-Bojalil, Juan

2014-01-01

Photocoagulation reduces the incidence of visual loss in diabetic patients with focal macular edema, but it can induce it for Efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema 6 weeks after treatment and produces visual improvement in some cases. Topical ketorolac may reduce the inflammation caused by photocoagulation and improve visual outcome. To determine the efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema. An experimental, comparative, prospective, longitudinal study in diabetic patients with focal macular edema was conducted. Eyes were randomized into two groups of topical treatment for 3 weeks after photocoagulation (A: ketorolac, B: placebo). Best corrected visual acuity before and after treatment was compared in each group (paired t test), and the proportion of eyes with visual improvement was compared between groups (χ(2)). The evaluation was repeated after stratifying for initial visual acuity (≥ 0.5, < 0.5). There were 105 eyes included. In group A (n= 46) mean visual acuity changed from 0.50 to 0.58 (p= 0.003), and from 0.55 to 0.55 in group B (n= 59, p= 0.83); mean percent change was 22.3% in group A and 3.5% in group B (p= 0.03). Visual improvement was identified in 25 eyes from group A (54.3%) and 19 from group B (32.2%, p= 0.019, RR 1.65); the difference only persisted when initial visual acuity was ≥ 0.5 (10 [40%], group A, 5 [14.7%], group B, p= 0.02, RR 2.72). Topical ketorolac was more effective than placebo to improve best corrected visual acuity in diabetic patients with focal macular edema.

Effects of Short-term Preoperative Topical Ketorolac on Pupil Diameter in Eyes Undergoing Femtosecond Laser-Assisted Capsulotomy.

PubMed

Diakonis, Vasilios F; Kontadakis, Georgios A; Anagnostopoulos, Apostolos G; Yesilirmak, Nilufer; Waren, Daniel P; Cabot, Florence; Yoo, Sonia H; Donaldson, Kendall E

2017-04-01

To assess pupil diameter before and after femtosecond laser-assisted capsulotomy in patients who were pretreated with a short-term topical nonsteroidal anti-inflammatory drug (NSAID) (ketorolac) versus those without pretreatment. This prospective, randomized, observational case series included consecutive patients scheduled to undergo cataract extraction using the Catalys femtosecond laser platform (Abbott Medical Optics, Inc., Santa Ana, CA) to perform only capsulotomies. The same protocol for preoperative medical mydriasis was used for all patients, whereas pupil diameter was assessed using a surgical ruler immediately before and 3 minutes after femtosecond laser-assisted capsulotomy. The patients were divided into two groups: one received short-term topical ketorolac preoperatively and the other did not receive NSAID pretreatment (control). A total of 42 eyes of 42 patients (1 eye per patient) were included in the study. Mean pupillary miosis was 0.79 ± 1.08 and 1.57 ± 1.19 mm for the ketorolac and control groups, respectively. There was a statistically significant decrease in pupil diameter for both groups individually (P < .05). There was also a statistically significant difference between the two groups (P < .05) with the induced miosis in the eyes that did not receive topical NSAIDs prior to cataract extraction being twofold greater when compared with the miosis of the eyes that received ketorolac pretreatment. Short-term topical use of ketorolac prior to femtosecond laser-assisted cataract surgery seems to induce significantly less pupillary miosis in comparison to eyes that did not receive NSAID pretreatment. NSAID use is advised prior to femtosecond laser-assisted cataract surgery to minimize pupil miosis-related surgical difficulties or complications during cataract extraction. [J Refract Surg. 2017;33(4):230-234.]. Copyright 2017, SLACK Incorporated.

Lidocaine/ketorolac-loaded biodegradable nanofibrous anti-adhesive membranes that offer sustained pain relief for surgical wounds.

PubMed

Kao, Ching-Wei; Lee, Demei; Wu, Min-Hsuan; Chen, Jan-Kan; He, Hong-Lin; Liu, Shih-Jung

2017-01-01

The aim of this study was to develop and evaluate the effectiveness of biodegradable nanofibrous lidocaine/ketorolac-loaded anti-adhesion membranes to sustainably release analgesics on abdominal surgical wounds. The analgesic-eluting membranes with two polymer-to-drug ratios (6:1 and 4:1) were produced via an electrospinning technique. A high-performance liquid chromatography (HPLC) assay was employed to characterize the in vivo and in vitro release behaviors of the pharmaceuticals from the membranes. It was found that all biodegradable anti-adhesion nanofibers released effective concentrations of lidocaine and ketorolac for over 20 days post surgery. In addition, a transverse laparotomy was setup in a rat model for an in vivo assessment of activity of postoperative recovery. No tissue adhesion was observed at 2 weeks post surgery, demonstrating the potential anti-adhesion capability of the drug-eluting nanofibrous membrane. The postoperative activities were recorded for two groups of rats as follows: rats that did not have any membrane implanted (group A) and rats that had the analgesic-eluting membrane implanted (group B). Rats in group B exhibited faster recovery times than those in group A with regard to postoperative activities, confirming the pain relief effectiveness of the lidocaine- and ketorolac-loaded nanofibrous membranes. The experimental results suggested that the anti-adhesion nanofibrous membranes with sustainable elution of lidocaine and ketorolac are adequately effective and durable for the purposes of postoperative pain relief in rats.

Lidocaine/ketorolac-loaded biodegradable nanofibrous anti-adhesive membranes that offer sustained pain relief for surgical wounds

PubMed Central

Kao, Ching-Wei; Lee, Demei; Wu, Min-Hsuan; Chen, Jan-Kan; He, Hong-Lin; Liu, Shih-Jung

2017-01-01

The aim of this study was to develop and evaluate the effectiveness of biodegradable nanofibrous lidocaine/ketorolac-loaded anti-adhesion membranes to sustainably release analgesics on abdominal surgical wounds. The analgesic-eluting membranes with two polymer-to-drug ratios (6:1 and 4:1) were produced via an electrospinning technique. A high-performance liquid chromatography (HPLC) assay was employed to characterize the in vivo and in vitro release behaviors of the pharmaceuticals from the membranes. It was found that all biodegradable anti-adhesion nanofibers released effective concentrations of lidocaine and ketorolac for over 20 days post surgery. In addition, a transverse laparotomy was setup in a rat model for an in vivo assessment of activity of postoperative recovery. No tissue adhesion was observed at 2 weeks post surgery, demonstrating the potential anti-adhesion capability of the drug-eluting nanofibrous membrane. The postoperative activities were recorded for two groups of rats as follows: rats that did not have any membrane implanted (group A) and rats that had the analgesic-eluting membrane implanted (group B). Rats in group B exhibited faster recovery times than those in group A with regard to postoperative activities, confirming the pain relief effectiveness of the lidocaine- and ketorolac-loaded nanofibrous membranes. The experimental results suggested that the anti-adhesion nanofibrous membranes with sustainable elution of lidocaine and ketorolac are adequately effective and durable for the purposes of postoperative pain relief in rats. PMID:28860755

Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta

PubMed Central

Lee, Seung Yoon; Choi, Jin Hwa; Jeon, Woo Jae; Cheong, Mi Ae

2010-01-01

Background Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in endothelium. We studied the influences of ketorolac and diclofenac on ROS effects using the endothelium of rabbit abdominal aorta. Methods Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O2 at 37.5℃. After being stimulated to contract with phenylephrine (PE, 10-6 M), changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh, 3 × 10-8 to 10-6 M). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with ketorolac or diclofenac at the same concentrations (10-5 M to 3 × 10-4 M), and the effects of these agents were compared with the effects of ROS scavengers: catalase, mannitol, sodium salicylate and deferoxamine and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT). Results Both ketorolac and diclofenac maintained endothlium-dependent relaxation induced by ACh in a dose-related manner inspite of ROS attack (P < 0.05 vs. control value). The 3AT pretreated ketorolac (3 × 10-3 M) group was decreased more significantly than un-pretreated ketorolac (P < 0.05). Conclusions These findings suggest that ketorlac and diclofenac preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a concentration-related manner. One of the endothelial protection mechanisms of ketorolac may be hydrogen peroxide scavenging. PMID:20877705

Rapid and Sensitive Reverse-phase High-performance Liquid Chromatography Method for Estimation of Ketorolac in Pharmaceuticals Using Weighted Regression

PubMed Central

Dubey, S. K.; Duddelly, S.; Jangala, H.; Saha, R. N.

2013-01-01

A reliable, rapid and sensitive isocratic reverse phase high-performance liquid chromatography method has been developed and validated for assay of ketorolac tromethamine in tablets and ophthalmic dosage forms using diclofenac sodium as an internal standard. An isocratic separation of ketorolac tromethamine was achieved on Oyster BDS (150×4.6 mm i.d., 5 μm particle size) column using mobile phase of methanol:acetonitrile:sodium dihydrogen phosphate (20 mM; pH 5.5) (50:10:40, %v/v) at a flow rate of 1.0 ml/min. The eluents were monitored at 322 nm for ketorolac and at 282 nm for diclofenac sodium with a photodiode array detector. The retention times of ketorolac and diclofenac sodium were found to be 1.9 min and 4.6 min, respectively. Response was a linear function of drug concentration in the range of 0.01-15 μg/ml (R2=0.994; linear regression model using weighing factor 1/x2) with a limit of detection and quantification of 0.002 μg/ml and 0.007 μg/ml, respectively. The % recovery and % relative standard deviation values indicated the method was accurate and precise. PMID:23901166

Effects on growth of human osteoblast-like cells of three nonsteroidal anti-inflammatory drugs: metamizole, dexketoprofen, and ketorolac.

PubMed

De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Manzano-Moreno, Francisco Javier; García-Martínez, Olga; Ruiz, Concepción

2015-01-01

Some nonsteroidal anti-inflammatory drugs (NSAIDs) have adverse effects on bone tissue. The objective of this study was to determine the effect of different doses of dexketoprofen, ketorolac, and metamizole on growth of the osteoblast MG63 cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide spectrophotometry results showed that MG63 cell growth was significantly inhibited after 24 hr of culture with doses of 10, 20, 100, or 1,000 µM of each NSAID and with doses of 0.1, 1, or 5 µM of dexketoprofen and ketorolac but not metamizole. Cell-cycle studies revealed that dexketoprofen and ketorolac treatments significantly arrested the cell cycle in phase G0/G1, increasing the percentage of cells in this phase. Apoptosis/necrosis studies showed significant changes versus control cells, with an increased percentage of cells in apoptosis after treatment with 10, 100, or 1,000 µM of metamizole and after treatment with 1, 10, 100, or 1,000 µM of dexketoprofen or ketorolac. In conclusion, treatment of osteoblast-like cells with high doses of the NSAIDs tested increased not only the percentage of cells in apoptosis but also the percentage of necrotic cells. © The Author(s) 2014.

Adverse drug reactions associated with off-label use of ketorolac, with particular focus on elderly patients. An analysis of the Italian pharmacovigilance database and a population based study.

PubMed

Viola, E; Trifirò, G; Ingrasciotta, Y; Sottosanti, L; Tari, M; Giorgianni, F; Moretti, U; Leone, R

2016-12-01

This study aims to evaluate the frequency of off-label use of ketorolac in Italy and the related suspected adverse drug reactions (ADRs) reported. All the suspected cases associated with ketorolac recorded in the Italian Pharmacovigilance database were retrieved. Case evaluations were carried out in order to identify the off-label use of ketorolac. Moreover, an analysis of the inappropriate use of ketorolac was conducted using the 'Arianna' database of Caserta local health unit. Up to December 2014, 822 reports of suspected ADRs related to ketorolac were retrieved in the database. The use of ketorolac was classified as off-label for 553 reports and on-label for 269. Among the off-label cases, 58.6% were serious compared to 39.0% of on-label cases. Gastrointestinal events were more frequently reported with off-label use. The analysis of Arianna database showed that 37,729 out of 61,910 patients, were treated off-label. The off-label use of ketorolac is widespread in Italy. This use increases the risk of serious ADR, especially in in case of prolonged duration of treatment and in elderly patients. The Italian Medicine Agency has decided to accurately monitor the appropriate use of the drug in Italy and, if necessary, take measures in order to minimize the risks.

Intrathecal ketorolac does not improve acute or chronic pain after hip arthroplasty: a randomized controlled trial

PubMed Central

Wang, Lu; Bauer, Maria; Curry, Regina; Larsson, Anders; Sessler, Daniel I.; Eisenach, James C.

2014-01-01

Hypersensitivity to mechanical stimuli following surgery has been reported in patients who subsequently develop chronic pain after surgery. In animals, peripheral injury increases prostaglandin production in the spinal cord, and spinal cyclooxygenase inhibitors reduce hypersensitivity after injury. We therefore tested the hypothesis that spinal ketorolac reduces hypersensitivity and acute and chronic pain after hip arthroplasty (www.clinicaltrials.gov NCT 00621530). Sixty-two patients having total hip arthroplasty with spinal anesthesia were randomized to receive 13.5 mg hyperbaric bupivacaine with spinal saline or 13.5 mg hyperbaric bupivacaine with 2 mg preservative-free ketorolac. The primary outcome was area of hypersensitivity surrounding the wound 48 hr after surgery, but this only occurred in 4 patients, precluding assessment of this outcome. The groups did not differ in acute pain, acute opioid use, or pain incidence or severity 2 and 6 months after surgery. There were no serious adverse events. Our results suggest that a single spinal dose of ketorolac does not substantially reduce acute surgical pain, and is thus unlikely to reduce the risk of persistent incisional pain. PMID:24535482

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

Sublingual ketorolac versus sublingual tramadol for moderate to severe post-traumatic bone pain in children: a double-blind, randomised, controlled trial.

PubMed

Neri, Elena; Maestro, Alessandra; Minen, Federico; Montico, Marcella; Ronfani, Luca; Zanon, Davide; Favret, Anna; Messi, Gianni; Barbi, Egidio

2013-09-01

To assess the effectiveness of sublingual ketorolac versus sublingual tramadol in reducing the pain associated with fracture or dislocation of extremities in children. A double-blind, randomised, controlled, non-inferiority trial was conducted in the paediatric emergency department of a research institute. One hundred and thirty-one children aged 4-17 years with suspected bone fracture or dislocation were enrolled. Eligible children were randomised to ketorolac (0.5 mg/kg) and placebo, or to tramadol (2 mg/kg) and placebo by sublingual administration, using a double-dummy technique. Pain was assessed by the patients every 20 min, for a maximum period of 2 h, using the McGrath scale for patients up to 6 years of age, and the Visual Analogue Scale for those older than 6 years of age. The mean pain scores fell significantly from eight to four and five in the ketorolac and tramadol groups, respectively, by 100 min (Wilcoxon sign rank test, p<0.001). The mean pain scores for ketorolac were lower than those for tramadol, but these differences were not significant at any time point (Mann-Whitney U Test, p values: 0-20 min: 0.167; 20-40 min: 0.314; 40-60 min: 0.223; 60-80 min: 0.348; 80-100 min: 0.166; 100-120 min: 0.08). The rescue dose of paracetamol-codeine was administered in 2/60 children in the ketorolac group versus 8/65 in the tramadol group (Fisher exact test, p=0.098). There were no statistically significant differences between the two groups in the frequency of adverse effects. Both sublingual ketorolac and tramadol were equally effective for pain management in children with suspected fractures or dislocations.

The Antinociceptive Effect of a Tapentadol-Ketorolac Combination in a Mouse Model of Trigeminal Pain is Mediated by Opioid Receptors and ATP-Sensitive K+ Channels.

PubMed

Barreras-Espinoza, Israel; Soto-Zambrano, José Alberto; Serafín-Higuera, Nicolás; Zapata-Morales, Ramón; Alonso-Castro, Ángel; Bologna-Molina, Ronell; Granados-Soto, Vinicio; Isiordia-Espinoza, Mario A

2017-02-01

Preclinical Research The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test. Tapentadol or ketorolac were administered ip 15 min before orofacial formalin injection. The effect of the individual drugs was used to calculate their ED 50 values and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in the orofacial test using isobolographic analysis and interaction index to evaluate the interaction between the drugs. The combination showed antinociceptive synergistic and additive effects in the first and second phase of the orofacial formalin test. Naloxone and glibenclamide were used to evaluate the possible mechanisms of action and both partially reversed the antinociception produced by the tapentadol-ketorolac combination. These data suggest that the mixture of tapentadol and ketorolac produces additive or synergistic interactions via opioid receptors and ATP-sensitive K + channels in the orofacial formalin-induced nociception model in mice. Drug Dev Res 78 : 63-70, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Intraoperative ketorolac dose of 15mg versus the standard 30mg on early postoperative pain after spine surgery: A randomized, blinded, non-inferiority trial.

PubMed

Duttchen, Kaylene M; Lo, Andy; Walker, Andrew; McLuckie, Duncan; De Guzman, Cecilia; Roman-Smith, Helen; Davis, Melinda

2017-09-01

The primary aim of this study is to show the non-inferiority of 15mg intraoperative dose of ketorolac as compared to the standard 30mg ketorolac by looking at the visual analog scale pain (VAS) scores 4h after an adult spine surgery. The study design is a prospective randomized non-inferiority clinical trial looking at non-inferiority of intraoperative 15mg ketorolac from the standard 30mg dose. Quaternary care center. 50 adult (18-65years of age) undergoing lumbar decompression spine surgery. Group A received a single intraoperative dose of 15mg ketorolac at the end of surgery and group B received single intraoperative dose of 30mg ketorolac. The primary outcome was the visual analog scale (VAS) pain scores 4h after an adult spine surgery. Secondary measures were morphine usage in the first 8 and 24h postoperatively, numeric rating scores (NRS) up to 24h, sedation, nausea, vomiting, respiratory depression, pruritus and bleeding complications. Intention to treat analysis showed a mean increase in 4h VAS pain score of 7.9mm (95% CI: -4.5mm to 20.4mm) in patients administered 15mg ketorolac. This difference was neither statistically (P=0.207) nor clinically significant (<18mm on VAS scale). A similar increase in the 15mg group was noted through a per protocol analysis, 6.9mm (95% CI: -6.6mm to 20.5mm, P=0.307) greater in the 15mg group. Non-inferiority of 15mg was not confirmed. No significant difference was found in secondary endpoints. Ketorolac 30mg intravenous was not superior to 15mg intravenous for post-operative pain management after spine surgery. However, 15mg failed to meet the pre-specified criteria for non-inferiority to the 30mg dose. Copyright © 2017 Elsevier Inc. All rights reserved.

The efficacy of intravenous ketorolac for pain relief in single-stage adjustable strabismus surgery: a prospective, randomized, placebo-controlled trial

PubMed Central

Rhiu, S; Chung, S A; Kim, W K; Chang, J H; Bae, S J; Lee, J B

2011-01-01

Purpose To determine the efficacy of preoperative intravenous ketorolac in reducing intraoperative and postoperative pain and improving patient satisfaction in patients undergoing single-stage adjustable strabismus surgery. Methods A prospective, randomized, placebo-controlled clinical trial was performed with 67 patients who underwent horizontal recti muscle surgery with adjustable sutures. The test group received intravenous ketorolac (60 mg) before surgery, and the control group received intravenous normal saline. Topical 0.5% proparacaine was administered to both groups during surgery. Vital signs including heart rate and blood pressure were recorded every 10 min throughout the surgery. The patients were asked to rate their maximum intraoperative and postoperative pain scores using a numerical pain rating scale. Patient satisfaction was also assessed using a five-point analogue scale. Results The ketorolac-premedicated patients had less pain both during and after surgery (P=0.033 and P=0.024, respectively). There were no differences in vital signs during surgery and patient satisfaction between the two groups. Conclusions Intravenous ketorolac, when administered preoperatively for single-stage adjustable strabismus surgery under topical anaesthesia, was effective in reducing pain during and after surgery. PMID:21102493

Local infiltration analgesia or femoral nerve block for postoperative pain management in patients undergoing total hip arthroplasty. A randomized, double-blind study.

PubMed

Kuchálik, Ján; Magnuson, Anders; Lundin, Anders; Gupta, Anil

2017-07-01

Several methods for pain management following total hip arthroplasty (THA) have been described but the best postoperative pain management technique remains uncertain. We compared surgeon applied local infiltration analgesia (LIA) with anaesthesiologist performed femoral nerve block (FNB) using ultrasound. The primary aim was to assess pain intensity 24h after THA. In this randomized, double-blind study, 56 patients (ASA I-III) undergoing THA consented to participate. In Group FNB, patients received an ultrasound-guided femoral nerve block using 30ml of ropivacaine 7.5mg/ml (225mg) while Group LIA received a similar volume of saline. Spinal anaesthesia was then performed and bupivacaine heavy, 3-3.5ml injected depending on patient characteristics. During surgery, patients in Group LIA received a mixture of 300mg (150ml) ropivacaine, ketorolac 30mg (1ml) and adrenaline 0.5mg (0.5ml) (total volume 151.5ml) peri-articularly and subcutaneously while Group FNB received 151.5ml of saline peri-articularly in a systematic way by the surgeon. A multi-hole catheter was placed with the tip placed intra-articularly at the end of surgery in both groups. After 23h, the LIA mixture consisting of 20ml ropivacaine (7.5mg/ml), ketorolac 30mg (1ml), adrenaline 0.1mg (1ml) (total volume 22ml) was injected in Group LIA and the same volume of saline in Group FNB. Postoperative pain, analgesic consumption (postoperative and post-discharge), side effects, home discharge, quality of life and hip function were recorded, the latter up to 6 months after surgery. Postoperative pain intensity was significantly lower in Group LIA compared to Group FNB during mobilization at 24h (primary endpoint), mean difference 1.8 NRS units (95% CI 0.7-2.9) (P=0.006), at rest after 4h (P=0.029) and on standing after 24 (P=0.0003) and 48h (P=0.043). Rescue morphine consumption was also significantly lower in Group LIA during 0-24, mean difference 13.5mg (95% CI, 6.1-20.9) (P=0.002) postoperatively. Motor block

Perioperative ketorolac in high risk breast cancer patients. Rationale, feasibility and methodology of a prospective randomized placebo-controlled trial.

PubMed

Forget, Patrice; Berlière, Martine; van Maanen, Aline; Duhoux, Francois P; Machiels, Jean-Pascal; Coulie, Pierre G; Bouche, Gauthier; De Kock, Marc

2013-10-01

Ketorolac, a NSAID routinely used during surgery proposed to have anticancer effects, is a promising way to improve postoperative oncological outcome. This effect may be particularly prominent in patients with elevated preoperative inflammatory scores, like the neutrophil:lymphocyte ratio. In this paper, we describe the rationale, the preliminary analyses in our patients, the feasibility and the methodology of a prospective randomized trial called "Ketorolac in Breast Cancer trial" (KBCt) (NCT01806259). Copyright © 2013 Elsevier Ltd. All rights reserved.

Postoperative pain after laparoscopic sleeve gastrectomy: comparison of three analgesic schemes (isolated intravenous analgesia, epidural analgesia associated with intravenous analgesia and port-sites infiltration with bupivacaine associated with intravenous analgesia).

PubMed

Ruiz-Tovar, Jaime; Muñoz, Jose Luis; Gonzalez, Juan; Zubiaga, Lorea; García, Alejandro; Jimenez, Montiel; Ferrigni, Carlos; Durán, Manuel

2017-01-01

Although bariatric surgery is actually mainly performed laparoscopically, analgesic optimization continues being essential to reduce complications and to improve the patients' comfort. The aim of this study is to evaluate the postoperative pain after analgesia iv exclusively, or associated with epidural analgesia or port-sites infiltration with bupivacaine. A prospective randomized study of patients undergoing laparoscopic sleeve gastrectomy between 2012 and 2014 was performed. Patients were divided into three groups: Analgesia iv exclusively (Group 1), epidural analgesia + analgesia iv (Group 2) and port-sites infiltration + analgesia iv (Group 3). Pain was quantified by means of a Visual Analogic Scale, and morphine rescue needs were determined 24 h after surgery. A total of 147 were included. Groups were comparable in age, gender and BMI. There were no differences in operation time, complications, mortality or hospital stay between groups. Median pain 24 h after surgery was 5 in Group 1, 2.5 in Group 2 and 2 in Group 3 (P = 0.01), without statistically significant differences between Groups 2 and 3. In Group 1, morphine rescue was necessary in 16.3 % of the cases, 2 % in Group 2 and 2 % in Group 3 (P = 0.014), without statistically significant differences between Groups 2 and 3. Epidural analgesia and port-sites infiltration with bupivacaine, associated with analgesia iv, reduce the postoperative pain, when compared with analgesia iv exclusively. ClinicalTrials.gov Identifier: NCT02662660.

A COMPARATIVE STUDY OF THE ANALGESIC EFFECT OF INTRAVENOUS PETHIDINE VS. KETOROLAC AFTER INGUINAL HERNIA SURGERY IN CHILDREN UNDER GENERAL ANESTHESIA.

PubMed

Saryazdi, Hamid Hajigholam; Aghadavoudi, Omid; Shafa, Amir; Masoumi, Amin; Saberian, Parnian

2016-06-01

Postoperative pain due to tissue damage caused during surgery not only causes discomfort for the patients, but can also result in prolonged hospitalization, increased morbidity and respiratory disorders, and readmission to the hospital. For postoperative pain control, numerous methods and medications have been suggested, such as non-steroidal anti-inflammatory drugs (NSAIDs) and narcotics. Pethidine, as a narcotic analgesic, and ketorolac, as an NSAID, are widely used for pain control. Thus, in this study, the effects of these two drugs were studied and compared in terms of pain control after inguinal hernia surgery in children of 1-12 years of age. Sixty-six children undergoing inguinal herniorrhaphy were selected and randomly divided into 2 groups. The first group received 0.5 mg/kg ketorolac and the second group received 1 mg/kg pethidine during extubation. Postoperative pain (using Wong Baker pain scale) and complications were measured until 24 hours after surgery. Mean and standard deviations of postoperative pain 1 hour after surgery in the pethidin and ketorolac groups were 5.06 ± 1.41 and 3.88 ± 0.93, respectively. The scale was significantly lower in the ketorolac group (P < 0.001). Postoperative pain intensity 2 hours after surgery in these two groups was 4.48 ± 1.52 and 3.55 ± 1.15, respectively, and the difference between the two groups was significant (P = 0.006). The variation in postoperative pain intensity in the ketorolac group was statistically lower than the pethidin group (P = 0.020). CONCLUSION.

Ketorolac, Oxymorphone, Tapentadol, and Tramadol: A Comprehensive Review.

PubMed

Vadivelu, Nalini; Chang, Daniel; Helander, Erik M; Bordelon, Gregory J; Kai, Alice; Kaye, Alan D; Hsu, Dora; Bang, Daniel; Julka, Inderjeet

2017-06-01

Pain remains a tremendous burden on patients and for the health care system, with uncontrolled pain being the leading cause of disability in this country. There are a variety of medications that can be used in the treatment of pain, including ketorolac, oxymorphone, tapentadol, and tramadol. Depending on the clinical situation, these drugs can be used as monotherapy or in conjunction with other types of medications in a multimodal approach. A strong appreciation of pharmacologic properties of these agents and potential side effects is warranted for clinicians. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of analgesic effect of preoperative topical diclofenac and ketorolac on postoperative pain after photorefractive keratectomy.

PubMed

Hong, Jin Pyo; Nam, Sang Min; Im, Chan Young; Yoon, Sangchul; Kim, Tae-Im; Kim, Eung Kweon; Seo, Kyoung Yul

2014-10-01

To investigate changes in the pain-suppressing potency of 2 preoperatively applied topical nonsteroidal antiinflammatory drugs (NSAIDs) after photorefractive keratectomy (PRK) using a time-serial pain-scoring system. Saeyan Eye Center, Seoul, South Korea. Comparative case series. Ninety-four patients were randomly assigned to 2 groups: ketorolac group (ketorolac 0.5% in 1 eye and ofloxacin 0.3% in the other eye) and diclofenac group (diclofenac 0.1% in 1 eye and ofloxacin 0.3% in the other eye). One drop of each ophthalmic drug was applied 3 times to each eye 30 minutes before PRK. No other NSAID or steroid was prescribed until 4 days after PRK. The patients were asked to score the postoperative pain in each eye with a visual analog scale at 6, 18, 24, 36, 48, 72, and 96 hours. The natural peak of pain was located between 24 and 36 hours. Initially, the degree of pain reduction was constant for both NSAIDs; it dropped after 24 hours and 36 hours in the ketorolac group and the diclofenac group, respectively. The postoperative time-serial pattern of the pain score changed in the diclofenac group but not in the ketorolac group compared with the pattern in the ofloxacin-treated eye. The visual outcome was not affected by either NSAID, and significant complications were not noticed for a mean of 7 months. The duration and pattern of the action may vary according to types of NSAIDs. Preemptive topical diclofenac 0.1% was a safe and effective method for post-PRK pain control. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Advances in labor analgesia

PubMed Central

Wong, Cynthia A

2010-01-01

The pain of childbirth is arguably the most severe pain most women will endure in their lifetimes. The pain of the early first stage of labor arises from dilation of the lower uterine segment and cervix. Pain from the late first stage and second stage of labor arises from descent of the fetus in the birth canal, resulting in distension and tearing of tissues in the vagina and perineum. An array of regional nerve blocks, systemic analgesic, and nonpharmacologic techniques are currently used for labor analgesia. Nonpharmacologic methods are commonly used, but the effectiveness of these techniques generally lacks rigorous scientific study. Continuous labor support has been shown to decrease the use of pharmacologic analgesia and shorten labor. Intradermal water injections decrease back labor pain. Neuraxial labor analgesia (most commonly epidural or combined spinal-epidural) is the most effective method of pain relief during childbirth, and the only method that provides complete analgesia without maternal or fetal sedation. Current techniques commonly combine a low dose of local anesthetic (bupivacaine or ropivacaine) with a lipid soluble opioid (fentanyl or sufentanil). Neuraxial analgesia does not increase the rate of cesarean delivery compared to systemic opioid analgesia; however, dense neuraxial analgesia may increase the risk of instrumental vaginal delivery. PMID:21072284

No evidence of a clinically important effect of adding local infusion analgesia administrated through a catheter in pain treatment after total hip arthroplasty

PubMed Central

2011-01-01

Background and purpose Postoperative analgesia after primary total hip arthroplasty (THA) using opioids is associated with troublesome side effects such as nausea and dizziness, and epidural analgesic means delayed mobilization. Thus, local infiltration analgesia (LIA) during surgery prolonged with local infusion analgesia (LINFA) into the soft tissue in the hip region through a catheter in the first postoperative days has gained major interest in THA fast-track settings within a short period of time. LIA at the time of surgery is a validated treatment. We investigated the additional effect of giving postoperative LINFA after THA in patients already having LIA during surgery. Patients and methods 60 consecutive patients undergoing non-cemented THA were randomized into two groups in a double-blind and controlled study. During surgery, all patients received standardized pain treatment with LIA. Postoperatively, they were treated either with a solution of Ropivacain, Ketorolac, and Adrenaline (LINFA group) or placebo (placebo group) administered through a catheter to the hip 10 and 22 h after surgery. Pain score, opioid consumption, and length of stay (LOS) were evaluated. Results After adjustment for multiple testing, there was no statistically significant postoperative difference between the LINFA group and the placebo group regarding pain and tiredness. We found some evidence of a short-term effect on nausea and vomiting. Opioid consumption and length of stay were similar in the two groups. Interpretation We found some evidence of a short-term effect of LINFA on nausea and vomiting, but no evidence of an effect on postoperative pain and tiredness. Thus, LINFA cannot be recommended as a standard pain treatment in patients with THA. PMID:21619503

Nitrous oxide for labor analgesia: Utilization and predictors of conversion to neuraxial analgesia.

PubMed

Sutton, Caitlin D; Butwick, Alexander J; Riley, Edward T; Carvalho, Brendan

2017-08-01

We examined the characteristics of women who choose nitrous oxide for labor analgesia and identified factors that predict conversion from nitrous oxide to labor neuraxial analgesia. Retrospective descriptive study. Labor and Delivery Ward. 146 pregnant women who used nitrous oxide for analgesia during labor and delivery between September 2014 and September 2015. Chart review only. Demographic, obstetric, and intrapartum characteristics of women using nitrous oxide were examined. Multivariable logistic regression was performed to identify factors associated with conversion from nitrous oxide to neuraxial analgesia. Data are presented as n (%), median [IQR], adjusted relative risk (aRR), and 95% confidence intervals (CI) as appropriate. During the study period, 146 women used nitrous oxide for labor analgesia (accounting for 3% of the total deliveries). The majority (71.9%) of women who used nitrous oxide were nulliparous, and over half (51.9%) had expressed an initial preference for "nonmedical birth." The conversion rate to neuraxial blockade was 63.2%, compared to a concurrent institutional rate of 85.1% in women who did not use nitrous oxide. Factors associated with conversion from nitrous oxide to neuraxial blockade were labor induction (aRR=2.0, CI 1.2-3.3) and labor augmentation (aRR=1.7, CI 1.0-2.9). Only a small number of women opted to use nitrous oxide during labor, analgesia was minimal, and most converted to neuraxial analgesia. Women with induced and augmented labors should be counseled about the increased likelihood that they will convert to neuraxial analgesia. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative study of intravenous Tramadol versus Ketorolac for preventing postoperative pain after third molar surgery--a prospective randomized study.

PubMed

Gopalraju, Prathibha; Lalitha, Ramanujapuram Manikarnike; Prasad, Kavitha; Ranganath, Krishnappa

2014-07-01

The aim of this comparative, prospective, randomized, controlled study was to evaluate two different regimens of analgesics: a preoperative intravenous dose of either Tramadol or Ketorolac given 10 min prior to surgery to assess their impact on clinical recovery after third molar surgery. Forty patients requiring surgical extraction of unilateral impacted mandibular third molars similar in position were enrolled in the study. Patients were randomly divided into two groups based on permuting the numbers. Patients in Group 1 and Group 2 were administered either Tramadol 50 mg or Ketorolac 30 mg, intravenously, 10 min prior to surgery. The difference in postoperative pain was assessed by four primary points: pain intensity as measured by a 10 mm visual analogue scale hourly for 12 h, median time to rescue analgesics, number of analgesics consumed and patient's overall 5-point global assessment scale. Throughout the 12 h investigation period, patients treated with Ketorolac reported significantly lower pain intensity scores, significantly longer time to rescue analgesics (Acetaminophen 500 mg) and less intake of postoperative analgesics. In Group 2, 40% of the patient had good overall assessment as compared to Group 1 where only 25% of patients had good overall assessment. The current study shows that pre-emptive use of Inj. Ketorolac 30 mg intravenously can reduce the severity of the postoperative sequelae of asymptomatic impacted mandibular third molar surgery. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Effect of a Combination of Intranasal Ketorolac and Nitrous Oxide on the Success of the Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis: A Prospective, Randomized, Double-blind Study.

PubMed

Stentz, Daniel; Drum, Melissa; Reader, Al; Nusstein, John; Fowler, Sara; Beck, Mike

2018-01-01

Previous studies in patients with irreversible pulpitis have reported increased success of the inferior alveolar nerve block (IANB) using premedication with ketorolac. Preemptive nitrous oxide administration has also shown an increase in the success of the IANB. Recently, ketorolac has been made available for intranasal delivery. Perhaps combining ketorolac and nitrous oxide would increase success. Therefore, the purpose of this prospective, randomized, double-blind study was to determine the effect of a combination of intranasal ketorolac and nitrous oxide/oxygen on the anesthetic success of the IANB in patients presenting with symptomatic irreversible pulpitis. One hundred two patients experiencing spontaneous moderate to severe pain with symptomatic irreversible pulpitis in a mandibular posterior tooth participated. Patients were randomly divided into 2 groups and received either 31.5 mg intranasal ketorolac or intranasal saline placebo 20 minutes before the administration of nitrous oxide/oxygen. Ten minutes after the administration of nitrous oxide/oxygen, the IANB was given. After profound lip numbness, endodontic treatment was performed. Success was defined as the ability to perform endodontic access and instrumentation with no pain or mild pain. The odds of success for the IANB was 1.631 in the intranasal saline/nitrous oxide group versus the intranasal ketorolac/nitrous oxide group with no significant difference between the groups (P = .2523). Premedication with intranasal ketorolac did not significantly increase the odds of success for the IANB over the use of nitrous oxide/oxygen alone. Supplemental anesthesia will still be needed to achieve adequate anesthesia. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

EPIDURAL ANALGESIA IN LABOR - CONTROVERSIES.

PubMed

Bilić, Nada; Djaković, Ivka; Kličan-Jaić, Katarina; Rudman, Senka Sabolović; Ivanec, Željko

2015-09-01

Labor pain is one of the most severe pains. Labor is a complex and individual process with varying maternal requesting analgesia. Labor analgesia must be safe and accompanied by minimal amount of unwanted consequences for both the mother and the child, as well as for the delivery procedure. Epidural analgesia is the treatment that best meets these demands. According to the American Congress of Obstetrics and Gynecology and American Society of Anesthesiologists, mother's demand is a reason enough for the introduction of epidural analgesia in labor, providing that no contraindications exist. The application of analgesics should not cease at the end of the second stage of labor, but it is recommended that lower concentration analgesics be then applied. Based on the latest studies, it can be claimed that epidural analgesia can be applied during the major part of the first and second stage of labor. According to previous investigations, there is no definitive conclusion about the incidence of instrumental delivery, duration of second stage of labor, time of epidural analgesia initiation, and long term outcomes for the newborn. Cooperation of obstetric and anesthesiology personnel, as well as appropriate technical equipment significantly decrease the need of instrumental completion of a delivery, as well as other complications encountered in the application of epidural analgesia. Our hospital offers 24/7 epidural analgesia service. The majority of pregnant women in our hospital were aware of the advantages of epidural analgesia for labor, however, only a small proportion of them used it, mainly because of inadequate level of information.

Efficacy of Ketorolac Buccal Infiltrations and Inferior Alveolar Nerve Blocks in Patients with Irreversible Pulpitis: A Prospective, Double-blind, Randomized Clinical Trial.

PubMed

Akhlaghi, Nahid Mohammadzadeh; Hormozi, Behnoush; Abbott, Paul V; Khalilak, Zohreh

2016-05-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine whether ketorolac buccal infiltrations (BIs) helped to improve the success of inferior alveolar nerve blocks (IANBs) in patients with acute irreversible pulpitis (AIP). Forty adult volunteers with AIP in a mandibular molar were included in this study. Patients were instructed to evaluate their pain by using a Heft-Parker visual analog scale. They were randomly divided into 2 groups (n = 20). All patients received standard IANB injection and after that a BI of 4% articaine with 1:100,000 epinephrine. After 5 minutes, 20 patients received a BI of 30 mg/mL ketorolac, and the other received a BI of normal saline (control group). Endodontic access cavity preparation (ACP) was initiated 15 minutes after the IANB when the patient reported lip numbness and had 2 electric pulp tests with no responses. The patient's pain during caries and dentin removal, ACP, and canal length measurements (CLM) was recorded by using Heft-Parker visual analog scale. Successful anesthesia was defined as no or mild pain during any of these steps, without the need for additional injection. Data were statistically analyzed by using Mann-Whitney U and χ(2) tests. Successful anesthesia after an IANB plus BI of articaine was obtained in 15% of patients in the control group at the end of CLM. Adding BI of ketorolac significantly increased the success rate to 40% (P < .05). Patient's pain during ACP and CLM was significantly lower in the ketorolac group (P < .05). Ketorolac BI can increase the success rate of anesthesia after IANB and BI with articaine in patients with AIP. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Patient-reported Outcomes from A National, Prospective, Observational Study of Emergency Department Acute Pain Management With an Intranasal Nonsteroidal Anti-inflammatory Drug, Opioids, or Both.

PubMed

Pollack, Charles V; Diercks, Deborah B; Thomas, Stephen H; Shapiro, Nathan I; Fanikos, John; Mace, Sharon E; Rafique, Zubaid; Todd, Knox H

2016-03-01

Patient compliance and satisfaction with analgesics prescribed after emergency department (ED) care for acute pain are poorly understood, largely because of the lack of direct patient follow-up with the ED provider. Our objective was to compare patient satisfaction with three analgesia regimens prescribed for post-ED care-a nasally administered nonsteroidal anti-inflammatory drug (NSAID), an opioid, or combination therapy-by collecting granular follow-up on analgesic use, pain scores, side effects, work activity levels, and overall satisfaction directly from patients. We designed a prospective registry linking ED assessment and analgesic management for acute pain of specific musculoskeletal or visceral etiologies with self-reported automated telephonic follow-up daily for the 4 days post-ED discharge. Patients were prescribed a specific NSAID (SPRIX, ketorolac tromethamine for nasal instillation) only, an oral opioid only, or both with the opioid clearly defined as rescue therapy, at the ED provider's discretion. There were 824 evaluable subjects. Maximum pain scores improved day to day more effectively with a ketorolac-based approach. Self-reported rates of return to work and work effectiveness were higher with SPRIX than with opioids or combination therapy. Adverse effects of nausea, constipation, drowsiness, and abdominal pain were higher each day among patients taking an opioid; nasal irritation was more common with SPRIX. Overall satisfaction at the end of the follow-up period was higher with SPRIX-based treatment than with opioid monotherapy. Automated telephonic follow-up of ED patients prescribed short-term analgesia is feasible. Ketorolac-based analgesia after an ED visit for many acute pain syndromes was associated with favorable patient outcomes and higher satisfaction than opioid-based therapy. SPRIX, an NSAID that is not available over the counter and has a novel delivery approach, may be useful for short-term post-ED outpatient analgesia. © 2016 by

Preemptive multimodal pain regimen reduces opioid analgesia for patients undergoing robotic-assisted laparoscopic radical prostatectomy.

PubMed

Trabulsi, Edouard J; Patel, Jitesh; Viscusi, Eugene R; Gomella, Leonard G; Lallas, Costas D

2010-11-01

Minimally invasive surgical techniques have many benefits, including reduced postoperative pain. Despite this, most patients require opioid analgesia, which can have significant side effects and toxicity. We report the first urologic study using multimodal analgesia with pregabalin, a gabapentinoid. The present retrospective study included 60 patients who underwent robotic-assisted laparoscopic radical prostatectomy. Of the 60 patients, 30 received multimodal treatment with pregabalin 150 mg, acetaminophen 975 mg, and celecoxib 400 mg orally 2 hours before the start of the procedure and continued postoperatively. These patients were compared with 30 consecutive previous patients, who had received a standard postoperative analgesic regimen with intravenous ketorolac 15 mg every 6 hours with oxycodone 5 mg and acetaminophen 325 mg, 1 to 2 tablets, every 4 hours as needed for pain. The patients in the multimodal treatment group had a significantly reduced intraoperative opioid requirement, as measured by the mean morphine equivalent dose administered (38.4 ± 2.73 mg vs 49.1 ± 2.65 mg; P < .01). The mean postoperative opioid use was also significantly reduced (10.7 ± 2.82 mg vs 26.2 ± 6.56 mg; P = .034), as was the mean total morphine equivalent dose administered (49.1 ± 2.7 mg vs 75.3 ± 4.6 mg; P < .001). The operative time, estimated operative blood loss, antiemetic use, postoperative creatinine and hemoglobin levels, and length of stay were similar in the 2 groups. No operative or treatment complications occurred in either group. The present retrospective review has indicated that a multimodal analgesic approach with pregabalin and celecoxib administered preoperatively decreases intraoperative and postoperative opioid use in patients undergoing robotic-assisted laparoscopic radical prostatectomy. Copyright © 2010 Elsevier Inc. All rights reserved.

Comparison of topical dorzolamide and ketorolac treatment for cystoid macular edema in retinitis pigmentosa and Usher's syndrome.

PubMed

Lemos Reis, Ricardo Filipe; Moreira-Gonçalves, Nuno; Estrela Silva, Sérgio E; Brandão, Elisete M; Falcão-Reis, Fernando M

2015-01-01

To investigate the topical effect of dorzolamide versus ketorolac on retinitis pigmentosa (RP) and Usher's syndrome (US) macular edema. Prospective, randomized and interventional study. A total of 28 eyes of 18 patients were included. Five eyes had US, 23 had RP. Fifteen eyes were allocated to ketorolac tromethamine 0.5% (4 drops daily regimen) and 13 eyes to dorzolamide hydrochloride 2% (3 drops daily regimen) treatment groups. Snellen's best-corrected visual acuity (BCVA), foveal thickness (FT) and foveal zone thickness (FZT) measured by Stratus® optical coherence tomography (OCT) were evaluated at baseline, 1, 3, 6 and 12 months after treatment. Patients assigned to ketorolac had a baseline BCVA of 0.37 ± 0.17 logMAR which improved at the end of 1 year to 0.28 ± 0.16 (p = 0.02). Three eyes (20%) of 2 patients improved by 7 letters or more. Mean FT and FZT did not change significantly during the study follow-up. After 1 year of treatment, 4 eyes (27%) of 3 patients showed an improvement of at least 16% of FT and 11% of FZT. Patients assigned to dorzolamide had a baseline BCVA of 0.48 ± 0.34 logMAR which improved in the first 6 months (0.40 ± 0.30; p = 0.01), with a decrease at 1 year (0.42 ± 0.27; p = 0.20). Seven eyes (54%) of 5 patients had an improvement of 7 letters or more. Mean FT and FZT did not change significantly either. After 1 year of treatment, 3 eyes (23%) of 2 patients showed an improvement of at least 16% on FT and 11% on FZT. RESULTS suggest that dorzolamide and ketorolac might improve visual acuity and therefore be of interest in selected cases. No relationship between retinal thickness fluctuation and visual acuity was found. Sample size was a limitation to the study. © 2014 S. Karger AG, Basel.

The Ablation or Reduction of Intraoperative Tourniquet Pain with Preoperative Administration of IV Ketorolac Tromethamine

DTIC Science & Technology

1994-08-01

non - steroidal anti - inflammatory drug . Anticipated conclusions of...tromethamine is a nonsteroidal, anti - inflammatory drug (NSAID) that does not have CNS activity. It is a potent analgesic with less anti - inflammatory ...nonsteroidal, anti - inflammatory drug that inhibits prostaglandin production. Administration of ketorolac tromethamine prior to tourniquet inflation

Gabapentina a dosis de 300 vs. 450 mg como premedicación anestésica para hipertensión reactiva, ansiedad y analgesia.

PubMed

Rascón-Martínez, Dulce María; Guzmán-Sánchez, Joaquín Antonio; Corral-Urdapilleta, Nora Paulina; Arguelles-Uribe, Gema Damaris; Velázquez-Loeza, Jazmín; Soto-Palma, Gustavo; Carrillo-Torres, Orlando

Observar el comportamiento de la gabapentina para aminorar la hipertensión reactiva secundaria a ansiedad y dolor en pacientes sometidos a cirugía oftálmica, así como el consumo de opiáceos entre los grupos. Ensayo clínico controlado aleatorizado y doble ciego que analizó a 125 pacientes divididos en tres grupos: grupo A, gabapentina 300 mg; grupo B, gabapentina 450 mg; grupo C, amaranto en grageas como control 2 horas antes del procedimiento quirúrgico. Se utilizó la prueba de ji al cuadrado para variables sociodemográficas y ANOVA de un factor para variables numéricas continuas. Se consideró como significativo un valor de p < 0.05 para un estudio de dos colas con un poder beta del 80%. La ansiedad y la analgesia transoperatoria y posoperatoria tuvieron diferencias significativas entre los grupos. Se encontró menor consumo de opiáceos en los grupos que usaron gabapentina. La gabapentina por vía oral, 300 o 450 mg, 2 horas antes de la cirugía, reduce el dolor, la ansiedad y el consumo de opiáceos durante el posoperatorio en pacientes sometidos a cirugía oftalmológica. Copyright: © 2018 SecretarÍa de Salud

Comparison of the efficacy and patients’ tolerability of Nepafenac and Ketorolac in the treatment of ocular inflammation following cataract surgery: A meta-analysis of randomized controlled trials

PubMed Central

Zhao, Xinyu; Xia, Song; Wang, Erqian

2017-01-01

As a new ophthalmic non-steroidal anti-inflammatory drug (NSAID) with prodrug structure, Nepafenac was supposed to have a better efficacy than conventional NSAIDs both in patients’ tolerability and ocular inflammation associated with cataract surgery. However, many current studies reached contradictory conclusions on the superiority of Nepafenac over Ketorolac. The objective of our study is to evaluate the efficacy and patients’ tolerability of Nepafenac and Ketorolac following cataract surgery. To clarify this, we conducted a meta-analysis of randomized controlled trials. Eleven articles were included in this study. The dataset consisted of 1165 patients, including 1175 cataract surgeries. Among them, 574 patients were in the Nepafenac group and 591 in the Ketorolac group. Our analysis indicated that these two drugs were equally effective in controlling post cataract surgery ocular inflammation, reducing macular edema, achieving a better visual ability and maintaining intraoperative mydriasis during cataract surgery. However, Nepafenac was more effective than Ketorolac in reducing the incidence of postoperative conjunctival hyperemia and ocular discomfort. This meta-analysis indicated that topical Nepafenac is superior to Ketorolac in patients’ tolerability following cataract surgery. However, these two drugs are equally desirable in the management of anterior chamber inflammation, visual rehabilitation and intraoperative mydriasis. Given the limitations in our study, more researches with larger sample sizes and focused on more specific indicators such as peak aqueous concentrations of drugs or PEG2 levels are required to reach a firmer conclusion. PMID:28253334

Comparison of the efficacy and patients' tolerability of Nepafenac and Ketorolac in the treatment of ocular inflammation following cataract surgery: A meta-analysis of randomized controlled trials.

PubMed

Zhao, Xinyu; Xia, Song; Wang, Erqian; Chen, Youxin

2017-01-01

As a new ophthalmic non-steroidal anti-inflammatory drug (NSAID) with prodrug structure, Nepafenac was supposed to have a better efficacy than conventional NSAIDs both in patients' tolerability and ocular inflammation associated with cataract surgery. However, many current studies reached contradictory conclusions on the superiority of Nepafenac over Ketorolac. The objective of our study is to evaluate the efficacy and patients' tolerability of Nepafenac and Ketorolac following cataract surgery. To clarify this, we conducted a meta-analysis of randomized controlled trials. Eleven articles were included in this study. The dataset consisted of 1165 patients, including 1175 cataract surgeries. Among them, 574 patients were in the Nepafenac group and 591 in the Ketorolac group. Our analysis indicated that these two drugs were equally effective in controlling post cataract surgery ocular inflammation, reducing macular edema, achieving a better visual ability and maintaining intraoperative mydriasis during cataract surgery. However, Nepafenac was more effective than Ketorolac in reducing the incidence of postoperative conjunctival hyperemia and ocular discomfort. This meta-analysis indicated that topical Nepafenac is superior to Ketorolac in patients' tolerability following cataract surgery. However, these two drugs are equally desirable in the management of anterior chamber inflammation, visual rehabilitation and intraoperative mydriasis. Given the limitations in our study, more researches with larger sample sizes and focused on more specific indicators such as peak aqueous concentrations of drugs or PEG2 levels are required to reach a firmer conclusion.

A randomized trial of intravenous ketorolac versus intravenous metoclopramide plus diphenhydramine for tension-type and all nonmigraine, noncluster recurrent headaches.

PubMed

Friedman, Benjamin W; Adewunmi, Victoria; Campbell, Caron; Solorzano, Clemencia; Esses, David; Bijur, Polly E; Gallagher, E John

2013-10-01

We compare metoclopramide 20 mg intravenously, combined with diphenhydramine 25 mg intravenously, with ketorolac 30 mg intravenously in adults with tension-type headache and all nonmigraine, noncluster recurrent headaches. In this emergency department (ED)-based randomized, double-blind study, we enrolled adults with nonmigraine, noncluster recurrent headaches. Patients with tension-type headache were a subgroup of special interest. Our primary outcome was a comparison of the improvement in pain score between baseline and 1 hour later, assessed on a 0 to 10 verbal scale. We defined a between-group difference of 2.0 as the minimum clinically significant difference. Secondary endpoints included need for rescue medication in the ED, achieving headache freedom in the ED and sustaining it for 24 hours, and patient's desire to receive the same medication again. We included 120 patients in the analysis. The metoclopramide/diphenhydramine arm improved by a median of 5 (interquartile range 3, 7) scale units, whereas the ketorolac arm improved by a median of 3 (IQR 2, 6) (95% confidence interval [CI] for difference 0 to 3). Metoclopramide+diphenhydramine was superior to ketorolac for all 3 secondary outcomes: the number needed to treat for not requiring ED rescue medication was 3 (95% CI 2 to 6); for sustained headache freedom, 6 (95% CI 3 to 20); and for wish to receive the same medication again, 7 (95% CI 4 to 65). Tension-type headache subgroup results were similar. For adults who presented to an ED with tension-type headache or with nonmigraine, noncluster recurrent headache, intravenous metoclopramide+diphenhydramine provided more headache relief than intravenous ketorolac. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Ethanol-induced analgesia

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

Pohorecky, L.A.; Shah, P.

1987-09-07

The effect of ethanol (ET) on nociceptive sensitivity was evaluated using a new tail deflection response (TDR) method. The IP injection of ET (0.5 - 1.5 g/kg) produced raid dose-dependent analgesia. Near maximal effect (97% decrease in TDR) was produced with the 1.5 g/kg dose of ET ten minutes after injection. At ninety minutes post-injection there was still significant analgesia. Depression of ET-induced nociceptive sensitivity was partially reversed by a 1 mg/kg dose of naloxone. On the other hand, morphine (0.5 or 5.0 mg/kg IP) did not modify ET-induced analgesia, while 3.0 minutes of cold water swim (known to producemore » non-opioid mediated analgesia) potentiated ET-induced analgesic effect. The 0.5 g/kg dose of ET by itself did not depress motor activity in an open field test, but prevented partially the depression in motor activity produced by cold water swim (CWS). Thus, the potentiation by ET of the depression of the TDR produced by CWS cannot be ascribed to the depressant effects of ET on motor activity. 21 references, 4 figures, 1 table.« less

Can local infiltration analgesia increase satisfaction in postoperative short-term pain control in total knee arthroplasty?

PubMed

Barastegui, David; Robert, I; Palau, E; Haddad, S; Reverte-Vinaixa, M; Lorente, L; Cots, M

2017-01-01

One of the major challenges to total knee arthroplasty (TKA) is optimal pain control. Effective analgesia is capital in fast-track surgery programs to allow patient's early functional outcomes. Compare length of stay (LOS) short-term pain control, and patients' satisfaction at 1 month between local infiltration analgesia (LIA) combined with femoral nerve block (FNB) and FNB only in patients undergoing TKA. Two hundred and fifty-four patients were included in a randomized prospective study and distributed in two groups. The first group received an intraoperative LIA (150 mL mixture of ropivacaine 2.0 mg/mL + ketorolac 30 mg + adrenaline 10 μg/mL) combined to an FNB. The control group had only an FNB. Demographical data and visual analog scale (VAS) score were obtained preoperatively, at 36 h after surgery and at the 15-day follow-up. Patients' satisfaction at 1 month was also evaluated. Statistical analysis data was performed. No differences in demographical data and preoperative VAS score were observed between both groups. LIA group had a lower VAS score at 36 h after surgery (1.34 ± 1.31 vs. 3.68 ± 1.932 in the control group, p = 0.00), but these differences were not maintained at the 15-day follow-up (4.51 ± 1.889 vs. 4.11 ± 1.940 in the control group, p > 0.05). LOS and patients' satisfaction were comparable between groups. Patients with LIA had no additional complications. LIA is a safe adjuvant to FNB to reduce perioperative pain during the first 36 h after TKA. Its effects wean with time, but do cover the first crucial hours of rehabilitation in a fast-track program. LIA seems don't modify postoperative course nor patient's satisfaction at short-term follow-up. The final impact of LIA on surgical outcome is still to be determined.

Intracameral phenylephrine and ketorolac during cataract surgery to maintain intraoperative mydriasis and reduce postoperative ocular pain: Integrated results from 2 pivotal phase 3 studies.

PubMed

Hovanesian, John A; Sheppard, John D; Trattler, William B; Gayton, Johnny L; Malhotra, Ranjan P; Schaaf, David T; Ng, Edmund; Dunn, Steven H

2015-10-01

To evaluate the efficacy and safety of phenylephrine 1.0%-ketorolac 0.3% (Omidria) for maintenance of mydriasis during, and reduction of ocular pain after, cataract surgery. Twenty centers in the United States and the Netherlands. Prospective randomized clinical trials. Patients having cataract surgery or refractive lens exchange were enrolled in 2 clinical trials. Phenylephrine 1.0%-ketorolac 0.3% or placebo was added to irrigation solution and administered intracamerally during the procedure. Integrated analyses of primary and secondary endpoints were conducted. The clinical trials comprised 808 patients (403 treatment and 405 placebo). Phenylephrine 1.0%-ketorolac 0.3% was superior to placebo for the maintenance of mydriasis during, and reduction of ocular pain following, cataract surgery. The mean area under the curve (AUC) change from baseline in pupil diameter was 0.08 mm for treatment compared with -0.50 mm for placebo (P < .0001). The mean AUC of ocular pain visual analog scale scores within 12 hours postoperatively was 4.16 mm for the treatment group and 9.06 mm for the placebo group (P < .001). Results of all secondary efficacy analyses demonstrated a significant treatment effect associated with phenylephrine 1.0%-ketorolac 0.3%. Treatment-emergent adverse events were as expected for a population having cataract surgery; no clinically significant differences in safety measures were observed between treatment groups. In this integrated analysis, phenylephrine 1.0%-ketorolac 0.3% administered intracamerally with irrigation solution during cataract surgery was safe and effective for maintaining mydriasis during the procedure and reducing postoperative ocular pain. Dr. Schaaf is an employee and holds an equity interest in Omeros Corporation. Drs. Hovanesian, Sheppard, Trattler, Gayton, and Ng are consultants to Omeros Corporation. No other author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 The Authors

Ketorolac Administered in the Recovery Room for Acute Pain Management Does Not Affect Healing Rates of Femoral and Tibial Fractures.

PubMed

Donohue, David; Sanders, Drew; Serrano-Riera, Rafa; Jordan, Charles; Gaskins, Roger; Sanders, Roy; Sagi, H Claude

2016-09-01

To determine whether ketorolac administered in the immediate perioperative period affects the rate of nonunion in femoral and tibial shaft fractures. Retrospective comparative study. Single Institution, Academic Level 1 Trauma Center. Three hundred and thirteen skeletally mature patients with 137 femoral shaft (OTA 32) and 191 tibial shaft (OTA 42) fractures treated with intramedullary rod fixation. Eighty patients with 33 femoral shaft and 52 tibial shaft fractures were administered ketorolac within the first 24 hours after surgery (group 1-study group). Two-hundred thirty-three patients with 104 femoral shaft and 139 tibial shaft fractures were not (group 2-control group). Rate of reoperation for repair of a nonunion and time to union. Average time to union of the femur was 147 days for group 1 and 159 days for group 2 (P = 0.57). Average time to union of the tibia was 175 days for group 1 and 175 days for group 2 (P = 0.57). There were 3 femoral nonunions (9%) in group 1 and eleven femoral nonunions (11.6%) in group 2 (P = 1.00). There were 3 tibial nonunions (5.8%) in group 1 and 17 tibial nonunions (12.2%) in group 2 (P = 0.29). The average dose of ketorolac for patients who healed their fracture was 85 mg, whereas it was 50 mg for those who did not (P = 0.27). All patients with a nonunion in the study group were current smokers. Ketorolac administered in the first 24 hours after fracture repair for acute pain management does not seem to have a negative impact on time to healing or incidence of nonunion for femoral or tibial shaft fractures. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Pavlovian second-order conditioned analgesia.

PubMed

Ross, R T

1986-01-01

Three experiments with rat subjects assessed conditioned analgesia in a Pavlovian second-order conditioning procedure by using inhibition of responding to thermal stimulation as an index of pain sensitivity. In Experiment 1, rats receiving second-order conditioning showed longer response latencies during a test of pain sensitivity in the presence of the second-order conditioned stimulus (CS) than rats receiving appropriate control procedures. Experiment 2 found that extinction of the first-order CS had no effect on established second-order conditioned analgesia. Experiment 3 evaluated the effects of post second-order conditioning pairings of morphine and the shock unconditioned stimulus (US). Rats receiving paired morphine-shock presentations showed significantly shorter response latencies during a hot-plate test of pain sensitivity in the presence of the second-order CS than did groups of rats receiving various control procedures; second-order analgesia was attenuated. These data extend the associative account of conditioned analgesia to second-order conditioning situations and are discussed in terms of the mediation of both first- and second-order analgesia by an association between the CS and a representation or expectancy of the US, which may directly activate endogenous pain inhibition systems.

Comparison Between the Effects of Intravenous Morphine, Tramadol, and Ketorolac on Stress and Immune Responses in Patients Undergoing Modified Radical Mastectomy.

PubMed

Bakr, Mohamed A-E-M; Amr, Samy A-E R; Mohamed, Sahar A; Hamed, Hosny B; Abd El-Rahman, Ahmad M; Mostafa, Mohamed A M; El Sherif, Fatma A

2016-10-01

Analgesics had been suspected of impairing various immune functions either directly or indirectly. Our primary objective was to compare the effects of intravenous (IV) morphine, tramadol, and ketorolac on stress and immune responses in patients who underwent modified radical mastectomy. Sixty patients randomly assigned to receive IV morphine 5 mg (group M, n=20), tramadol 100 mg (group T, n=20), or ketorolac 60 mg (group K, n=20) at the end of surgery. Serum cortisol, prolactin were measured immediately, 40 minutes, and 24 hours postoperatively. Expressions of peripheral T lymphocytes (CD3, CD3CD4, CD3CD8) and natural killer cells (CD3, CD56) were measured as percentages of total lymphocytes by flow cytometry immediately, 90 minutes, and 24 hours postoperatively. After 40 minutes, cortisol level increased but prolactin decreased significantly (P=0.001), then both decreased after 24 hours (P=0.001) compared with baseline within the 3 groups. CD3, CD4, CD8, and CD56 significantly decreased at 90 minutes and 24 hours (P≤0.033) compared with baseline in the 3 groups. CD4, CD8, and CD56 significantly decreased in group M, compared with group T and K (P≤0.016) and CD3, CD8, and CD56 in group T compared with group K at 90 minutes (P≤0.024) postoperatively. After 24 hours, CD4, and CD8 decreased in group M compared with group T (P≤0.048) and CD4 and CD56 in groups M and T compared with group K (P≤0.049). IV morphine, tramadol, and ketorolac suppressed stress and immune responses. Ketorolac was the least immunosuppressive among the 3 drugs.

Modulation of opioid analgesia by agmatine.

PubMed

Kolesnikov, Y; Jain, S; Pasternak, G W

1996-01-18

Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, agmatine enhances morphine analgesia in a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater effect is observed when morphine is given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to the potentiation of morphine analgesia, agmatine (10 mg/kg) has no effect on morphine's inhibition of gastrointestinal transit. delta-Opioid receptor-mediated analgesia also is potentiated by agmatine, but kappa1-receptor-mediated (U50,488H; trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetemide) and kappa3-opioid receptor-mediated (naloxone benzoylhydrazone) analgesia is not significantly enhanced by any dose of agmatine tested in this acute model. In chronic studies, agmatine at a low dose (0.1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days. A higher agmatine dose (10 mg/kg) has a similar effect. Agmatine also blocks tolerance to the delta-opioid receptor ligand [D-Pen2,D-Pen5]enkephalin given intrathecally, but not to the kappa3-opioid receptor agonist naloxone benzoylhydrazone. Despite its inactivity on kappa1-opioid analgesia in the acute model, agmatine prevents kappa1-opioid receptor-mediated tolerance. These studies demonstrate the dramatic interactions between agmatine and opioid analgesia and tolerance.

Patient considerations in cataract surgery - the role of combined therapy using phenylephrine and ketorolac.

PubMed

Gonzalez-Salinas, Roberto; Guarnieri, Adriano; Guirao Navarro, María Concepción; Saenz-de-Viteri, Manuel

2016-01-01

Cataract, a degradation of the optical quality of the crystalline lens, progressive and age-related, is the leading cause of treatable blindness worldwide. Cataract surgery is the most common surgical procedure performed by ophthalmologists and is the only effective treatment for cataracts. Advances in the surgical techniques and better postoperative visual outcomes have progressively changed the primary concern of cataract surgery to become a procedure refined to yield the best possible refractive results. Sufficient mydriasis during cataract removal is critical to a successful surgical outcome. Poor pupil dilation can lead to serious sight-threatening complications that significantly increase the cost of surgery and decrease patients comfort. Mydriasis is obtained using anticholinergic and sympathomimetic drugs. Phenylephrine, an α1-adrenergic receptor agonist, can efficiently dilate the pupil when administered by intracameral injection. Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs) like ketorolac, which inhibit the synthesis of prostaglandins, are used to decrease intraoperative miosis, control pain and inflammation associated with cataract surgery, and to prevent the development of cystoid macular edema following surgery. Recently, a new combination of phenylephrine and ketorolac (Omidria ® ) has been approved by United States Food and Drug Administration for use during cataract surgery to maintain intraoperative mydriasis, prevent miosis, and reduce postoperative pain and inflammation. Clinical trials have shown that this new combination is effective, combining the positive effects of both drugs with a good safety profile and patient tolerability. Moreover, recent reports suggest that this combination is also effective in patients with high risk of poor pupil dilation. In conclusion, cataract is a global problem that significantly affects patients' quality of life. However, they can be managed with a safe and minimally invasive surgery

Development, evaluation and pharmacokinetics of time-dependent ketorolac tromethamine tablets.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy

2013-01-01

The present study was intended to develop a time-dependent colon-targeted compression-coated tablets of ketorolac tromethamine (KTM) using hydroxypropyl methylcellulose (HPMC) that release the drug slowly but completely in the colonic region by retarding the drug releases in stomach and small intestine. KTM core tablets were prepared by direct compression method and were compression coated with HPMC. The formulation is optimized based on the in vitro drug release studies and further evaluated by X-ray imaging technique in healthy humans to ensure the colonic delivery. To prove these results, in vivo pharmacokinetic studies in human volunteers were designed to study the in vitro-in vivo correlation. From the in vitro dissolution study, optimized formulation F3 showed negligible drug release (6.75 ± 0.49%) in the initial lag period followed by slow release (97.47 ± 0.93%) for 24 h which clearly indicates that the drug is delivered to the colon. The X-ray imaging studies showed that the tablets reached the colon without disintegrating in upper gastrointestinal system. From the pharmacokinetic evaluation, the immediate-release tablets producing peak plasma concentration (C(max)) was 4482.74 ng/ml at 2 h T(max) and colon-targeted tablets showed C(max) = 3562.67 ng/ml at 10 h T(max). The area under the curve for the immediate-release and compression-coated tablets was 10595.14 and 18796.70 ng h/ml and the mean resident time was 3.82 and 10.75 h, respectively. Thus, the compression-coated tablets based on time-dependent approach were preferred for colon-targeted delivery of ketorolac.

Rabbit analgesia.

PubMed

Barter, Linda S

2011-01-01

With the increasing popularity of rabbits as household pets, the complexity of diagnostic and surgical procedures performed on rabbits is increasing, along with the frequency of routine surgical procedures. More practitioners are faced with the need to provide adequate analgesia for this species. Preemptive analgesia prior to planned surgical interventions may reduce nervous system changes in response to noxious input, as well as reduce postoperative pain levels and analgesic drug requirements. Concurrent administration of analgesic drugs to anesthetized rabbits undergoing painful procedures is warranted both pre- and intraoperatively as well as postoperatively. This article discusses the neuropharmacologic and pharmacologic aspects of pain in rabbits, and reviews current protocols for the use of analgesic drugs. Published by Elsevier Inc.

1,2,3-Triazolyl ester of Ketorolac: A "Click Chemistry"-based highly potent PAK1-blocking cancer-killer.

PubMed

Nguyen, Binh Cao Quan; Takahashi, Hideaki; Uto, Yoshihiro; Shahinozzaman, M D; Tawata, Shinkichi; Maruta, Hiroshi

2017-01-27

An old anti-inflammatory/analgesic drug called Toradol is a racemic form of Ketorolac (50% R-form and 50% S-form) that blocks the oncogenic RAC-PAK1-COX-2 (cyclooxygenase-2) signaling, through the direct inhibition of RAC by the R-form and of COX-2 by the S-form, eventually down-regulating the production of prostaglandins. However, due to its COOH moiety which is clearly repulsive to negatively-charged phospholipid-based plasma membrane, its cell-permeability is rather poor (the IC 50 against the growth of human cancer cells such as A549 is around 13 μM). In an attempt to boost its anti-cancer activity, hopefully by increasing its cell-permeability through abolishing the negative charge, yet keeping its water-solubility, here we synthesized a 1,2,3-triazolyl ester of Toradol through "Click Chemistry". The resultant water-soluble "azo" derivative called "15K" was found to be over 500 times more potent than Toradol with the IC 50 around 24 nM against the PAK1-dependent growth of A549 cancer cells, inactivating PAK1 in cell culture with the apparent IC 50 around 65 nM, and inhibiting COX-2 in vitro with the IC 50 around 6 nM. Furthermore, the Click Chemistry boosts the anti-cancer activity of Ketorolac by 5000 times against the PAK1-independent growth of B16F10 melanoma cells. Using a multi-drug-resistant (MDR) cancer cell line (EMT6), we found that the esterization of Ketorolac boosts its cell-permeability by at least 10 folds. Thus, the Click Chemistry dramatically boosts the anti-cancer activity of Ketorolac, at least in three ways: increasing its cell-permeability, the anti-PAK1 activity of R-form and anti-COX-2 activity of S-form. The resultant "15K" is so far among the most potent PAK1-blockers, and therefore would be potentially useful for the therapy of many different PAK1-dependent diseases/disorders such as cancers. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Partial reinforcement, extinction, and placebo analgesia

PubMed Central

Yeung, Siu Tsin Au; Colagiuri, Ben; Lovibond, Peter F.; Colloca, Luana

2014-01-01

Numerous studies indicate that placebo analgesia can be established via conditioning procedures. However, these studies have exclusively involved conditioning under continuous reinforcement. Thus, it is currently unknown whether placebo analgesia can be established under partial reinforcement and how durable any such effect would be. We tested this possibility using electro-cutaneous pain in healthy volunteers. Sixty undergraduates received placebo treatment (activation of a sham electrode) under the guise of an analgesic trial. The participants were randomly allocated to different conditioning schedules, namely continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning was achieved by surreptitiously reducing pain intensity during training when the placebo was activated compared with when it was inactive. For the CRF group, the placebo was always followed by a surreptitious reduction in pain during training. For the PRF group, the placebo was followed by a reduction in pain stimulation on 62.5% of trials only. In the test phase, pain stimulation was equivalent across placebo and no placebo trials. Both continuous and partial reinforcement produced placebo analgesia, with the magnitude of initial analgesia being larger following continuous reinforcement. However, while the placebo analgesia established under continuous reinforcement extinguished during test phase, the placebo analgesia established under partial reinforcement did not. These findings indicate that partial reinforcement can induce placebo analgesia and that these effects are more resistant to extinction than those established via continuous reinforcement. Partial reinforcement may, therefore, reflect a novel way of enhancing clinical outcomes via the placebo effect. PMID:24602997

Progress in analgesia for labor: focus on neuraxial blocks

PubMed Central

Ranasinghe, J Sudharma; Birnbach, David J

2010-01-01

Neuraxial analgesia is widely accepted as the most effective and the least depressant method of providing pain relief in labor. Over the last several decades neuraxial labor analgesia techniques and medications have progressed to the point now where they provide high quality pain relief with minimal side effects to both the mother and the fetus while maximizing the maternal autonomy possible for the parturient receiving neuraxial analgesia. The introduction of the combined spinal epidural technique for labor has allowed for the rapid onset of analgesia with minimal motor blockade, therefore allowing the comfortable parturient to ambulate. Patient-controlled epidural analgesia techniques have evolved to allow for more flexible analgesia that is tailored to the individual needs of the parturient and effective throughout the different phases of labor. Computer integrated systems have been studied to provide seamless analgesia from induction of neuraxial block to delivery. New adjuvant drugs that improve the effectiveness of neuraxial labor analgesia while decreasing the side effects that may occur due to high dose of a single drug are likely to be added to future labor analgesia practice. Bupivacaine still remains a popular choice of local anesthetic for labor analgesia. New local anesthetics with less cardiotoxicity have been introduced, but their cost effectiveness in the current labor analgesia practice has been questioned. PMID:21072273

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

NOP Receptor Mediates Anti-analgesia Induced by Agonist-Antagonist Opioids

PubMed Central

Gear, Robert W.; Bogen, Oliver; Ferrari, Luiz F.; Green, Paul G.; Levine, Jon D.

2014-01-01

Clinical studies have shown that agonist-antagonist opioid analgesics that produce their analgesic effect via action on the kappa-opioid receptor, produce a delayed-onset anti-analgesia in men but not women, an effect blocked by co-administration of a low dose of naloxone. We now report the same time-dependent anti-analgesia and its underlying mechanism in an animal model. Using the Randall-Selitto paw-withdrawal assay in male rats, we found that nalbuphine, pentazocine, and butorphanol each produced analgesia during the first hour followed by anti-analgesia starting at ~90 minutes after administration in males but not females, closely mimicking its clinical effects. As observed in humans, co-administration of nalbuphine with naloxone in a dose ratio of 12.5:1 blocked anti-analgesia but not analgesia. Administration of the highly selective kappa-opioid receptor agonist U69,593 produced analgesia without subsequent anti-analgesia, and confirmed by the failure of the selective kappa antagonist nor-binaltorphimine to block nalbuphine-induced anti-analgesia, indicating that anti-analgesia is not mediated by kappa-opioid receptors. We therefore tested the role of other receptors in nalbuphine anti-analgesia. Nociceptin/orphanin FQ (NOP) and sigma-1 and sigma-2 receptors were chosen on the basis of their known anti-analgesic effects and receptor binding studies. The selective NOP receptor antagonists, JTC801, and J113397, but not the sigma receptor antagonist, BD 1047, antagonized nalbuphine anti-analgesia. Furthermore, the NOP receptor agonist NNC 63-0532 produced anti-analgesia with the same delay in onset observed with the three agonist-antagonists, but without producing preceding analgesia and this anti-analgesia was also blocked by naloxone. These results strongly support the suggestion that clinically used agonist-antagonists act at the NOP receptor to produce anti-analgesia. PMID:24188792

Nasal Ketorolac Challenge Using Acoustic Rhinometry in Patients With Aspirin-Exacerbated Respiratory Disease.

PubMed

Quiralte-Castillo, J; Ávila-Castellano, M R; Cimbollek, S; Benaixa, P; Leguisamo, S; Baynova, K; Labella, M; Quiralte, J

Safer and less time-consuming alternatives to single-blind placebo-controlled oral challenge (SBPCOC) have been sought for the diagnosis of aspirin-exacerbated respiratory disease (AERD). Nasal challenges with various nonsteroidal anti-inflammatory drugs and assessment methods have been developed. Objective: Our objective was to evaluate the utility and safety of nasal ketorolac challenge (NKC) using acoustic rhinometry in patients with suspected AERD. The study population comprised 36 patients with suspected AERD. NKC was performed with placebo (saline) and 13 mg of ketorolac sprayed as aerosol into both nostrils. A positive challenge result was defined as an increase of ≥30% in nasal symptoms (recorded using a visual analog scale) and a 30% drop in the sum of the volumes of both nasal cavities at 2-8 cm. Patients with a negative NKC result underwent SBPCOC with aspirin (cumulative dose of 750 mg). A naso-ocular reaction during NKC was detected in 21 patients. Four patients also developed mild asthma exacerbations (although only 1 experienced a decrease in FEV1 >15%). No other significant adverse events occurred. The remaining 15 patients with a negative NKC result had a negative response during aspirin SBPCOC. NKC assessed using acoustic rhinometry is a reliable method for the study of patients with AERD. We suggest that NKC assessed with acoustic rhinometry was useful and safe for selection of candidates for safe oral aspirin challenge.

Preemptive, preventive, multimodal analgesia: what do they really mean?

PubMed

Rosero, Eric B; Joshi, Girish P

2014-10-01

To improve postoperative pain management, several concepts have been developed, including preemptive analgesia, preventive analgesia, and multimodal analgesia. This article will discuss the role of these concepts in improving perioperative pain management. Preemptive analgesia refers to the administration of an analgesic treatment before the surgical insult or tissue injury. Several randomized clinical trials have, however, provided equivocal evidence regarding the benefits of preincisional compared with postincisional analgesic administration. Current general consensus, therefore, indicates that use of preemptive analgesia does not translate into consistent clinical benefits after surgery. Preventive analgesia is a wider concept where the timing of analgesic administration in relation to the surgical incision is not critical. The aim of preventive analgesia is to minimize sensitization induced by noxious stimuli arising throughout the perioperative period. Multimodal analgesia consists of the administration of 2 or more drugs that act by different mechanisms for providing analgesia. These drugs may be administered via the same route or by different routes. Thus, the aim of multimodal analgesia is to improve pain relief while reducing opioid requirements and opioid-related adverse effects. Analgesic modalities currently available for postoperative pain control include opioids, local anesthetic techniques [local anesthetic infiltration, peripheral nerve blocks, and neuraxial blocks (epidural and paravertebral)], acetaminophen, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2-specific inhibitors as well as analgesic adjuncts such as steroids, ketamine, α-2 agonists, and anticonvulsants.

Local infiltration for postsurgical analgesia following total hip arthroplasty: a comparison of liposomal bupivacaine to traditional bupivacaine.

PubMed

Asche, Carl V; Ren, Jinma; Kim, Minchul; Gordon, Kate; McWhirter, Marie; Kirkness, Carmen S; Maurer, Brian T

2017-07-01

To assess postsurgical clinical and economic outcomes of patients who received local infiltration containing liposomal bupivacaine versus traditional bupivacaine for pain management following total hip arthroplasty (THA). This retrospective study included two groups of consecutive patients undergoing THA. The experimental group received local infiltration with a combination of liposomal bupivacaine, bupivacaine HCl 0.25% with epinephrine 1:200,000, and ketorolac for postsurgical analgesia. The historical control group received the previous standard of care: local infiltration with a combination of bupivacaine HCl 0.25% with epinephrine 1:200,000 and ketorolac. Key outcomes included distance walked, length of stay (LOS), opioid medication use, numeric pain scores, hospital charges, hospital costs, all-cause 30 day readmission rate, and adverse events (AEs). Both unadjusted and adjusted (i.e. age, sex, insurance type, living situation, body mass index, procedure side, and comorbidity) outcomes were compared between the two groups. The experimental group (n = 64) demonstrated statistically significant improvement versus the historical control group (n = 66) in mean distance walked on discharge day (249.2 vs. 180.0 feet; unadjusted p = .025, adjusted p = .070), mean LOS (2.0 vs. 2.7 days; p < .001, p = .002), proportion of patients who used opioid rescue medication on postoperative day (POD) 1 (29.7% vs. 56.1%; p = .002, p = .003) and POD 2 (7.8% vs. 30.3%; p = .001, p = .003), mean cumulative area under the curve for pain score on POD 0 (127.6 vs. 292.5; p < .001, both), POD 1 (92.9 vs. 185.0; p < .001, both), and POD 2 (93.8 vs. 213.8; p = .006, both). Among a subgroup of patients with available financial information, mean hospital charges were lower in the experimental group ($43,794 [n = 24] vs. $48,010 [n = 66]; p < .001, both). Rates of all-cause 30 day readmission and AEs were not significantly

The assessment of changes in macular thickness in diabetic and non-diabetic patients: the effect of topical ketorolac on macular thickness change after ND:YAG laser capsulotomy.

PubMed

Yılmaz, Uğur; Küçük, Erkut; Ulusoy, Döndü Melek; Özköse, Ayşe; Ataş, Mustafa; Demircan, Süleyman; Yuvacı, Isa

2016-03-01

The purpose of our study is to assess the changes in macular thickness (MT) in diabetic and non-diabetic patients and to research effects of topical ketorolac (Acular®, Allergan, Irvine, CA) on MT change after neodymium:yttrium aluminum garnet (Nd:YAG) laser capsulotomy. This study involved 88 eyes of 88 patients diagnosed as posterior capsule opacification (PCO). Patients were divided into four groups according to presence of diabetes mellitus (DM) and drugs used after capsulotomy. Group 1: Patients with DM using only 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) after capsulotomy (22 patients). Group 2: Patients with DM using 0.5% ketorolac (Acular®) and 0.1 Fluorometholon (FML®, Allergan, Irvine, CA) after capsulotomy (20 patients). Group 3: Patients without DM using only 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) (22 patients). Group 4: Patients without DM using 0.5% ketorolac (Acular®) and 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) (24 patients). A plus-shaped capsulotomy was performed using VISULAS® YAGIII (Carl Zeiss) laser microscope. MT measurement with Cirrus SD-OCT (Carl Zeiss Opthalmic System Inc., Model 400, Dublin, CA, Software 5) were done. Measurements were done before laser, and on the first day, first week, first month, third month and sixth month after laser capsulotomy. We compared the four groups for MT change during 6 months. Group 1 involving patients with DM using only 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) after capsulotomy had increased MT at the first week, and the first, third, and sixth month after laser (p < 0.001). Group 3 involving patients without DM using only 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) had increased MT at the first week, and at the first and third month, there was no statistically significant difference at the sixth month (p > 0.05). There was no statistically significant increase in MT during the follow-up period in group 2 involving patients with DM using 0

The Effects of Two Non-Steroidal Anti-Inflammatory Drugs, Bromfenac 0.1% and Ketorolac 0.45%, on Cataract Surgery.

PubMed

Jung, Ji Won; Chung, Byung Hoon; Kim, Eung Kweon; Seo, Kyoung Yul; Kim, Tae-im

2015-11-01

To compare the additive effects of two types of non-steroidal anti-inflammatory drugs (NSAIDs), bromfenac 0.1% or ketorolac 0.45%, relative to topical steroid alone in cataract surgery. A total 91 subjects scheduled to undergo cataract operation were randomized into three groups: Group 1, pre/postoperative bromfenac 0.1%; Group 2, pre/postoperative preservative-free ketorolac 0.45%; and Group 3, postoperative steroid only, as a control. Outcome measures included intraoperative change in pupil size, postoperative anterior chamber inflammation control, change in macular thickness and volume, and ocular surface status after operation. Both NSAID groups had smaller intraoperative pupil diameter changes compared to the control group (p<0.05). There was significantly less ocular inflammation 1 week and 1 month postoperatively in both NSAID groups than the control group. The changes in central foveal subfield thickness measured before the operation and at postoperative 1 month were 4.30±4.25, 4.87±6.03, and 12.47±12.24 μm in groups 1 to 3, respectively. In the control group, macular thickness and volume increased more in patients with diabetes mellitus (DM), compared to those without DM. In contrast, in both NSAID groups, NSAIDs significantly reduced macular changes in subgroups of patients with or without DM. Although three ocular surface parameters were worse in group 1 than in group 2, these differences were not significant. Adding preoperative and postoperative bromfenac 0.1% or ketorolac 0.45% to topical steroid can reduce intraoperative miosis, postoperative inflammation, and macular changes more effectively than postoperative steroid alone.

[Local infiltration analgesia in total joint replacement].

PubMed

de Jonge, Tamás; Görgényi, Szabolcs; Szabó, Gabriella; Torkos, Miklós Bulcsú

2017-03-01

Total hip and knee replacment surgeries are characterized by severe postoperative pain. Local infiltration analgesia is proved to be very effective. However this method has not been widely used in Hungary. To evaluate the efficacy of the local infiltration analgesia with modified components in patients underwent total hip or knee replacement surgery. Data of 99 consecutive patients underwent primary total hip or knee replacement surgery were evaluated prospectively. In all the 99 surgeries modified local infiltration analgesia was applied. Postoperative pain reported on a visual analog scale was recorded as well as the need for further analgetics during the first 18 hours after surgery. The cost of the analgetic drugs was calculated. The control group comprised 97 consecutive patients underwent total hip or knee replacement, where local infiltration analgesia was not applied. Statistical analysis was done. Patients received local infiltration analgesia reported significantly less pain (p<0.001). The need for postoperatively given analgetics was almost 50% less, and the cost of all postoperative analgetics was 47% less than in the control group. In total hip and knee replacement surgeries the modified local infiltration analgesia decreases postoperative pain effectively and contribute to the early mobilization of the patients. Orv. Hetil., 2017, 158(9), 352-357.

Effect of topical ketorolac 0.4%, nepafenac 0.1%, and bromfenac 0.09% on postoperative inflammation using laser flare photometry in patients having phacoemulsification.

PubMed

Sahu, Sabin; Ram, Jagat; Bansal, Reema; Pandav, Surinder S; Gupta, Amod

2015-10-01

To study the effect of topical ketorolac 0.4% (Acular LS), bromfenac 0.09% (Megabrom), and nepafenac 0.1% (Nevanac) on postoperative inflammation using laser flare photometry in patients having phacoemulsification with posterior chamber intraocular lens (PC IOL) implantation. Tertiary care center, Chandigarh, India. Prospective randomized case series. Patients with age-related cataract having phacoemulsification with PC IOL implantation were randomized into 4 groups receiving topical ketorolac 0.4% (Group A), bromfenac 0.09% (Group B), nepafenac 0.1% (Group C), or no nonsteroidal antiinflammatory drugs (NSAIDs) (Group D, control). The topical NSAIDs were started 1 day prior to the surgery and continued for 6 weeks postoperatively. All patients received a standard regimen of moxifloxacin 0.5% (Vigamox) and prednisolone acetate 1.0% (Pred Forte) eyedrops in tapering doses postoperatively. Visual acuity, intraocular pressure (IOP), laser flare photometry, and fundus examination were done preoperatively and postoperatively at 1 day and 1, 2, 4, and 8 weeks. The study comprised 120 patients (120 eyes) (Group A = 33 patients, Group B = 30 patients, Group C = 31 patients, and Group D = 26 patients). The laser flare photometry values at the end of 4 weeks and 8 weeks were minimal in the nepafenac group compared with the other NSAID groups and the no-NSAID group (P = .032 at 4 weeks and P = .252 at 8 weeks). The topical NSAIDs ketorolac 0.4%, bromfenac 0.09%, and nepafenac 0.1% were effective for the reduction of postoperative inflammation following phacoemulsification. Compared with ketorolac tromethamine, bromfenac, and the control, nepafenac was significantly effective 1 month postoperatively in reducing anterior chamber flare, as evidenced by decreased laser flare photometry. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia

PubMed Central

Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J.

2015-01-01

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated. PMID:26678391

Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia.

PubMed

Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J

2015-01-01

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.

Proximal Versus Distal Continuous Adductor Canal Blocks: Does Varying Perineural Catheter Location Influence Analgesia? A Randomized, Subject-Masked, Controlled Clinical Trial.

PubMed

Sztain, Jacklynn F; Khatibi, Bahareh; Monahan, Amanda M; Said, Engy T; Abramson, Wendy B; Gabriel, Rodney A; Finneran, John J; Bellars, Richard H; Nguyen, Patrick L; Ball, Scott T; Gonzales, Francis B; Ahmed, Sonya S; Donohue, Michael C; Padwal, Jennifer A; Ilfeld, Brian M

2018-07-01

A continuous adductor canal block provides analgesia after surgical procedures of the knee. Recent neuroanatomic descriptions of the thigh and knee led us to speculate that local anesthetic deposited in the distal thigh close to the adductor hiatus would provide superior analgesia compared to a more proximal catheter location. We therefore tested the hypothesis that during a continuous adductor canal nerve block, postoperative analgesia would be improved by placing the perineural catheter tip 2-3 cm cephalad to where the femoral artery descends posteriorly to the adductor hiatus (distal location) compared to a more proximal location at the midpoint between the anterior superior iliac spine and the superior border of the patella (proximal location). Preoperatively, subjects undergoing total knee arthroplasty received an ultrasound-guided perineural catheter inserted either in the proximal or distal location within the adductor canal in a randomized, subject-masked fashion. Subjects received a single injection of lidocaine 2% via the catheter preoperatively, followed by an infusion of ropivacaine 0.2% (8 mL/h basal, 4 mL bolus, 30 minutes lockout) for the study duration. After joint closure, the surgeon infiltrated the entire joint using 30 mL of ropivacaine (0.5%), ketorolac (30 mg), epinephrine (5 μg/mL), and tranexamic acid (2 g). The primary end point was the median level of pain as measured on a numeric rating scale (NRS) during the time period of 8:00 AM to 12:00 PM the day after surgery. For the primary end point, the NRS of subjects with a catheter inserted at the proximal location (n = 24) was a median (10th, 25th-75th, 90th quartiles) of 0.5 (0.0, 0.0-3.2, 5.0) vs 3.0 (0.0, 2.0-5.4, 7.8) for subjects with a catheter inserted in the distal location (n = 26; P = .011). Median and maximum NRSs were lower in the proximal group at all other time points, but these differences did not reach statistical significance. There were no clinically relevant or

Registered nurses' and midwives' knowledge of epidural analgesia.

PubMed

Bird, Annette; Wallis, Marianne; Chaboyer, Wendy

2009-01-01

Despite epidural analgesia increasingly being utilized in hospitals, very little research-based evidence is available about registered nurses' (RNs) and midwives' knowledge of this technique. To describe the current epidural knowledge levels of RNs and midwives in a multi-site setting. RNs and midwives at four, regional teaching facilities completed an epidural knowledge test. The instrument included demographic items and five knowledge subscales relating to epidural analgesia: spinal cord anatomy and physiology; epidural pharmacology; complications of epidural analgesia; assessment of sensory and motor blockade and the general management of patients with epidural analgesia. A total of 408 (99.7% response) RNs and midwives completed the test. Respondents demonstrated good knowledge of sensory and motor blockade assessment and the general management of epidural analgesia subscales with correct responses to 75 and 77% of the questions in these subscales, respectively. Fair knowledge relating to the spinal cord anatomy and physiology subscale was demonstrated with 69% of the questions answered correctly. The knowledge subscales relating to epidural pharmacology (57% correct responses) and the complications of epidural analgesia (56% correct responses) were problematic for the sample. The research results provide generalizable information about what RNs and midwives know about epidural analgesia. These results are an important guide in the development of new and existing dedicated epidural education programs. The results also provide some direction for further research into this important topic.

The Effects of Two Non-Steroidal Anti-Inflammatory Drugs, Bromfenac 0.1% and Ketorolac 0.45%, on Cataract Surgery

PubMed Central

Jung, Ji Won; Chung, Byung Hoon; Kim, Eung Kweon; Seo, Kyoung Yul

2015-01-01

Purpose To compare the additive effects of two types of non-steroidal anti-inflammatory drugs (NSAIDs), bromfenac 0.1% or ketorolac 0.45%, relative to topical steroid alone in cataract surgery. Materials and Methods A total 91 subjects scheduled to undergo cataract operation were randomized into three groups: Group 1, pre/postoperative bromfenac 0.1%; Group 2, pre/postoperative preservative-free ketorolac 0.45%; and Group 3, postoperative steroid only, as a control. Outcome measures included intraoperative change in pupil size, postoperative anterior chamber inflammation control, change in macular thickness and volume, and ocular surface status after operation. Results Both NSAID groups had smaller intraoperative pupil diameter changes compared to the control group (p<0.05). There was significantly less ocular inflammation 1 week and 1 month postoperatively in both NSAID groups than the control group. The changes in central foveal subfield thickness measured before the operation and at postoperative 1 month were 4.30±4.25, 4.87±6.03, and 12.47±12.24 µm in groups 1 to 3, respectively. In the control group, macular thickness and volume increased more in patients with diabetes mellitus (DM), compared to those without DM. In contrast, in both NSAID groups, NSAIDs significantly reduced macular changes in subgroups of patients with or without DM. Although three ocular surface parameters were worse in group 1 than in group 2, these differences were not significant. Conclusion Adding preoperative and postoperative bromfenac 0.1% or ketorolac 0.45% to topical steroid can reduce intraoperative miosis, postoperative inflammation, and macular changes more effectively than postoperative steroid alone. PMID:26446653

Stability and compatibility of the mixture of tramadol, ketorolac, metoclopramide and ranitidine in a solution for intravenous perfusion.

PubMed

Cabrera, J; Mancuso, M; Cabrera-Fránquiz, F; Limiñana, J; Díez, A

2011-01-01

To determine whether a mixture for intravenous perfusion containing tramadol (5 mg/ml), ranitidine (1.5 mg/ml), ketorolac (1.5 mg/ml) and metoclopramide (0.5 mg/ml) in a 0.9% sodium chlorides solution is compatible and stable at room temperature during a 48-hour period. We tested the mixture for stability using the HPLC technique (high performance liquid chromatography), with parallel visual assessments of any changes in colour, appearance of precipitate or phase separation indicating incompatibilities between the components. At the end of the trial, chromatography data showed a mean metoclopramide concentration between 100% and 105% of the initial level, while concentrations of tramadol, ketorolac and ranitidine were between 99% and 102% of initial levels. There was no evidence of incompatibility between the drugs at any time during the study period. The combination is stable as a solution and its components are physically and chemically compatible in the concentrations used in the study, during at least 48 hours at room temperature. Copyright © 2008 SEFH. Published by Elsevier Espana. All rights reserved.

Demand and utilisation of labour analgesia service by Nigerian women.

PubMed

Imarengiaye, C O; Ande, A B A

2006-02-01

This study sought to determine the clinical correlates of the demand and utilisation of labour analgesia resources by Nigerian women in labour. All consenting women were interviewed on arrival at the Unit and while in labour. Biodata, options for relief of labour pain, request for analgesia, method of analgesia, VAS score and cervical score at time of request for analgesia were obtained. A total of 288 women in labour were studied. Of these, 108 (37.5%) patients were aware that the pain of labour can be relieved but only 26.0% had prenatal information on labour analgesia. However, 85.1% of the patients would want their pain of labour relieved. A total of 112 (38.9%) did receive analgesia during labour. Cervical dilatation of <4 cm at presentation to the Unit and nulliparity were likely factors for pain treatment during labour (p = 0.001, chi2 test). There is poor utilisation of labour analgesia services. Improved antenatal information on labour analgesia may boost the utilisation of these resources by Nigerian women in labour.

Comparison of Preoperative Oral Ketorolac on Anesthetic Efficacy of Inferior Alveolar Nerve Block and Buccal and Lingual Infiltration with Articaine and Lidocaine in Patients with Irreversible Pulpitis: A Prospective, Randomized, Controlled, Double-blind Study.

PubMed

Yadav, Meetu; Grewal, Mandeep S; Grewal, Stutee; Deshwal, Parul

2015-11-01

Irreversible pulpitis (IP) commonly results in decreased anesthetic efficacy of the inferior alveolar nerve block (IANB) for mandibular molar. It has been shown that supplementary buccal and/or lingual infiltration as well as premedication with ketorolac result in improved efficacy of the IANB. One hundred fifty emergency patients who had their lower first or/and second molar diagnosed with IP participated in the study. All patients were randomly divided into 2 major IANB groups: 1 group received 4% articaine with 1:100,000 epinephrine, and the other group received 2% lidocaine with 1:80,000 epinephrine. Each group was further divided into 3 subgroups of 25 each: (1) buccal and lingual infiltration with articaine and lidocaine, respectively; (2) preoperative oral medication of ketorolac; and (3) preoperative oral medication of ketorolac followed by buccal and lingual infiltration with articaine and lidocaine, respectively. Endodontic access was initiated 15 minutes after solution deposition, and all patients were required to have profound lip numbness. Success of the anesthetic was defined as none or mild pain on endodontic access and initial instrumentation. Statistical analysis was performed using multiple-comparison analysis of variance (Kruskal-Wallis) and t tests. Articaine IANB with infiltrations plus oral ketorolac premedication significantly increased the success rate to 76%. The success rate after the administration of an articaine IANB with infiltration injections was 64%, whereas with lidocaine it was 32% (P < .05). Premedication with ketorolac significantly increases the anesthetic efficacy of articaine IANB plus infiltration in mandibular molars with IP. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Successful practice of electroacupuncture analgesia in equine surgery.

PubMed

Sheta, Eldessouky; Ragab, Safwat; Farghali, Haithem; El-Sherif, Asmaa

2015-02-01

Electroacupuncture analgesia was used for surgery in horses and donkeys. A KWD-808 electrical stimulator was used to incrementally induce a dense, dispersed wave output at frequencies from 20 to 55 Hz, which was maintained at a frequency of 55 Hz, and to change the amplitude of the wave to the best grading number for the suggested operation in each animal. Induction of analgesia lasted for 20-30 minutes, and the effect of analgesia was maintained for 20-45 minutes depending on the type of surgery performed. The exhibited clinical signs, physical examination data, and the responses of all animals were used for evaluating the periods of analgesia. Although the majority of the cases (95%) had no response to strong surgical pain, they experienced significant increases in heart rates and respiratory rates during induction. The lack of pain, relaxed surgical procedures, reduced intraoperative bleeding, and improved healing without complications were all definite benefits of using electroacupuncture analgesia in surgery. Thus, this study has provided surgical evidence supporting the effectiveness of electroacupuncture analgesia, as well as confirming its reliability, in the field of equine anesthesia and surgery. Copyright © 2015. Published by Elsevier B.V.

Epidural labour analgesia using Bupivacaine and Clonidine

PubMed Central

Syal, K; Dogra, RK; Ohri, A; Chauhan, G; Goel, A

2011-01-01

Background: To compare the effects of addition of Clonidine (60 μg) to Epidural Bupivacaine (0.125%) for labour analgesia, with regard to duration of analgesia, duration of labour, ambulation, incidence of instrumentation and caesarean section, foetal outcome, patient satisfaction and side effects. Patients & Methods: On demand, epidural labour analgesia was given to 50 nulliparous healthy term parturients (cephalic presentation), divided in two groups randomly. Group I received bupivacaine (0.125%) alone, whereas Group II received bupivacaine (0.125%) along with Clonidine (60 μg). 10 ml of 0.125% bupivacaine was injected as first dose and further doses titrated with patient relief (Numerical Rating Scale <3). Top ups were given whenever Numerical Rating Scale went above 5. Results: There was statistically significant prolongation of duration of analgesia in Group II, with no difference in duration of labour, ambulation, incidence of instrumentation and caesarean section or foetal outcome. Also clonidine gave dose sparing effect to bupivacaine and there was better patient satisfaction without any significant side effects in Group II. Conclusion: Clonidine is a useful adjunct to bupivacaine for epidural labour analgesia and can be considered as alternative to opioids. PMID:21804714

Comparison of Transversus Abdominis Plane Infiltration with Liposomal Bupivacaine versus Continuous Epidural Analgesia versus Intravenous Opioid Analgesia.

PubMed

Ayad, Sabry; Babazade, Rovnat; Elsharkawy, Hesham; Nadar, Vinayak; Lokhande, Chetan; Makarova, Natalya; Khanna, Rashi; Sessler, Daniel I; Turan, Alparslan

2016-01-01

Epidural analgesia is considered the standard of care but cannot be provided to all patients Liposomal bupivacaine has been approved for field blocks such as transversus abdominis plane (TAP) blocks but has not been clinically compared against other modalities. In this retrospective propensity matched cohort study we thus tested the primary hypothesis that TAP infiltration are noninferior (not worse) to continuous epidural analgesia and superior (better) to intravenous opioid analgesia in patients recovering from major lower abdominal surgery. 318 patients were propensity matched on 18 potential factors among three groups (106 per group): 1) TAP infiltration with bupivacaine liposome; 2) continuous Epidural analgesia with plain bupivacaine; and; 3) intravenous patient-controlled analgesia (IV PCA). We claimed TAP noninferior (not worse) over Epidural if TAP was noninferior (not worse) on total morphine-equivalent opioid and time-weighted average pain score (10-point scale) within first 72 hours after surgery with noninferiority deltas of 1 (10-point scale) for pain and an increase less of 20% in the mean morphine equivalent opioid consumption. We claimed TAP or Epidural groups superior (better) over IV PCA if TAP or Epidural was superior on opioid consumption and at least noninferior on pain outcome. Multivariable linear regressions within the propensity-matched cohorts were used to model total morphine-equivalent opioid dose and time-weighted average pain score within first 72 hours after surgery; joint hypothesis framework was used for formal testing. TAP infiltration were noninferior to Epidural on both primary outcomes (p<0.001). TAP infiltration were noninferior to IV PCA on pain scores (p = 0.001) but we did not find superiority on opioid consumption (p = 0.37). We did not find noninferiority of Epidural over IV PCA on pain scores (P = 0.13) and nor did we find superiority on opioid consumption (P = 0.98). TAP infiltration with liposomal bupivacaine and

Comparing analgesia and μ-opioid receptor internalization produced by intrathecal enkephalin

PubMed Central

Chen, Wenling; Song, Bingbing; Lao, Lijun; Pérez, Orlando A.; Kim, Woojae; Marvizón, Juan Carlos G.

2007-01-01

Summary Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude μ-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is also precluded by peptidases, and whether it is mediated by MORs or δ-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu-enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol, whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at 1 nmol. Leu-enkephalin was ten times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-enkephalin. Unlike Leu-enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia. PMID:17845806

Labour analgesia: Recent advances

PubMed Central

Pandya, Sunil T

2010-01-01

Advances in the field of labour analgesia have tread a long journey from the days of ether and chloroform in 1847 to the present day practice of comprehensive programme of labour pain management using evidence-based medicine. Newer advances include introduction of newer techniques like combined spinal epidurals, low-dose epidurals facilitating ambulation, pharmacological advances like introduction of remifentanil for patient-controlled intravenous analgesia, introduction of newer local anaesthetics and adjuvants like ropivacaine, levobupivacaine, sufentanil, clonidine and neostigmine, use of inhalational agents like sevoflourane for patient-controlled inhalational analgesia using special vaporizers, all have revolutionized the practice of pain management in labouring parturients. Technological advances like use of ultrasound to localize epidural space in difficult cases minimizes failed epidurals and introduction of novel drug delivery modalities like patient-controlled epidural analgesia (PCEA) pumps and computer-integrated drug delivery pumps have improved the overall maternal satisfaction rate and have enabled us to customize a suitable analgesic regimen for each parturient. Recent randomized controlled trials and Cochrane studies have concluded that the association of epidurals with increased caesarean section and long-term backache remains only a myth. Studies have also shown that the newer, low-dose regimes do not have a statistically significant impact on the duration of labour and breast feeding and also that these reduce the instrumental delivery rates thus improving maternal and foetal safety. Advances in medical technology like use of ultrasound for localizing epidural space have helped the clinicians to minimize the failure rates, and many novel drug delivery modalities like PCEA and computer-integrated PCEA have contributed to the overall maternal satisfaction and safety. PMID:21189877

Three-times-daily subcutaneous unfractionated heparin and neuraxial anesthesia: a retrospective review of 928 cases.

PubMed

Davis, Jennifer J; Bankhead, Byron R; Eckman, Erik J; Wallace, Austin; Strunk, Joseph

2012-01-01

Subcutaneous (SC) unfractionated heparin (UFH) administered 3 times daily (TID) is widely used for venous thromboembolism prophylaxis in the perioperative period. There are no data in the literature regarding the incidence of adverse outcomes with neuraxial analgesia in the setting of this regimen. In this retrospective review, we report the incidence of untoward events related to anticoagulation with SC UFH TID in patients with indwelling epidural catheters. We queried the electronic hospital databases to identify patients receiving thoracic epidural analgesia in conjunction with 5000 U UFH SC TID from July 2008 to October 2010. In this group, we identified the diagnoses of neuraxial hematoma, deep vein thrombosis, or pulmonary embolism and examined measured blood coagulation parameters. In addition, we determined the percentage of patients receiving concomitant therapy with ketorolac. We identified 928 patients who received thoracic epidural analgesia in conjunction with 5000 U UFH SC TID during this period. There were no cases of neuraxial bleeding. Seven patients had a diagnosed deep vein thrombosis or pulmonary embolism. Thirty-four percent (315/928) of patients received ketorolac. The measured activated thromboplastin time was more than 40 seconds (35 seconds being the upper limit of normal) in 115 patients (12%). Given the rare incidence of neuraxial hematoma, statements regarding the appropriateness of epidural analgesia in the setting of TID SC UFH cannot be made from this limited sample size. At present, information regarding epidural hematoma in the setting of a TID SC UFH dosing regimen does not exist in the literature. Our study represents an initial step in the accumulation of data needed to prove or disprove the safety of this practice.

Comparing adductor canal block with local infiltration analgesia in total knee arthroplasty: A prospective, blinded and randomized clinical trial.

PubMed

Tong, Qian Jun; Lim, Yean Chin; Tham, Huae Min

2018-05-01

Total knee arthroplasty (TKA) is associated with significant pain post-operatively. Our hypothesis is that adductor canal block (ACB) would be superior to local infiltration analgesia (LIA) in terms of providing analgesia, while still preserving quadriceps strength and enabling early postoperative rehabilitation. A prospective, blinded and randomized clinical trial between LIA and ACB was conducted. Tertiary care urban hospital. 40 patients (ASA I to III) undergoing primary TKA under single-dose spinal anesthesia were prospectively randomized from January 2014 to October 2015. The LIA group received local infiltration of Ropivacaine 150 mg, Ketorolac 30 mg, Morphine 10 mg, and Adrenaline 200 mcg in a total volume of 75 mls, administered intraoperatively by the surgeon. The ACB group was given an ACB postoperatively by one of the study investigators at the end of surgery with 30 mls of 0.5% Ropivacaine. The primary outcome was total Morphine consumption in the first 24 h. Secondary outcomes included total Morphine consumption in the first 48 h, pain scores, quadriceps strength, the Timed Up and Go test (TUG), the 30 s Chair Stand Test (30s-CST) and length of hospital stay. The median (interquartile range) 24 h Morphine consumption was 6 mg (2.3-18.3) in the ACB group and 17.5 mg (12-24.3) in the LIA group, p = 0.004. The 48 h Morphine consumption was 14.5 mg (7.5-28.5) in the ACB group as compared to 24 mg (14-33.8) in the LIA group, p = 0.03. There were no statistically significant differences in the other secondary outcomes. ACB group had statistically significant reduced total Morphine consumption in the first 24 and 48 hours as compared to LIA group, with no statistically significant differences in functional outcomes of TKA patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Ketorolac-tobramycin combination vs fluorometholone-tobramycin combination in reducing inflammation following phacoemulsification cataract extraction with scleral tunnel incision.

PubMed

Guzey, M; Karadede, S; Dogan, Z; Satici, A

2000-01-01

The objective of this study was to compare the efficacy of ketorolac-tobramycin combination with fluorometholone-tobramycin combination in the control of ocular inflammation after endocapsular phacoemulsification cataract surgery with scleral tunnel incision. This was a prospective, randomized, investigator masked, 2-week, single-center study. Ocular examinations were carried out preoperatively and postoperatively on days 1 (baseline), 2, 3, 7, and 14. There were 60 patients (30 in each treatment group) undergoing uncomplicated cataract-lens implant surgery enrolled and randomized in the study. The baseline parameters were similar in the two study groups. At each visit comprehensive ocular examinations were performed and a 4-point (0 to 3) grading system was used to record findings of the burning/stinging sensation, blurred vision, ocular discomfort, conjunctival hyperemia, anterior chamber flare, and anterior chamber cells. There was no statistically significant difference between the treatment groups in the findings of the ocular inflammation at any of the postoperative visits. Both treatments were equally well tolerated. This study suggests that ketorolac may be an alternative to some corticosteroids (fluorometholone). It is generally accepted that fluorometholone is not as potent an anti-inflammatory as prednisolone the most commonly used steroid following cataract extraction.

Intrathecal Analgesia and Palliative Care: A Case Study

PubMed Central

Salins, Naveen S; Crawford, Gregory B

2010-01-01

Intrathecal analgesia is an interventional form of pain relief with definite advantages and multiple complications. Administration of intrathecal analgesia needs a good resource setting and expertise. Early complications of intrathecal analgesia can be very distressing and managing these complications will need a high degree of knowledge, technical expertise and level of experience. Pain control alone cannot be the marker of quality in palliative care. A holistic approach may need to be employed that is more person and family oriented. PMID:20859471

[Clinical study on painless labor under drugs combined with acupuncture analgesia].

PubMed

Jin, Y; Wu, L; Xia, Y

1996-01-01

To study the analgesia efficacy of drugs combined with acupuncture analgesia for painless labor, 462 normal pregnancy women were observed. During the latent phase in labor, several analgesia methods: acupuncture analgesia, analgesics, magnetotherapy and auricular acupressure, TENS combined with dihydroetorphine were used respectively. While the intrauterine pressure and the peripheral content of beta-EP were measured during labor, the experiments of SEPS were also performed on healthy adults to demonstrate the analgesia efficacy of those analgesia methods. The combination of drugs with acupuncture is an excellent method for painless labor without any complications and all the mothers and babies are safety. The effectiveness is 97.5%. The results demonstrate that the mechanism of analgesia efficacy should be regulated the incoordinate uterine action and improve the hypertonic status of uterus, but also can decrease the pain threshold and elevate the tolerance of uterine contractions during labor.

Assisting informed decision making for labour analgesia: a randomised controlled trial of a decision aid for labour analgesia versus a pamphlet.

PubMed

Raynes-Greenow, Camille H; Nassar, Natasha; Torvaldsen, Siranda; Trevena, Lyndal; Roberts, Christine L

2010-04-08

Most women use some method of pain relief during labour. There is extensive research evidence available of pharmacological pain relief during labour; however this evidence is not readily available to pregnant women. Decision aids are tools that present evidence based information and allow preference elicitation. We developed a labour analgesia decision aid. Using a RCT design women either received a decision aid or a pamphlet. Eligible women were primiparous, > or = 37 weeks, planning a vaginal birth of a single infant and had sufficient English to complete the trial materials. We used a combination of affective (anxiety, satisfaction and participation in decision-making) and behavioural outcomes (intention and analgesia use) to assess the impact of the decision aid, which were assessed before labour. 596 women were randomised (395 decision aid group, 201 pamphlet group). There were significant differences in knowledge scores between the decision aid group and the pamphlet group (mean difference 8.6, 95% CI 3.70, 13.40). There were no differences between decisional conflict scores (mean difference -0.99 (95% CI -3.07, 1.07), or anxiety (mean difference 0.3, 95% CI -2.15, 1.50). The decision aid group were significantly more likely to consider their care providers opinion (RR 1.28 95%CI 0.64, 0.95). There were no differences in analgesia use and poor follow through between antenatal analgesia intentions and use. This decision aid improves women's labour analgesia knowledge without increasing anxiety. Significantly, the decision aid group were more informed of labour analgesia options, and considered the opinion of their care providers more often when making their analgesia decisions, thus improving informed decision making. Trial registration no: ISRCTN52287533.

Does meperidine analgesia affect the incidence of obstetric lacerations at vaginal delivery?

PubMed

Mizrachi, Yossi; Leytes, Sophia; Levy, Michal; Ginath, Shimon; Bar, Jacob; Ezri, Tiberiu; Kovo, Michal

2018-03-01

To study whether meperidine analgesia affects the incidence of obstetric lacerations at normal vaginal deliveries. A retrospective cohort study of all women with term vertex singleton pregnancies, who underwent normal vaginal deliveries, in a single tertiary hospital, between 2011 and 2015, was performed. The incidence of various obstetric lacerations was compared between deliveries with meperidine analgesia and deliveries with no analgesia. Deliveries with epidural analgesia and instrumental deliveries were excluded. An intravenous infusion of 75 mg of meperidine was administered together with 25 mg of promethazine. A multivariate logistic regression analysis was performed to assess the association between meperidine analgesia and obstetric lacerations, after controlling for confounders. Overall, 5227 (91.8%) deliveries with no analgesia and 466 (8.1%) deliveries with meperidine analgesia were included. Meperidine analgesia was associated with a decreased risk of first- and second-degree perineal lacerations (adjusted OR = 0.63, 95% CI = 0.49-0.81), and a decreased risk of any suturing (adjusted OR = 0.73, 95% CI = 0.59-0.91), after controlling for confounders. Meperidine analgesia did not affect the risk of severe perineal lacerations or episiotomies. Meperidine analgesia may have a protective effect against first- and second-degree perineal lacerations.

Epidural analgesia practices for labour: results of a 2005 national survey in Ireland.

PubMed

Fanning, Rebecca A; Briggs, Liam P; Carey, Michael F

2009-03-01

The last 25 years have seen changes in the management of epidural analgesia for labour, including the advent of low-dose epidural analgesia, the development of new local anaesthetic agents, various regimes for maintaining epidural analgesia and the practice of combined spinal-epidural analgesia. We conducted a survey of Irish obstetric anaesthetists to obtain information regarding the conduct and management of obstetric epidural analgesia in Ireland in 2005. The specific objective of this survey was to discover whether new developments in obstetric anaesthesia have been incorporated into clinical practice. A postal survey was sent to all anaesthetists with a clinical commitment for obstetric anaesthesia in the sites approved for training by the College of Anaesthetists, Ireland. Fifty-three per cent of anaesthetists surveyed responded. The majority of anaesthetists (98%) use low-dose epidural analgesia for the maintenance of analgesia. Only 11% use it for test-dosing and 32% for the induction of analgesia. The combined spinal-epidural analgesia method is used by 49%, but two-thirds of those who use it perform fewer than five per month. Patient-controlled epidural analgesia was in use at only one site. It appears that Irish obstetric anaesthetists have adopted the low-dose epidural analgesia trend for the maintenance of labour analgesia. This practice is not as widespread, however, for test dosing, the induction of analgesia dose or in the administration of intermittent epidural boluses to maintain analgesia when higher concentrations are used. Since its introduction in 2000, levobupivacaine has become the most popular local anaesthetic agent.

Electroacupuncture analgesia in a rabbit ovariohysterectomy.

PubMed

Parmen, Valentin

2014-02-01

This study investigated the effectiveness of electroacupuncture analgesia (EAA) at local and paravertebral acupoints for a rabbit undergoing an ovariohysterectomy. Twelve clinically healthy New Zealand white rabbits were chosen and divided into two groups: the control group (5 rabbits) and the experimental group (7 rabbits). A neuroleptanalgesic (ketamine + xylazine) was administered to the control group (NLA group); the experimental group received EAA treatment (EAA group). The EAA treatment includes one acupuncture formula for local stimulation at the incision site and systemic stimulation. Results of clinical research have shown postoperative analgesia using EAA treatment to be superior to that using NLA. The average postoperative recovery time was 5.2 times longer in the NLA group than in the EAA group. Because consciousness was maintained, EAA presented an advantage in thermoregulation. Animals administered NLA had prolonged thermal homeostasis because of neurovegetative disconnection. For the EAA group, the operative times were characterized as excellent (28%, p = 0.28) or good (72%, p = 0.72). Local stimulation at the incision site provided excellent analgesia of the abdominal wall (100%). In conclusion, EA can provide general analgesia with a considerable analgesic effect for a rabbit undergoing an ovariohysterectomy, resulting in a short postoperative recovery time. Copyright © 2014. Published by Elsevier B.V.

Is epidural analgesia during labor related to retained placenta?

PubMed

Sarit, Avraham; Sokolov, Amit; Many, Ariel

2016-05-01

To explore the influence of epidural analgesia on the course of the third stage of labor and on the incidence of the complete retained placenta as well as retained parts of the placenta. This is a population-based cohort study in a tertiary medical center. We collected data from all 4227 spontaneous singleton vaginal deliveries during 6 months and compared the incidence of retained placenta in deliveries with epidural analgesia with those without analgesia. Multivariable logistic regression was used to control for possible confounders. More than two-thirds of the women (69.25%) used epidural analgesia during their delivery. A need for intervention due to placental disorder during the third stage of labor was noted in 4.2% of all deliveries. Epidural analgesia appeared to be significantly (P=0.028) related to placental disorders compared with no analgesia: 4.8% vs. 3%, respectively. Deliveries with manual interventions during the third stage, for either complete retained placenta or suspected retained parts of the placenta, were associated with the use of epidural analgesia (P=0.008), oxytocin (P=0.002) and older age at delivery (P=0.000), but when including all factors in a multivariable analysis, using a stepwise logistic regression, the factors that were independently associated with interventions for placental disruption during the third stage of delivery were previous cesarean section, oxytocin use and, marginally, older age. Complete retained placenta and retained parts of the placenta share the same risk factors. Epidural analgesia does not directly influence the incidence of complete retained placenta or retained parts, though clinically linked through increased oxytocin use. The factors that were independently associated with interventions for placental disruption during the third stage of delivery were previous cesarean section, oxytocin use and older age.

Epidural analgesia in labour and risk of caesarean delivery.

PubMed

Bannister-Tyrrell, Melanie; Ford, Jane B; Morris, Jonathan M; Roberts, Christine L

2014-09-01

A Cochrane Systematic Review of randomised controlled trials of epidural analgesia compared with other or no analgesia in labour reported no overall increased risk of caesarean delivery. However, many trials were affected by substantial non-compliance, and there are concerns about the external validity of some trials for contemporary maternity populations. We aimed to explore the association between epidural analgesia in labour and caesarean delivery in clinical practice and compare with findings from randomised controlled trials. Population-based cohort of pregnant women (n = 210 708) without major obstetrical complications who delivered a singleton live infant in hospitals in New South Wales, Australia, 2007-10. Data were obtained from linked, validated population-based data collections. Propensity score matching was used to examine the association between epidural analgesia in labour and caesarean delivery. Epidural analgesia in labour was used by a third (31.5%, n = 66 317) of the women, and 9.8% (n = 20 531) had a caesarean delivery. Epidural analgesia in labour was associated with increased risk of caesarean delivery {risk ratio [RR] 2.5, [95% confidence interval (CI) 2.5, 2.6]}. The association with epidural analgesia in labour was higher for caesarean delivery for failure to progress {RR 3.0, [95% CI 2.9, 3.0]} than for caesarean delivery for fetal distress {RR 1.9, [95% CI 1.8, 2.0]}. Epidural analgesia in labour is associated with caesarean delivery in a large maternity population. Population-based studies contribute important data about obstetrical care, when research settings and participants may not represent the clinical settings or broader population in which obstetrical interventions in labour are applied. © 2014 John Wiley & Sons Ltd.

Analgesia Following Major Gynecological Laparoscopic Surgery - PCA versus Intermittent Intramuscular Injection

PubMed Central

Lam, Alan M.; Carlton, Mark A.; Cario, Gregory M.; McBride, Lindsay

1998-01-01

Background and Objectives: To compare the use of patient-controlled analgesia to intermittent intramuscular injections of morphine following major gynecological laparoscopic procedures in order to assess differences in level of pain, sedation, episodes of nausea and/or vomiting, hospitalization time and patient satisfaction with their postoperative analgesia. Methods: Seventy-two patients undergoing major gynecological laparoscopic surgery were randomized to receive either postoperative analgesia via intermittent intramuscular injection of morphine (Group 1) or patient controlled analgesia (PCA - Group 2). All patients received anesthesia via a standardized protocol. Postoperative pain levels were recorded via a 10 cm visual analogue scale, and sedation scores were recorded on a standard PCA form. Episodes of nausea and vomiting were also recorded on the same form. Results: There were no statistically significant differences between intramuscular analgesia and PCA for any of the factors studied. Most significantly it was found that most patients ceased to require either form of parenteral analgesia within 24 hours of their procedure, regardless of the operating time. Conclusion: It is important for the surgeon to be aware of the effects of postoperative analgesia on his or her patients' level of satisfaction. We do not recommend the use of PCA analgesia following major laparoscopic gynecological surgery. PMID:9876706

Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions.

PubMed

Wakai, Abel; Lawrenson, John G; Lawrenson, Annali L; Wang, Yongjun; Brown, Michael D; Quirke, Michael; Ghandour, Omar; McCormick, Ryan; Walsh, Cathal D; Amayem, Ahmed; Lang, Eddy; Harrison, Nick

2017-05-18

, France and Portugal. These studies compared five types of topical NSAIDs (0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac) to control (consisting of standard care and in four studies used placebo eye drops). Overall, the studies were at an unclear or high risk of bias (particularly selection and reporting bias). None of the included studies reported the primary outcome measures of this review, namely participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials, that included data on 481 participants receiving NSAIDs or control (placebo/standard care), reported on the use of 'rescue' analgesia at 24 hours as a proxy measure of pain control. Topical NSAIDs were associated with a reduction in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4 out of 10 people in the control group used rescue analgesia at 24 hours. No data were available on the use of analgesia at 48 or 72 hours.One trial (28 participants) reported on the proportion of abrasions healed after 24 and 48 hours. These outcomes were similar in both arms of the trial. (at 24 hours RR 1.00 (0.81 to 1.23); at 48 hours RR 1.00 (0.88 to 1.14); low-certainty evidence). In the control group nine out of 10 abrasions were healed within 24 hours and all were healed by 48 hours. Complications of corneal abrasions were reported in 6 studies (609 participants) and were infrequently reported (4 complications, 1 in NSAID groups (recurrent corneal erosion) and 3 in control groups (2 recurrent corneal erosions and 1 corneal abscess), very low-certainty evidence). Possible drug-related adverse events (AEs) were reported in two trials (163 participants), with the number of adverse events low (4 AEs, 3 in NSAID group, including discomfort/photophobia on instillation, conjunctival hyperaemia and urticaria, and 1 in the control group, corneal abscess

Epidural analgesia versus intravenous patient-controlled analgesia following minimally invasive pectus excavatum repair: a systematic review and meta-analysis

PubMed Central

Stroud, Andrea M.; Tulanont, Darena D.; Coates, Thomasena E.; Goodney, Philip P.; Croitoru, Daniel P.

2017-01-01

Background/Purpose The minimally invasive pectus excavatum repair (MIPER) is a painful procedure. The ideal approach to postoperative analgesia is debated. We performed a systematic review and meta-analysis to assess the efficacy and safety of epidural analgesia compared to intravenous Patient Controlled Analgesia (PCA) following MIPER. Methods We searched MEDLINE (1946–2012) and the Cochrane Library (inception–2012) for randomized controlled trials (RCT) and cohort studies comparing epidural analgesia to PCA for postoperative pain management in children following MIPER. We calculated weighted mean differences (WMD) for numeric pain scores and summarized secondary outcomes qualitatively. Results Of 699 studies, 3 RCTs and 3 retrospective cohorts met inclusion criteria. Compared to PCA, mean pain scores were modestly lower with epidural immediately (WMD −1.04, 95% CI −2.11 to 0.03, p = 0.06), 12 hours (WMD −1.12; 95% CI −1.61 to −0.62, p < 0.001), 24 hours (WMD −0.51, 95%CI −1.05 to 0.02, p = 0.06), and 48 hours (WMD −0.85, 95% CI −1.62 to −0.07, p = 0.03) after surgery. We found no statistically significant differences between secondary outcomes. Conclusions Epidural analgesia may provide superior pain control but was comparable with PCA for secondary outcomes. Better designed studies are needed. Currently the analgesic technique should be based on patient preference and institutional resources. PMID:24851774

Expectant fathers' experience during labor with or without epidural analgesia.

PubMed

Capogna, G; Camorcia, M; Stirparo, S

2007-04-01

For men the worst aspect of childbirth is witnessing their partner in pain. The aim of this study was to investigate fathers' attitudes towards labor and delivery with and without epidural analgesia. The study was performed using a questionnaire that included yes/no, multiple choice or 6-point ordinal scale answers. Expectant fathers whose partners were nullipara between 36 and 38 weeks of gestation were recruited and the questionnaires were administered on the day after the birth. To investigate paternal anxiety during labor, the State part of the State-Trait Anxiety Inventory was used. The questionnaire was completed by 243 fathers. Sixty percent (145) of the parturients received epidural analgesia and 40% (98) did not. Paternal characteristics were comparable. Fathers whose partners did not receive epidural analgesia felt their presence as troublesome and unnecessary (P<0.001). The presence of maternal epidural analgesia increased threefold paternal feelings of helpfulness and was associated with a greater involvement (P<0.001) and less anxiety and stress (P<0.001). Median (range) State-Trait Anxiety Inventory score was respectively 75 (50-80) and 30 (20-60) in fathers whose partners did not or did receive epidural analgesia (P<0.0001). Maternal analgesia greatly increased paternal satisfaction (P<0.0001). Epidural analgesia reduces paternal anxiety and stress and increases paternal involvement, participation and satisfaction with the experience of childbirth.

Posterior paramedian subrhomboidal analgesia versus thoracic epidural analgesia for pain control in patients with multiple rib fractures.

PubMed

Shelley, Casey L; Berry, Stepheny; Howard, James; De Ruyter, Martin; Thepthepha, Melissa; Nazir, Niaman; McDonald, Tracy; Dalton, Annemarie; Moncure, Michael

2016-09-01

Rib fractures are common in trauma admissions and are associated with an increased risk of pulmonary complications, intensive care unit admissions, and mortality. Providing adequate pain control in patients with multiple rib fractures decreases the risk of adverse events. Thoracic epidural analgesia is currently the preferred method for pain control. This study compared outcomes in patients with multiple acute rib fractures treated with posterior paramedian subrhomboidal (PoPS) analgesia versus thoracic epidural analgesia (TEA). This prospective study included 30 patients with three or more acute rib fractures admitted to a Level I trauma center. Thoracic epidural analgesia or PoPS catheters were placed, and local anesthesia was infused. Data were collected including patients' pain level, adjunct morphine equivalent use, adverse events, length of stay, lung volumes, and discharge disposition. Nonparametric tests were used and two-sided p < 0.05 were considered statistically significant. Nineteen (63%) of 30 patients received TEA and 11 (37%) of 30 patients received PoPS. Pain rating was lower in the PoPS group (2.5 vs. 5; p = 0.03) after initial placement. Overall, there was no other statistically significant difference in pain control or use of oral morphine adjuncts between the groups. Hypotension occurred in eight patients, 75% with TEA and only 25% with PoPS. No difference was found in adverse events, length of stay, lung volumes, or discharge disposition. In patients with rib fractures, PoPS analgesia may provide pain control equivalent to TEA while being less invasive and more readily placed by a variety of hospital staff. This pilot study is limited by its small sample size, and therefore additional studies are needed to prove equivalence of PoPS compared to TEA. Therapeutic study, level IV.

The Role of Multimodal Analgesia in Spine Surgery.

PubMed

Kurd, Mark F; Kreitz, Tyler; Schroeder, Gregory; Vaccaro, Alexander R

2017-04-01

Optimal postoperative pain control allows for faster recovery, reduced complications, and improved patient satisfaction. Historically, pain management after spine surgery relied heavily on opioid medications. Multimodal regimens were developed to reduce opioid consumption and associated adverse effects. Multimodal approaches used in orthopaedic surgery of the lower extremity, especially joint arthroplasty, have been well described and studies have shown reduced opioid consumption, improved pain and function, and decreased length of stay. A growing body of evidence supports multimodal analgesia in spine surgery. Methods include the use of preemptive analgesia, NSAIDs, the neuromodulatory agents gabapentin and pregabalin, acetaminophen, and extended-action local anesthesia. The development of a standard approach to multimodal analgesia in spine surgery requires extensive assessment of the literature. Because a substantial number of spine surgeries are performed annually, a standardized approach to multimodal analgesia may provide considerable benefits, particularly in the context of the increased emphasis on accountability within the healthcare system.

[Observation on analgesia effect of electroacupuncture during gynecologic outpatient operation].

PubMed

Wang, Xiao-Hui; Wu, Xue-Lei; Jin, Ping-Lin; Wang, Lu-Dong; Zhao, Zhi-En; Qin, Xue-Yu; Zhang, Zhi-Yan; Hu, Xue-Zhu; Cai, Zhen-Lin

2012-10-01

To verify the feasibility of electroacupuncture analgesia applied to gynecologic outpatient operation. Two hundred patients were randomly divided into an electroacupuncture analgesia group and an intravenous anesthesia group, 100 cases in each group. Operation types included artificial abortion, diagnostic curettage and remove of intrauterine divice. The electroacupuncture analgesia group was treated with electroacupuncture at bilateral Hegu (LI 4) and Neiguan (PC 6), and the routine gynecologic outpatient operation was performed under patients' waking state. The intravenous anesthesia group was treated with routine gynecologic outpatient operation after intravenous injection of fentanyl and propofol. The excellent rate and the effective rate of analgesia were 88.0% (88/100) and 100.0% (100/100) in the electroacupuncture analgesia group, and 94.0% (94/100) and 100.0% (100/100) in the intravenous anesthesia group, with no statistically significant differences between the two groups (all P > 0.05). There was no adverse reaction in the electroacupuncture anesthesia group, but 11 cases of adverse reactions in the intravenous anesthesia group. Electroacupuncture analgesia can effectively alleviate the pain during gynecologic outpatient operation and it is simple and safe without adverse reactions.

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.

Reduced anaesthetic requirements and postoperative analgesics in patients undergoing laparoscopic cholecystectomy: premedication with intravenous paracetamol versus ketorolac, a double blind and randomised clinical trial.

PubMed

Medina-Vera, A J; Novoa, L M

2017-02-01

To compare the effects of premedication with intravenous paracetamol versus ketorolac, in decreasing intraoperative anaesthetic and postoperative opioid analgesics requirements in patients undergoing laparoscopic cholecystectomy. An experimental, prospective, comparative, double blind, and randomised clinical trial was conducted to determine intraoperative opioid requirements, and pain and analgesic requirements in the postoperative period in 100 healthy patients undergoing laparoscopic cholecystectomy. They were randomised into 2 groups: Group 1: pre-medicated with paracetamol 1g, and Group 2: with ketorolac 30mg (both administered intravenously 30minutes prior to surgery). There were no statistically significant differences between groups as regards intraoperative remifentanil use (Group 1: 0.0739±0.016μg/kg/min, Group 2: 0.0741±0.018μg/kg/min). The number of patients in Group 2 that had values of VAS>4 points (22.4%) was lower than in Group 1 (28.6%), but with no statistically significant difference. Of the patients who needed postoperative opioid rescue, most required a single rescue and application of analgesics during hospitalisation, that prevailed between 3 and 12hours, without any significant differences between groups. No adverse effects were observed in the study sample. Paracetamol 1g IV given preoperatively decreased anaesthetic requirements and the need for postoperative analgesics similar to the preoperative administration of ketorolac 30mg IV. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Proinflammatory cytokines oppose opioid induced acute and chronic analgesia

PubMed Central

Hutchinson, Mark R.; Coats, Benjamen D.; Lewis, Susannah S.; Zhang, Yingning; Sprunger, David B.; Rezvani, Niloofar; Baker, Eric M.; Jekich, Brian M.; Wieseler, Julie L.; Somogyi, Andrew A.; Martin, David; Poole, Stephen; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.

2008-01-01

Spinal proinflammatory cytokines are powerful pain-enhancing signals that contribute to pain following peripheral nerve injury (neuropathic pain). Recently, one proinflammatory cytokine, interleukin-1, was also implicated in the loss of analgesia upon repeated morphine exposure (tolerance). In contrast to prior literature, we demonstrate that the action of several spinal proinflammatory cytokines oppose systemic and intrathecal opioid analgesia, causing reduced pain suppression. In vitro morphine exposure of lumbar dorsal spinal cord caused significant increases in proinflammatory cytokine and chemokine release. Opposition of analgesia by proinflammatory cytokines is rapid, occurring ≤5 minutes after intrathecal (perispinal) opioid administration. We document that opposition of analgesia by proinflammatory cytokines cannot be accounted for by an alteration in spinal morphine concentrations. The acute anti-analgesic effects of proinflammatory cytokines occur in a p38 mitogen-activated protein kinase and nitric oxide dependent fashion. Chronic intrathecal morphine or methadone significantly increased spinal glial activation (toll-like receptor 4 mRNA and protein) and the expression of multiple chemokines and cytokines, combined with development of analgesic tolerance and pain enhancement (hyperalgesia, allodynia). Statistical analysis demonstrated that a cluster of cytokines and chemokines was linked with pain-related behavioral changes. Moreover, blockade of spinal proinflammatory cytokines during a stringent morphine regimen previously associated with altered neuronal function also attenuated enhanced pain, supportive that proinflammatory cytokines are importantly involved in tolerance induced by such regimens. These data implicate multiple opioid-induced spinal proinflammatory cytokines in opposing both acute and chronic opioid analgesia, and provide a novel mechanism for the opposition of acute opioid analgesia. PMID:18599265

Comparison of Epidural Analgesia with Transversus Abdominis Plane Analgesia for Postoperative Pain Relief in Patients Undergoing Lower Abdominal Surgery: A Prospective Randomized Study.

PubMed

Iyer, Sadasivan Shankar; Bavishi, Harshit; Mohan, Chadalavada Venkataram; Kaur, Navdeep

2017-01-01

Anesthesiologists play an important role in postoperative pain management. For analgesia after lower abdominal surgery, epidural analgesia and ultrasound-guided transversus abdominis plane (TAP) block are suitable options. The study aims to compare the analgesic efficacy of both techniques. Seventy-two patients undergoing lower abdominal surgery under spinal anesthesia were randomized to postoperatively receive lumbar epidural catheter (Group E) or ultrasound-guided TAP block (Group T) through intravenous cannulas placed bilaterally. Group E received 10 ml 0.125% bupivacaine stat and 10 ml 8 th hourly for 48 h. Group T received 20 ml 0.125% bupivacaine bilaterally stat and 20 ml bilaterally 8 th hourly for 48 h. Pain at rest and on coughing, total paracetamol and tramadol consumption were recorded. Analgesia at rest was comparable between the groups in the first 16 h. At 24 and 48 h, Group E had significantly better analgesia at rest ( P = 0.001 and 0.004 respectively). Patients in Group E had significantly higher number of patients with nil or mild pain on coughing at all times. Paracetamol consumption was comparable in both groups, but tramadol consumption was significantly higher in Group T at the end of 48 h ( P = 0.001). For lower abdominal surgeries, analgesia provided by intermittent boluses of 0.125% is comparable for first 16 h between epidural and TAP catheters. However, the quality of analgesia provided by the epidural catheter is superior to that provided by TAP catheters beyond that both at rest and on coughing with reduced opioid consumption.

Comparison of Epidural Analgesia with Transversus Abdominis Plane Analgesia for Postoperative Pain Relief in Patients Undergoing Lower Abdominal Surgery: A Prospective Randomized Study

PubMed Central

Iyer, Sadasivan Shankar; Bavishi, Harshit; Mohan, Chadalavada Venkataram; Kaur, Navdeep

2017-01-01

Background: Anesthesiologists play an important role in postoperative pain management. For analgesia after lower abdominal surgery, epidural analgesia and ultrasound-guided transversus abdominis plane (TAP) block are suitable options. The study aims to compare the analgesic efficacy of both techniques. Materials and Methods: Seventy-two patients undergoing lower abdominal surgery under spinal anesthesia were randomized to postoperatively receive lumbar epidural catheter (Group E) or ultrasound-guided TAP block (Group T) through intravenous cannulas placed bilaterally. Group E received 10 ml 0.125% bupivacaine stat and 10 ml 8th hourly for 48 h. Group T received 20 ml 0.125% bupivacaine bilaterally stat and 20 ml bilaterally 8th hourly for 48 h. Pain at rest and on coughing, total paracetamol and tramadol consumption were recorded. Results: Analgesia at rest was comparable between the groups in the first 16 h. At 24 and 48 h, Group E had significantly better analgesia at rest (P = 0.001 and 0.004 respectively). Patients in Group E had significantly higher number of patients with nil or mild pain on coughing at all times. Paracetamol consumption was comparable in both groups, but tramadol consumption was significantly higher in Group T at the end of 48 h (P = 0.001). Conclusion: For lower abdominal surgeries, analgesia provided by intermittent boluses of 0.125% is comparable for first 16 h between epidural and TAP catheters. However, the quality of analgesia provided by the epidural catheter is superior to that provided by TAP catheters beyond that both at rest and on coughing with reduced opioid consumption. PMID:28928569

Nefopam and Ketamine Comparably Enhance Postoperative Analgesia

PubMed Central

Kapfer, Barbara; Alfonsi, Pascal; Guignard, Bruno; Sessler, Daniel I.; Chauvin, Marcel

2005-01-01

Summary Opioids alone sometimes provide insufficient postoperative analgesia. Co-administration of drugs may reduce opioid use and to improve opioid efficacy. We therefore tested the hypothesis that administration of ketamine or nefopam, to postoperative patients with pain only partly alleviated by morphine, limits the amount of subsequent opioid necessary to produce adequate analgesia. Patients (n=77) recovering from major surgery were given up to 9 mg intravenous morphine. Those still suffering from pain were randomly assigned to blinded administration of: 1) isotonic saline (Control, n=21); 2) ketamine 10 mg (Ketamine, n=22); or, 3) nefopam 20 mg (Nefopam, n=22). Three-mg morphine boluses were subsequently given at 5-minute intervals until adequate analgesia was obtained, or 60 minutes elapsed after the beginning of the study drug administration, or ventilation became insufficient (respiratory rate < 10 breath/minute or saturation by pulse oxymetery < 95%). Supplemental morphine (i.e., after test drug administration) requirements were significantly greater in the Control group [17 ± 10 (SD) mg] than in the Nefopam (10 ± 5 mg, P < 0.005) or Ketamine (9 ± 5 mg, P < 0.001) groups. Morphine titration was successful in all Ketamine and Nefopam patients, but failed in four Control patients (two from respiratory toxicity and two from persistent pain). Tachycardia and profuse sweating were more frequent in patients given nefopam and sedation was greater with ketamine; however, the incidence of other potential complications did not differ between groups. Implications We conclude that ketamine 10 mg and nefopam 20 mg comparably potentiate opioid analgesia, each reducing opioid need by approximately 40%. Ketamine administration was associated with sedation whereas nefopam produced tachycardia and sweating. However, none of the side effects was serious. Either drug can thus be used to potentiate opioid analgesia. PMID:15616073

A history of intraspinal analgesia, a small and personal journey.

PubMed

Krames, Elliot S

2012-01-01

There is a large and robust literature on the spinal use of opioids and non-opioids alike, but unless one is my age and older, very few persons know how we got here. This small history offering tells us how we got to where we are today regarding the science, clinical uses, and management of intraspinal analgesia. I have reviewed the literature bases of Google Scholar and the National Library of Medicine using the key words: history, opium, spinal analgesia, spinal morphine, intrathecal (IT), opioid receptors, endogenous opioids, IT delivery of opioids, and IT side-effects/complications. In this personal review of the history of intraspinal analgesia, I relate my own early and later experiences of the science and clinical uses of intraspinal morphine, other opioids, and non-opioids alike to a historical context. This review outlines a rather small history of opium, the historical use of opium and its various compounds, and the search for and answer to the question, "why was the poppy created for wondrous medicinal uses for mankind?" This search led to the discovery of endogenous opioid like chemicals, the discovery of opiate receptors for these endogenous opioids, the first uses of intraspinal opioids in animal models and man, and, finally, our understanding of the appropriate and inappropriate clinical uses of intraspinal analgesia. Within this paper, I acknowledge the works of my colleagues and the "heroes" who have laid the foundation for our understanding of intraspinal analgesia. The history of the use of intraspinal analgesia is rich and guides us to advance the science and clinical use of intraspinal analgesia without reinventing the wheel. © 2012 International Neuromodulation Society.

Safety and risks of nitrous oxide labor analgesia: a review.

PubMed

Rooks, Judith P

2011-01-01

This review of the safety and risks of nitrous oxide (N(2) O) labor analgesia presents results of a search for evidence of its effects on labor, the mother, the fetus, the neonate, breastfeeding, and maternal-infant bonding. Concerns about apoptotic damage to the brains of immature mammals exposed to high doses of N(2) O during late gestation, possible cardiovascular risks from hyperhomocysteinemia caused by N(2) O, a hypothesis that children exposed to N(2) O during birth are more likely to become addicted to amphetamine drugs as adults, and possible occupational risks for those who provide care to women using N(2) O/O(2) labor analgesia are discussed in detail. Research relevant to the 4 special concerns and to the effects of N(2) O analgesia on labor and the mother-child dyad were examined in depth. Three recent reviews of the biologic, toxicologic, anesthetic, analgesic, and anxiolytic effects of N(2) O; 3 reviews of the safety of 50% N(2) O/oxygen (O(2) ) in providing analgesia in a variety of health care settings; and a 2002 systematic review of N(2) O/O(2) labor analgesia were used. Nitrous oxide analgesia is safe for mothers, neonates, and those who care for women during childbirth if the N(2) O is delivered as a 50% blend with O(2) , is self-administered, and good occupational hygiene is practiced. Because of the strong correlation between dose and harm from exposure to N(2) O, concerns based on effects of long exposure to high anesthetic-level doses of N(2) O have only tenuous, hypothetical pertinence to the safety of N(2) O/O(2) labor analgesia. Nitrous oxide labor analgesia is safe for the mother, fetus, and neonate and can be made safe for caregivers. It is simple to administer, does not interfere with the release and function of endogenous oxytocin, and has no adverse effects on the normal physiology and progress of labor. © 2011 by the American College of Nurse-Midwives.

[Comparison of two different methods of analgesia. Postoperative course after colorectal cancer surgery].

PubMed

Rimaitis, Kestutis; Marchertiene, Irena; Pavalkis, Dainius

2003-01-01

The purpose of our study is to compare two methods of postoperative analgesia in colorectal cancer patients after resectional operations, and to evaluate advantages and limitations of each method on the postoperative course of these patients. One hundred patients scheduled to undergo elective colorectal cancer surgery were randomized into two groups; after general anesthesia, one group received epidural analgesia (n=50) and the second one - intramuscular pethidine analgesia (n=50). Visual analogue scale at rest and on coughing was used to compare intensiveness of pain between the two groups during the day of surgery and first three postoperative days. Patients' mood and self-satisfaction were evaluated using self-assessment manikin scale. Side effects of both analgesia techniques were registered. All complications and postoperative hospital stay were also evaluated. Visual analogue scale pain scores at rest and on coughing were significantly better in epidural analgesia group as compared to systemic intramuscular pethidine analgesia group (p<0.05). Additional analgesics were needed for 10 (20%) and 28 (56%) patients respectively to keep visual analogue scale pain scores below 5. Adverse effects such as profound sedation, nausea and vomiting were more frequent in systemic intramuscular pethidine group, but pruritus - very uncommon to compare with epidural analgesia group (p<0.05). There were no significant differences between the two groups in respect to complications and postoperative hospital stay. Epidural analgesia has demonstrated significantly better effectiveness than intramuscular pethidine analgesia after colorectal cancer surgery with fewer adverse events. Self-assessment manikin scores showed better self-satisfaction in patients of epidural analgesia group as compared to patients in systemic pethidine group.

The Effects of Meperidine Analgesia during Labor on Fetal Heart Rate

PubMed Central

Sekhavat, Leila; Behdad, Shecoofah

2009-01-01

To estimate the effects of intramuscular meperidine analgesia on fetal heart rate (FHR) patterns compared with placebo. In a prospective randomized study, 150 healthy women with singleton term pregnancy requesting analgesia during active labor were planned to receive either intramuscular meperidin 50 mg (meperidin group) or normal saline (control group) when they requested analgesia. Fetal heart rate patterns occurring within 40 minutes of initiation of labor analgesia were retrospectively read by maternal fetal medicine specialist who was blind to type of labor analgesia. Meperidine, compared with placebo, was associated with statistically significantly less beat to beat variability (absent or less than 5 beats per minute) (28% versus 5% of fetuses, P<0.05), lower proportion of accelerations (37.3% versus 17.3% P<0.05) and of the FHR. Also FHR deceleration was significantly more than control group (25.5% versus 4%, P<0.05). Meperidine has deleterious effects on FHR. PMID:23675116

Oral oxycodone offers equivalent analgesia to intravenous patient-controlled analgesia after total hip replacement: a randomized, single-centre, non-blinded, non-inferiority study.

PubMed

Rothwell, M P; Pearson, D; Hunter, J D; Mitchell, P A; Graham-Woollard, T; Goodwin, L; Dunn, G

2011-06-01

To determine if oral oxycodone (OOXY) could provide equivalent postoperative analgesia and a similar side-effect profile to i.v. patient-controlled morphine in patients undergoing elective primary total hip replacement (THR) under spinal anaesthesia. We studied 110 consecutive patients aged 60-85 yr. After operation, patients were randomly allocated to receive either oral controlled- and immediate-release OOXY or i.v. patient-controlled analgesia (IVPCA) with morphine. Both groups received regular co-analgesia and antiemetics. The primary outcome measures were: (i) postoperative pain at rest and movement and (ii) nausea score recorded 12 hourly. The secondary outcome measures were: (i) time to first mobilization, (ii) total amount of opioid consumed, (iii) number of additional antiemetic doses, and (iv) time to analgesic discontinuation. There were no statistically significant differences in the primary outcome measures of pain at rest and movement (P>0.05, 95% confidence intervals -0.41, +0.96) or nausea score (P>0.5). The secondary outcome measures showed no significant difference in the total amount of opioid consumed (102 vs 63 mg; P>0.05) or time to mobilization (24.45 vs 26.6 h, P=0.2). The number of antiemetic doses required in the first 24 h was significantly lower in the OOXY group (1.1 vs 1.4, P<0.05). The time to analgesic discontinuation was significantly shorter in the OOXY group (50.5 vs 56.6 h, P<0.05). Oral analgesia with OOXY was approximately GBP 10 less expensive per patient than IVPCA. Oral analgesia with OOXY after THR offers non-inferior analgesia to IVPCA and may offer some logistical and cost advantages.

Duration of Analgesia Induced by Acupuncture-Like TENS on Experimental Heat Pain.

PubMed

Tousignant-Laflamme, Yannick; Brochu, Marilyne; Dupuis-Michaud, Cynthia; Pagé, Catherine; Popovic, Draga; Simard, Marie-Eve

2013-01-01

Background. Acupuncture-like TENS (AL-TENS) is a treatment modality that can be used to temporarily reduce pain. However, there is no clear data in the literature regarding the specific duration of analgesia induced by AL-TENS. Objectives. To describe and quantify the duration and magnitude of AL-TENS analgesia on experimental heat pain in healthy subjects and verify if the duration or magnitude of analgesia induced by the AL-TENS was influenced by the duration of the application of the AL-TENS (15 versus 30 minutes). Methods. A repeated-measures, intrasubject randomized experimental design was used, where each participant was his/her own control. 22 healthy volunteers underwent heat pain stimulations with a contact thermode before (pretest) and after (posttest) AL-TENS application (15 and 30 minutes). Outcome measures included subjective pain during AL-TENS, duration, and magnitude of AL-TENS-induced analgesia. Results. Survival analysis showed that the median duration of AL-TENS analgesia was 10 minutes following the application of either 15 or 30 minutes of AL-TENS. The magnitude of analgesia following either application was comparable at all points in time (P values > 0.05) and ranged between -20% and -36% pain reduction. Conclusion. Only half of the participants still had heat-pain analgesia induced by the AL-TENS at 15 minutes postapplication.

Naltrexone-sensitive analgesia following exposure of mice to 2450-MHz radiofrequency radiation (RFR)

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

Maillefer, R.H.; Quock, R.M.

1991-03-11

This study was conducted to determine whether exposure to RFR might induce sufficient thermal stress to activate endogenous opioid mechanisms and induce analgesia. Male Swiss Webster mice, 20-25 g, were exposed to 10, 15 or 20 mV/cm{sup 2} RFR in a 2,450-MHz waveguide system for 10 min, then tested in the abdominal constriction paradigm. Specific absorption rates (SAR) were 23.7 W/kg at 10 mW/cm{sup 2}, 34.6 W/kg at 15 mW/cm{sup 2} and 45.5 W/kg at 20 mW/cm{sup 2}. Confinement in the exposure chamber alone did not appreciably alter body temperature but did appear to induce a stress-associated analgesia that wasmore » insensitive to the opioid receptor blocker naltrexone. Exposure of confined mice to RFR elevated body temperature and further increased analgesia in SAR-dependent manner. The high-SAR RFR-induced analgesia, but not the hyperthermia, was reduced by naltrexone. These findings suggest that (1) RFR produces SAR-dependent hyperthermia and analgesia and (2) RFR-induced analgesia is mediated by opioid mechanisms while confinement-induced analgesia involves non-opioid mechanisms.« less

Labour epidural analgesia in Poland in 2009 - a survey.

PubMed

Furmanik, Jacek

2013-01-01

Labour analgesia in most developed countries is funded by the state, available to every woman in labour, and plays an important role in the everyday activities of most anaesthetists. This paper presents the second part of an Obstetric Anaesthesia Survey which was conducted in 2009. The first part of the Survey, relating to anaesthesia for caesarean sections, was published in 2010. The author sent out 432 questionnaires containing questions about hospital size and location, staffing levels and numbers of deliveries per year. There were also questions regarding regional and other pain relief methods used in labour, ways of administration, drugs used and monitoring of patients. The response rate was 24%. Around 45% of responding hospitals had only 1-3 deliveries per year, which makes it difficult to provide separate obstetric anaesthetic cover. Only ten hospitals (11%) employed an anaesthetist for the labour ward. Epidural analgesia was used in 55% of hospitals but only 20% provided the service for 24 hours per day and free of charge. Entonox was used very occasionally, but the most common means of pain relief was pethidine injection. There were marked differences in the medication used for labour epidurals, with 18% of units using high concentrations of local anaesthetics which could result in motor block. Despite a lack of regulations in Polish law and a lack of proper training in 50% of units, midwives were looking after the patients with established labour epidural which could create medico-legal consequences. There was also a marked variation in the parameters monitored during labour analgesia. Epidural labour analgesia was offered for 24 hours per day and free of charge in only 20% of hospitals. Without public pressure it will be difficult to get more funding from the National Health Fund (NFZ) to enable other hospitals, especially those with small obstetric units, to introduce regional labour analgesia. Although the 2009 guidelines addressed most of the issues

Patient-controlled analgesia after coronary bypass: Remifentanil or sufentanil?

PubMed

Alavi, Seyed Mostafa; Ghoreishi, Seyed Mohammadmehran; Chitsazan, Mitra; Ghandi, Iman; Fard, Alireza Jahangiri; Hosseini, Seyed Saeed; Mahjoobifard, Maziar; Fani, Kamal

2014-07-01

adequate pain control after cardiac surgery is mandatory to reduce its remarkable morbidity. In this study, we aimed to compare the efficacy of patient-controlled analgesia with remifentanil or sufentanil for pain management after coronary artery bypass grafting. 249 patients who underwent coronary artery bypass were randomly assigned to receive patient-controlled analgesia with remifentanil or sufentanil during the first 24 h postoperatively. Pain intensity during patient-controlled analgesia was assessed using 4 different pain rating scales. patients given remifentanil had lower Visual Analog Scale scores at 24 h compared to those given sufentanil (p = 0.002). The Numeric Rating Scale at 24 h was also significantly lower in patients using remifentanil (p = 0.004). The Faces Pain Scale scores at 4, 18, and 24 h were significantly lower in patients using remifentanil compared to those using sufentanil (p = 0.045, 0.036, and 0.011, respectively). No significant differences between groups were seen in the pain intensity assessed by the Behavior Rating Scale at any time point during the first 24 h postoperatively. our study showed that both remifentanil and sufentanil patient-controlled analgesia can provide acceptable analgesia after coronary artery bypass. The difference between their efficacies was inconspicuous until 24 h postoperatively. Remifentanil seems to result in better pain relief at 24 h postoperatively. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Effect of premedication to provide analgesia as a supplement to inferior alveolar nerve block in patients with irreversible pulpitis.

PubMed

Lapidus, Daniel; Goldberg, Jack; Hobbs, Edward H; Ram, Saravanan; Clark, Glenn T; Enciso, Reyes

2016-06-01

The authors' objective was to determine whether scientific evidence supports the use of oral premedication to increase the efficacy of inferior alveolar nerve block (IANB) and to decrease endodontic treatment pain in patients with diagnosed irreversible pulpitis. The authors included randomized controlled trials that involved enteral premedication and 2% lidocaine IANB for adults with irreversible pulpitis compared with placebo. In particular, the authors reviewed studies comparing nonsteroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, acetaminophen, and corticosteroids with placebo. The authors searched the following electronic databases: the Cochrane Library, MEDLINE, and Web of Science. The authors analyzed 9 randomized controlled clinical trials. Patients who took the NSAIDs under study, including ibuprofen, ketorolac, diclofenac, indomethacin, and lornoxicam, 1 hour before endodontic treatment showed statistically significant improvement in the outcome of having "little or no pain" during endodontic treatment compared with patients who took a placebo 1 hour before endodontic treatment (risk ratio [RR], 1.989; 95% confidence interval [CI], 1.495-2.646; P < .001). Benzodiazepines were not as well represented in the literature, but the 2 included studies did not show a significant improvement in patients' having "little or no pain" during endodontic treatment over placebo (RR, 0.989; 95% CI, 0.677-1.444; P = .954). There is moderate evidence to support the use of oral NSAIDs-in particular, ibuprofen (600 milligrams)-1 hour before the administration of IANB local anesthetic (1.8-3.6 milliliters of 2% lidocaine) to provide additional analgesia to the patient. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

[Analgesia, sedation and relaxation in the child with mechanical ventilation].

PubMed

Valdivielso-Serna, A

2008-02-01

The basic concepts of sedation and analgesia and the tools to asses the level of sedation and analgesia are review. The different methods of sedation and the non pharmacological interventions are described. Sedatives, analgesics and muscle relaxants, their pharmacodynamics and pharmacokinetics in children, their indications in specific situations (intubation, pain control, sedation and neuromuscular blocking) are reviewed. The etiology of patient-ventilator asynchrony in ventilated children and how to treat it are analyzed, giving guides of how to adapt sedation to the level of mechanical ventilation therapy. Finally, general recommendations are given for the analgesia and sedation in mechanically ventilated children.

Ovariohysterectomy requires more post-operative analgesia than orchiectomy in dogs and cats.

PubMed

Quarterone, Carolina; Luna, Stelio Pacca Loureiro; Crosignani, Nadia; de Oliveira, Flávia Augusta; Lopes, Carlize; da Maia Lima, Alfredo Feio; de Araújo Aguiar, Antonio Jose

2017-11-01

The requirement for post-operative analgesia after ovariohysterectomy (OH) versus orchiectomy in dogs and cats was compared. Twelve male and 12 female cats and 12 male and 12 female dogs received meloxicam, 0.1 mg/kg body weight, PO, 2 h before surgery. Eleven female cats and 3 female dogs received rescue analgesia ( P = 0.002). No male of either species required rescue analgesia. The number of cats receiving rescue analgesia was greater in females than in males ( P < 0.0001). One should not rely solely on preoperative short-acting opioid and preemptive use of NSAIDs to control postoperative pain following OH, in dogs or cats. Postoperative pain after OH should be assessed for at least 2 h for cats and 4 h for dogs, using species-specific validated tools, to ensure proper postoperative pain diagnosis and management. Male dogs and cats subjected to orchiectomy required less postoperative analgesia intervention than female dogs and cats submitted to OH.

Methoxyflurane analgesia for burns dressings

PubMed Central

Packer, Kathleen J.

1972-01-01

The requirements for analgesia for burns dressings are discussed. Methoxyflurane has proved satisfactory in a clinical trial, and can be administered by one of two types of vaporizer. The possibility of nephrotoxicity due to methoxyflurane has not been eliminated. PMID:5024149

The Analgesia Nociception Index: a pilot study to evaluation of a new pain parameter during labor.

PubMed

Le Guen, M; Jeanne, M; Sievert, K; Al Moubarik, M; Chazot, T; Laloë, P A; Dreyfus, J F; Fischler, M

2012-04-01

Objective pain assessment that is not subject to influences from either cultural or comprehension issues is desirable. Analysis of heart rate variability has been proposed as a potential method. This pilot study aimed to assess the performance of the PhysioDoloris™ analgesia monitor which calculates an Analgesia Nociception Index derived from heart rate variability. It was compared with visual analogical pain scores. Forty-five parturients who requested epidural analgesia were recruited. Simultaneous couplets of pain scores and Analgesia Nociception Index values were recorded every 5 min regardless of the presence or absence of uterine contractions. The relationship between indices was characterized, and a cut-off value of Analgesia Nociception Index corresponding to a visual analogical score >30 (range 0-100) was used to determine the positive and negative predictive value of the Analgesia Nociception Index. There was a negative linear relationship between visual analogical pain scores and Analgesia Nociception Index values regardless of the presence of uterine contractions (regression coefficient ± SEM=-0.18 ± 0.032 for entire dataset). Uterine contraction significantly reduced the Analgesia Nociception Index (P<0.0001). Using a visual analogical pain score >30 to define a painful sensation, the lower 95% confidence limit for the Analgesia Nociception Index score was 49. The Analgesia Nociception Index has an inverse linear relationship with visual analogical pain scores. Further studies are necessary to confirm the results of this pilot study and to look at the influence of epidural analgesia on the Analgesia Nociception Index. Copyright © 2012 Elsevier Ltd. All rights reserved.

21 CFR 868.5160 - Gas machine for anesthesia or analgesia.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gas machine for anesthesia or analgesia. 868.5160... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5160 Gas machine for anesthesia or analgesia. (a) Gas machine for anesthesia—(1) Identification. A gas machine for anesthesia is a...

21 CFR 868.5160 - Gas machine for anesthesia or analgesia.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gas machine for anesthesia or analgesia. 868.5160... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5160 Gas machine for anesthesia or analgesia. (a) Gas machine for anesthesia—(1) Identification. A gas machine for anesthesia is a...

21 CFR 868.5160 - Gas machine for anesthesia or analgesia.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gas machine for anesthesia or analgesia. 868.5160... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5160 Gas machine for anesthesia or analgesia. (a) Gas machine for anesthesia—(1) Identification. A gas machine for anesthesia is a...

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

PubMed

Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

2016-05-04

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] μmol/kg) greater than dopamine (190 [181-203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pain Management After Outpatient Anterior Cruciate Ligament Reconstruction: A Systematic Review of Randomized Controlled Trials.

PubMed

Secrist, Eric S; Freedman, Kevin B; Ciccotti, Michael G; Mazur, Donald W; Hammoud, Sommer

2016-09-01

Effective pain management after anterior cruciate ligament (ACL) reconstruction improves patient satisfaction and function. To collect and evaluate the available evidence from randomized controlled trials (RCTs) on pain control after ACL reconstruction. Systematic review. A systematic literature review was performed using PubMed, Medline, Google Scholar, UpToDate, Cochrane Reviews, CINAHL, and Scopus following PRISMA guidelines (July 2014). Only RCTs comparing a method of postoperative pain control to another method or placebo were included. A total of 77 RCTs met inclusion criteria: 14 on regional nerve blocks, 21 on intra-articular injections, 4 on intramuscular/intravenous injections, 12 on multimodal regimens, 6 on oral medications, 10 on cryotherapy/compression, 6 on mobilization, and 5 on intraoperative techniques. Single-injection femoral nerve blocks provided superior analgesia to placebo for up to 24 hours postoperatively; however, this also resulted in a quadriceps motor deficit. Indwelling femoral catheters utilized for 2 days postoperatively provided superior analgesia to a single-injection femoral nerve block. Local anesthetic injections at the surgical wound site or intra-articularly provided equivalent analgesia to regional nerve blocks. Continuous-infusion catheters of a local anesthetic provided adequate pain relief but have been shown to cause chondrolysis. Cryotherapy improved analgesia compared to no cryotherapy in 4 trials, while in 4 trials, ice water and water at room temperature provided equivalent analgesic effects. Early weightbearing decreased pain compared to delayed weightbearing. Oral gabapentin given preoperatively and oral zolpidem given for the first week postoperatively each decreased opioid consumption as compared to placebo. Ibuprofen reduced pain compared to acetaminophen. Oral ketorolac reduced pain compared to hydrocodone-acetaminophen. Regional nerve blocks and intra-articular injections are both effective forms of analgesia

[Eutopic parturition: psychoprophylaxis or extradural analgesia. Influence on the endocrine response].

PubMed

Carrasco, M S; Iglesias, J; Freire, J; Martín, M L; Marín Santana, A; Cobo, I; García Rendón, A

1989-01-01

Prolactin, ACTH, cortisol and HGH levels have been studied on 30 pregnant women in three different periods: during the labour, at the delivery and 24 hours later. They were divided into 3 groups depending on the analgesia: I) no analgesia (n = 10); II) psychoprophylaxis (n = 10), and III) extradural analgesia (n = 10). Prolactin levels increased during delivery and 24 hours later. A significant increase of ACTH levels (p less than 0.01) was observed during the delivery in the 3 groups even though they were under hasal values 24 hours later. Cortisol increased 38% (p less than 0.01) and 52% (p less than 0.02) in II and III groups, respectively during the delivery. No difference was found with HGH. Our results suggest that endocrine response modified by labour and delivery doesn't change with different analgesia techniques.

Subcutaneous L-tyrosine elicits cutaneous analgesia in response to local skin pinprick in rats.

PubMed

Hung, Ching-Hsia; Chiu, Chong-Chi; Liu, Kuo-Sheng; Chen, Yu-Wen; Wang, Jhi-Joung

2015-10-15

The purpose of the study was to estimate the ability of L-tyrosine to induce cutaneous analgesia and to investigate the interaction between L-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with L-tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug-drug interaction was analyzed by using an isobolographic method. We showed that both L-tyrosine and lidocaine produced dose-dependent cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was lidocaine (5.09 [4.88-5.38] μmol)>L-tyrosine (39.1 [36.5-41.8] μmol) (P<0.05). At the equipotent doses (ED25, ED50, and ED75), the duration of cutaneous analgesia caused by L-tyrosine lasted longer than that caused by lidocaine (P<0.01). Lidocaine co-administered with L-tyrosine exhibited an additive effect on infiltrative cutaneous analgesia. Our pre-clinical study demonstrated that L-tyrosine elicits the local/cutaneous analgesia, and the interaction between L-tyrosine and lidocaine is additive. L-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding L-tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone. Copyright © 2015 Elsevier B.V. All rights reserved.

Sedation and analgesia in gastrointestinal endoscopy: What’s new?

PubMed Central

Fanti, Lorella; Testoni, Pier Alberto

2010-01-01

Various types of sedation and analgesia technique have been used during gastrointestinal endoscopy procedures. The best methods for analgesia and sedation during gastrointestinal endoscopy are still debated. Providing an adequate regimen of sedation/analgesia might be considered an art, influencing several aspects of endoscopic procedures: the quality of the examination, the patient’s cooperation and the patient’s and physician’s satisfaction with the sedation. The properties of a model sedative agent for endoscopy would include rapid onset and offset of action, analgesic and anxiolytic effects, ease of titration to desired level of sedation, rapid recovery and an excellent safety profile. Therefore there is an impulse for development of new approaches to endoscopic sedation. This article provides an update on the methods of sedation today available and future directions in endoscopic sedation. PMID:20503443

Focused review: ropivacaine versus bupivacaine for epidural labor analgesia.

PubMed

Beilin, Yaakov; Halpern, Stephen

2010-08-01

Neuraxial analgesia is frequently administered to women in labor. For many years, bupivacaine has been used because of its long duration of action, lack of excessive motor block, and minimal fetal and neonatal effects. However, bupivacaine is one of the most cardiotoxic local anesthetics in current use and motor block is still a problem. Many local anesthetics such as bupivacaine exist in 2 forms, levorotatory and dextrorotatory. Ropivacaine, an amide local anesthetic produced in the pure levorotatory form addresses some of the concerns related to bupivacaine. In this article, we present the literature comparing ropivacaine and bupivacaine to determine whether there is an advantage to using one of these local anesthetics for labor analgesia. We found that there is no advantage to the routine use of ropivacaine for labor analgesia.

Comparative evaluation of effect of preoperative oral medication of ibuprofen and ketorolac on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis: a prospective, double-blind, randomized clinical trial.

PubMed

Aggarwal, Vivek; Singla, Mamta; Kabi, Debipada

2010-03-01

Anesthetic efficacy of inferior alveolar nerve block decreases in patients with irreversible pulpitis. It was hypothesized that premedication with nonsteroidal anti-inflammatory drugs might improve the success rates in patients with inflamed pulps. Sixty-nine adult volunteers who were actively experiencing pain participated in this prospective, randomized, double-blind study. The patients were divided into 3 groups on a random basis and were randomly given 1 of the 3 drugs including ibuprofen, ketorolac, and placebo 1 hour before anesthesia. All patients received standard inferior alveolar nerve block of 2% lidocaine with 1:200,000 epinephrine. Endodontic access preparation was initiated after 15 minutes of initial inferior alveolar nerve block. Pain during treatment was recorded by using a Heft Parker visual analog scale. Success was recorded as none or mild pain. Statistical analysis with nonparametric chi2 tests showed that placebo gave 29% success rate. Premedication with ibuprofen gave 27%, and premedication with ketorolac gave 39% success rate. There was no significant difference between the 3 groups. Preoperative administration of ibuprofen or ketorolac has no significant effect on success rate of inferior alveolar nerve block in patients with irreversible pulpitis. Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Clonidine intensifies memantine cutaneous analgesia in response to local skin noxious pinprick in the rat.

PubMed

Wu, Bor-Tsang; Chen, Kuan-Ting; Liu, Kuo-Sheng; Chen, Yu-Wen; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-06-01

The purposes of this study were to evaluate the co-administration of clonidine with memantine and to determine whether it has a peripheral action in intensifying cutaneous analgesia. Cutaneous analgesia was examined through inhibition of the cutaneous trunci muscle reflex in response to the local noxious pinprick in rats. Effect of the added subcutaneous clonidine to memantine on infiltrative cutaneous analgesia was assessed and compared with the local anesthetic lidocaine. On the 50% effective dose (ED50) basis, the rank of drug potency was memantine [4.05 (3.95-4.18) μmol]>lidocaine [5.81 (5.70-5.98) μmol] (p<0.01). Clonidine at a dose of 0.12 μmol did not elicit cutaneous analgesia. Mixtures of clonidine (0.12 μmol) with drug (memantine or lidocaine) at ED50 or ED95 prolonged the duration of action and enhanced the potency as infiltrative cutaneous analgesia. Clonidine enhanced the lidocaine cutaneous analgesia in which had a better effect than added to memantine. Our resulting data showed that memantine displayed more potent cutaneous analgesia than lidocaine. Co-administration of memantine or lidocaine with clonidine increased the potency and duration of the cutaneous analgesia. Clonidine intensified the effects of lidocaine promoting cutaneous analgesia than added to memantine. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Analgesics for orthopedic postoperative pain.

PubMed

Bourne, Michael H

2004-03-01

Postoperative pain management is critical for optimal care of orthopedic surgery patients. Opioids, administered intramuscularly, as epidurals, or IV as patient-controlled analgesia, are effective for severe pain. Adjunctive therapy and preemptive analgesia such as nerve blocks, and methods of delivery such as infusion pumps, may be used after total knee arthroplasty and anterior cruciate ligament (ACL) reconstruction. Oral opioids are effective for moderate to severe pain, and tramadol, with efficacy comparable to morphine but with fewer severe side effects, is selected for moderate to moderately severe pain. Opioid-sparing NSAIDs, such as ketorolac, and COX-2-specific NSAIDS have use in pain management of hip, knee, and ACL procedures. An individualized regimen of appropriate analgesics, combined with nonpharmacologic treatments such as physical therapy or cryotherapy and patient education, can aid orthopedic surgery patients' recovery.

Sex-dependent components of the analgesia produced by athletic competition.

PubMed

Sternberg, W F; Bokat, C; Kass, L; Alboyadjian, A; Gracely, R H

2001-02-01

Competing in various athletic events (track meet, basketball game, or fencing match) can produce analgesia to cold pressor stimuli in male and female college athletes compared with baseline assessments. This competition-induced analgesia has been attributed to the stress associated with competition, which has components related to both physical exercise and the cognitive aspects of competing. This study evaluated the analgesic effect of exercise-related stress, and that caused by the cognitively stressful components of competing independent of exercise. Cold pressor pain ratings were assessed after competition in a track meet and after treadmill exercise or sedentary video game competition in both athletes and nonathletes. As expected, competing in athletics resulted in a decrease in cold pressor ratings in both male and female athletes. Independent of athletic status, treadmill running induced analgesia in women, but not in males, whereas sedentary video game competition produced analgesia in men, but not in women. These findings suggest that different components of the competitive athletic experience might be responsible for the analgesic effects in a sex-dependent manner.

Effects of magnesium sulphate on intraoperative neuromuscular blocking agent requirements and postoperative analgesia in children with cerebral palsy.

PubMed

Na, H-S; Lee, J-H; Hwang, J-Y; Ryu, J-H; Han, S-H; Jeon, Y-T; Do, S-H

2010-03-01

In this double-blind, randomized, placebo-controlled study, we evaluated the effects of magnesium sulphate on neuromuscular blocking agent requirements and analgesia in children with cerebral palsy (CP). We randomly divided 61 children with CP undergoing orthopaedic surgery into two groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and 15 mg kg(-1) h(-1) by continuous infusion during the operation. The control group (Group S) received the same amount of isotonic saline. Rocuronium was administered 0.6 mg kg(-1) before intubation and 0.1 mg kg(-1) additionally when train-of-four counts were 2 or more. I.V. fentanyl and ketorolac were used to control postoperative pain. Total infused analgesic volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and 48 h. The rocuronium requirement of Group M was significantly less than that of Group S [0.29 (0.12) vs 0.42 (0.16) mg kg(-1) h(-1), P<0.05]. Cumulative analgesic consumption in Group M was significantly less after operation at 24 and 48 h (P<0.05), and pain scores in Group M were lower than in Group S during the entire postoperative period (P<0.05). Serum magnesium concentrations in Group M were higher until 24 h after operation (P<0.05). The incidence of postoperative nausea and vomiting and rescue drug injections was similar in the two groups. No shivering or adverse effects related to hypermagnesaemia were encountered. I.V. magnesium sulphate reduces rocuronium requirements and postoperative analgesic consumption in children with CP.

Intrathecal opioids versus epidural local anesthetics for labor analgesia: a meta-analysis.

PubMed

Bucklin, Brenda A; Chestnut, David H; Hawkins, Joy L

2002-01-01

Some anesthesiologists contend that intrathecal opioid administration has advantages over conventional epidural techniques during labor. Randomized clinical trials comparing analgesia and obstetric outcome using single-injection intrathecal opioids versus epidural local anesthetics suggest that intrathecal opioids provide comparable analgesia with few serious side effects. This meta-analysis compared the analgesic efficacy, side effects, and obstetric outcome of single-injection intrathecal opioid techniques versus epidural local anesthetics in laboring women. Relevant clinical studies were identified using electronic and manual searches of the literature covering the period from 1989 to 2000. Searches used the following descriptors: intrathecal analgesia, spinal opioids, epidural analgesia, epidural local anesthetics, and analgesia for labor. Data were extracted from 7 randomized clinical trials comparing analgesic measures, incidence of motor block, pruritus, nausea, hypotension, mode of delivery, and/or Apgar scores. Combined test results indicated comparable analgesic efficacy 15 to 20 minutes after injection with single-injection intrathecal opioid administration. Intrathecal opioid injections were associated with a greater incidence of pruritus (odds ratio, 14.01; 99% confidence interval, 6.9 to 28.3), but there was no difference in the incidence of nausea or in the method of delivery. Published studies suggest that intrathecal opioids provide comparable early labor analgesia when compared with epidural local anesthetics. Intrathecal opioid administration results in a greater incidence of pruritus. The choice of technique does not appear to affect the method of delivery.

A Subanalgesic Dose of Morphine Eliminates Nalbuphine Anti-analgesia in Postoperative Pain

PubMed Central

Gear, Robert W.; Gordon, Newton C.; Hossaini-Zadeh, Mehran; Lee, Janice S.; Miaskowski, Christine; Paul, Steven M.; Levine, Jon D.

2008-01-01

The agonist-antagonist kappa-opioid nalbuphine administered for postoperative pain produces greater analgesia in females than in males. In fact, males administered nalbuphine (5 mg) experience pain greater than those receiving placebo, suggesting the existence of an anti-analgesic effect. These sexually dimorphic effects on postoperative pain can be eliminated by co-administration of a fixed ratio of the prototypical opioid receptor antagonist naloxone with nalbuphine, implying a role for opioid receptors in the anti-analgesic as well as analgesic effects of nalbuphine. In the present study, we further evaluated the role of opioid receptors in the sex-specific effects on pain produced by nalbuphine by co-administering a dose of morphine low enough that it does not produce analgesia. Following extraction of bony impacted third molar teeth, nalbuphine (5 mg) was administered alone or in combination with either of two low doses of morphine (2 mg or 4 mg). Both doses of morphine reversed nalbuphine-induced anti-analgesia in males, but only the lower dose (2 mg) reached statistical significance. Neither dose affected nalbuphine-induced analgesia in females, and when administered alone in either males or females, morphine (2 mg) had no analgesic effect. Though not observed in females, the effect of morphine in males argues that, like naloxone, low dose morphine may act as an anti-analgesia opioid receptor antagonist. Perspective Previously we reported that the nalbuphine produces both analgesic and anti-analgesic effects, and that the opioid antagonist naloxone can enhance nalbuphine analgesia by selectively antagonizing the anti-analgesic effect. Here we show that morphine, given in a subanalgesic dose, reverses nalbuphine-induced anti-analgesia in males, perhaps by a similar mechanism. PMID:18201935

Primary Spoken Language and Neuraxial Labor Analgesia Use Among Hispanic Medicaid Recipients.

PubMed

Toledo, Paloma; Eosakul, Stanley T; Grobman, William A; Feinglass, Joe; Hasnain-Wynia, Romana

2016-01-01

Hispanic women are less likely than non-Hispanic Caucasian women to use neuraxial labor analgesia. It is unknown whether there is a disparity in anticipated or actual use of neuraxial labor analgesia among Hispanic women based on primary language (English versus Spanish). In this 3-year retrospective, single-institution, cross-sectional study, we extracted electronic medical record data on Hispanic nulliparous with vaginal deliveries who were insured by Medicaid. On admission, patients self-identified their primary language and anticipated analgesic use for labor. Extracted data included age, marital status, labor type, delivery provider (obstetrician or midwife), and anticipated and actual analgesic use. Household income was estimated from census data geocoded by zip code. Multivariable logistic regression models were estimated for anticipated and actual neuraxial analgesia use. Among 932 Hispanic women, 182 were self-identified as primary Spanish speakers. Spanish-speaking Hispanic women were less likely to anticipate and use neuraxial anesthesia than English-speaking women. After controlling for confounders, there was an association between primary language and anticipated neuraxial analgesia use (adjusted relative risk: Spanish- versus English-speaking women, 0.70; 97.5% confidence interval, 0.53-0.92). Similarly, there was an association between language and neuraxial analgesia use (adjusted relative risk: Spanish- versus English-speaking women 0.88; 97.5% confidence interval, 0.78-0.99). The use of a midwife compared with an obstetrician also decreased the likelihood of both anticipating and using neuraxial analgesia. A language-based disparity was found in neuraxial labor analgesia use. It is possible that there are communication barriers in knowledge or understanding of analgesic options. Further research is necessary to determine the cause of this association.

Increased analgesia administration in emergency medicine after implementation of revised guidelines.

PubMed

Van Woerden, Geesje; Van Den Brand, Crispijn L; Den Hartog, Cornelis F; Idenburg, Floris J; Grootendorst, Diana C; Van Der Linden, M Christien

2016-12-01

The most common complaint of patients attending the emergency department (ED) is pain, caused by different diseases. Yet the treatment of pain at the ED is suboptimal, and oligoanalgesia remains common. The objective of this study is to determine whether the administration of analgesia at the ED increases by implementation of revised guidelines in pain management. We conducted a prospective pre-post intervention cohort study with implementation of a revised guideline for pain management at our ED, in which nurses are allowed to administer analgesia (including low-dosage piritramid (opioid) intravenous) without doctor intervention. Numeric Rating Scales (NRS) were measured, and administration of medication (main outcome) was documented. We included every adult patient presenting with pain (NRS 4-10) at the ED. A total of 2107 patients (1089 pre-implementation phase and 1018 post-implementation phase) were included in our study. During pre-implementation, 25.4 % of the patients with NRS between 4 and 10 received analgesia. After implementation, 32.0 % of these patients received analgesia (p < 0.001). After implementation of the revised guidelines in pain management at the ED, the administration of pain medication increased significantly. Nevertheless, the percentage of patients in pain receiving analgesia remain low (32 % after implementation).

[PERIOPERATIVE ANALGESIA INFLUENCE ON MOTHER REHABILITATION PERIOD AFTER CESAREAN SECTION].

PubMed

Sedykh, S V

2015-01-01

Early breast-feeding is a standard of perinatal care currently. After cesarean section it can be possible in case of early mother activation (verticalization). Assessment of perioperative analgesia influence on activation timing was the aim of our research. We included 120 parturient women. It was proved, that local analgesia using in postoperative period promotes early mother verticaliration, and optimal breast-feeding starting.

Staff education, regular sedation and analgesia quality feedback, and a sedation monitoring technology for improving sedation and analgesia quality for critically ill, mechanically ventilated patients: a cluster randomised trial.

PubMed

Walsh, Timothy S; Kydonaki, Kalliopi; Antonelli, Jean; Stephen, Jacqueline; Lee, Robert J; Everingham, Kirsty; Hanley, Janet; Phillips, Emma C; Uutela, Kimmo; Peltola, Petra; Cole, Stephen; Quasim, Tara; Ruddy, James; McDougall, Marcia; Davidson, Alan; Rutherford, John; Richards, Jonathan; Weir, Christopher J

2016-10-01

Optimal sedation of patients in intensive care units (ICUs) requires the avoidance of pain, agitation, and unnecessary deep sedation, but these outcomes are challenging to achieve. Excessive sedation can prolong ICU stay, whereas light sedation can increase pain and frightening memories, which are commonly recalled by ICU survivors. We aimed to assess the effectiveness of three interventions to improve sedation and analgesia quality: an online education programme; regular feedback of sedation-analgesia quality data; and use of a novel sedation-monitoring technology (the Responsiveness Index [RI]). We did a cluster randomised trial in eight ICUs, which were randomly allocated to receive education alone (two ICUs), education plus sedation-analgesia quality feedback (two ICUs), education plus RI monitoring technology (two ICUs), or all three interventions (two ICUs). Randomisation was done with computer-generated random permuted blocks, stratified according to recruitment start date. A 45 week baseline period was followed by a 45 week intervention period, separated by an 8 week implementation period in which the interventions were introduced. ICU and research staff were not masked to study group assignment during the intervention period. All mechanically ventilated patients were potentially eligible. We assessed patients' sedation-analgesia quality for each 12 h period of nursing care, and sedation-related adverse events daily. Our primary outcome was the proportion of care periods with optimal sedation-analgesia, defined as being free from excessive sedation, agitation, poor limb relaxation, and poor ventilator synchronisation. Analysis used multilevel generalised linear mixed modelling to explore intervention effects in a single model taking clustering and patient-level factors into account. A concurrent mixed-methods process evaluation was undertaken to help understand the trial findings. The trial is registered with ClinicalTrials.gov, number NCT01634451. Between

Epidural analgesia is infrequently used in patients with acute pancreatitis : a retrospective cohort study.

PubMed

Sasabuchi, Y; Yasunaga, H; Matsui, H; Lefor, A K; Fushimi, K; Sanui, M

2017-01-01

Epidural analgesia is an option for pain control in patients with acute pancreatitis. The aim of this study is to describe characteristics, morbidity and mortality of patients with acute pancreatitis treated with epidural analgesia. Data was extracted from a national inpatient database in Japan on patients hospitalized with acute pancreatitis between July 2010 and March 2013. A total of 44,146 patients discharged from acute care hospitals were included in this retrospective cohort study. The patient background, timing and duration of epidural analgesia, complications (epidural hematoma or abscess), surgery (for cholelithiasis / cholecystitis or complications) and mortality were verified. Epidural analgesia was used in 307 patients (0.70 %). The mean age was 64.0 years (standard deviation, 15.4 years) and 116 (37.8%) of the patients were female. The median duration of epidural analgesia was four days (interquartile range, 3-5 days). No patient underwent surgery for epidural hematoma or abscess. Six (2.0%) patients died during hospitalization. Most likely causes of death were pulmonary embolism, multiple organ failure, sepsis, and methicillin-resistant staphylococcus aureus enterocolitis. The responsible physician for 250 of the patients (81.4%) was a gastroenterological surgeon. Epidural analgesia was started on the day of surgery in 278 (90.6%) patients. Epidural analgesia is rarely used in patients with acute pancreatitis. None of the patients included in the study required surgery for epidural hematoma or abscess. Further research to evaluate the efficacy and safety of epidural analgesia in patients with acute pancreatitis is warranted. © Acta Gastro-Enterologica Belgica.

Stability of piritramide in patient-controlled analgesia (PCA) solutions.

PubMed

Remane, D; Scriba, G; Meissner, W; Hartmann, M

2009-06-01

For patient controlled analgesia, syringes with solutions of 1.5 mg/ml piritramide in 0.9% aqueous sodium chloride are used. The physical and chemical stability for dilutions of the commercially available preparation of piritramide is limited up to 72 hours by the manufacturer. Since application duration for patient-controlled analgesia can exceed that limited time, stability was investigated by HPLC. Our results show that these solutions are chemically stable over a time period of 60 days.

Phorbol ester suppression of opioid analgesia in rats

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

Zhang, L.J.; Wang, X.J.; Han, J.S.

1990-01-01

Protein kinase C (PKC) has been shown to be an important substrate in intracellular signal transduction. Very little is known concerning its possible role in mediating opiate-induced analgesia. In the present study, 12-O-tetradecanoylphorbol 13-acetate (TPA), a selective activator of PKC, was injected intrathecally (ith) to assess its influence on the analgesia induced by intrathecal injection of the mu opioid agonist PL017, the delta agonist DPDPE and the kappa agonist 66A-078. Radiant heat-induced tail flick latency (TFL) was taken as an index of nociception. TPA in the dose of 25-50 ng, which did not affect the baseline TFL, produced a markedmore » suppression of opioid antinociception, with a higher potency in blocking mu and delta than the kappa effect. In addition, mu and delta agonists induced remarkable decreases in spinal cyclic AMP (cAMP) content whereas the kappa effect was weak. The results suggest a cross-talk between the PKC system and the signal transduction pathway subserving opioid analgesia.« less

Effects of subtle cognitive manipulations on placebo analgesia - An implicit priming study.

PubMed

Rosén, A; Yi, J; Kirsch, I; Kaptchuk, T J; Ingvar, M; Jensen, K B

2017-04-01

Expectancy is widely accepted as a key contributor to placebo effects. However, it is not known whether non-conscious expectancies achieved through semantic priming may contribute to placebo analgesia. In this study, we investigated if an implicit priming procedure, where participants were unaware of the intended priming influence, affected placebo analgesia. In a double-blind experiment, healthy participants (n = 36) were randomized to different implicit priming types; one aimed at increasing positive expectations and one neutral control condition. First, pain calibration (thermal) and a credibility demonstration of the placebo analgesic device were performed. In a second step, an independent experimenter administered the priming task; Scrambled Sentence Test. Then, pain sensitivity was assessed while telling participants that the analgesic device was either turned on (placebo) or turned off (baseline). Pain responses were recorded on a 0-100 Numeric Response Scale. Overall, there was a significant placebo effect (p < 0.001), however, the priming conditions (positive/neutral) did not lead to differences in placebo outcome. Prior experience of pain relief (during initial pain testing) correlated significantly with placebo analgesia (p < 0.001) and explained 34% of placebo variance. Trait neuroticism correlated positively with placebo analgesia (p < 0.05) and explained 21% of placebo variance. Priming is one of many ways to influence behaviour, and non-conscious activation of positive expectations could theoretically affect placebo analgesia. Yet, we found no SST priming effect on placebo analgesia. Instead, our data point to the significance of prior experience of pain relief, trait neuroticism and social interaction with the treating clinician. Our findings challenge the role of semantic priming as a behavioural modifier that may shape expectations of pain relief, and affect placebo analgesia. © 2016 The Authors. European Journal of Pain published by John

Expectancy-induced placebo analgesia in children and the role of magical thinking.

PubMed

Krummenacher, Peter; Kossowsky, Joe; Schwarz, Caroline; Brugger, Peter; Kelley, John M; Meyer, Andrea; Gaab, Jens

2014-12-01

Expectations and beliefs shape the experience of pain. This is most evident in context-induced, placebo analgesia, which has recently been shown to interact with the trait of magical thinking (MT) in adults. In children, placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored. Using a paradigm in which heat pain stimuli were applied to both forearms, we investigated whether MT and gender can influence the magnitude of placebo analgesia in children. Participants were 49 right-handed children (aged 6-9 years) who were randomly assigned-stratified for MT and gender-to either an analgesia-expectation or a control-expectation condition. For both conditions, the placebo was a blue-colored hand disinfectant that was applied to the children's forearms. Independent of MT, the placebo treatment significantly increased both heat pain threshold and tolerance. The threshold placebo effect was more pronounced for girls than boys. In addition, independent of the expectation treatment, low-MT boys showed a lower tolerance increase on the left compared to the right side. Finally, MT specifically modulated tolerance on the right forearm side: Low-MT boys showed an increase, whereas high-MT boys showed a decrease in heat pain tolerance. This study documented a substantial expectation-induced placebo analgesia response in children (girls > boys) and demonstrated MT and gender-dependent laterality effects in pain perception. The findings may help improve individualized pain management for children. The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children aged 6 to 9 years (girls > boys). Moreover, the effect was substantially higher than the placebo response typically found in adults. The findings may help improve individualized pain management for children. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All

A Leptin-Mediated Central Mechanism in Analgesia-Enhanced Opioid Reward in Rats

PubMed Central

Lim, Grewo; Kim, Hyangin; McCabe, Michael F.; Chou, Chiu-Wen; Wang, Shuxing; Chen, Lucy L.; Marota, John J.A.; Blood, Anne; Breiter, Hans C.

2014-01-01

Opioid analgesics are commonly used in chronic pain management despite a potential risk of rewarding. However, it remains unclear whether opioid analgesia would enhance the opioid rewarding effect thereby contributing to opioid rewarding. Utilizing a rat paradigm of conditioned place preference (CPP) combined with ankle monoarthritis as a condition of persistent nociception, we showed that analgesia induced by either morphine or the nonsteroid anti-inflammatory drug ibuprofen increased CPP scores in arthritic rats, suggesting that analgesia itself had a rewarding effect. However, arthritic rats exhibited a significantly higher CPP score in response to morphine than ibuprofen. Thus, the rewarding effect of morphine was enhanced in the presence of persistent nociception, producing a phenomenon of analgesia-enhanced opioid reward. At the cellular level, administration of morphine activated a cascade of leptin expression, glial activation, and dopamine receptor upregulation in the nucleus accumbens (NAc), while administration of ibuprofen decreased glial activation with no effect on leptin expression in the NAc. Furthermore, the morphine rewarding effect was blocked in leptin deficient ob/ob mice or by neutralizing leptin or interleukin-1β in the NAc without diminishing morphine analgesia. The data indicate that systemic opioid can activate a leptin-mediated central mechanism in the NAc that led to the enhanced opioid rewarding effect. These findings provide evidence for an interaction between opioid analgesia and opioid rewarding, which may have implications in clinical opioid dose escalation in chronic pain management. PMID:25031415

Gender-specific and gonadectomy-specific effects upon swim analgesia: role of steroid replacement therapy.

PubMed

Romero, M T; Cooper, M L; Komisaruk, B R; Bodnar, R J

1988-01-01

Both gender-specific and gonadectomy-specific effects have been observed for the analgesic responses following continuous and intermittent cold-water swims (CCWS and ICWS respectively): female rats display significantly less analgesia than males, and gonadectomized rats display significantly less analgesia than sham-operated controls. The present study evaluated the effects of steroid replacement therapy with testosterone propionate (TP: 2 mg/kg, SC) upon CCWS and ICWS analgesia on the tail-flick and jump tests and hypothermia in sham-operated or gonadectomized male and female rats. Thirty days following surgery, rats received either no treatment, a sesame oil vehicle or TP for 14 days prior to, and then during testing. Relative to the no treatment condition, repeated vehicle injections in sham-operated rats eliminated the gender-specific, but did not affect the gonadectomy-specific effects upon CCWS and ICWS analgesia. TP reversed the deficits in CCWS and ICWS analgesia observed in both castrated and ovariectomized rats on both pain tests. TP only potentiated CCWS analgesia in sham-operated males on the tail-flick test. TP potentiated CCWS and ICWS hypothermia in gonadectomized rats and in male sham-operated rats. These data indicate that gonadal steroids play a major modulatory role in the etiology of swim analgesia, and that the observed gender effects are sensitive to possible adaptational variables.

Anesthesia, analgesia, and euthanasia of invertebrates.

PubMed

Cooper, John E

2011-01-01

Invertebrate animals have long played an important role in biomedical research in such fields as genetics, physiology, and development. However, with few exceptions, scientists, veterinarians, and technicians have paid little attention to the anesthesia, analgesia, and euthanasia of these diverse creatures. Indeed, some standard research procedures are routinely performed without anesthesia. Yet various chemical agents are available for the immobilization or anesthesia of invertebrates, ranging from gases or volatile liquids that can be pumped into either an anesthetic chamber (for terrestrial species) or a container of water (aquatic species), to benzocaine and other substances for fish. Many invertebrates are not difficult to immobilize or anesthetize and the procedures recommended in this article appear to be safe; however, none should be considered totally risk-free. Analgesia of invertebrates is as yet a largely unexplored field; until scientific data are available, other measures can promote the well-being of these animals in the laboratory. For euthanasia, various methods (physical or chemical or a combination of both) have been recommended for different taxa of invertebrates, but most have not been properly studied under laboratory conditions and some can be problematic in the context of research procedures and tissue harvesting. Furthermore, relevant data are scattered, sometimes available only in languages other than English, and there is no international approach for seeking and collating such information. In this article I review various methods of anesthesia, analgesia, and euthanasia for terrestrial and aquatic invertebrates, as well as areas requiring further research.

Perioperative epidural analgesia reduces cancer recurrence after gastro-oesophageal surgery.

PubMed

Hiller, J G; Hacking, M B; Link, E K; Wessels, K L; Riedel, B J

2014-03-01

Recent interest has focused on the role of perioperative epidural analgesia in improving cancer outcomes. The heterogeneity of studies (tumour type, stage and outcome endpoints) has produced inconsistent results. Clinical practice also highlights the variability in epidural effectiveness. We considered the novel hypothesis that effective epidural analgesia improves cancer outcomes following gastro-oesophageal cancer surgery in patients with grouped pathological staging. Following institutional approval, a database analysis identified 140 patients, with 2-year minimum follow-up after gastro-oesophageal cancer surgery. All patients were operated on by a single surgeon (2005-2010). Information pertaining to cancer and survival outcomes was extracted. Univariate analysis demonstrated a 1-year 14% vs. 33% (P = 0.01) and 2-year 27% vs. 40% [hazard ratio (HR)=0.59; 95% CI, 0.32-1.09, P = 0.087] incidence of cancer recurrence in patients with (vs. without) effective (> 36 h duration) epidural analgesia, respectively. Multivariate analysis demonstrated increased time to cancer recurrence (HR = 0.33; 95% CI: 0.17-0.63, P < 0.0001) and overall survival benefit (HR = 0.42; 95% CI: 0.21-0.83, P < 0.0001) at 2-year follow-up following effective epidural analgesia. Subgroup analysis identified epidural-related cancer recurrence benefit in patients with oesophageal cancer (HR = 0.34; 95% CI: 0.16-0.75, P = 0.005) and in patients with tumour lymphovascular space infiltration (LVSI), (HR = 0.49; 95% CI: 0.26-0.94, P = 0.03). Effective epidural analgesia improved estimated median time to death (2.9 vs. 1.8 years, P = 0.029) in patients with tumour LVSI. This study found an association between effective post-operative epidural analgesia and medium-term benefit on cancer recurrence and survival following oesophageal surgery. A prospective study that controls for disease type, stage and epidural effectiveness is warranted. © 2014 The Acta

The potential contributing effect of ketorolac and fluoxetine to a spinal epidural hematoma following a cervical interlaminar epidural steroid injection: a case report and narrative review.

PubMed

Chien, George C Chang; McCormick, Zack; Araujo, Marco; Candido, Kenneth D

2014-01-01

Cervical interlaminar epidural steroid injections (ESIs) are commonly performed as one part of a multi-modal analgesic regimen in the management of upper extremity radicular pain. Spinal epidural hematoma (SEH) is a rare complication with a reported incidence ranging from 1.38 in 10,000 to 1 in 190,000 epidurals. Current American Society of Regional Anesthesia (ASRA), American Society of Interventional Pain Physicians (ASIPP), and the International Spine Intervention Society (ISIS) recommendations are that non-steroidal anti-inflammatory drugs (NSAIDs) do not need to be withheld prior to epidural anesthesia. We report a case wherein intramuscular ketorolac and oral fluoxetine contributed to a SEH and tetraplegia following a cervical interlaminar (ESI). A 66 year-old woman with chronic renal insufficiency and neck pain radiating into her right upper extremity presented for evaluation and was deemed an appropriate CESI candidate. Cervical magnetic resonance imaging (MRI) revealed multi-level neuroforaminal stenosis and degenerative intervertebral discs. Utilizing a loss of resistance to saline technique, an 18-gauge Tuohy-type needle entered the epidural space at C6-7. After negative aspiration, 4 mL of saline with 80 mg of methyl-prednisolone was injected. Immediately thereafter, the patient reported significant spasmodic-type localized neck pain with no neurologic status changes. A decision was made to administer 30 mg intramuscular ketorolac as treatment for the spasmodic-type pain. En route home, she developed a sudden onset of acute tetraplegia. She was brought to the emergency department for evaluation including platelet and coagulation studies which were normal. MRI demonstrated an epidural hematoma extending from C5 to T7. She underwent a bilateral C5-T6 laminectomy with epidural hematoma evacuation and was discharged to an acute inpatient rehabilitation hospital. Chronic renal insufficiency, spinal stenosis, female gender, and increasing age have been

Ketorolac alters blood flow during normothermia but not during hyperthermia in middle-aged human skin

PubMed Central

Jennings, John D.; Lang, James A.; Kenney, W. Larry

2009-01-01

In young healthy humans full expression of reflex cutaneous vasodilation is dependent on cyclooxygenase (COX)- and nitric oxide synthase (NOS)-dependent mechanisms. Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation potentially through both platelet and vascular COX-dependent mechanisms. We hypothesized the contribution of COX-dependent vasodilators to reflex cutaneous vasodilation during localized acute COX inhibition would be attenuated in healthy middle-aged humans due to a shift toward COX-dependent vasoconstrictors. Four microdialysis fibers were placed in forearm skin of 13 middle-aged (53 ± 2 yr) normotensive healthy humans, serving as control (Ringer), COX-inhibited (10 mM ketorolac), NOS-inhibited (10 mM NG-nitro-l-arginine methyl ester), and combined NOS- and COX-inhibited sites. Red blood cell flux was measured over each site by laser-Doppler flowmetry as reflex vasodilation was induced by increasing oral temperature (Tor) 1.0°C using a water-perfused suit. Cutaneous vascular conductance was calculated (CVC = flux/mean arterial pressure) and normalized to maximal CVC (CVCmax; 28 mM sodium nitroprusside). CVCmax was not affected by localized microdialysis drug treatment (P > 0.05). Localized COX inhibition increased baseline (18 ± 3%CVCmax; P < 0.001) compared with control (9 ± 1%CVCmax), NOS-inhibited (7 ± 1%CVCmax), and combined sites (10 ± 1%CVCmax). %CVCmax in the COX-inhibited site remained greater than the control site with ΔTor ≤ 0.3°C; however, there was no difference between these sites with ΔTor ≥ 0.4°C. NOS inhibition and combined COX and NOS inhibition attenuated reflex vasodilation compared with control (P < 0.001), but there was no difference between these sites. Localized COX inhibition with ketorolac significantly augments baseline CVC but does not alter the subsequent skin blood flow response to hyperthermia, suggesting a limited role for COX-derived vasodilator prostanoids in reflex cutaneous

Reported provision of analgesia to patients with acute abdominal pain in Canadian paediatric emergency departments.

PubMed

Poonai, Naveen; Cowie, Allyson; Davidson, Chloe; Benidir, Andréanne; Thompson, Graham C; Boisclair, Philippe; Harman, Stuart; Miller, Michael; Butter, Andreana; Lim, Rod; Ali, Samina

2016-09-01

Evidence exists that analgesics are underutilized, delayed, and insufficiently dosed for emergency department (ED) patients with acute abdominal pain. For physicians practicing in a Canadian paediatric ED setting, we (1) explored theoretical practice variation in the provision of analgesia to children with acute abdominal pain; (2) identified reasons for withholding analgesia; and (3) evaluated the relationship between providing analgesia and surgical consultation. Physician members of Paediatric Emergency Research Canada (PERC) were prospectively surveyed and presented with three scenarios of undifferentiated acute abdominal pain to assess management. A modified Dillman's Tailored Design method was used to distribute the survey from June to July 2014. Overall response rate was 74.5% (149/200); 51.7% of respondents were female and mean age was 44 (SD 8.4) years. The reported rates of providing analgesia for case scenarios representative of renal colic, appendicitis, and intussusception, were 100%, 92.1%, and 83.4%, respectively, while rates of providing intravenous opioids were 85.2%, 58.6%, and 12.4%, respectively. In all 60 responses where the respondent indicated they would obtain a surgical consultation, analgesia would be provided. In the 35 responses where analgesia would be withheld, 21 (60%) believed pain was not severe enough, while 5 (14.3%) indicated it would obscure a surgical condition. Pediatric emergency physicians self-reported rates of providing analgesia for acute abdominal pain scenarios were higher than previously reported, and appeared unrelated to request for surgical consultation. However, an unwillingness to provide opioid analgesia, belief that analgesia can obscure a surgical condition, and failure to take self-reported pain at face value remain, suggesting that the need exists for further knowledge translation efforts.

Peri-operative epidural may not be the preferred form of analgesia in select patients undergoing pancreaticoduodenectomy.

PubMed

Axelrod, Trevor M; Mendez, Bernardino M; Abood, Gerard J; Sinacore, James M; Aranha, Gerard V; Shoup, Margo

2015-03-01

Epidural analgesia has become the preferred method of pain management for major abdominal surgery. However, the superior form of analgesia for pancreaticoduodenecomy (PD), with regard to non-analgesic outcomes, has been debated. In this study, we compare outcomes of epidural and intravenous analgesia for PD and identify pre-operative factors leading to early epidural discontinuation. A retrospective review was performed on 163 patients undergoing PD between 2007 and 2011. We performed regression analyses to measure the predictive success of two groups of analgesia on morbidity and mortality and to identify predictors of epidural failure. Intravenous analgesia alone was given to 14 (9%) patients and 149 patients (91%) received epidural analgesia alone or in conjunction with intravenous analgesia. Morbidity and mortality were not significantly different between the two groups. Early epidural discontinuation was necessary in 22 patients (15%). Those older than 72 and with a BMI < 20 (n = 5) had their epidural discontinued in 80% of cases compared to 12% not meeting these criteria. However, early epidural discontinuation was not associated with increased morbidity and mortality. Epidural analgesia may be contraindicated in elderly, underweight patients undergoing PD given their increased risk of epidural-induced hypotension or malfunction. © 2014 Wiley Periodicals, Inc.

Labor induction just after external cephalic version with epidural analgesia at term.

PubMed

Cuerva, Marcos J; Piñel, Carlos S; Caceres, Javier; Espinosa, Jose A

2017-06-01

To analyze the benefits of external cephalic version (ECV) with epidural analgesia at term and labor induction just after the procedure. This is a retrospective observational study with patients who did not want trying a breech vaginal delivery and decided trying an ECV with epidural analgesia at term and wanted labor induction or cesarean section after the procedure. We present the results of 40 ECV with epidural analgesia at term and labor induction or cesarean section just after the ECV. ECV succeeded in 26 out of 40 (65%) patients. Among the 26 successful ECV, 6 delivered by cesarean (23.1%). 20 patients delivered vaginally (76.9%; 50% of all patients). Considering that a high number of cesarean deliveries can be avoided, induction of labor after ECV with epidural analgesia at term can be considered after being discussed in selected patient. Copyright © 2017. Published by Elsevier B.V.

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

Antagonism of stress-induced analgesia by D-phenylalanine, an anti-enkephalinase.

PubMed

Bodnar, R J; Lattner, M; Wallace, M M

1980-12-01

Methionine- and leucine-enkephalin produce mild and transient analgesic effects, presumably because of enzymatic degradation. Administration of high (250 mg/kg) doses of D-phenylalanine retards the degradation process and elicits analgesia which is reversed by naloxone and which summates with electroacupuncture analgesia. The present study evaluated D-phenylalanine's dose-dependent effects upon a non-opioid analgesic treatment, cold-water swims (CWS), and compared this with morphine. following determination of flinch-jump baselines, three groups of rats received respectively either 25, 50 or 100 mg/kg of D-phenylalanine intraperitoneally in three conditions: alone, with CWS (2 degrees C for 3.5 min), and with morphine (5 mg/kg, SC). Parallel controls with saline were also tested. Simultaneous exposure with each minimally analgesic dose of D-phenylalanine reduced significantly the analgesic, but not hypothermic effects of CWS. By contrast, morphine analgesia was unaffected by D-phenylalanine. These data provide further support that different pain-inhibitory systems mediate CWS and morphine analgesia and suggest that activation of one system is capable of exerting collateral inhibition upon the other.

Neuraxial analgesia effects on labor progression: facts, fallacies, uncertainties, and the future

PubMed Central

Grant, Erica N.; Tao, Weike; Craig, Margaret; McIntire, Donald; Leveno, Kenneth

2014-01-01

Approximately 60% of women who labor receive some form of neuraxial analgesia, but concerns have been raised regarding whether it negatively impacts the labor and delivery process. In this review, we attempt to clarify what has been established as truths, falsities, and uncertainties regarding the effects of this form of pain relief on labor progression, negative and/or positive. Additionally, although the term “epidural” has become synonymous with neuraxial analgesia, we discuss two other techniques, combined spinal-epidural and continuous spinal analgesia, that are gaining popularity, as well as their effects on labor progression. PMID:25088476

Analgesia Induced by Isolated Bovine Chromaffin Cells Implanted in Rat Spinal Cord

NASA Astrophysics Data System (ADS)

Sagen, Jacqueline; Pappas, George D.; Pollard, Harvey B.

1986-10-01

Chromaffin cells synthesize and secrete several neuroactive substances, including catecholamines and opioid peptides, that, when injected into the spinal cord, induce analgesia. Moreover, the release of these substances from the cells can be stimulated by nicotine. Since chromaffin cells from one species have been shown to survive when transplanted to the central nervous system of another species, these cells are ideal candidates for transplantation to alter pain sensitivity. Bovine chromaffin cells were implanted into the subarachnoid space of the lumbar spinal region in adult rats. Pain sensitivity and response to nicotine stimulation was determined at various intervals following cell implantation. Low doses of nicotine were able to induce potent analgesia in implanted animals as early as one day following their introduction into the host spinal cord. This response could be elicited at least through the 4 months the animals were tested. The induction of analgesia by nicotine in implanted animals was dose related. This analgesia was blocked by the opiate antagonist naloxone and partially attenuated by the adrenergic antagonist phentolamine. These results suggest that the analgesia is due to the stimulated release of opioid peptides and catecholamines from the implanted bovine chromaffin cells and may provide a new therapeutic approach for the relief of pain.

Effects of Multimodal Analgesia on the Success of Mouse Embryo Transfer Surgery

PubMed Central

Parker, John M.; Austin, Jamie; Wilkerson, James; Carbone, Larry

2011-01-01

Multimodal analgesia is promoted as the best practice pain management for invasive animal research procedures. Universal acceptance and incorporation of multimodal analgesia requires assessing potential effects on study outcome. The focus of this study was to assess effects on embryo survival after multimodal analgesia comprising an opioid and nonsteroidal antiinflammatory drug (NSAID) compared with opioid-only analgesia during embryo transfer procedures in transgenic mouse production. Mice were assigned to receive either carprofen (5 mg/kg) with buprenorphine (0.1 mg/kg; CB) or vehicle with buprenorphine (0.1 mg/kg; VB) in a prospective, double-blinded placebo controlled clinical trial. Data were analyzed in surgical sets of 1 to 3 female mice receiving embryos chimeric for a shared targeted embryonic stem-cell clone and host blastocyst cells. A total of 99 surgical sets were analyzed, comprising 199 Crl:CD1 female mice and their 996 offspring. Neither yield (pups weaned per embryo implanted in the surgical set) nor birth rate (average number of pups weaned per dam in the set) differed significantly between the CB and VB conditions. Multimodal opioid–NSAID analgesia appears to have no significant positive or negative effect on the success of producing novel lines of transgenic mice by blastocyst transfer. PMID:21838973

Multimodal analgesia and regional anaesthesia.

PubMed

Tornero Tornero, C; Fernández Rodríguez, L E; Orduña Valls, J

Multimodal analgesia provides quality analgesia, with fewer side effects due to the use of combined analgesics or analgesic techniques. Regional anaesthesia plays a fundamental role in achieving this goal. The different techniques of regional anaesthesia that include both peripheral and central blocks in either a single dose or in continuous infusion help to modulate the nociceptive stimuli that access the central level. The emergence of the ultrasound as an effective system to perform regional anaesthesia techniques has allowed the development of new regional anaesthesia techniques that formerly could not be carried out since only neurostimulation or skin references were used. It is essential to take into account that even with effective blocking it is advisable to associate other drugs by other routes, in this way we will be able to reduce the required doses individually and attempt to achieve a synergistic, not purely additive, effect. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Involvement of peripheral mechanism in the verapamil-induced potentiation of morphine analgesia in mice.

PubMed

Shimizu, Norifumi; Kishioka, Shiroh; Maeda, Takehiko; Fukazawa, Yohji; Dake, Yoshihiro; Yamamoto, Chizuko; Ozaki, Masanobu; Yamamoto, Hiroyuki

2004-08-01

Morphine's analgesic actions are thought to be mediated through both the central and peripheral nervous systems. L-type calcium channel blockers have been reported to potentiate the analgesic effects of morphine, but the locus of this interaction is not known. In this experiment, we examined the site of verapamil-induced potentiation of morphine analgesia in mice using the quaternary opioid receptor antagonist naloxone-methiodide (NLX-M). Subcutaneous injections of morphine increased locomotor activity and serum corticosterone level, which are mediated by the central nervous system. These central effects were not antagonized by 0.1 mg/kg of NLX-M, whereas this dose of NLX-M partially antagonized the analgesic effect of morphine. Treatment with verapamil potentiated morphine analgesia in a dose-dependent manner. The verapamil-induced potentiation of morphine analgesia was abolished by pretreatment with NLX-M (0.1 and 1 mg/kg). These findings suggest that peripheral mechanisms partially contribute to morphine analgesia and mediate the potentiation of morphine analgesia by verapamil.

Post-tonsillectomy analgesia: the use of benzocaine lozenges.

PubMed

Dempster, J H

1988-09-01

Tonsillectomy frequently results in a significant degree of post-operative pain. Conventional management consists of the administration of intra-muscular opiates prior to the commencement of oral analgesia and is often inadequate, producing variable levels of pain relief. One of the recommended uses of benzocaine lozenges is the relief of throat discomfort following tonsillectomy, but there are no clinical trials to support this claim. Therefore, a prospective placebo controlled trial was undertaken to compare the efficacy of benzocaine lozenges (10 mg.) with standard oral analgesia in the management of post-operative pain following tonsillectomy in an adult population. Consecutive patients undergoing elective tonsillectomy were randomised to receive either benzocaine lozenges (10 mg.) or placebo. Intake of supplementary oral analgesia was recorded, and the level of post-operative pain was assessed by use of a visual linear analogue scale. There was no significant difference in analgesic intake or pain severity as measured by linear analogue between the two groups. These results suggest that there is no benefit in administering benzocaine lozenges for the relief of post-tonsillectomy pain, and its use in this situation cannot be recommended.

The effect of epidural education on Primigravid Women's decision to request epidural analgesia: a cross-sectional study.

PubMed

Alakeely, Maha Heshaam; Almutari, Arwa Khalaf; Alhekail, Ghadah Abdulrhman; Abuoliat, Zainah Ahmad; Althubaiti, Alaa; AboItai, Laila Abdul-Rahman; Al-Kadri, Hanan

2018-05-03

Epidural analgesia represents one of the most effective pharmacological ways to relieve labour pain. Women's awareness regarding the use of epidurals is increasing. As the decision to use epidural analgesia during labour is affected by many social, personal and medical factors, this study aimed to explore the factors contributing to a pregnant women's decision to use epidurals and to understand the benefit of implementing a health education program regarding epidural analgesia. A cross-sectional study was conducted with primigravid women visiting the Obstetric Clinics for their routine antenatal care at King Abdul-Aziz Medical City in Riyadh from October 2014 to December 2016. The participating pregnant women were educated on the use of epidural analgesia during labour by a professional health educator utilizing specially designed educational materials. We assessed the relationship between the women's decision to request epidural analgesia and their age, place of residence, occupation, income and education level using a questionnaire. A total of 81 primigravid women were included in the study. Employed pregnant women were more likely to request epidural analgesia than non-employed women (46.7% vs. 18.2%, P = 0.019). After education, significantly more pregnant women were planning to request epidurals (mean score for answers before education was 2.12 ± 0.578 vs. 2.27 ± 0.592 after education, P = 0.013). Other variables, such as age, level of education, income and place of residence were not significantly associated with the participants' decision to request epidural analgesia. Health education on epidural analgesia is an important factor in increasing primigravid women's desire to request epidural analgesia. Education on epidural analgesia during antenatal care is needed for better decision making regarding the use of epidural analgesia during labour.

Quality of Labor Epidural Analgesia and Maternal Outcome With Levobupivacaine and Ropivacaine: A Double-Blinded Randomized Trial.

PubMed

Kumar, T Senthil; Rani, P; Hemanth Kumar, V R; Samal, Sunita; Parthasarathy, S; Ravishankar, M

2017-01-01

Quality of labor analgesia plays a vital role in the maternal outcome. Very few literature are available analyzing the quality of epidural labor analgesia. The aim of this study was to compare the effectiveness of 0.1% levobupivacaine and 0.1% ropivacaine with fentanyl as an adjuvant for epidural labor analgesia in terms of onset, duration, quality of analgesia, and degree of motor blockade. Sixty nulliparous parturients, with singleton uncomplicated pregnancy, were recruited by continuous sampling. Parturients were randomized to receive either levobupivacaine 0.1% or ropivacaine 0.1% with 2 μg/ml fentanyl as an intermittent epidural bolus. The epidural analgesia was initiated with 12 ml of study drug solution in the active stage of labor (cervix 3 cm dilated). Demand bolus was given whenever the visual analog scale (VAS) score >3. Onset, duration, and quality of analgesia and degree of motor blockade were analyzed. Maternal outcome was evaluated in terms of mode of delivery, duration of labor, and assisted vaginal delivery. All the data were recorded in Microsoft Office Excel. Statistical analysis was carried out using SPSS version 19.0 (IBM SPSS, USA) software with Regression Modules installed. Descriptive analyses were reported as mean and standard deviation of continuous variables. The mean onset of analgesia was shorter in ropivacaine (21.43 ± 2 min) than in levobupivacaine group (23.57 ± 1.71 min) ( P = 0.000). Duration of analgesia was shorter in ropivacaine (60 ± 14 min) than levobupivacaine (68 ± 11 min) ( P = 0.027). Levobupivacaine produced a better quality of analgesia in terms of not perceiving pain and uterine contraction during labor analgesia but was associated with 37% incidence of instrumental delivery. Duration of labor and rate of cesarean section were comparable between the groups. Quality of analgesia in labor epidural was superior to levobupivacaine but was associated with higher incidence of instrumental vaginal delivery.

Common office procedures and analgesia considerations.

PubMed

Baxter, Amy

2013-10-01

This article reviews common office procedures and analgesia considerations for pediatric outpatients. Layer times of onset of analgesics to coincide with procedures. Pediatric procedural distress is multimodal. Always address parent and child fear and attention, along with pain. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects on skin blood flow by provocation during local analgesia.

PubMed

Arildsson, M; Nilsson, G E; Strömberg, T

2000-01-01

Although topical analgesia cream has been used for several years, little is known about its effects on the microcirculation. Previous studies have shown a vasoconstrictive effect after short application times and a vasodilatation after longer application. It has also been shown that vasomotion does not occur in the analgesized skin. The present study was undertaken to investigate the alterations in skin blood perfusion following local cooling, local heating and pin-pricking after the establishment of analgesia. In 11 healthy volunteers, skin analgesia was attained by use of a eutectic mixture of lidocaine and prilocaine (EMLA, Astra Pain Control AB, Sweden) applied to the skin three hours prior to provocation. The changes in skin blood perfusion, after applying three different provocation methods, were studied using the laser Doppler technique. Local cooling and heating to temperatures of +10 and +45 degrees C, respectively, were applied for 9 s by use of a copper probe (O12 mm). In the pin-prick provocation method, a combined effect of deflection and penetration of the skin to in total 3 mm was attained. Identical provocation methods were applied to placebo treated and untreated skin areas. After heat provocation, significant differences in the perfusion response between the treatments were seen (P < 0.0001). Skin areas treated with analgesia cream responded with a slow increase in perfusion that persisted beyond the four minute measurement period. Placebo and untreated areas decreased their perfusion over time. After cooling a significant reduction in skin perfusion was seen, irrespective of the treatment. Similarly, after pin-pricking a perfusion increase was seen for all treatments. The findings indicate that topical analgesia influences the myogenic control of the blood flow in those vascular plexa measured by laser Doppler following heat provocation. No differences could be seen in the response to pin-pricking and cooling for the different treatments

TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain

PubMed Central

Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B.; Jordt, Sven-Eric

2013-01-01

Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, while other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol and WS-12 induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively with diminished side effects. PMID:23820004

Sedation and Analgesia in Transportation of Acutely and Critically Ill Patients.

PubMed

Johnston, Dawn; Franklin, Kevin; Rigby, Paul; Bergman, Karen; Davidson, Scott B

2016-06-01

Transportation of acutely or critically ill patients is a challenge for health care providers. Among the difficulties that providers face is the balance between adequate sedation and analgesia for the transportation event and maintaining acceptable respiratory and physiologic parameters of the patient. This article describes common challenges in providing sedation and analgesia during various phases of transport. Copyright © 2016 Elsevier Inc. All rights reserved.

Epoxy fatty acids mediate analgesia in murine diabetic neuropathy.

PubMed

Wagner, K; Lee, K S S; Yang, J; Hammock, B D

2017-03-01

Neuropathic pain is a debilitating condition with no adequate therapy. The health benefits of omega-3 fatty acids are established, however, the role of docosahexaenoic acid (DHA) in limiting pain has only recently been described and the mechanisms of this action remain unknown. DHA is metabolized into epoxydocosapentanoic acids (EDPs) via cytochrome P450 (CYP450) enzymes which are substrates for the soluble epoxide hydrolase (sEH) enzyme. Here, we tested several hypotheses; first, that the antinociceptive action of DHA is mediated by the EDPs. Second, based on evidence that DHA and CYP450 metabolites elicit analgesia through opioid signalling, we investigated this as a possible mechanism of action. Third, we tested whether the analgesia mediated by epoxy fatty acids had similar rewarding effects as opioid analgesics. We tested diabetic neuropathic wild-type and sEH null mice in a conditioned place preference assay for their response to EDPs, sEHI and antagonism of these treatments with naloxone, a mu-opioid receptor antagonist. The EDPs and sEH inhibitors were efficacious against chronic pain, and naloxone antagonized the action of both EDPs and sEH inhibitors. Despite this antagonism, the sEH inhibitors lacked reward side effects differing from opioids. The EpFA are analgesic against chronic pain differing from opioids which have limited efficacy in chronic conditions. EDPs and sEHI mediate analgesia in modelled chronic pain and this analgesia is blocked by naloxone. However, unlike opioids, sEHI are highly effective in neuropathic pain models and importantly lack rewarding side effects. © 2016 European Pain Federation - EFIC®.

Nationwide incidence of serious complications of epidural analgesia in the United States.

PubMed

Rosero, E B; Joshi, G P

2016-07-01

This study aimed to describe the incidence and risk factors of in-hospital spinal hematoma and abscess associated with epidural analgesia in adult obstetric and non-obstetric populations in the United States. The Nationwide Inpatient Sample was analyzed to identify patients receiving epidural analgesia from 1998 to 2010. Primary outcomes were incidence of spinal hematoma and epidural abscess. Use of decompressive laminectomy was also investigated. Regression analyses were conducted to assess predictors of epidural analgesia complications. Differences in mortality and disposition of patients at discharge were compared in patients with and without neuraxial complications. Obstetric and non-obstetric patients were studied separately. A total of 3,703,755 epidural analgesia procedures (2,320,950 obstetric and 1,382,805 non-obstetric) were identified. In obstetric patients, the incidence of spinal hematoma was 0.6 per 100,000 epidural catheterizations (95% CI, 0.3 to 1.0 × 10(-5) ). The incidence of epidural abscess was zero. In non-obstetric patients, the incidence of spinal hematoma and epidural abscess were, respectively, 18.5 per 100,000 (95% CI, 16.3 to 20.9 × 10(-5) ) and 7.2 per 100,000 (95% CI, 5.8 to 8.7 × 10(-5) ) catheterizations. Predictors of spinal hematoma included type of surgical procedure (higher in vascular surgery), teaching status of hospital, and comorbidity score. Patients with spinal complications had higher in-hospital mortality (12.2% vs. 1.1%, P < 0.0001) and were significantly less likely to be discharged to home. This large nationwide data analysis reveals that the incidence of epidural analgesia-related complications is very low in obstetric population epidural analgesia and much higher in patients having vascular surgery. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Analgesia induced by localized injection of opiate peptides into the brain of infant rats.

PubMed

Barr, G A; Wang, S

2013-05-01

Stimulation of a variety of brain sites electrically or by opiates activates descending inhibitory pathways to attenuate noxious input to the spinal cord dorsal horn and produce analgesia. Analgesia induced by electrical stimulation of the periaqueductal grey (PAG) of the midbrain or medial rostral ventral medulla (RVM) matures late, towards the end or past the pre-weaning period. Descending facilitation takes precedence over inhibition. Yet opiates injected intracerebroventricularly or directly into the PAG induce analgesia relatively early in development. Our goal was to re-examine the role of opiates specific to individual receptor types in analgesia at several supraspinal sites. Antinociception was tested following microinjection of DAMGO (μ-opiate agonist), DPDPE (∂-opiate agonist) or U50,488 (κ-opiate agonist) into the PAG, RVM or dorsal lateral pons (DLP) in 3-, 10- and 14-day-old rats. DAMGO produced analgesia at 3 days of age at each brain area; the RVM was the most effective and the dorsal PAG was the least effective site. DPDPE produced modest analgesia at 10 and 14 days of age at the ventral PAG, RVM or DLP, but not the dorsal PAG. U50,488H was ineffective at all sites and all ages. Antinociception could be elicited at all three sites by DAMGO as early as 3 days of age and DPDPE at 10 and 14 days of age. The degree of analgesia increased gradually during the first 2 weeks of life, and likely reflects the maturation of connections within the brain and of descending inhibitory paths from these sites. © 2012 European Federation of International Association for the Study of Pain Chapters.

Update on modern neuraxial analgesia in labour: a review of the literature of the last 5 years.

PubMed

Loubert, C; Hinova, A; Fernando, R

2011-03-01

Several strategies and alternative therapies have been used to provide analgesia for labour pain. Over the last few years, a number of improvements have enhanced the efficacy and safety of neuraxial analgesia and ultimately have improved mothers' satisfaction with their birth experience. As labour analgesia is a field of obstetric anaesthesia that is rapidly evolving, this review is an update, from a clinical point of view, of developments over the last 5-7 years. We discuss advantages and controversies related to combined spinal-epidural analgesia, patient controlled epidural analgesia and the integration of computer systems into analgesic modalities. We also review the recent literature on future clinical and research perspectives including ultrasound guided neuraxial block placement, epidural adjuvants and pharmacogenetics. We finally look at the latest work with regards to epidural analgesia and breastfeeding. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

Diclofenac vs oxybuprocaine eyedrops for analgesia in paediatric strabismus surgery.

PubMed

Morton, N S; Benham, S W; Lawson, R A; McNicol, L R

1997-01-01

Forty children undergoing strabismus surgery as day patients were randomly allocated to receive oxybuprocaine 0.4% eyedrops or 0.1% diclofenac eyedrops for perioperative analgesia. A non-invasive anaesthetic technique using the reinforced laryngeal mask airway was used. The study demonstrated that both topical analgesics provided good to excellent analgesia and the anaesthetic technique was associated with a relatively low incidence of nausea and vomiting. Complications were limited to two children who were admitted with persistent postoperative nausea and vomiting.

[Pro: Epidural Analgesia Remains the Gold Standard for Abdominal and Thoracic Surgery].

PubMed

Listing, Hannah; Pöpping, Daniel

2018-04-01

Pain relief with epidural analgesia is superior compared to systemic opioid analgesia after major abdominal and thoracic surgery. It remains a safe procedure, as long as it is embedded in a concept covering the whole perioperative period. This includes the knowledge of the anesthesiologist how to operate the process of catheter insertion as well as to treat complications like the hypotension, associated with the application of epidural local anesthetics. A close postoperative monitoring by an acute pain service team is a responsible task and should be available 24/7. Despite the low incidence of complications, their consequences could be disastrous for patients. To avoid persisting neurological damage, standardized diagnostic procedures must be established and surgical intervention should be available within six hours if necessary. Non-analgetic benefits of epidural analgesia include reduced pulmonary complications like pneumonia and lower incidences for cardiac arrhythmia. Furthermore, perioperative mortality could be decreased by epidural analgesia. These effects should be considered as "add-on". The excellent pain relief is more than enough to recommend this method. Georg Thieme Verlag KG Stuttgart · New York.

Continuous wound infusion and local infiltration analgesia for postoperative pain and rehabilitation after total hip arthroplasty.

PubMed

Fusco, Pierfrancesco; Cofini, Vincenza; Petrucci, Emiliano; Scimia, Paolo; Fiorenzi, Maurizio; Paladini, Giuseppe; Behr, Astrid U; Borghi, Battista; Flamini, Stefano; Pizzoferrato, Renzo; Colafarina, Olivo; Di Francesco, Alexander; Tabacco, Tito; Necozione, Stefano; Marinangeli, Franco

2018-05-01

Total hip arthroplasty is one of the most common procedures in orthopedic surgery. We hypothesized that local infiltration of analgesia and continuous wound infusion of anesthetics in the first 72 hours after surgery could provide more effective postoperative analgesia with better rehabilitation. A double-blind, randomized, controlled study was conducted with 96 patients who underwent total hip arthroplasty. The patients were randomized to receive either a local infiltration analgesia and continuous wound infusion of anesthetics or a local infiltration analgesia and continuous wound infusion of saline solution. The patients in both groups received subarachnoid anesthesia and a local infiltration analgesia. A multihole catheter was placed next to the implant and connected to an electronic pump containing a 300-mL solution of 0.2% levobupivacaine (experimental group) or saline (control group). A total of 96 consecutive patients were enrolled and randomized. Of these, 48 patients received local infiltration analgesia and continuous wound infusion of local anesthetics, and the remainder received local infiltration analgesia and continuous wound infusion of saline solution. The analysis showed a significant main effect of treatment on the postoperative incident of pain (Ftreat(1,93)=22.62, P=0.000) and on resting pain during the post-surgery follow-up (Ftreat(1,93)=15.62, P=0.0002). The pain scores during the rehabilitation period were significantly less in the experimental group. Analgesic consumption was less in the experimental group. The addition of continuous wound infusion of anesthetics to local infiltration analgesia provided an extended analgesic effect associated with good rehabilitation performance.

Women’s Experiences with Neuraxial Labor Analgesia in the Listening to Mothers II Survey: A Content Analysis of Open-Ended Responses

PubMed Central

Attanasio, Laura; Kozhimannil, Katy B.; Jou, Judy; McPherson, Marianne E.; Camann, William

2014-01-01

Background Most women who give birth in United States (US) hospitals receive neuraxial analgesia to manage pain during labor. In this analysis we examined themes of the patient experience of neuraxial analgesia among a national sample of US mothers. Methods Data are from the Listening to Mothers II survey, conducted among a national sample of women who delivered a singleton baby in a US hospital in 2005 (N=1,573). Our study population consisted of women who experienced labor, did not deliver by planned cesarean, and who reported neuraxial analgesia use (n = 914). We analyzed open-ended responses about the best and worst parts of women’s birth experiences for themes related to neuraxial analgesia using qualitative content analysis. Results Thirty-three percent of women (n=300) mentioned neuraxial analgesia in their open-ended responses. We found that effective pain relief was frequently spontaneously mentioned as a key positive theme in women’s experiences with neuraxial analgesia. However, some women perceived timing-related challenges with neuraxial analgesia, including waiting in pain for neuraxial analgesia, receiving neuraxial analgesia too late in labor, or feeling that the pain relief from neuraxial analgesia wore off too soon, as negative aspects. Other themes in women’s experiences with neuraxial analgesia were information and consent, adverse effects of neuraxial analgesia, and plans and expectations. Conclusion Findings from this analysis underscored the fact that women appreciate the effective pain relief that neuraxial analgesia provides during childbirth. While pain control was one important facet of women’s experiences with neuraxial analgesia, their experiences were also influenced by other factors. Anesthesiologists can work with obstetric clinicians, nurses, childbirth educators, and with pregnant and laboring patients to help mitigate some of the challenges with timing, communication, neuraxial analgesia administration, or expectations

Maternal positioning affects fetal heart rate changes after epidural analgesia for labour.

PubMed

Preston, R; Crosby, E T; Kotarba, D; Dudas, H; Elliott, R D

1993-12-01

Adverse fetal heart rate (FHR) changes suggestive of fetal hypoxia are seen in patients with normal term pregnancies after initiation of epidural block for labour analgesia. It was our hypothesis that, in some parturients, these changes were a consequence of concealed aortocaval compression resulting in decreased uterine blood flow. We expected that the full lateral position compared with the wedged supine position would provide more effective prophylaxis against aortocaval compression. To test our hypothesis we studied the role of maternal positioning on FHR changes during onset of epidural analgesia for labour. Eighty-eight ASA Class I or II term parturients were randomized into two groups: those to be nursed in the wedged supine position and those to be nursed in the full lateral position during induction of an epidural block. External FHR monitoring was employed to assess the fetal response to initiation of labour epidural analgesia. Epidural catheters were sited with the parturients in the sitting position and the patients then assumed the study position. After a negative test dose, a standardized regimen of bupivacaine 0.25% was employed to provide labour analgesia. The quality and efficacy of the block were assessed using VAS pain scores, motor block scores and sensory levels. The results demonstrated that there was no difference in the quality of analgesia provided nor in the incidence of asymmetric blocks. There was no difference in the observed incidence of FHR changes occurring during the initiation of the epidural block.(ABSTRACT TRUNCATED AT 250 WORDS)

[Subcostal transversus abdominis plane block can improve analgesia after laparoscopic cholecystectomy].

PubMed

Vrsajkov, Vladimir; Mančić, Nedjica; Mihajlović, Dunja; Milićević, Suzana Tonković; Uvelin, Arsen; Vrsajkov, Jelena Pantić

After laparoscopic cholecystectomy, patients have moderate pain in the early postoperative period. Some studies shown beneficial effects of subcostal transversus abdominis plane block on reducing this pain. Our goal was to investigate influence of subcostal transversus abdominis plane block on postoperative pain scores and opioid consumption. We have randomized 76 patients undergoing laparoscopic cholecystectomy to receive either subcostal transversus abdominis plane block (n=38) or standard postoperative analgesia (n=38). First group received bilateral ultrasound guided subcostal transversus abdominis plane block with 20mL of 0.33% bupivacaine per side before operation and tramadol 1mg.kg -1 IV for pain breakthrough (≥6). Second group received after operation tramadol 1mg.kg -1 /6h as standard hospital analgesia protocol. Both groups received acetaminophen 1g/8h IV and metamizole 2.5g/12h. Pain at rest was recorded for each patient using NR scale (0-10) in period of 10min, 30min, 2h, 4h, 8h, 12h and 16h after the surgery. We obtained no difference between groups according age, weight, intraoperative fentanyl consumption and duration of surgery. Subcostal transversus abdominis plane block significantly reduced postoperative pain scores compared to standard analgesia in all periods after surgery. Tramadol consumption was significantly lower in the subcostal transversus abdominis plane (24.29±47.54g) than in the standard analgesia group (270.2±81.9g) (p=0.000). Our results show that subcostal transversus abdominis plane block can provide superior postoperative analgesia and reduction in opioid requirements after laparoscopic cholecystectomy. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Diclofenac vs oxybuprocaine eyedrops for analgesia in paediatric strabismus surgery.

PubMed

Morton, N; Benham, S; Lawson, R; McNICOL, L

1997-05-01

Forty children undergoing strabismus surgery as day patients were randomly allocated to receive oxybuprocaine 0.4% eyedrops or 0.1% diclofenac eyedrops for perioperative analgesia. A non-invasive anaesthetic technique using the reinforced laryngeal mask airway was used. The study demonstrated that both topical analgesics provided good to excellent analgesia and the anaesthetic technique was associated with a relatively low incidence of nausea and vomiting. Complications were limited to two children who were admitted with persistent postoperative nausea and vomiting. 1997 Blackwell Science Ltd.

Functional network architecture predicts psychologically mediated analgesia related to treatment in chronic knee pain patients.

PubMed

Hashmi, Javeria Ali; Kong, Jian; Spaeth, Rosa; Khan, Sheraz; Kaptchuk, Ted J; Gollub, Randy L

2014-03-12

Placebo analgesia is an indicator of how efficiently the brain translates psychological signals conveyed by a treatment procedure into pain relief. It has been demonstrated that functional connectivity between distributed brain regions predicts placebo analgesia in chronic back pain patients. Greater network efficiency in baseline brain networks may allow better information transfer and facilitate adaptive physiological responses to psychological aspects of treatment. Here, we theorized that topological network alignments in resting state scans predict psychologically conditioned analgesic responses to acupuncture treatment in chronic knee osteoarthritis pain patients (n = 45). Analgesia was induced by building positive expectations toward acupuncture treatment with verbal suggestion and heat pain conditioning on a test site of the arm. This procedure induced significantly more analgesia after sham or real acupuncture on the test site than in a control site. The psychologically conditioned analgesia was invariant to sham versus real treatment. Efficiency of information transfer within local networks calculated with graph-theoretic measures (local efficiency and clustering coefficients) significantly predicted conditioned analgesia. Clustering coefficients in regions associated with memory, motivation, and pain modulation were closely involved in predicting analgesia. Moreover, women showed higher clustering coefficients and marginally greater pain reduction than men. Overall, analgesic response to placebo cues can be predicted from a priori resting state data by observing local network topology. Such low-cost synchronizations may represent preparatory resources that facilitate subsequent performance of brain circuits in responding to adaptive environmental cues. This suggests a potential utility of network measures in predicting placebo response for clinical use.

Predicting Individual Differences in Placebo Analgesia: Contributions of Brain Activity during Anticipation and Pain Experience

PubMed Central

Wager, Tor D.; Atlas, Lauren Y.; Leotti, Lauren A.; Rilling, James K.

2012-01-01

Recent studies have identified brain correlates of placebo analgesia, but none have assessed how accurately patterns of brain activity can predict individual differences in placebo responses. We reanalyzed data from two fMRI studies of placebo analgesia (N = 47), using patterns of fMRI activity during the anticipation and experience of pain to predict new subjects’ scores on placebo analgesia and placebo-induced changes in pain processing. We used a cross-validated regression procedure, LASSO-PCR, which provided both unbiased estimates of predictive accuracy and interpretable maps of which regions are most important for prediction. Increased anticipatory activity in a frontoparietal network and decreases in a posterior insular/temporal network predicted placebo analgesia. Patterns of anticipatory activity across the cortex predicted a moderate amount of variance in the placebo response (~12% overall, ~40% for study 2 alone), which is substantial considering the multiple likely contributing factors. The most predictive regions were those associated with emotional appraisal, rather than cognitive control or pain processing. During pain, decreases in limbic and paralimbic regions most strongly predicted placebo analgesia. Responses within canonical pain-processing regions explained significant variance in placebo analgesia, but the pattern of effects was inconsistent with widespread decreases in nociceptive processing. Together, the findings suggest that engagement of emotional appraisal circuits drives individual variation in placebo analgesia, rather than early suppression of nociceptive processing. This approach provides a framework that will allow prediction accuracy to increase as new studies provide more precise information for future predictive models. PMID:21228154

Attenuation of Activity in an Endogenous Analgesia Circuit by Ongoing Pain in the Rat

PubMed Central

Ferrari, Luiz F.; Gear, Robert W.; Levine, Jon D.

2010-01-01

Analgesic efficacy varies depending on the pain syndrome being treated. One reason for this may be a differential effect of individual pain syndromes on the function of endogenous pain control circuits at which these drugs act to produce analgesia. To test this hypothesis we examined the effects of diverse (i.e., ongoing inflammatory, neuropathic, or chronic widespread) pain syndromes on analgesia induced by activation of an opioid-mediated noxious stimulus-induced endogenous pain control circuit. This circuit was activated by subdermal capsaicin injection at a site remote from the site of nociceptive testing. Analgesia was not affected by carrageenan-induced inflammatory pain nor the early-phase of oxaliplatin neuropathy (a complication of cancer chemotherapy). However, the duration of analgesia was markedly shorter in the late-phase of oxaliplatin neuropathy and in alcoholic neuropathy. A model of fibromyalgia syndrome produced by chronic unpredictable stress and proinflammatory cytokines also shortened analgesia duration, but so did the same stress alone. Therefore, since chronic pain can activate neuroendocrine stress axes, we tested whether they are involved in the attenuation of analgesic duration induced by these pain syndromes. Rats in which the sympathoadrenal axis was ablated by adrenal medullectomy showed normal duration pain-induced analgesia in groups with either late-phase oxaliplatin neuropathy, alcoholic neuropathy, or exposure to sound stress. These results support the suggestion that pain syndromes can modulate activity in endogenous pain control circuits, and this effect is sympathoadrenal dependent. PMID:20943910

Early versus late initiation of epidural analgesia for labour.

PubMed

Sng, Ban Leong; Leong, Wan Ling; Zeng, Yanzhi; Siddiqui, Fahad Javaid; Assam, Pryseley N; Lim, Yvonne; Chan, Edwin S Y; Sia, Alex T

2014-10-09

Pain during childbirth is arguably the most severe pain some women may experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour. Many women have concerns regarding its safety. Furthermore, epidural services and anaesthetic support may not be available consistently across all centres. Observational data suggest that early initiation of epidural may be associated with an increased risk of caesarean section, but the same findings were not seen in recent randomised controlled trials. More recent guidelines suggest that in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labour. The choice of analgesic technique, agent, and dosage is based on many factors, including patient preference, medical status, and contraindications. There is no systematically reviewed evidence on the maternal and foetal outcomes and safety of this practice. This systematic review aimed to summarise the effectiveness and safety of early initiation versus late initiation of epidural analgesia in women. We considered the obstetric and fetal outcomes relevant to women and side effects of the treatments, including risk of caesarean section, instrumental birth and time to birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 February 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (January 1966 to February 2014), Embase (January 1980 to February 2014) and reference lists of retrieved studies. We included all randomised controlled trials involving women undergoing epidural labour analgesia that compared early initiation versus late initiation of epidural labour analgesia. Two review authors independently assessed trials for inclusion, extracted the data and assessed the trial quality. Data were checked for accuracy. We included nine studies with a total of 15,752 women.The overall risk of bias of

Evolving Role of Local Anesthetics in Managing Postsurgical Analgesia.

PubMed

Golembiewski, Julie; Dasta, Joseph

2015-06-01

Opioid analgesics, the cornerstone of effective postsurgical pain management, may be associated with risk of opioid-related adverse drug events (ADEs) that may complicate the postsurgical experience. Perioperative multimodal analgesic regimens have the potential to improve postsurgical pain control and may permit use of lower analgesic doses and reduce the incidence of opioid-related ADEs. Utility of traditional local anesthetic formulations to provide analgesia over the entire postsurgical period is limited by their short duration of action. Liposome bupivacaine, a liposomal formulation of bupivacaine indicated for single-dose administration into the surgical site to produce postsurgical analgesia, was evaluated in multiple surgical models as part of multimodal analgesic regimens and was found in clinical trials to provide postsurgical analgesia for up to 72 hours. Here, we provide an overview of the available multimodal analgesic options and recent recommendations for optimal postsurgical pain management. A review of the literature was conducted, and results from recent clinical trials are included. The use of a multimodal analgesic regimen, including liposome bupivacaine, can extend the time to first postsurgical opioid use, may reduce postsurgical opioid consumption, and reduce hospital length of stay and costs compared with an opioid-only analgesic regimen. Use of multimodal analgesic regimens is a practical way to achieve good postsurgical analgesia while minimizing reliance on opioids and associated adverse events. Taken as a whole, evidence from the clinical studies of liposome bupivacaine suggests this local anesthetic formulation may be a useful component of multimodal analgesic regimens for managing postsurgical pain in select patients, with the potential to reduce opioid use and opioid-related ADEs in the postsurgical setting. As with bupivacaine, appropriate use of liposome bupivacaine to optimize clinical effects, economic implications, and patient

Subdural Hematoma Associated With Labor Epidural Analgesia: A Case Series

PubMed Central

Lim, Grace; Zorn, Jamie M.; Dong, Yuanxu J.; DeRenzo, Joseph S.; Waters, Jonathan H.

2016-01-01

Objective This report describes the characteristics and impact of subdural hematoma (SDH) after labor epidural analgesia. Case Reports Eleven obstetric patients had subdural hematomas (SDH) associated with the use of labor epidural analgesia over 7 years at a tertiary care hospital. Ten of 11 patients had signs consistent with post-dural puncture headache (PDPH) prior to the diagnosis of SDH. Five patients (45%) had a recognized unintentional dural puncture, 1 (9%) had a combined spinal-epidural with a 24-gauge needle, and 5 (45%) had no recognized dural puncture. For 10 of the 11 cases, SDH was diagnosed an average of 4.1 (range 1–7) days after performance of labor epidural analgesia; one case was diagnosed at 25 days. Ten of 11 (91%) cases had a second hospital stay for an average of 2.8 (range 2–4) days for observation, without further requirement for neurosurgical intervention. One case (9%) had decompressive hemicraniectomy after becoming unresponsive. The observed rate of labor epidural analgesia-associated SDH was 0.026% (11 in 42,969, about 1:3900), and the rate of SDH was 1.1% (5 in 437, about 1:87) if a recognized dural puncture occurred during epidural catheter placement. Conclusions SDH after labor epidural anesthesia is rare, but potentially more common than historically estimated. Cases of PDPH after labor epidural anesthesia should be monitored closely for severe neurologic signs and symptoms that could herald SDH. PMID:27512937

Subdural Hematoma Associated With Labor Epidural Analgesia: A Case Series.

PubMed

Lim, Grace; Zorn, Jamie M; Dong, Yuanxu J; DeRenzo, Joseph S; Waters, Jonathan H

2016-01-01

This report aimed to describe the characteristics and impact of subdural hematoma (SDH) after labor epidural analgesia. Eleven obstetric patients had SDHs associated with the use of labor epidural analgesia over 7 years at a tertiary care hospital. Ten of 11 patients had signs consistent with postdural puncture headache before the diagnosis of SDH. Five patients (45%) had a recognized unintentional dural puncture, 1 (9%) had a combined spinal-epidural with a 24-gauge needle, and 5 (45%) had no recognized dural puncture. For 10 of the 11 cases, SDH was diagnosed at a mean of 4.1 days (range, 1-7 days) after performance of labor epidural analgesia; one case was diagnosed at 25 days. Ten (91%) of 11 cases had a second hospital stay for a mean of 2.8 days (range, 2-4 days) for observation, without further requirement for neurosurgical intervention. One case (9%) had decompressive hemicraniectomy after becoming unresponsive. The observed rate of labor epidural analgesia-associated SDH was 0.026% (11 in 42,969, approximately 1:3900), and the rate of SDH was 1.1% (5 in 437, approximately 1:87) if a recognized dural puncture occurred during epidural catheter placement. Subdural hematoma after labor epidural anesthesia is rare but potentially more common than historically estimated. Cases of postdural puncture headache after labor epidural anesthesia should be monitored closely for severe neurologic signs and symptoms that could herald SDH.

Pitfalls in chronobiology: a suggested analysis using intrathecal bupivacaine analgesia as an example.

PubMed

Shafer, Steven L; Lemmer, Bjoern; Boselli, Emmanuel; Boiste, Fabienne; Bouvet, Lionel; Allaouchiche, Bernard; Chassard, Dominique

2010-10-01

The duration of analgesia from epidural administration of local anesthetics to parturients has been shown to follow a rhythmic pattern according to the time of drug administration. We studied whether there was a similar pattern after intrathecal administration of bupivacaine in parturients. In the course of the analysis, we came to believe that some data points coincident with provider shift changes were influenced by nonbiological, health care system factors, thus incorrectly suggesting a periodic signal in duration of labor analgesia. We developed graphical and analytical tools to help assess the influence of individual points on the chronobiological analysis. Women with singleton term pregnancies in vertex presentation, cervical dilation 3 to 5 cm, pain score >50 mm (of 100 mm), and requesting labor analgesia were enrolled in this study. Patients received 2.5 mg of intrathecal bupivacaine in 2 mL using a combined spinal-epidural technique. Analgesia duration was the time from intrathecal injection until the first request for additional analgesia. The duration of analgesia was analyzed by visual inspection of the data, application of smoothing functions (Supersmoother; LOWESS and LOESS [locally weighted scatterplot smoothing functions]), analysis of variance, Cosinor (Chronos-Fit), Excel, and NONMEM (nonlinear mixed effect modeling). Confidence intervals (CIs) were determined by bootstrap analysis (1000 replications with replacement) using PLT Tools. Eighty-two women were included in the study. Examination of the raw data using 3 smoothing functions revealed a bimodal pattern, with a peak at approximately 0630 and a subsequent peak in the afternoon or evening, depending on the smoother. Analysis of variance did not identify any statistically significant difference between the duration of analgesia when intrathecal injection was given from midnight to 0600 compared with the duration of analgesia after intrathecal injection at other times. Chronos-Fit, Excel, and

Separating Analgesia from Reward within the Ventral Tegmental Area

PubMed Central

Schifirneţ, Elena; Bowen, Scott E.; Borszcz, George S.

2014-01-01

Activation of the dopaminergic mesolimbic reward circuit that originates in the ventral tegmental area (VTA) is postulated to preferentially suppress emotional responses to noxious stimuli, and presumably contributes to the addictive liability of strong analgesics. VTA dopamine neurons are activated via cholinergic afferents and microinjection of carbachol (cholinergic agonist) into VTA is rewarding. Here, we evaluated regional differences within VTA in the capacity of carbachol to suppress rats' affective response to pain (vocalization afterdischarges, VADs) and to support conditioned place preference (CPP) learning. As carbachol is a non-specific agonist, muscarinic and nicotinic receptor involvement was assessed by administering atropine (muscarinic antagonist) and mecamylamine (nicotinic antagonist) into VTA prior to carbachol treatment. Unilateral injections of carbachol (4 μg) into anterior VTA (aVTA) and posterior VTA (pVTA) suppressed VADs and supported CPP; whereas, injections into midVTA failed to effect either VADs or CPP. These findings corroborate the hypothesis that the neural substrates underlying affective analgesia and reward overlap. However, the extent of the overlap was only partial. Whereas both nicotinic and muscarinic receptors contributed to carbachol-induced affective analgesia in aVTA, only muscarinic receptors mediated the analgesic action of carbachol in pVTA. The rewarding effects of carbachol are mediated by the activation of both nicotinic and muscarinic receptors in both aVTA and pVTA. The results indicate that analgesia and reward are mediated by separate cholinergic mechanisms within pVTA. Nicotinic receptor antagonism within pVTA failed to attenuate carbachol-induced analgesia, but prevented carbachol-induced reward. As addictive liability of analgesics stem from their rewarding properties, the present findings suggest that these processes can be neuropharmacologically separated within pVTA. PMID:24434773

Involvement of spinal orexin A in the electroacupuncture analgesia in a rat model of post-laparotomy pain.

PubMed

Feng, Xiao-Ming; Mi, Wen-Li; Xia, Fang; Mao-Ying, Qi-Liang; Jiang, Jian-Wei; Xiao, Sheng; Wang, Zhi-Fu; Wang, Yan-Qing; Wu, Gen-Cheng

2012-11-22

Orexin A (OXA, hypocretin/hcrt 1) is a newly discovered potential analgesic substance. However, whether OXA is involved in acupuncture analgesia remains unknown. The present study was designed to investigate the involvement of spinal OXA in electroacupuncture (EA) analgesia. A modified rat model of post-laparotomy pain was adopted and evaluated. Von Frey filaments were used to measure mechanical allodynia of the hind paw and abdomen. EA at 2/15 Hz or 2/100 Hz was performed once on the bilateral ST36 and SP6 for 30 min perioperatively. SB-334867, a selective orexin 1 receptor (OX1R) antagonist with a higher affinity for OXA than OXB, was intrathecally injected to observe its effect on EA analgesia. OXA at 0.3 nmol and EA at 2/15 Hz produced respective analgesic effects on the model (P<0.05). Pre-surgical intrathecal administered of SB-334867 30 nmol antagonized OXA analgesia and attenuated the analgesic effect of EA (P<0.05). However, SB-334867 did not block fentanyl-induced analgesia (P>0.05). In addition, naloxone, a selective opioid receptor antagonist, failed to antagonize OXA-induced analgesia (P>0.05). The results of the present study indicate the involvement of OXA in EA analgesia via OX1R in an opioid-independent way.

Pain management for joint arthroplasty: preemptive analgesia.

PubMed

Mallory, Thomas H; Lombardi, Adolph V; Fada, Robert A; Dodds, Kathleen L; Adams, Joanne B

2002-06-01

Scheduled preoperative and postoperative analgesia should be offered in a multimodal management model. By a combined drug synergy effect, the central nervous system, afferent pathways, and peripheral wound site are modified collectively. In an ongoing effort to improve perioperative pain management, we retrospectively compared the results of a previously reported pain management protocol with 2 more recent groups of patients managed with modified pain protocols. In the earlier control protocol, epidural anesthesia was discontinued on arrival to the postanesthesia care unit, and regularly scheduled oral opioids and intravenous hydromorphone for breakthrough pain were initiated. The first more recent group used epidural anesthesia, and the second group used spinal anesthesia. Both protocols featured the use of cyclooxygenase-2-inhibiting anti-inflammatory medication administered for 2 weeks preoperatively and continued for 10 days postoperatively and patient-controlled analgesia for 24 hours followed by scheduled oral opioids. Copyright 2002, Elsevier Science (USA).

Dexmedetomidine as an adjuvant to bupivacaine in caudal analgesia in children

PubMed Central

Goyal, Vigya; Kubre, Jyotsna; Radhakrishnan, Krishnaprabha

2016-01-01

Context: Postoperative pain management is becoming an integral part of anesthesia care. Various techniques of pediatric pain relief have been designed among which the most commonly practiced is caudal epidural block. Several adjuvants have been used to prolong the duration of caudal analgesia such as clonidine, neostigmine, ketamine, opioids, and ephedrine. We have designed the study using dexmedetomidine as an adjuvant to assess analgesic efficacy, duration of postoperative analgesia, hemodynamic stability, postoperative sedation, and any adverse effects in children. Aims: The aim is to study the effects of dexmedetomidine as an adjuvant to bupivacaine in caudal analgesia in pediatric patients posted for infraumbilical surgeries. Settings and Design: This is a randomized, double-blind study in which effect of dexmedetomidine is studied when added to bupivacaine in the caudal epidural block. The observations are made intraoperatively for hemodynamic stability and postoperatively for the duration of analgesia. Subjects and Methods: This study was conducted in 100 children of American Society of Anesthesiologists physical status I and II, aged 2–10 years, undergoing elective infraumbilical surgeries. They were divided into two groups as follows: Group A: (0.25%) bupivacaine 1 ml/kg + normal saline (NS) 1 ml. Group B: (0.25%) bupivacaine 1 ml/kg + 1 μg/kg dexmedetomidine in 1 ml NS. As this study was double-blind, patients were randomly assigned to receive either (bupivacaine + saline) or (bupivacaine + dexmedetomidine) in each group. The patients were observed for hemodynamic stability, respiratory depression, and postoperative pain using face, legs, activity, cry, consolability (FLACC) pain scale for 24 h postoperatively. Statistical Analysis Used: Unpaired Student's t-test. Results: The mean duration of effective analgesia in Group A patients was 4.33 ± 0.98 h versus 9.88 ± 0.90 h in Group B patients. Likewise, the difference in mean FLACC score of both the

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.

Formulation and in Vitro, ex Vivo and in Vivo Evaluation of Elastic Liposomes for Transdermal Delivery of Ketorolac Tromethamine.

PubMed

Nava, Guadalupe; Piñón, Elizabeth; Mendoza, Luis; Mendoza, Néstor; Quintanar, David; Ganem, Adriana

2011-12-15

The objective of the current study was to formulate ketorolac tromethamine-loaded elastic liposomes and evaluate their in vitro drug release and their ex vivo and in vivo transdermal delivery. Ketorolac tromethamine (KT), which is a potent analgesic, was formulated in elastic liposomes using Tween 80 as an edge activator. The elastic vesicles were prepared by film hydration after optimizing the sonication time and number of extrusions. The vesicles exhibited an entrapment efficiency of 73 ± 11%, vesicle size of 127.8 ± 3.4 nm and a zeta potential of -12 mV. In vitro drug release was analyzed from liposomes and an aqueous solution, using Franz diffusion cells and a cellophane dialysis membrane with molecular weight cut-off of 8000 Da. Ex vivo permeation of KT across pig ear skin was studied using a Franz diffusion cell, with phosphate buffer (pH 7.4) at 32 °C as receptor solution. An in vivo drug permeation study was conducted on healthy human volunteers using a tape-stripping technique. The in vitro results showed (i) a delayed release when KT was included in elastic liposomes, compared to an aqueous solution of the drug; (ii) a flux of 0.278 mg/cm2h and a lag time of about 10 h for ex vivo permeation studies, which may indicate that KT remains in the skin (with the possibility of exerting a local effect) before reaching the receptor medium; (iii) a good correlation between the total amount permeated, the penetration distance (both determined by tape stripping) and transepidermal water loss (TEWL) measured during the in vivo permeation studies. Elastic liposomes have the potential to transport the drug through the skin, keep their size and drug charge, and release the drug into deep skin layers. Therefore, elastic liposomes hold promise for the effective topical delivery of KT.

A pilot study of inhaled methoxyflurane for procedural analgesia in children.

PubMed

Babl, Franz; Barnett, Peter; Palmer, Greta; Oakley, Ed; Davidson, Andrew

2007-02-01

Methoxyflurane (MF), a potent volatile anesthetic, can be used as an analgesic in subanesthetic concentrations. In Australia, MF is extensively used in children and adults as an analgesic in the prehospital setting via a hand-held inhaler device. We conducted a pilot study to explore its use as a patient controlled analgesic for painful procedures in children in the emergency department (ED). This is a prospective observational case series of children aged 5 years and older requiring procedural analgesia for brief painful procedures. Pain scores, depth of sedation, adverse events and patient, parent and staff satisfaction were assessed as well as consumption of MF measured. Fourteen patients (aged 6-13 years) received MF mainly for extremity injuries. Amount of MF consumed ranged from 0.36 to 3.06 g per patient inhaled over 4-25 min. There were no serious adverse events. No patient was deeply sedated. Five patients had mild brief self-resolving adverse events including agitation, euphoria, blurry vision, dizziness and cough. Four patients with fractures with initial high pain scores (> or =6) received MF for bridging analgesia with large drops in pain scores. Four patients who required fracture reductions with initial low scores did not achieve adequate analgesia. The remaining six patients had painful procedures undertaken with satisfactory analgesia. On the basis of this small pilot study of MF use in children in the ED, this agent appears to be a powerful analgesic. MF seems most useful as a self-titrated bridging analgesic agent in patients after extremity trauma. It appears less useful as a procedural agent when patients are unable to anticipate and achieve a sufficient level of analgesia before painful stimulus infliction. Pre- and intraprocedure coaching is an important aspect of its use especially if initial pain scores are low.

Effect of parecoxib combined with thoracic epidural analgesia on pain after thoracotomy.

PubMed

Ling, Xiao-Min; Fang, Fang; Zhang, Xiao-Guang; Ding, Ming; Liu, Qiu-A-Xue; Cang, Jing

2016-05-01

Thoracotomy results in severe postoperative pain potentially leading to chronic pain. We investigated the potential benefits of intravenous parecoxib on postoperative analgesia combined with thoracic epidural analgesia (TEA). Eighty-six patients undergoing thoracic surgery were randomized into two groups. Patient-controlled epidural analgesia (PCEA) was used until chest tubes were removed. Patients received parecoxib (group P) or placebo (group C) intravenously just 0.5 h before the operation and every 12 h after operation for 3 days. The intensity of pain was measured by using a visual analogue scale (VAS) and recorded at 2, 4, 8, 24, 48, 72 h after operation. The valid number of PCA, the side effects and the overall satisfaction to analgesic therapy in 72 h were recorded. Venous blood samples were taken before operation, the 1(st) and 3(rd) day after operation for plasma cortisol, adrenocorticotropic hormone (ACTH), interleukin-6 and tumor necrosis factor-α level. The occurrence of residual pain was recorded using telephone questionnaire 2 and 12 months after surgery. Postoperative pain scores at rest and on coughing were significantly lower with the less valid count of PCA and greater patient satisfaction in group P (P<0.01). Adverse effect and the days fit for discharge were comparable between two groups. The cortisol levels in placebo group were higher than parecoxib group at T2. The level of ACTH both decreased in two groups after operation but it was significantly lower in group P than that in group C. There were no changes in plasma IL-6 and TNF-α levels before and after analgesia at T1 and T2 (P>0.05). The occurrence of residual pain were 25% and 51.2% separately in group P and C 3 months postoperatively (P<0.05). Intravenous parecoxib in multimodal analgesia improves postoperative analgesia provided by TEA, relieves stress response after thoracotomy, and may restrain the development of chronic pain.

Postoperative analgesia in the cat after ovariohysterectomy by use of carprofen, ketoprofen, meloxicam or tolfenamic acid.

PubMed

Slingsby, L S; Waterman-Pearson, A E

2000-10-01

The adequacy of postoperative analgesia was assessed in 40 cats following ovariohysterectomy. At extubation, cats were given one dose of carprofen, ketoprofen, meloxicam or tolfenamic acid. Postoperative analgesia was assessed using visual analogue scale (VAS) scoring for pain and sedation; measurement of mechanical nociceptive thresholds at the wound; recognition of the requirement for rescue intervention analgesia; and an overall clinical assessment score at 18 hours. VAS pain scores were low throughout the trial, with no significant differences found between the groups. Postoperative mechanical nociceptive thresholds decreased significantly from baseline in all four groups, with no significant differences between the groups. One cat in each of the tolfenamic acid, ketoprofen and meloxicam groups required rescue intervention analgesia. Nine out of 10 cats in all four groups were classified as having desirable overall clinical assessment scores. In summary, all four drugs provided good postoperative analgesia, although none was able to prevent postoperative wound tenderness.

Pharmacokinetics and analgesic effect of ketorolac floating delivery system.

PubMed

Radwan, Mahasen A; Abou El Ela, Amal El Sayeh F; Hassan, Maha A; El-Maraghy, Dalia A

2015-05-01

The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form. KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay. The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8 h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the Cmax (2.2 ± 0.3 µg/ml) was achieved at ∼2 h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets. KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.

A survey on informed consent process for epidural analgesia in labor pain in Korea

PubMed Central

Lee, Nan-Ju; Sim, Jiyeon; Lee, Mi Soon; Han, Sun Sook; Lee, Hwa Mi

2010-01-01

Background There is a legal obligation to explain the procedure and use of epidural analgesia in labor primarily due to the possibility of potential risks and associated complications. The present study details on the survey carried out to ascertain the current status of obtaining informed consent (IC) for explaining the epidural analgesia in labor. Methods The present study is based on a survey through a telephone questionnaire that covered all the hospitals in Korea where the anesthesiologists' belonged to and are registered with Korean Society of Anesthesiologists. The questionnaire included questions pertaining to administration of epidural analgesia to a parturient, information on different steps of obtaining an IC, whether patient status was evaluated, when the consent was obtained, and the reasons behind, if the consent had not being given. Results A total of 1,434 respondents took part in the survey, with a response rate of 97% (1,434/1,467). One hundred seventy-four hospitals had conducted epidural analgesia on the parturient. The overall rate of obtaining IC for epidural analgesia during labor was 85%, of which only 13% was conducted by anesthesiologists. The rate of evaluating preoperative patient status was 74%, of which 45% was conducted by anesthesiologists. Almost all of the consent was obtained prior to the procedure. Conclusions The rate of obtaining IC for epidural analgesia in labor is relatively high (85%) in Korea. However, it is necessary to discuss the content of the consent and the procedure followed for obtaining IC during the rapid progress of labor. PMID:20651996

Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy.

PubMed

Talamo, Giampaolo; Liao, Jason; Bayerl, Michael G; Claxton, David F; Zangari, Maurizio

2010-03-01

Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of patients undergoing BMAB. Eighty-four consecutive adult patients underwent BMAB after local anesthesia with 5 mL of lidocaine hydrochloride 1% aqueous solution in the left posterior superior iliac crest. Analgesia was obtained with acetaminophen 650 mg and oxycodone 10 mg, and anxiolysis was obtained with lorazepam 2 mg, all drugs given once orally 30 min before the procedure. We assessed the pain level with the Wong-Baker Faces Pain Rating Scale, which distinguishes six levels of pain, from 0 to 5. The 34 patients who received an oral administration of analgesia and anxiolysis reported pain at lower levels, i.e., in the range of 0-2, more frequently than the 50 patients who underwent BMAB without analgesia/anxiolysis (78% vs 64%, respectively). Among several predictors analyzed using a multivariate regression model, three were found to be associated with decreased pain level: the use of analgesia/anxiolysis, male sex, and increase in age (all with p values <0.05). Length of the extracted bone specimen, body mass index, and need of a spinal needle for anesthesia in obese patients did not predict for pain level. An oral administration of prophylactic regimen of analgesia and anxiolysis, at the above-mentioned doses, produced a statistically significant reduction of the perception of pain in patients undergoing BMAB, but its effect did not seem to provide a major and clinically significant reduction of pain level.

Knowledge and decision-making for labour analgesia of Australian primiparous women.

PubMed

Raynes-Greenow, Camille H; Roberts, Christine L; McCaffery, Kirsten; Clarke, Judith

2007-06-01

to assess and investigate knowledge of labour pain management options and decision-making among primiparous women. a semi-structured guide was used in focus groups to gather pregnant women's knowledge concerning labour analgesia. Attitudes to labour and pain relief, knowledge of pain relief, trustworthiness of knowledge sources, and plans and expectations for labour pain relief were investigated. a major tertiary obstetric hospital in metropolitan Sydney, Australia. twenty five primiparous women, who were 25 weeks or more gestation, and planning a vaginal birth. although women considered themselves knowledgeable, they were unable to describe labour analgesic risks or benefits. There was a large discrepancy between perception and actual knowledge. The main source of knowledge was anecdotal information. Late in pregnancy was considered the ideal time to be given information about labour analgesia. Women described their labour pain relief plans as flexible in relation to their labour circumstances; however, most women wanted to take an active role in decision-making. the large discrepancy between perceived knowledge and actual knowledge of the likely consequences of labour analgesia suggests that women rely too heavily on anecdotal information. clinicians should be aware that some women overestimate their knowledge and understanding of analgesic options, which is often based on anecdotal information. Standardised labour analgesia information at an appropriate time in their pregnancy may benefit some women and assist health-care providers and women to practice shared decision-making.

Epidural Analgesia Versus Patient-Controlled Analgesia for Pain Relief in Uterine Artery Embolization for Uterine Fibroids: A Decision Analysis

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

Kooij, Sanne M. van der, E-mail: s.m.vanderkooij@amc.uva.nl; Moolenaar, Lobke M.; Ankum, Willem M.

Purpose: This study was designed to compare the costs and effects of epidural analgesia (EDA) to those of patient-controlled intravenous analgesia (PCA) for postintervention pain relief in women having uterine artery embolization (UAE) for systematic uterine fibroids. Methods: Cost-effectiveness analysis (CEA) based on data from the literature by constructing a decision tree to model the clinical pathways for estimating the effects and costs of treatment with EDA and PCA. Literature on EDA for pain-relief after UAE was missing, and therefore, data on EDA for abdominal surgery were used. Outcome measures were compared costs to reduce one point in visual analoguemore » score (VAS) or numeric rating scale (NRS) for pain 6 and 24 h after UAE and risk for complications. Results: Six hours after the intervention, the VAS was 3.56 when using PCA and 2.0 when using EDA. The costs for pain relief in women undergoing UAE with PCA and EDA were Euro-Sign 191 and Euro-Sign 355, respectively. The costs for EDA to reduce the VAS score 6 h after the intervention with one point compared with PCA were Euro-Sign 105 and Euro-Sign 179 after 24 h. The risk of having a complication was 2.45 times higher when using EDA. Conclusions: The results of this indirect comparison of EDA for abdominal surgery with PCA for UAE show that EDA would provide superior analgesia for post UAE pain at 6 and 24 h but with higher costs and an increased risk of complications.« less

Bayesian prediction of placebo analgesia in an instrumental learning model

PubMed Central

Jung, Won-Mo; Lee, Ye-Seul; Wallraven, Christian; Chae, Younbyoung

2017-01-01

Placebo analgesia can be primarily explained by the Pavlovian conditioning paradigm in which a passively applied cue becomes associated with less pain. In contrast, instrumental conditioning employs an active paradigm that might be more similar to clinical settings. In the present study, an instrumental conditioning paradigm involving a modified trust game in a simulated clinical situation was used to induce placebo analgesia. Additionally, Bayesian modeling was applied to predict the placebo responses of individuals based on their choices. Twenty-four participants engaged in a medical trust game in which decisions to receive treatment from either a doctor (more effective with high cost) or a pharmacy (less effective with low cost) were made after receiving a reference pain stimulus. In the conditioning session, the participants received lower levels of pain following both choices, while high pain stimuli were administered in the test session even after making the decision. The choice-dependent pain in the conditioning session was modulated in terms of both intensity and uncertainty. Participants reported significantly less pain when they chose the doctor or the pharmacy for treatment compared to the control trials. The predicted pain ratings based on Bayesian modeling showed significant correlations with the actual reports from participants for both of the choice categories. The instrumental conditioning paradigm allowed for the active choice of optional cues and was able to induce the placebo analgesia effect. Additionally, Bayesian modeling successfully predicted pain ratings in a simulated clinical situation that fits well with placebo analgesia induced by instrumental conditioning. PMID:28225816

Comparison of pethidine, buprenorphine and ketoprofen for postoperative analgesia after ovariohysterectomy in the cat.

PubMed

Slingsby, L S; Waterman-Pearson, A E

1998-08-15

Sixty cats which underwent an ovariohysterectomy were randomly allocated into four treatment groups. One group (controls) received no analgesics postoperatively, and the others received either a single dose of buprenorphine (0.006 mg/kg) intramuscularly, or pethidine (5 mg/kg) intramuscularly, or ketoprofen (2 mg/kg) subcutaneously. The analgesia obtained after each treatment was assessed by three measures. There were significant differences between the groups both for the requirement for intervention analgesia (P = 0.0008) and for the overall clinical assessment (P = 0.0003) with ketoprofen requiring least intervention analgesia and having the best overall clinical assessment, followed by buprenorphine then pethidine. The control group required the most intervention analgesia and had the worst overall clinical assessment. Visual analogue scale scoring for pain produced significant differences between the groups from one hour after the operation, with the cats which were given ketoprofen tending to have lower pain scores than the other groups.

Hospitalization for partial nephrectomy was not associated with intrathecal opioid analgesia: Retrospective analysis.

PubMed

Weingarten, Toby N; Del Mundo, Serena B; Yeoh, Tze Yeng; Scavonetto, Federica; Leibovich, Bradley C; Sprung, Juraj

2014-10-01

The aim of this retrospective study is to test the hypothesis that the use of spinal analgesia shortens the length of hospital stay after partial nephrectomy. We reviewed all patients undergoing partial nephrectomy for malignancy through flank incision between January 1, 2008, and June 30, 2011. We excluded patients who underwent tumor thrombectomy, used sustained-release opioids, or had general anesthesia supplemented by epidural analgesia. Patients were grouped into "spinal" (intrathecal opioid injection for postoperative analgesia) versus "general anesthetic" group, and "early" discharge group (within 3 postoperative days) versus "late" group. Association between demographics, patient physical status, anesthetic techniques, and surgical complexity and hospital stay were analyzed using multivariable logistic regression analysis. Of 380 patients, 158 (41.6%) were discharged "early" and 151 (39.7%) were "spinal" cases. Both spinal and early discharge groups had better postoperative pain control and used less postoperative systemic opioids. Spinal analgesia was associated with early hospital discharge, odds ratio 1.52, (95% confidence interval 1.00-2.30), P = 0.05, but in adjusted analysis was no longer associated with early discharge, 1.16 (0.73-1.86), P = 0.52. Early discharge was associated with calendar year, with more recent years being associated with early discharge. Spinal analgesia combined with general anesthesia was associated with improved postoperative pain control during the 1(st) postoperative day, but not with shorter hospital stay following partial nephrectomy. Therefore, unaccounted practice changes that occurred during more recent times affected hospital stay.

[Infusional therapy: an alternative for shouder pain post-laparoscopy].

PubMed

Ureña-Frausto, Cielo Alborada; Plancarte-Sánchez, Ricardo; Reyes-Torres, Juan Ignacio; Ramírez-Aranda, José Manuel

2013-01-01

Neuraxial anesthesia in upper abdominal laparoscopic surgery decreases perioperative morbidity and mortality. However, shoulder pain is common and difficult to control. Use of a major opioid (e.g., fentanyl) for the control of this event may depress respiratory function. This is why we believe that a safe and effective therapeutic control of this disease pain is a multimodal analgesic scheme which we have called infusional therapy. To compare various schemes for controlling shoulder pain secondary to pneumoperitoneum. Nonrandomized clinical trial with 56 patients ASA I-II divided into four groups undergoing laparoscopic cholecystectomy. Group I (n= 15) managed with ketorolac 1 mg kg, group II (n = 12) ketoprofen 100 mg, group III (n = 14) ketoprofen 50 mg + 50 mg tramadol, and group IV (n = 15) ketoprofen 100 mg + 100 mg tramadol. The following ariables were analyzed: presence and intensity of pain, analgesia rescue and operative time. Group I had more shoulder pain events compared to other groups (p= 0.002) in the same way the group IV required less rescue analgesia (p= 0.034). preemptive analgesia to infusional therapy with ketoprofen-tramadol at doses of 100 mg each is safe for laparoscopic surgery.

Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice.

PubMed

Kambur, Oleg; Männistö, Pekka T; Viljakka, Kaarin; Reenilä, Ilkka; Lemberg, Kim; Kontinen, Vesa K; Karayiorgou, Maria; Gogos, Joseph A; Kalso, Eija

2008-10-01

Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.

Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis.

PubMed

Rubinstein, M; Mogil, J S; Japón, M; Chan, E C; Allen, R G; Low, M J

1996-04-30

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms.

Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis.

PubMed Central

Rubinstein, M; Mogil, J S; Japón, M; Chan, E C; Allen, R G; Low, M J

1996-01-01

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms. Images Fig. 1 Fig. 2 PMID:8633004

Comparison of analgesic efficacy of four-quadrant transversus abdominis plane (TAP) block and continuous posterior TAP analgesia with epidural analgesia in patients undergoing laparoscopic colorectal surgery: an open-label, randomised, non-inferiority trial.

PubMed

Niraj, G; Kelkar, A; Hart, E; Horst, C; Malik, D; Yeow, C; Singh, B; Chaudhri, S

2014-04-01

Posterior transversus abdominis plane blocks have been reported to be an effective method of providing analgesia after lower abdominal surgery. We compared the efficacy of a novel technique of providing continuous transversus abdominis plane analgesia with epidural analgesia in patients on an enhanced recovery programme following laparoscopic colorectal surgery. A non-inferiority comparison was used. Adult patients undergoing elective laparoscopic colorectal surgery were randomly assigned to receive continuous transversus abdominis plane analgesia (n = 35) vs epidural analgesia (n = 35), in addition to a postoperative analgesic regimen comprising regular paracetamol, regular diclofenac and tramadol as required. Sixty-one patients completed the study. The transversus group received four-quadrant transversus abdominis plane blocks and bilateral posterior transversus abdominis plane catheters that were infused with levobupivacaine 0.25% for 48 h. The epidural group received an infusion of bupivacaine and fentanyl. The primary outcome measure was visual analogue scale pain score on coughing at 24 h after surgery. We found no significant difference in median (IQR [range]) visual analogue scores during coughing at 24 h between the transversus group 2.5 (1.0-3.0 [0-5.5]) and the epidural group 2.5 (1.0-5.0 [0-6.0]). The one-sided 97.5% CI was a 0.0 (∞-1.0) difference in means, establishing non-inferiority. There were no significant differences between the groups for tramadol consumption. Success rate was 28/30 (93%) in the transversus group vs 27/31 (87%) in the epidural group. Continuous transversus abdominis plane infusion was non-inferior to epidural infusion in providing analgesia after laparoscopic colorectal surgery. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

PubMed

Sng, Ban Leong; Zeng, Yanzhi; de Souza, Nurun Nisa A; Leong, Wan Ling; Oh, Ting Ting; Siddiqui, Fahad Javaid; Assam, Pryseley N; Han, Nian-Lin R; Chan, Edwin Sy; Sia, Alex T

2018-05-17

Childbirth may cause the most severe pain some women experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour and is considered to be the reference standard. Traditionally epidural analgesia has been delivered as a continuous infusion via a catheter in the epidural space, with or without the ability for the patient to supplement the analgesia received by activating a programmable pump to deliver additional top-up doses, known as patient-controlled epidural analgesia (PCEA). There has been interest in delivering maintenance analgesic medication via bolus dosing (automated mandatory bolus - AMB) instead of the traditional continuous basal infusion (BI); recent randomized controlled trials (RCTs) have shown that the AMB technique leads to improved analgesia and maternal satisfaction. To assess the effects of automated mandatory bolus versus basal infusion for maintaining epidural analgesia in labour. We searched CENTRAL, MEDLINE, Embase, the World Health Organization International Clinial Trials Registry Platform (WHO-ICTRP) and ClinicalTrials.gov on 16 January 2018. We screened the reference lists of all eligible trials and reviews. We also contacted authors of included studies in this field in order to identify unpublished research and trials still underway, and we screened the reference lists of the included articles for potentially relevant articles. We included all RCTs that compared the use of bolus dosing AMB with continuous BI for providing pain relief during epidural analgesia for labour in women. We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: risk of breakthrough pain with the need for anaesthetic intervention; risk of caesarean delivery; risk of instrumental delivery. Secondary outcomes included: duration of labour; local anaesthetic consumption. We used GRADE to assess the certainty of evidence for each outcome. We included 12 studies with a total of 1121 women. Ten

The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal

PubMed Central

Karrasch, Nicole M.; Lerche, Phillip; Aarnes, Turi K.; Gardner, Heather L.; London, Cheryl A.

2015-01-01

This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period. PMID:26246627

The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal.

PubMed

Karrasch, Nicole M; Lerche, Phillip; Aarnes, Turi K; Gardner, Heather L; London, Cheryl A

2015-08-01

This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period.

Gastric pentadecapeptide BPC 157 counteracts morphine-induced analgesia in mice.

PubMed

Boban Blagaic, A; Turcic, P; Blagaic, V; Dubovecak, M; Jelovac, N; Zemba, M; Radic, B; Becejac, T; Stancic Rokotov, D; Sikiric, P

2009-12-01

Previously, the gastric pentadecapeptide BPC 157, (PL 14736, Pliva) has been shown to have several beneficial effects, it exert gastroprotective, anti-inflammatory actions, stimulates would healing and has therapeutic value in inflammatory bowel disease. The present study aimed to study the effect of naloxone and BPC 157 on morphine-induced antinociceptive action in hot plate test in the mouse. It was found that naloxone and BPC 157 counteracted the morphine (16 mg/kg s.c.) - analgesia. Naloxone (10 mg/kg s.c.) immediately antagonised the analgesic action and the reaction time returned to the basic values, the development of BPC 157-induced action (10 pg/kg, 10 ng/kg, 10 microg/kg i.p.) required 30 minutes. When haloperidol, a central dopamine-antagonist (1 mg/kg i.p.), enhanced morphine-analgesia, BPC 157 counteracted this enhancement and naloxone reestablished the basic values of pain reaction. BPC 157, naloxone, and haloperidol per se failed to exert analgesic action. In summary, interaction between dopamine-opioid systems was demonstrated in analgesia, BPC 157 counteracted the haloperidol-induced enhancement of the antinociceptive action of morphine, indicating that BPC acts mainly through the central dopaminergic system.

External cephalic version for breech presentation with or without spinal analgesia in nulliparous women at term: a randomized controlled trial.

PubMed

Weiniger, Carolyn F; Ginosar, Yehuda; Elchalal, Uriel; Sharon, Einav; Nokrian, Malka; Ezra, Yossef

2007-12-01

To compare the success of external cephalic version using spinal analgesia with no analgesia among nulliparas. A prospective randomized controlled trial was performed in a tertiary referral center delivery suite. Nulliparous women at term requesting external cephalic version for breech presentation were randomized to receive spinal analgesia (7.5 mg bupivacaine) or no analgesia before the external cephalic version. An experienced obstetrician performed the external cephalic version. Primary outcome was successful conversion to vertex presentation. Seventy-four women were enrolled, and 70 analyzed (36 spinal, 34 no analgesia). Successful external cephalic version occurred among 24 of 36 (66.7%) women randomized to receive spinal analgesia compared with 11 of 34 (32.4%) without, P=.004 (95% confidence interval [CI] of the difference: 0.0954-0.5513). External cephalic version with spinal analgesia resulted in a lower visual analog pain score, 1.76+/-2.74 compared with 6.84+/-3.08 without, P<.001. A secondary analysis logistic regression model demonstrated that the odds of external cephalic version success was 4.0-fold higher when performed with spinal analgesia P=.02 (95% CI, odds ratio [OR] 1.2-12.9). Complete breech presentation before attempting external cephalic version increased the odds of success 8.2-fold, P=.001 (95% CI, OR 2.2-30.3). Placental position, estimated fetal weight, and maternal weight did not contribute to the success rate when spinal analgesia was used. There were no cases of placental abruption or fetal distress. Administration of spinal analgesia significantly increases the success rate of external cephalic version among nulliparous women at term, which allows possible normal vaginal delivery. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00119184 I.

[Clinical research about the consecutive pain and flubiprofen axetil analgesia following uvulopalatopharyngoplasty].

PubMed

Zhao, Y Q; Wang, H M; Ma, Y; Yang, H A; Jiang, X J

2017-04-05

Objective: To evaluate the postoperative pain degree on OSAHS patients following UPPP, analyze the pain characteristic during seven consecutive days, and discuss the mechanism. To observe the analgesia effect by using flubiprofen axetil. Finally making a comprehensive understanding about UPPP perioperative period and providing more choices about analgesia treatment. Method: Fifty-five patients who underwent UPPP in the First Hospital of China Medical University were divided into analgesia group（n=30）and control group（n=25）.Normal saline 50 ml+ flubiprofen axetil 100 mg was used bid for pain relief in analgesia group during seven days following operation, and normal saline 50ml was used in control group.A visual analog scale(VAS) was used for measuring mean pain intensity each day during the period from operative day to the post-operative 7th day，scores were recorded. Continuous changes about pharynx pain were observed and VAS pain scores were compared betweenanalgesia groupand control group. Result: VAS pain scores were the highest on the operative day and the post-operative 1st day, median (interquartile range) was 7（5.5-8.25），7（6-8）respectively,then decreased gradually. The most significantly decrease happened on the post-operative 2nd and 5th day( P <0.01). Pain scores in analgesia group were most significantly lower than control group from the operative day to the post-operative 4th day( P <0.01), were lower during the post-operative 5th and 6th day( P <0.05),no difference on the post-operative 7th day. Conclusion: The most painful period following UPPP is from the operative day to the post-operative 1st day, then pain decreases gradually. The pain reduces significantly on the post-operative 2nd and 5,6th day.Surgical trauma, in flammatory reaction and suture pulling may be the reason of pain. Flubiprofen axetil effectively reduces pain and the suggested analgesia period is from the operative day to the post-operative 4th-6th day

Effect of led photobiomodulation on analgesia during labor: Study protocol for a randomized clinical trial.

PubMed

Traverzim, Maria Aparecida Dos Santos; Makabe, Sergio; Silva, Daniela Fátima Teixeira; Pavani, Christiane; Bussadori, Sandra Kalil; Fernandes, Kristianne Santos Porta; Motta, Lara Jansiski

2018-06-01

Labor pain is one of the most intense pains experienced by women, which leads to an increase in the number of women opting to undergo a cesarean delivery. Pharmacological and nonpharmacological analgesia methods are used to control labor pain. Epidural analgesia is the most commonly used pharmacological analgesia method. However, it may have side effects on the fetus and the mother. Light-emitting diode (LED) photobiomodulation is an effective and noninvasive alternative to pharmacological methods. To evaluate the effects of LED photobiomodulation on analgesia during labor. In total, 60 women in labor admitted to a public maternity hospital will be selected for a randomized controlled trial. The participants will be randomized into 2 groups: intervention group [analgesia with LED therapy (n = 30)] and control group [analgesia with bath therapy (n = 30)]. The perception of pain will be assessed using the visual analogue scale (VAS), with a score from 0 to 10 at baseline, that is, before the intervention. In both the groups, the procedures will last 10 minutes and will be performed at 3 time points during labor: during cervical dilation of 4 to 5 cm, 6 to 7 cm, and 8 to 9 cm. At all 3 time points, pain perception will be evaluated using VAS shortly after the intervention. In addition, the evaluation of membrane characteristics (intact or damaged), heart rate, uterine dynamics, and cardiotocography will be performed at all time points. The use of LED photobiomodulation will have an analgesic effect superior to that of the bath therapy.

Hospitalization for partial nephrectomy was not associated with intrathecal opioid analgesia: Retrospective analysis

PubMed Central

Weingarten, Toby N.; Del Mundo, Serena B.; Yeoh, Tze Yeng; Scavonetto, Federica; Leibovich, Bradley C.; Sprung, Juraj

2014-01-01

Background: The aim of this retrospective study is to test the hypothesis that the use of spinal analgesia shortens the length of hospital stay after partial nephrectomy. Materials and Methods: We reviewed all patients undergoing partial nephrectomy for malignancy through flank incision between January 1, 2008, and June 30, 2011. We excluded patients who underwent tumor thrombectomy, used sustained-release opioids, or had general anesthesia supplemented by epidural analgesia. Patients were grouped into “spinal” (intrathecal opioid injection for postoperative analgesia) versus “general anesthetic” group, and “early” discharge group (within 3 postoperative days) versus “late” group. Association between demographics, patient physical status, anesthetic techniques, and surgical complexity and hospital stay were analyzed using multivariable logistic regression analysis. Results: Of 380 patients, 158 (41.6%) were discharged “early” and 151 (39.7%) were “spinal” cases. Both spinal and early discharge groups had better postoperative pain control and used less postoperative systemic opioids. Spinal analgesia was associated with early hospital discharge, odds ratio 1.52, (95% confidence interval 1.00-2.30), P = 0.05, but in adjusted analysis was no longer associated with early discharge, 1.16 (0.73-1.86), P = 0.52. Early discharge was associated with calendar year, with more recent years being associated with early discharge. Conclusion: Spinal analgesia combined with general anesthesia was associated with improved postoperative pain control during the 1st postoperative day, but not with shorter hospital stay following partial nephrectomy. Therefore, unaccounted practice changes that occurred during more recent times affected hospital stay. PMID:25422611

Alfentanil and placebo analgesia: no sex differences detected in models of experimental pain.

PubMed

Olofsen, Erik; Romberg, Raymonda; Bijl, Hans; Mooren, René; Engbers, Frank; Kest, Benjamin; Dahan, Albert

2005-07-01

To assess whether patient sex contributes to the interindividual variability in alfentanil analgesic sensitivity, the authors compared male and female subjects for pain sensitivity after alfentanil using a pharmacokinetic-pharmacodynamic modeling approach. Healthy volunteers received a 30-min alfentanil or placebo infusion on two occasions. Analgesia was measured during the subsequent 6 h by assaying tolerance to transcutaneous electrical stimulation (eight men and eight women) of increasing intensity or using visual analog scale scores during treatment with noxious thermal heat (five men and five women). Sedation was concomitantly measured. Population pharmacokinetic-pharmacodynamic models were applied to the analgesia and sedation data using NONMEM. For electrical pain, the placebo and alfentanil models were combined post hoc. Alfentanil and placebo analgesic responses did not differ between sexes. The placebo effect was successfully incorporated into the alfentanil pharmacokinetic-pharmacodynamic model and was responsible for 20% of the potency of alfentanil. However, the placebo effect did not contribute to the analgesic response variability. The pharmacokinetic-pharmacodynamic analysis of the electrical and heat pain data yielded similar values for the potency parameter, but the blood-effect site equilibration half-life was significantly longer for electrical pain (7-9 min) than for heat pain (0.2 min) or sedation (2 min). In contrast to the ample literature demonstrating sex differences in morphine analgesia, neither sex nor subject expectation (i.e., placebo) contributes to the large between-subject response variability with alfentanil analgesia. The difference in alfentanil analgesia onset and offset between pain tests is discussed.

Prolonging the duration of single-shot intrathecal labour analgesia with morphine: A systematic review.

PubMed

Al-Kazwini, Hadeel; Sandven, Irene; Dahl, Vegard; Rosseland, Leiv Arne

2016-10-01

Single-shot spinal with bupivacaine plus fentanyl or sufentanil is commonly used as analgesia during labour, but the short duration limits the clinical feasibility. Different drugs have been added to prolong the analgesic duration. The additional effect of intra-thecal morphine has been studied during labour pain as well as after surgery. We assessed whether adding morphine to intra-thecal bupivacaine+fentanyl or sufentanil prolongs pain relief during labour. Meta-analysis of placebo-controlled randomized clinical trials of analgesia prolongation after single-shot intrathecal morphine ≤250μg during labour when given in combination with bupivacaine+fentanyl or sufentanil. After identifying 461 references, 24 eligible studies were evaluated after excluding duplicate publications, case reports, studies of analgesia after caesarean delivery, and epidural labour analgesia. Mean duration in minutes was the primary outcome measure and was included in the calculation of the standardized mean difference. Duration was defined as the time between a single shot spinal until patient request of rescue analgesia. All reported side effects were registered. Results of individual trials were combined using a random effect model. Cochrane tool was used to assess risk of bias. Five randomized placebo-controlled clinical trials (286 patients) were included in the meta-analysis. A dose of 50-250μg intrathecal morphine prolonged labour analgesia by a mean of 60.6min (range 3-155min). Adding morphine demonstrated a medium beneficial effect as we found a pooled effect of standardized mean difference=0.57 (95% CI: -0.10 to 1.24) with high heterogeneity (I 2 =88.1%). However, the beneficial effect was statistically non-significant (z=1.66, p=0.096). The lower-bias trials showed a small statistically non-significant beneficial effect with lower heterogeneity. In influential analysis, that excluded one study at a time from the meta-analysis, the effect size appears unstable and the results

Impact of Preemptive Analgesia on inflammatory responses and Rehabilitation after Primary Total Knee Arthroplasty: A Controlled Clinical Study.

PubMed

Jianda, Xu; Yuxing, Qu; Yi, Gao; Hong, Zhao; Libo, Peng; Jianning, Zhao

2016-08-31

The aim of this study was to investigate the effects of preemptive analgesia on the inflammatory response and rehabilitation in TKA. 75 patients with unilateral primary knee osteoarthritis were conducted in this prospective study. All patients were randomly divided into two groups (MMA with/without preemptive analgesia group). The following parameters were used to evaluate analgesic efficacy: knee flexion, pain at rest and walking, functional walking capacity (2 MWT and 6 MWT), WOMAC score, and hs-CRP level. Patients in MMA with preemptive analgesia group had lower hs-CRP level and less pain at rest and walking during the first week postoperatively (P < 0.05). The 2 MWT was significantly better in MMA with preemptive analgesia group (17.13 ± 3.82 VS 14.19 ± 3.56, P = 0.001). The 6 MWT scores and WOMAC scores increased significantly within Groups (P = 0.020, 0.000), but no difference between groups postoperatively (P > 0.05). Less cumulative consumption of morphine was found in MMA with preemptive analgesia group at 48 h (P = 0.017, 0.023), but no difference at total requirement (P = 0.113). Preemptive analgesia added to a multimodal analgesic regime improved analgesia, reduced inflammatory reaction and accelerated functional recovery at the first week postoperatively, but not improved long-term function.

Impact of Preemptive Analgesia on inflammatory responses and Rehabilitation after Primary Total Knee Arthroplasty: A Controlled Clinical Study

PubMed Central

Jianda, Xu; Yuxing, Qu; Yi, Gao; Hong, Zhao; Libo, Peng; Jianning, Zhao

2016-01-01

The aim of this study was to investigate the effects of preemptive analgesia on the inflammatory response and rehabilitation in TKA. 75 patients with unilateral primary knee osteoarthritis were conducted in this prospective study. All patients were randomly divided into two groups (MMA with/without preemptive analgesia group). The following parameters were used to evaluate analgesic efficacy: knee flexion, pain at rest and walking, functional walking capacity (2 MWT and 6 MWT), WOMAC score, and hs-CRP level. Patients in MMA with preemptive analgesia group had lower hs-CRP level and less pain at rest and walking during the first week postoperatively (P < 0.05). The 2 MWT was significantly better in MMA with preemptive analgesia group (17.13 ± 3.82 VS 14.19 ± 3.56, P = 0.001). The 6 MWT scores and WOMAC scores increased significantly within Groups (P = 0.020, 0.000), but no difference between groups postoperatively (P > 0.05). Less cumulative consumption of morphine was found in MMA with preemptive analgesia group at 48 h (P = 0.017, 0.023), but no difference at total requirement (P = 0.113). Preemptive analgesia added to a multimodal analgesic regime improved analgesia, reduced inflammatory reaction and accelerated functional recovery at the first week postoperatively, but not improved long-term function. PMID:27578313

Conditioned placebo analgesia persists when subjects know they are receiving a placebo

PubMed Central

Schafer, Scott M.; Colloca, Luana; Wager, Tor D.

2015-01-01

Belief in the effectiveness of a placebo treatment is widely thought to be critical for placebo analgesia. Many types of placebo responses—even those that depend on conditioning—appear to be mediated by expectations that are strengthened as treatment cues are reinforced with positive outcomes. However, placebo effects may occur even when participants are aware they are receiving placebo. To address the question of whether conditioned placebo analgesia can persist in the absence of expectations, we studied the effects of long (4 days) vs. short (1 day) conditioning to a placebo treatment. After an initial placebo test, a “reveal” manipulation convincingly demonstrated to participants that they had never received an active drug. Placebo analgesia persisted after the reveal in the long conditioning group only. These findings suggest that reinforcing treatment cues with positive outcomes can create placebo effects that are independent of reported expectations for pain relief. PMID:25617812

Effects of Flurbiprofen Axetil on Postoperative Analgesia and Cytokines in Peripheral Blood of Thoracotomy Patients.

PubMed

Zhou, Mi; Li, Beiping; Kong, Ming

2015-06-01

The objective is to study the effects of flurbiprofen axetil (FA) with fentanyl together in postoperative controlled intravenous analgesia (PCIA) on pain intensity, cytokine levels in peripheral blood and adverse reactions of thoracotomy patients. Fifty thoracotomy patients were divided into a FA and a control group, each with 25 cases. Postoperative analgesia was administered in the two groups using PCIA. The pressing times of analgesia pump, the visual analog scale (VAS) scores during resting and coughing at 2, 6, 24, 48, 72 h after surgery and the incidence of adverse drug reactions were recorded. Levels of IL-1β, IL-6, IL-8, IL-2, and TNF-α in peripheral blood were determined before the administration of FA (T0), and at 24 h (T1), 48 h (T2), 72 h (T3) after surgery. The analgesia pump pressing times in the FA group was less than that of the control group. The VAS scores during resting and coughing at 2, 6, 24, 48, 72 h after surgery, were statistically less than those of control group. The incidence rate of nausea and vomiting was insignificantly different between the two groups. Administration of FA together with PCIA in thoracotomy patients can improve postoperative analgesia.

Melanocortin-1 receptor gene variants affect pain and µ-opioid analgesia in mice and humans

PubMed Central

Mogil, J; Ritchie, J; Smith, S; Strasburg, K; Kaplan, L; Wallace, M; Romberg, R; Bijl, H; Sarton, E; Fillingim, R; Dahan, A

2005-01-01

Background: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on κ-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant µ-opioid receptor. Objective: To characterise sensitivity to pain and µ-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. Methods: Comparisons of spontaneous mutant C57BL/6-Mc1re/e mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants. Results: C57BL/6-Mc1re/e mutant mice and human redheads—both with non-functional MC1Rs—display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the µ-opioid selective morphine metabolite, M6G. In both species the differential analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are similar across genotype. Conclusions: Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics. PMID:15994880

The Effect of the Time of Injection of Intrathecal Analgesia on the Length of Early and Advanced Labor

DTIC Science & Technology

2000-01-03

drug combinations. Intrathecal Analgesia 36 Future Studies Recommendations for future studies include a prospective randomized clinical trial to examine...second stages of labor because of the variations in client population and in clinical practice. Friedman (1978) Intrathecal Analgesia 7 however, does...that the administration of morphine into the subarchnoid space of rats produced potent analgesia (Wang, 1977). These effects were then clinically applied

Psychophysical testing of spatial and temporal dimensions of endogenous analgesia: conditioned pain modulation and offset analgesia.

PubMed

Honigman, Liat; Yarnitsky, David; Sprecher, Elliot; Weissman-Fogel, Irit

2013-08-01

The endogenous analgesia (EA) system is psychophysically evaluated using various paradigms, including conditioned pain modulation (CPM) and offset analgesia (OA) testing, respectively, the spatial and temporal filtering processes of noxious information. Though both paradigms assess the function of the EA system, it is still unknown whether they reflect the same aspects of EA and consequently whether they provide additive or equivalent data. Twenty-nine healthy volunteers (15 males) underwent 5 trials of different stimulation conditions in random order including: (1) the classic OA three-temperature stimulus train ('OA'); (2) a three-temperature stimulus train as control for the OA ('OAcon'); (3) a constant temperature stimulus ('constant'); (4) the classic parallel CPM ('CPM'); and (5) a combination of OA and CPM ('OA + CPM'). We found that in males, the pain reduction during the OA + CPM condition was greater than during the OA (P = 0.003) and CPM (P = 0.07) conditions. Furthermore, a correlation was found between OA and CPM (r = 0.62, P = 0.01) at the time of maximum OA effect. The additive effect found suggests that the two paradigms represent at least partially different aspects of EA. The moderate association between the CPM and OA magnitudes indicates, on the other hand, some commonality of their underlying mechanisms.

An Update on Drugs Used for Lumbosacral Epidural Anesthesia and Analgesia in Dogs

PubMed Central

Steagall, Paulo V. M.; Simon, Bradley T.; Teixeira Neto, Francisco J.; Luna, Stelio P. L.

2017-01-01

This review aims to report an update on drugs administered into the epidural space for anesthesia and analgesia in dogs, describing their potential advantages and disadvantages in the clinical setting. Databases searched include Pubmed, Google scholar, and CAB abstracts. Benefits of administering local anesthetics, opioids, and alpha2 agonists into the epidural space include the use of lower doses of general anesthetics (anesthetic “sparing” effect), perioperative analgesia, and reduced side effects associated with systemic administration of drugs. However, the potential for cardiorespiratory compromise, neurotoxicity, and other adverse effects should be considered when using the epidural route of administration. When these variables are considered, the epidural technique is useful as a complementary method of anesthesia for preventive and postoperative analgesia and/or as part of a balanced anesthesia technique. PMID:28553642

Erector spinae plane block for analgesia after lower segment caesarean section: Case report.

PubMed

Yamak Altinpulluk, E; García Simón, D; Fajardo-Pérez, M

2018-05-01

Effective postoperative analgesia after emergency caesarean section is important because it provides early recovery, ambulation and breast-feeding. The ultrasound-guided erector spinae plane block has been orginally described for providing thoracic analgesia at the T5 transverse process by Forero et al. We performed post-operative bilateral erector spinae plane blocks with 20ml bupivacaine 0.25% at the level of the T9 transverse process in a pregnant woman after caesarean section. In this report, we described that bilateral erector spinae plane block at T9 level provides effective and long-lasting postoperative analgesia for lower abdominal surgery. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Local infiltration analgesia with ropivacaine in acute fracture of thoracolumbar junction surgery.

PubMed

Swennen, C; Bredin, S; Eap, C; Mensa, C; Ohl, X; Girard, V

2017-04-01

Retrospective study. Local infiltration analgesia is effective in many surgeries as knee arthroplasty, but the analgesic efficacy of local infiltration analgesia with ropivacaine in trauma spine surgery in T10 to L2 has not been clarified. We conducted a trial to assess the analgesic efficacy of intraoperative local infiltration analgesia (LIA) with ropivacaine. The aim of the present study was to clarify the effect of intraoperative local infiltration analgesia with ropivacaine on postoperative pain for patients undergoing thoracolumbar junction fracture surgery. In a retrospective study, in 76 patients undergoing spine surgery for thoracolumbar junction fracture, 20ml of ropivacaine 7.5% (n R group=38) was infiltrated using a systematic technique, or no infiltration was realized (n M group=38). We assessed postoperative pain with Visual Analogue Scale (VAS) and morphine consumption in the 24 first hours. VAS pain score upon awakening and at 2hours postoperatively were significantly lower in the ropivacaine group (P=0.01 and P=0.002). Rescue opioid requirement during the 24 first hours were about 50% lower in the ropivacaine group (P=0.01). No local or systemic side effects were observed. Intraoperative LIA with ropivacaine in thoracolumbar junction fracture surgery may have an analgesic effect in postoperative pain control (24hours) with a reduction of VAS and morphine consumption. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Opioid, calcium, and adrenergic receptor involvement in protopine analgesia.

PubMed

Xu, Q; Jin, R L; Wu, Y Y

1993-11-01

The analgesic effect of protopine (Pro), an alkaloid isolated from Papaveraceae, was confirmed by tail-pinch and hot-plate tests when given sc 10-40 mg.kg-1, and 20-40 mg.kg-1 inhibited the spontaneous movements of mice. Pro 40 mg.kg-1 increased the sleeping rate, prolonged the sleeping duration, and shortened the sleeping latency in mice hypnotized by ip pentobarbital sodium 30 mg.kg-1. Pro 10-40 mg.kg-1 did not affect the inflammatory reaction induced by xylene and egg white. An icv injection of Pro 20-200 micrograms/mouse showed a remarkable analgesic effect in mice. The icv pretreatment of naloxone 2 micrograms blocked the analgesic effect completely. CaCl2 40 micrograms/mouse (ICV) or methotrexate 10 mg.kg-1 (ip), an agonist of Ca2+ channel, showed a complete blockade of the analgesia, while nifedipine 100 mg.kg-1(po), a blocker of Ca2+ channel, enhanced the analgesic effect. The ip pretreatment of reserpine 4 mg.kg-1 reduced the Pro analgesia. Phentolamine 10 mg.kg-1(ip), an alpha-adrenergic blocker, tended to weaken the analgesia, but propranolol 10 mg.kg-1(ip), a beta-blocker, did not affect it. These results suggest that Pro displays its analgesic effect mainly through the opioid and calcium systems and partly through the adrenergic mechanism.

The evolution of analgesia in an 'accelerated' recovery programme for resectional laparoscopic colorectal surgery with anastomosis.

PubMed

Zafar, N; Davies, R; Greenslade, G L; Dixon, A R

2010-02-01

The study set out to analyse the outcomes of an evolving accelerated recovery programme after laparoscopic colorectal resection (LCR). The results of a prospective electronic database (March 2000 - April 2008) were analysed. There were 353 consecutive patients undergoing 'three port' high anterior resection (AR) (237 without covering stoma) and 166 a right hemicolectomy (RHC). One hundred thirty-eight had postoperative analgesia using paracetamol IV and oral analgesia (IVP); 27 (16.3%) received additional parenteral morphine and were excluded. Patient controlled morphine analgesia (PCA) was used in 138. Transversus abdominis plane (TAP) blocks, supplemented by IV paracetamol and oral analgesia were used in the last 50 patients. The time to the resumption of diet was significantly reduced with TAP analgesia (median 12 h) and IVP (median 12 h) compared with PCA median (36 h) (chi(2) = 143; 4df: P < 0.001). The postoperative hospital stay was significantly reduced with TAP analgesia (median 2 days) and IVP (median 3 days) compared with PCA (median 5 days); chi(2) = 73; 2df: P < 0.001. Seventeen (34%) TAP and nine (6.5%) IVP patients were discharged within 24 h of surgery compared with no patient in the PCA group. Ninety-three per cent of PCA, 35% IVP and 10% TAP patients were discharged in more than 3 days. The movement towards 'accelerated recovery' was not associated with any increased risk of urinary retention, return to theatre, readmission and/or 30 day mortality. Laparoscopic surgery utilizing IV paracetamol and TAP blocks for postoperative analgesia aids safe effective 'accelerated recovery' in an unselected patient population undergoing right hemicolectomy and high anterior resection. Routine epidural anaesthesia is unnecessary for LCR. Morphine PCA is associated with delayed recovery.

Four quadrant transversus abdominis plane block and continuous transversus abdominis plane analgesia: a 3-year prospective audit in 124 patients.

PubMed

Niraj, G; Kelkar, Aditi; Hart, Elaine; Kaushik, Vipul; Fleet, Danny; Jameson, John

2015-11-01

Transversus abdominis plane (TAP) blocks have been reported to be an effective method of providing analgesia after abdominal surgery. To perform a prospective audit on the effectiveness of a novel technique of providing continuous transversus abdominis plane (TAP) analgesia in patients undergoing emergency and elective abdominal surgery. Prospective single center audit over a 3-year period. University hospital. One hundred twenty-four American Society of Anesthesiologists I to IV adult patients presenting for elective as well as emergency abdominal surgery in whom epidural analgesia was contraindicated or refused. Four quadrant TAP blocks and continuous TAP analgesia. Numerical rating scale pain scores at rest and on coughing, nausea scores, satisfaction scores, complications, frequency of analgesia failure, therapeutic failure with continuous TAP analgesia and opioid consumption. One hundred twenty-four patients who received continuous TAP analgesia were audited. This included 34 patients for elective open surgery, 36 patients for emergency laparotomy, and 54 patients who underwent elective laparoscopic colorectal surgery. Surgical incision was within the dermatomal limit of the block in 70% of the patients (88/124). Therapeutic failure with the technique was 10%. Frequency of analgesic failure over the 48-hour period was none in 39% and below 5 episodes in 57%. Four quadrant transversus abdominis plane blocks and continuous TAP analgesia is an effective technique for providing postoperative analgesia after abdominal surgery. It has the potential to be used as a sole analgesic technique when the surgical incision is within its dermatomal limit. Copyright © 2015 Elsevier Inc. All rights reserved.

The Analgesic Efficiency of Ultrasound-Guided Rectus Sheath Analgesia Compared with Low Thoracic Epidural Analgesia After Elective Abdominal Surgery with a Midline Incision: A Prospective Randomized Controlled Trial.

PubMed

Yassin, Hany Mahmoud; Abd Elmoneim, Ahmed Tohamy; El Moutaz, Hatem

2017-06-01

Ultrasound-guided rectus sheath blockade has been described to provide analgesia for midline abdominal incisions. We aimed to compare thoracic epidural analgesia (TEA) and rectus sheath analgesia (RSA) with respect to safety and efficacy. Sixty patients who underwent elective laparotomies through a midline incision were assigned randomly to receive either continuous TEA (TEA group, n = 31) or intermittent RSA (RSA group, n = 29). The number of patients who required analgesia, the time to first request analgesia, the interval and the cumulative morphine doses consumption during 72 hours postoperatively, and pain intensity using visual analog score (VAS) at rest and upon coughing were reported in addition to any side effects related to both techniques or administered drugs. While 17 (54.84 %) patients were in the TEA group, 25 (86.21%) patients in the RSA group required analgesia postoperatively, P = 0.008. Cumulative morphine consumed during the early 72 hours postoperatively median (interquartile range) = 33 mg (27 - 39 mg), 95% confidence interval (28.63 - 37.37 mg) for the TEA group. While in the RSA group, it was 51 mg (45 - 57 mg), 95% CI (47.4 - 54.6 mg), P < 0.001. The time for the first request of morphine was 256.77 ± 73.45 minutes in the TEA group versus 208.82 ± 64.65 min in the RSA group, P = 0.031. VAS at rest and cough were comparable in both groups at all time points of assessment, P > 0.05. The time to the ambulation was significantly shorter in the RSA group (38.47 ± 12.34 hours) as compared to the TEA group (45.89 ± 8.72 hours), P = 0.009. Sedation scores were significantly higher in the RSA group, only at 12 hours and 24 hours postoperatively than in TEA group, with P = 0.041 and 0.013, respectively. The incidence of other morphine-related side effects, time to pass flatus, and patients satisfaction scores were comparable between both groups. Continuous TEA had better opioid sparing effects markedly during the early 72 hours postoperatively

The Analgesic Efficiency of Ultrasound-Guided Rectus Sheath Analgesia Compared with Low Thoracic Epidural Analgesia After Elective Abdominal Surgery with a Midline Incision: A Prospective Randomized Controlled Trial

PubMed Central

Yassin, Hany Mahmoud; Abd Elmoneim, Ahmed Tohamy; El Moutaz, Hatem

2017-01-01

Background Ultrasound-guided rectus sheath blockade has been described to provide analgesia for midline abdominal incisions. We aimed to compare thoracic epidural analgesia (TEA) and rectus sheath analgesia (RSA) with respect to safety and efficacy. Methods Sixty patients who underwent elective laparotomies through a midline incision were assigned randomly to receive either continuous TEA (TEA group, n = 31) or intermittent RSA (RSA group, n = 29). The number of patients who required analgesia, the time to first request analgesia, the interval and the cumulative morphine doses consumption during 72 hours postoperatively, and pain intensity using visual analog score (VAS) at rest and upon coughing were reported in addition to any side effects related to both techniques or administered drugs. Results While 17 (54.84 %) patients were in the TEA group, 25 (86.21%) patients in the RSA group required analgesia postoperatively, P = 0.008. Cumulative morphine consumed during the early 72 hours postoperatively median (interquartile range) = 33 mg (27 - 39 mg), 95% confidence interval (28.63 - 37.37 mg) for the TEA group. While in the RSA group, it was 51 mg (45 - 57 mg), 95% CI (47.4 - 54.6 mg), P < 0.001. The time for the first request of morphine was 256.77 ± 73.45 minutes in the TEA group versus 208.82 ± 64.65 min in the RSA group, P = 0.031. VAS at rest and cough were comparable in both groups at all time points of assessment, P > 0.05. The time to the ambulation was significantly shorter in the RSA group (38.47 ± 12.34 hours) as compared to the TEA group (45.89 ± 8.72 hours), P = 0.009. Sedation scores were significantly higher in the RSA group, only at 12 hours and 24 hours postoperatively than in TEA group, with P = 0.041 and 0.013, respectively. The incidence of other morphine-related side effects, time to pass flatus, and patients satisfaction scores were comparable between both groups. Conclusions Continuous TEA had better opioid sparing effects markedly

Multimodal analgesia without parenteral narcotics for total knee arthroplasty.

PubMed

Dorr, Lawrence D; Raya, Julio; Long, William T; Boutary, Myriam; Sirianni, Leigh Ellen

2008-06-01

Use of parenteral narcotics after total knee arthroplasty is considered by most orthopedic surgeons to be the standard of care. This study tested the hypothesis that a multimodal oral pain medication protocol could control pain and minimize complications of parenteral narcotics. Postoperative oral analgesia was augmented with either continuous epidural infusion or continuous femoral infusion using ropivacaine only. Seventy patients had total knee arthroplasty with a protocol that included preemptive oral analgesics, epidural anesthesia, pericapsular analgesic injection, and postoperative analgesia without parenteral opioids. The average daily pain score was less than 4 out of 10, nausea occurred in 15 patients (21%), emesis in 1 patient (1.4%), and there were no severe complications. This study proved the hypothesis that pain after total knee arthroplasty could be effectively managed without routine use of parenteral opioids.

Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities.

PubMed

Flick, Randall P; Lee, Kunmoo; Hofer, Ryan E; Beinborn, Charles W; Hambel, Ellen M; Klein, Melissa K; Gunn, Paul W; Wilder, Robert T; Katusic, Slavica K; Schroeder, Darrell R; Warner, David O; Sprung, Juraj

2011-06-01

In prior work, children born to mothers who received neuraxial anesthesia for cesarean delivery had a lower incidence of subsequent learning disabilities compared with vaginal delivery. The authors speculated that neuraxial anesthesia may reduce stress responses to delivery, which could affect subsequent neurodevelopmental outcomes. To further explore this possibility, we examined the association between the use of neuraxial labor analgesia and development of childhood learning disabilities in a population-based birth cohort of children delivered vaginally. The educational and medical records of all children born to mothers residing in the area of 5 townships of Olmsted County, Minnesota from 1976 to 1982 and remaining in the community at age 5 years were reviewed to identify those with learning disabilities. Cox proportional hazards regression was used to compare the incidence of learning disabilities between children delivered vaginally with and without neuraxial labor analgesia, including analyses adjusted for factors of either potential clinical relevance or that differed between the 2 groups in univariate analysis. Of the study cohort, 4684 mothers delivered children vaginally, with 1495 receiving neuraxial labor analgesia. The presence of childhood learning disabilities in the cohort was not associated with use of labor neuraxial analgesia (adjusted hazard ratio, 1.05; 95%confidence interval, 0.85-1.31; P = 0.63). The use of neuraxial analgesia during labor and vaginal delivery was not independently associated with learning disabilities diagnosed before age 19 years. Future studies are needed to evaluate potential mechanisms of the previous finding indicating that the incidence of learning disabilities is lower in children born to mothers via cesarean delivery under neuraxial anesthesia compared with vaginal delivery.

Epidural analgesia and severe perineal tears: a literature review and large cohort study.

PubMed

Loewenberg-Weisband, Yiska; Grisaru-Granovsky, Sorina; Ioscovich, Alexander; Samueloff, Arnon; Calderon-Margalit, Ronit

2014-12-01

Our objectives were to study the association between epidural analgesia and risk of severe perineal tears (SPT), and identify additional risk factors for SPT. We conducted a historical cohort study of women with term delivery between 2006 and 2011. Inclusion criteria were an uncomplicated singleton pregnancy, cephalic presentation and vaginal delivery. Multivariate logistic regression models were constructed to study the association between epidural analgesia and SPT, controlling for potential confounders. Additional models studied the association between prolonged second stage and instrumental labor and SPT. During the study period, 61,308 eligible women gave birth, 31,631 (51.6%) of whom received epidural analgesia. SPT occurred in 0.3% of births. Deliveries with epidural had significantly higher rates of primiparity, induction and augmentation of labor, prolonged second stage of labor, instrumental births and midline episiotomies. The univariate analysis showed a significant association between the use of epidural and SPT (OR: 1.78, 95% CI: 1.34-2.36); however, this association disappeared when parity was introduced (OR: 0.95, 95% CI: 0.69-1.29). Instrumental deliveries and prolonged second stage of labor were both strongly associated with SPT (ORs of 1.82 and 1.77) CONCLUSIONS: Epidural analgesia was not associated with SPT once confounding factors were controlled for.

A romifidine and morphine combination for epidural analgesia of the flank in cattle

PubMed Central

2004-01-01

Abstract The objective of the study reported here was to determine the onset, duration, and degree of analgesia achieved with a combination of romifidine (50 μg/kg body weight [BW]) and morphine (0.1 mg/kg BW) administered epidurally. Ten adult Holstein Friesen cows were assigned to either a treatment group receiving the romifidine and morphine combination or a control group receiving 0.9% saline in a randomized, blinded, crossover design. Cows were assessed for degree of flank analgesia and systemic sedation at various time intervals over a period of 24 hours. The romifidine and morphine combination, compared with saline, provided significant analgesia for at least 10 minutes (P = 0.016) and up to 12 hours (P = 0.004) after epidural administration. Treated cows were sedate between 10 minutes (P = 0.016) and 6 hours (P = 0.002) after epidural administration. These results provide evidence for a potential cost-effective intra- and postoperative method of analgesia; however, the sedation seen in this study could be detrimental to patients expected return to the farm shortly after surgery. Further research into withdrawal times, systemic effects, and potential adverse effects are needed before an opiod and α2-adrenergic agonist combination can be used safely in a clinical setting PMID:15600157

Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty.

PubMed

Moucha, Calin Stefan; Weiser, Mitchell C; Levin, Emily J

2016-02-01

Total knee arthroplasty is associated with substantial postoperative pain that may impair mobility, reduce the ability to participate in rehabilitation, lead to chronic pain, and reduce patient satisfaction. Traditional general anesthesia with postoperative epidural and patient-controlled opioid analgesia is associated with an undesirable adverse-effect profile, including postoperative nausea and vomiting, hypotension, urinary retention, respiratory depression, delirium, and an increased infection rate. Multimodal anesthesia--incorporating elements of preemptive analgesia, neuraxial perioperative anesthesia, peripheral nerve blockade, periarticular injections, and multimodal oral opioid and nonopioid medications during the perioperative and postoperative periods--can provide superior pain control while minimizing opioid-related adverse effects, improving patient satisfaction, and reducing the risk of postoperative complications.

Analgesia use during pregnancy and risk of cryptorchidism: a systematic review and meta-analysis.

PubMed

Gurney, Jason; Richiardi, Lorenzo; McGlynn, Katherine A; Signal, Virginia; Sarfati, Diana

2017-05-01

Are boys who are born to mothers who use analgesics during pregnancy at increased risk of cryptorchidism compared to those born to mothers who do not take analgesia? In this systematic review and meta-analysis of 10 published studies, we observed only weak evidence of an association between analgesia use during pregnancy and risk of cryptorchidism in the son. Concentrations of analgesia relevant to human exposure have been implicated as causing endocrine disturbances in the developing foetal testis. However, when viewed collectively there appears to be conflicting evidence regarding an association between maternal use of analgesics and development of cryptorchidism. A systematic review and meta-analysis of studies on analgesia use during pregnancy and risk of cryptorchidism was performed. The search terms used were (analges* OR paracetamol OR acetaminophen) AND (cryptorchidism OR cryptorchism OR undescended test* OR non-descended test* OR non descended test*) for the databases Ovid Medline, Embase, Scopus and Web of Science. The search included all published articles up until 23 May 2016 and no limits were set in terms of language. Abstracts were screened by one reviewer to remove irrelevant studies, with a 10% random sample of these verified by a second reviewer. The full text of all remaining papers was assessed by two reviewers. Abstracts included in the final analysis were studies which reported associations between the exposure (analgesia) and the outcome (cryptorchidism). Studies were only included if data were provided from which summary associations (odds ratios (ORs) or relative risks) and their 95% CIs could be calculated, or if summary associations were provided by the authors themselves. For each included study, two reviewers independently extracted study meta-data in line with PRISMA recommendations. We assessed study quality and potential for bias using the criteria outlined in the Newcastle-Ottawa Quality Assessment Scale, but did not determine a

[Contra: Is Postoperative Epidural Analgesia the Gold Standard?

PubMed

Gerbershagen, Hans Jürgen

2018-04-01

As strategy for postoperative pain therapy, epidural analgesia (EDA) is superior to systemic opiate analgesia after abdominal and thoracic surgery. In addition, EDA may significantly reduce the incidence of complications in some large operations, such as, e.g. cardiac (myocardial infarction, atrial fibrillation) and pulmonary complications (pneumonia, atelectasis), and even reduce mortality. Intestinal motility can also be improved. However, these positive effects do not appear in all interventions and not to the same degree. Therefore, for benefit-risk assessment, it is important to know both the operation-specific benefits and disadvantages of EDA. In the meantime, the distinctly different complication rates of epidural bleeding and abscesses after EDA are also known for different surgical interventions. In large open abdominal interventions, open thorax operations, and especially open abdominal aortic surgeries, EDA reduces pain and complications. It should be noted that the positive effects of EDA have so far hardly been directly compared with those of intraoperative lidocaine administration. Georg Thieme Verlag KG Stuttgart · New York.

Spinal cord distribution of sup 3 H-morphine after intrathecal administration: Relationship to analgesia

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

Nishio, Y.; Sinatra, R.S.; Kitahata, L.M.

1989-09-01

The distribution of intrathecally administered {sup 3}H-morphine was examined by light microscopic autoradiography in rat spinal cord and temporal changes in silver grain localization were compared with results obtained from simultaneous measurements of analgesia. After tissue processing, radio-activity was found to have penetrated in superficial as well as in deeper layers (Rexed lamina V, VII, and X) of rat spinal cord within minutes after application. Silver grain density reached maximal values at 30 min in every region of cord studied. Radioactivity decreased rapidly between 30 min and 2 hr and then more slowly over the next 24 hr. In ratsmore » tested for responses to a thermal stimulus (tail flick test), intrathecal administration of morphine (5 and 15 micrograms) resulted in significant dose dependent analgesia that peaked at 30 min and lasted up to 5 hr (P less than 0.5). There was a close relationship between analgesia and spinal cord silver grain density during the first 4 hr of the study. It is postulated that the onset of spinal morphine analgesia depends on appearance of molecules at sites of action followed by the activation of anti-nociceptive mechanisms.« less

Positive Impact of Epidural Analgesia on Oncologic Outcomes in Patients Undergoing Resection of Colorectal Liver Metastases.

PubMed

Zimmitti, Giuseppe; Soliz, Jose; Aloia, Thomas A; Gottumukkala, Vijaya; Cata, Juan P; Tzeng, Ching-Wei D; Vauthey, Jean-Nicolas

2016-03-01

Previous studies have suggested that the use of regional anesthesia can reduce recurrence risk after oncologic surgery. The purpose of this study was to assess the effect of epidural anesthesia on recurrence-free (RFS) and overall survival (OS) after hepatic resection for colorectal liver metastases (CLM). After approval of the institutional review board, the records of all adult patients who underwent elective hepatic resection between January 2006 and October 2011 were retrospectively reviewed. Patients were categorized according to use of perioperative epidural analgesia versus intravenous analgesia. Univariate and multivariate analyses were performed to identify factors influencing RFS and OS. Of 510 total patients, 390 received epidural analgesia (EA group) and 120 patients received intravenous analgesia (IVA group). Compared with the IVA group, more patients in the EA group underwent associated surgical procedures with consequently longer operative times (p < 0.001). In addition, the EA group received more intraoperative fluids and had higher urine output volumes (p ≤ 0.001). Five-year RFS was longer in the EA group (34.7%) compared with the IVA group (21.1%). On multivariate analysis, the receipt of epidural analgesia was an independent predictor of improved RFS (p = 0.036, hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.56-0.95), but not OS (p = 0.102, HR 0.72; 95% CI 0.49-1.07). This study suggests an association between epidural analgesia and improved RFS, but not OS, after CLM resection. These results warrant further prospective, randomized studies on the benefits of regional anesthesia on oncologic outcomes after hepatic resection for CLM.

Epidural analgesia during labour, routinely or on request: a cost-effectiveness analysis.

PubMed

Bonouvrié, Kimberley; van den Bosch, Anouk; Roumen, Frans J M E; van Kuijk, Sander M; Nijhuis, Jan G; Evers, Silvia M A A; Wassen, Martine M L H

2016-12-01

To assess the cost-effectiveness of routine labour epidural analgesia (EA), from a societal perspective, as compared with labour analgesia on request. Women delivering of a singleton in cephalic presentation beyond 36+0 weeks' gestation were randomly allocated to routine labour EA or analgesia on request in one university and one non-university teaching hospital in the Netherlands. Costs included all medical, non-medical and indirect costs from randomisation to 6 weeks postpartum. Effectiveness was defined as a non-operative, spontaneous vaginal delivery without EA-related maternal adverse effects. Incremental cost-effectiveness ratio (ICER) was defined as the ratio of the difference in costs and the difference in effectiveness between both groups. Data were analysed according to intention to treat and divided into a base case analysis and a sensitivity analysis. Total delivery costs in the routine EA group (n=233) were higher than in the labour on request group (n=255) (difference -€ 322, 95% CI -€ 60 to € 355) due to more medication costs (including EA), a longer stay in the labour ward, and more operations including caesarean sections. Total postpartum hospital costs in the routine EA group were lower (difference -€ 344, 95% CI -€ 1338 to € 621) mainly due to less neonatal admissions (difference -€ 472, 95% CI -€ 1297 to € 331), whereas total postpartum home and others costs were comparable (difference -€ 20, 95% CI -€ 267 to € 248, and -€ 1, 95% CI -€ 67 to € 284, respectively). As a result, the overall mean costs per woman were comparable between the routine EA group and the analgesia on request group (€ 8.708 and € 8.710, respectively, mean difference -€ 2, 95% CI -€ 1.012 to € 916). Routine labour EA resulted in more deliveries with maternal adverse effects, nevertheless the ICER remained low (€ 8; bootstrap 95% CI -€ 6.120 to € 8.659). The cost-effectiveness acceptability curve indicated a low probability that

Comparison of carprofen and tramadol for postoperative analgesia in dogs undergoing enucleation.

PubMed

Delgado, Cherlene; Bentley, Ellison; Hetzel, Scott; Smith, Lesley J

2014-12-15

To compare analgesia provided by carprofen and tramadol in dogs after enucleation. Randomized, masked clinical trial. 43 dogs. Client-owned dogs admitted for routine enucleation were randomly assigned to receive either carprofen or tramadol orally 2 hours prior to surgery and 12 hours after the first dose. Dogs were scored for signs of pain at baseline (ie, before carprofen or tramadol administration) and at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 30 hours after extubation. Dogs received identical premedication and inhalation anesthesia regimens, including premedication with hydromorphone. If the total pain score was ≥ 9 (maximum possible score of 20), there was a score ≥ 3 in any of 5 behavioral categories (highest score possible per category was 3 or 4), or the visual analog scale (VAS) score was ≥ 35 (maximum possible score of 100) combined with a palpation score > 0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded. No differences were found in age, sex, or baseline pain scores between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21), compared with dogs receiving carprofen (1/22). Pain and VAS scores decreased linearly over time. No significant differences were found in pain or VAS scores between groups at any time point (dogs were excluded from analysis after rescue). Results of this study suggested that carprofen, with opioid premedication, may provide more effective postoperative analgesia than tramadol in dogs undergoing enucleation.

Effects of epidural lidocaine analgesia on labor and delivery: A randomized, prospective, controlled trial

PubMed Central

Nafisi, Shahram

2006-01-01

Background Whether epidural analgesia for labor prolongs the active-first and second labor stages and increases the risk of vacuum-assisted delivery is a controversial topic. Our study was conducted to answer the question: does lumbar epidural analgesia with lidocaine affect the progress of labor in our obstetric population? Method 395 healthy, nulliparous women, at term, presented in spontaneous labor with a singleton vertex presentation. These patients were randomized to receive analgesia either, epidural with bolus doses of 1% lidocaine or intravenous, with meperidine 25 to 50 mg when their cervix was dilated to 4 centimeters. The duration of the active-first and second stages of labor and the neonatal apgar scores were recorded, in each patient. The total number of vacuum-assisted and cesarean deliveries were also measured. Results 197 women were randomized to the epidural group. 198 women were randomized to the single-dose intravenous meperidine group. There was no statistical difference in rates of vacuum-assisted delivery rate. Cesarean deliveries, as a consequence of fetal bradycardia or dystocia, did not differ significantly between the groups. Differences in the duration of the active-first and the second stages of labor were not statistically significant. The number of newborns with 1-min and 5-min Apgar scores less than 7, did not differ significantly between both analgesia groups. Conclusion Epidural analgesia with 1% lidocaine does not prolong the active-first and second stages of labor and does not increase vacuum-assisted or cesarean delivery rate. PMID:17176461

Evaluation of Pain Assessment Techniques and Analgesia Efficacy in a Female Guinea Pig (Cavia porcellus) Model of Surgical Pain

PubMed Central

Oliver, Vanessa L; Athavale, Stephanie; Simon, Katherine E; Kendall, Lon V; Nemzek, Jean A; Lofgren, Jennifer L

2017-01-01

Guinea pigs (Cavia porcellus) are a frequently used species in research, often involving potentially painful procedures. Therefore, evidence-based recommendations regarding analgesia are critically needed to optimize their wellbeing. Our laboratory examined the efficacy of carprofen and extended-release (ER) buprenorphine, alone and as a multimodal combination, for relieving postsurgical pain in guinea pigs. Animals were assessed by using evoked (mechanical hypersensitivity), nonevoked (video ethogram, cageside ethogram, time-to-consumption test), and clinical (weight loss) measurements for 96 h during baseline, anesthesia–analgesia, and hysterectomy conditions. In addition, ER buprenorphine was evaluated pharmacologically. Guinea pigs treated with a single analgesic showed increased mechanical sensitivity for at least 96 h and indices of pain according to the video ethogram for as long as 8 h, compared with levels recorded during anesthesia–analgesia. In contrast, animals given both analgesics demonstrated increased mechanical sensitivity and behavioral evidence of pain for only 2 h after surgery compared with anesthesia–analgesia. The cageside ethogram and time-to-consumption tests failed to identify differences between conditions or treatment groups, highlighting the difficulty of identifying pain in guinea pigs without remote observation. Guinea pigs treated with multimodal analgesia or ER buprenorphine lost at least 10% of their baseline weights, whereas weight loss in carprofen animals was significantly lower (3%). Plasma levels for ER buprenorphine exceeded 0.9 ng/mL from 8 to 96 h after injection. Of the 3 analgesia regimens evaluated, multimodal analgesia provided the most effective pain control in guinea pigs. However the weight loss in the ER buprenorphine–treated animals may need to be considered during analgesia selection. PMID:28724492

Intrapleural bupivacaine analgesia after thoraco-abdominal incision for oesophagectomy.

PubMed

Tartiere, J; Samba, D; Lefrancois, C; Deshayes, J P; Samii, K; Bricard, H; Quesnel, J

1991-03-01

Intrapleural bupivacaine administration is said to produce good analgesia for the pain induced by a subcostal incision. However, reports of its efficacy after thoracotomy are conflicting. The goal of this study was to compare the analgesia produced by intrapleural administration of bupivacaine after oesophagectomy using a thoraco-abdominal incision with that obtained from intrapleural saline. After informed consent and institutional approval were obtained, 20 patients were randomly assigned to two groups of 10 patients each. Subjects received intrapleurally 10 ml of either 0.25% bupivacaine with 1:200,000 adrenaline or normal saline, every 8 h, beginning on the first post-operative day and lasting for 4 days. Pain was evaluated using a visual-analogue scale 2 h after the first daily treatment at rest and during physiotherapy. Pain scores were significantly lower in the bupivacaine group than in the saline group. Additionally, PaO2 was significantly higher in the bupivacaine group than in the saline group on Day 1 (P less than 0.05). The plasma bupivacaine concentration never reached the level of toxicity. Plasma bupivacaine concentrations on Day 1 after the first intrapleural bupivacaine injection were less than 350 ng ml-1; on Day 4 after the last injection they were less than 1300 ng ml-1. In conclusion, intrapleural administration of bupivacaine produces effective analgesia after oesophagectomy performed with a thoracoabdominal incision. The technique is easy to perform and is safe.

Local Infiltration of Analgesics at Surgical Wound to Reduce Postoperative Pain After Laparotomy in Rats.

PubMed

Kroin, Jeffrey S; Li, Jinyuan; Moric, Mario; Birmingham, Brian W; Tuman, Kenneth J; Buvanendran, Asokumar

There is an increasing use of local infiltration analgesia (LIA) to reduce postoperative pain. Despite widespread use of LIA, wide variations in drug combinations and concomitant use of systemic analgesics have made it difficult to determine the optimal drug combinations for LIA. Using a previously validated rat laparotomy model, the optimal LIA combination of medications to reduce postoperative pain was determined. Laparotomy was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, and dexamethasone were injected over the sutured muscle wound before skin closing, and compared to saline (placebo). The same medications were injected systemically as controls. Postoperative pain was assessed by measuring spontaneous rearing activity. A high-dose 3-drug LIA combination (50 μL of bupivacaine 0.75%, ketorolac 6.0 mg/mL, and dexamethasone 2.0 mg/mL) increased rearing (decreased pain) at 2 hours (P = 0.0032) postsurgery compared to saline. However, the same 3 drugs injected systemically had a similar analgesic effect (P = 0.0002). Bupivacaine 0.75% alone was not effective for LIA. When low-dose (9-fold reduction) 3-drug LIA combination was used, LIA increased rearing (P = 0.0034) whereas the same 3 drugs injected systemically had no effect. Low-dose LIA ketorolac/dexamethasone (2-drug combination) also increased rearing (P = 0.0393). Our animal study suggests that clinical trials with low-dose LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid may be useful for reducing postoperative pain after laparotomy.

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study.

PubMed

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study

PubMed Central

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas

Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient-controlled analgesia.

PubMed

McInnes, Rhona J; Hillan, Edith; Clark, Diana; Gilmour, Harper

2004-10-01

To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour. Randomised controlled trial. The South Glasgow University Hospitals NHS Trust. Primigravidae and multigravidae in labour at term (37-42 weeks). Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks. Analgesia requirements during labour and women's satisfaction with the method of pain relief. Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS. Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.

Quality of labour neuraxial analgesia and maternal satisfaction at a tertiary care teaching hospital: a prospective observational study.

PubMed

Clivatti, Jefferson; Siddiqui, Naveed; Goel, Akash; Shaw, Melissa; Crisan, Ioana; Carvalho, Jose C A

2013-08-01

Current labour analgesia practices are evidence-based; however, such evidence often originates in controlled trials, the results of which may not be readily applicable in the context of day-to-day clinical practice. The objective of this study was to evaluate the effectiveness of and maternal satisfaction with the neuraxial labour analgesia regimen provided at a tertiary care teaching hospital. All women with a viable pregnancy who requested neuraxial analgesia for labour during November 2011 at our institution were approached to participate in this prospective study. Patients were managed as per departmental routine based on a patient-controlled epidural analgesia regimen with a maintenance solution of 0.0625% bupivacaine and fentanyl 2 μg·mL(-1). Demographic and obstetric data, characteristics of the neuraxial analgesia, pain scores, side effects, and complications were recorded. After delivery, patients completed a satisfaction questionnaire. All 332 eligible women were approached, and 294 completed the study. Most women received epidural analgesia and considered its placement comfortable. A large number of women reported having experienced pain during the first or second stages of labour (38% and 26%, respectively). Although 24.4% of women required top-ups both by nurses and physicians, adjustment in the local anesthetic maintenance concentration was made in only 7.8% of the cases. Most women (92%) were satisfied with the quality of analgesia. Unintentional dural puncture occurred in three (1%) cases, and there were no cases of intravascular catheter insertion or systemic local anesthetic toxicity. Overweight women (body mass index 25-30 kg·m(-2)) (adjusted odds ratio [AOR] = 2.56; 95% confidence interval [CI]: 1.1 to 5.97), those undergoing induced labour (AOR = 2.4; 95% CI: 1.2 to 5.2), and those requiring top-ups by the anesthesiologist (AOR = 5.08; 95% CI: 2.31 to 11.11) were associated with more dissatisfaction with pain control during the first stage

Self-administered methoxyflurane for procedural analgesia: experience in a tertiary Australasian centre.

PubMed

Gaskell, A L; Jephcott, C G; Smithells, J R; Sleigh, J W

2016-04-01

Methoxyflurane, an agent formerly used as a volatile anaesthetic but that has strong analgesic properties, will soon become available again in the UK and Europe in the form of a small hand-held inhaler. We describe our experience in the use of inhaled methoxyflurane for procedural analgesia within a large tertiary hospital. In a small pilot crossover study of patients undergoing burns-dressing procedures, self-administered methoxyflurane inhalation was preferred to ketamine-midazolam patient-controlled analgesia by five of eight patients. Patient and proceduralist outcomes and satisfaction were recorded from a subsequent case series of 173 minor surgical and radiological procedures in 123 patients performed using inhaled methoxyflurane. The procedures included change of dressing, minor debridement, colonoscopy and incision-and-drainage of abscess. There was a 97% success rate of methoxyflurane analgesia to facilitate these procedures. Limitations of methoxyflurane include maximal daily and weekly doses, and uncertainty regarding its safety in patients with pre-existing renal disease. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

The use of intrathecal analgesia and contrast radiography as preoperative diagnostic methods for digital flexor tendon sheath pathology.

PubMed

Fiske-Jackson, A R; Barker, W H J; Eliashar, E; Foy, K; Smith, R K W

2013-01-01

The sensitivity of ultrasonography for the diagnosis of manica flexoria (MF) tears within the digital flexor tendon sheath (DFTS) is lower than for diagnosis of marginal tears of the deep digital flexor tendon (DDFT). Additional diagnostic tools would assist in appropriate decision making for either conservative or surgical management. To evaluate the improvement in lameness of horses with MF or DDFT tears following intrathecal analgesia and to assess the sensitivity and specificity of contrast radiography for the diagnosis of these tears. The case records of horses presented to a referral clinic over a 7-year period that underwent intrathecal diagnostic analgesia, or intrathecal analgesia and contrast radiography, of the DFTS with subsequent tenoscopy were examined. Fifty-three limbs had intrathecal diagnostic analgesia performed and 23 contrast tenograms were assessed in horses undergoing DFTS tenoscopy. Horses with DDFT tears were significantly more likely to respond positively to intrathecal diagnostic analgesia than those with MF tears (P = 0.02). Using contrast radiography, tears of the MF were predicted with an overall sensitivity of 96% and specificity of 80%; marginal tears of the DDFT were predicted with an overall sensitivity of 57% and specificity of 84%. The results of intrathecal analgesia of the DFTS in combination with contrast radiography have a high sensitivity for predicting MF tears. The sensitivity of contrast radiography for predicting tears of the DDFT is lower but the specificity remains high. Contrast radiography performed at the same time as intrathecal analgesia provides useful information regarding the presence of MF tears and DDFT tears, which can assist in the decision of whether to manage the lameness conservatively or with tenoscopic evaluation. © 2012 EVJ Ltd.

Intact proprioception and control of labour pain during epidural analgesia.

PubMed

Abrahams, M; Higgins, P; Whyte, P; Breen, P; Muttu, S; Gardiner, J

1999-01-01

Accurate proprioception is critical while walking, yet an ambulatory epidural regimen that provides adequate analgesia for labour while simultaneously preserving proprioceptive input has not been described. Sixty primigravidae in established labour received bupivacaine 15 mg (15 ml of 0.1% w/v) and fentanyl 100 micrograms through a lumbar epidural catheter. Clinical assessment of dorsal column sensory function included: vibration sense, distal proprioception and the Romberg test, and were all performed before catheter insertion and 30 min after the study bolus. Sensory modalities were also tested compared to an unblocked dermatome. Pain was scored on a 0-10 cm visual analogue scale (VAS) before and 30 min after induction. Intensity of the motor block was tested using a modified Bromage score (grade 1-6). The study bolus provided reliable analgesia with 43 parturients attaining a VAS pain score of zero. Mean duration of analgesia was 67.5 min (SD 22.85). All parturients retained the ability to perform a partial knee bend while standing (grade 6). No mothers exhibited impaired distal proprioception, altered vibration sense or a positive Romberg sign. This study confirms that the addition of lumbar epidural fentanyl 100 micrograms to 15 mg of epidural bupivacaine provides good control of labour pain with no motor block and establishes that this combination preserves dorsal column sensory function.

Side effects of pain and analgesia in animal experimentation.

PubMed

Jirkof, Paulin

2017-03-22

This review highlights selected effects of untreated pain and of widely used analgesics such as opioids, non-steroid anti-inflammatory drugs and antipyretics, to illustrate the relevance of carefully planned, appropriate and controlled analgesia for greater reproducibility in animal experiments involving laboratory rodents.

Effect of Peripheral μ-, δ-, and κ-Opioid Ligands on the Development of Tolerance to Ethanol-Induced Analgesia.

PubMed

Sudakov, S K; Alekseeva, E V; Nazarova, G A

2017-06-01

We studied the rate of development of tolerance to the ethanol-induced analgesia under the effect of μ-, δ-, and κ-opioid agonists and antagonists not crossing the blood-brain barrier and rapidly inactivated by gastric and duodenal proteolytic enzymes. Activation of gastric κ-opioid receptors eliminated the analgesic effect of ethanol and accelerated the development of tolerance to ethanol-induced analgesia. In contrast, activation of gastric μ-opioid receptors decelerated the development of this tolerance. Activation of gastric δ-opioid receptors produced no effect on examined tolerance. μ-Opioid receptor antagonist decelerated and δ-opioid receptor antagonist accelerated the development of tolerance to ethanol-induced analgesia. Thus, the state of gastric opioid receptors affects the manifestation of ethanol-induced analgesia and the development of tolerance to this effect.

Use of Epidural Analgesia as an Adjunct in Elective Abdominal Wall Reconstruction: A Review of 4983 Cases.

PubMed

Karamanos, Efstathios; Dream, Sophie; Falvo, Anthony; Schmoekel, Nathan; Siddiqui, Aamir

2017-01-01

Use of epidural analgesia in patients undergoing elective abdominal wall reconstruction is common. To assess the impact of epidural analgesia in patients undergoing abdominal wall reconstruction. All patients who underwent elective ventral hernia repair from 2005 to 2014 were retrospectively identified. Patients were divided into two groups by the postoperative use of epidural analgesics as an adjunct analgesic method. Preoperative comorbidities, American Society of Anesthesiologists status, operative findings, postoperative pain management, and venothromboembolic prophylaxis were extracted from the database. Logistic regressions were performed to assess the impact of epidural use. Severity of pain on postoperative days 1 and 2. During the study period, 4983 patients were identified. Of those, 237 patients (4.8%) had an epidural analgesic placed. After adjustment for differences between groups, use of epidural analgesia was associated with significantly lower rates of 30-day presentation to the Emergency Department (adjusted odds ratio [AOR] = 0.53, 95% confidence interval [CI] = 0.32-0.87, adjusted p = 0.01). Use of epidural analgesia resulted in higher odds of abscess development (AOR = 5.89, CI = 2.00-17.34, adjusted p < 0.01) and transfusion requirement (AOR = 2.92, CI = 1.34-6.40, adjusted p < 0.01). Use of epidural analgesia resulted in a significantly lower pain score on postoperative day 1 (3 vs 4, adjusted p < 0.01). Use of epidural analgesia in patients undergoing abdominal wall reconstruction may result in longer hospital stay and higher incidence of complications while having no measurable positive clinical impact on pain control.

A Comparison of Nonopioid and Opioid Oral Analgesia Following Pediatric Palatoplasty.

PubMed

Pierson, Brandon W; Cardon, Brandon S; Anderson, Michael P; Glade, Robert S

2017-03-01

  This article evaluates postoperative analgesia in pediatric palatoplasty patients using nonopioid oral medications.   This study was a retrospective chart review.   The setting for this study was a tertiary-care children's hospital.   Study participants were pediatric patients who underwent palatoplasty procedures performed by a single surgeon.   Interventions included nonopioid and opioid oral medications for postoperative analgesia.   The adequacy of nonopioid versus opioid oral analgesia was assessed by (1) time to discontinue IV fluid, (2) total IV morphine doses for breakthrough pain, (3) daily IV morphine doses for breakthrough pain, (4) time to discharge from the hospital, and (5) perioperative weight change. Group comparisons of outcome measures were performed using a two one-sided test.   A total of 61 patients were identified who received three standard pain regimens: acetaminophen + ibuprofen (12), hydrocodone/acetaminophen (23), and hydrocodone/acetaminophen + ibuprofen (26). There was sufficient evidence to suggest equivalence in outcome measures for acetaminophen + ibuprofen versus hydrocodone/acetaminophen and hydrocodone/acetaminophen + ibuprofen for the following: time to discontinue IV fluid (P = .02, 90% confidence interval [CI] = -0.42 to 0.17; P = .007, 90% CI = -0.28 to 0.34), daily IV morphine doses (P = .023, 90% CI = -0.83 to 0.65; P = .032, 90% CI = -0.92 to 0.28), time to discharge from the hospital (P = .017, 90% CI = -0.40 to 0.27; P = .015, 90% CI = -0.24 to 0.39), and perioperative weight change (P = .002; 90% CI = -0.25 to 0.46; P < .0001; 90% CI = -0.34 to 0.18). There was no sufficient evidence to suggest equivalence for total IV morphine doses (P = .189, 90% CI = -1.51 to 1.78; P = .169, 90% CI = -1.51 to 0.88).   Oral acetaminophen and ibuprofen alone may provide similar analgesia to traditional regimens with reduced risks following pediatric palatoplasty.

DL-phenylalanine markedly potentiates opiate analgesia - an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system.

PubMed

Russell, A L; McCarty, M F

2000-10-01

In the author's clinical experience, concurrent treatment with DL-phenylalanine (DLPA) often appears to potentiate pain relief and also ease depression in patients receiving opiates for chronic non-malignant pain. An analysis of this phenomenon suggests that it may be mediated, at least in part, by up-regulation of the 'endogenous analgesia system' (EAS), a neural pathway that projects caudally from medullary nuclei to the dorsal horn of the spinal column; when stimulated by chronic pain or therapeutic measures such as opiates or acupuncture, the EAS suppresses activation of second-order pain-receptive neurons in the dorsal horn, and thereby alleviates pain. Since serotonin and enkephalins are key neurotransmitters in the EAS, it is reasonable to predict that measures which promote serotonin activity (such as 5-hydroxytryptophan and serotonin-reuptake inhibitors) as well as enkephalin activity (such as D-phenylalanine, an enkephalinase inhibitor) should potentiate EAS-mediated analgesia - a view consistent with much previous medical research. Comprehensive support of the EAS with well-tolerated nutrients and pharmaceuticals may amplify the analgesic efficacy of chronic opiate therapy, while enabling dosage reductions that minimize opiate side-effects. Analogously, this approach may complement the efficacy of acupuncture and other analgesic measures that activate the EAS. Copyright 2000 Harcourt Publishers Ltd.

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast)

PubMed Central

Hutchinson, Mark R.; Lewis, Susannah S.; Coats, Benjamen D.; Skyba, David A.; Crysdale, Nicole Y.; Berkelhammer, Debra L.; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M.; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.; Johnson, Kirk W.

2009-01-01

Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused 3-to-5-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, whilst improving analgesia. PMID:18938237

Epidural analgesia in children. A survey of current opinions and practices amongst UK paediatric anaesthetists.

PubMed

Williams, D G; Howard, R F

2003-11-01

Despite the widespread use of epidural analgesia in children its place in paediatric pain management has not been clearly established. In order to investigate the current practice of paediatric epidural analgesia in the UK paediatric anaesthetists and paediatric pain management teams were surveyed. Questionnaires were sent to the members of the Association of Paediatric Anaesthetists (APA) working within the UK and to lead clinicians and clinical nurse specialists for acute pain in the 26 designated major paediatric centres. The response rate was 72%. There was little consensus regarding drugs and drug combinations used for epidural analgesia. A total of 36% of paediatric centres did not audit their epidural practice, and of those that did the reported incidences of side-effects showed wide variation. Important differences in practice were also identified in the areas of patient selection, informed consent, the use of epidural test doses, drug delivery systems, monitoring and the management of side-effects. Twelve per cent of specialist paediatric hospitals did not have an acute pain team and elsewhere the provision was often limited to staff with few or no specialist skills. There is wide variation in the practice of paediatric epidural analgesia in the UK. Inconsistencies are likely to be related to the poor evidence base available to guide clinical decision making and the lack of a specialized paediatric acute pain service in some centres. More research is required to determine the optimal management of epidural analgesia, and suitable clinical support for paediatric pain control should be more widely available.

Effect of epidural analgesia in patients with traumatic rib fractures: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Carrier, François M; Turgeon, Alexis F; Nicole, Pierre C; Trépanier, Claude A; Fergusson, Dean A; Thauvette, Daniel; Lessard, Martin R

2009-03-01

A consensus group recently proposed epidural analgesia as the optimal analgesic modality for patients with multiple traumatic rib fractures. However, its beneficial effects are not consistently recognized in the literature. We performed a systematic review and a meta-analysis of randomized controlled trials (RCT) of epidural analgesia in adult patients with traumatic rib fractures. A systematic search strategy was applied to MEDLINE, EMBASE, the Cochrane Library and to the annual meeting of relevant societies (up to July 2008). All randomized controlled trials comparing epidural analgesia with other analgesic modalities in adult patients with traumatic rib fractures were included. Primary outcomes were mortality, ICU length of stay (LOS), hospital LOS and duration of mechanical ventilation. Eight studies (232 patients) met eligibility criteria. Epidural analgesia did not significantly affect mortality (odds ratio [OR] 1.6, 95% CI, 0.3, 9.3, 3 studies, n = 89), ICU LOS (weighted mean difference [WMD] -3.7 days, 95% CI, -11.4, 4.0, 4 studies, n = 135), hospital LOS (WMD -6.7, 95% CI, -19.8, 6.4, 4 studies, n = 140) or duration of mechanical ventilation (WMD -7.5, 95% CI, -16.3, 1.2, 3 studies, n = 101). Duration of mechanical ventilation was decreased when only studies using thoracic epidural analgesia with local anesthetics were evaluated (WMD -4.2, 95% CI, -5.5, -2.9, 2 studies, n = 73). However, hypotension was significantly associated with the use of thoracic epidural analgesia with local anesthetics (OR 13.76, 95% CI, 2.89, 65.51, 3 studies, n = 99). No significant benefit of epidural analgesia on mortality, ICU and hospital LOS was observed compared to other analgesic modalities in adult patients with traumatic rib fractures. However, there may be a benefit on the duration of mechanical ventilation with the use of thoracic epidural analgesia with local anesthetics. Further research is required to evaluate the benefits and harms of epidural analgesia in this

Frequency of colonization and isolated bacteria from the tip of epidural catheter implanted for postoperative analgesia.

PubMed

Stabille, Débora Miranda Diogo; Diogo Filho, Augusto; Mandim, Beatriz Lemos da Silva; de Araújo, Lúcio Borges; Mesquita, Priscila Miranda Diogo; Jorge, Miguel Tanús

2015-01-01

The increased use of epidural analgesia with catheter leads to the need to demonstrate the safety of this method and know the incidence of catheter colonization, inserted postoperatively for epidural analgesia, and the bacteria responsible for this colonization. From November 2011 to April 2012, patients electively operated and maintained under epidural catheter for postoperative analgesia were evaluated. The catheter tip was collected for semiquantitative and qualitative microbiological analysis. Of 68 cultured catheters, six tips (8.8%) had positive cultures. No patient had superficial or deep infection. The mean duration of catheter use was 43.45 h (18-118) (p=0.0894). The type of surgery (contaminated or uncontaminated), physical status of patients, and surgical time showed no relation with the colonization of catheters. Microorganisms isolated from the catheter tip were Staphylococcus aureus, Pseudomonas aeruginosa and Sphingomonas paucimobilis. Postoperative epidural catheter analgesia, under these study conditions, was found to be low risk for bacterial colonization in patients at surgical wards. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Overdose of opioid from patient-controlled analgesia pumps.

PubMed

Notcutt, W G; Knowles, P; Kaldas, R

1992-07-01

Two incidence have occurred in our hospital when a patient-controlled analgesia pump has accidentally delivered the whole contents of the syringe of diamorphine (60 mg) over a period of approximately 1 h. Electrical corruption of the pumps' program has been identified as the probable cause. All pumps of this type have been modified to prevent such occurrences.

[Comparative assessment of prolonged femoral nerve blockade and epidural analgesia for postoperative pain in total knee joint arthroplasty].

PubMed

Churadze, B T; Sevalkin, S A; Zadorozhnyĭ, M V; Volkov, P A; Gur'ianov, V A

2013-01-01

The study deals with two mostly discussed techniques of postoperative analgesia for total knee joint arthroplasty. Surgeries were performed under subarachnoid anaesthesia with intravenous sedation. 9 patients of first group in received prolonged femoral nerve blockade as a component of multimodal analgesia. 8 patients of second group received epidural infusion of naropine. If basic technique of analgesia was not effective patients received trimeperidine 20 mg intramuscular. Patients of second group had less pain syndrome (in order to visual analogue scale) and did not need additional administration of opioids.

Use of hydrotherapy during labour: Assessment of pain, use of analgesia and neonatal safety.

PubMed

Mallen-Perez, Laura; Roé-Justiniano, M Teresa; Colomé Ochoa, Núria; Ferre Colomat, Alicia; Palacio, Montse; Terré-Rull, Carme

2017-11-24

To evaluate the effectiveness of the use of hydrotherapy in pain perception and requesting analgesia in women who use hydrotherapy during childbirth and to identify possible adverse effects in infants born in water. A multicentre prospective cohort study was performed between September 2014 and April 2016. A total of 200 pregnant women were selected and assigned to the hydrotherapy group (HG) or the control group (CG) according to desire and availability of use, data collection started at 5cm dilatation. The instruments used were the numerical rating scale (NRS), use of analgesia, Apgar Test, umbilical cord pH and NICU admission. Participants were distributed into: HG (n=111; 50 water birth) and CG (n=89). Pain at 30 and 90min was lower in the HG than in the CG (NRS 30min 6.7 [SD 1.6] vs 7.8 [SD 1.2] [P<.001] and NRS 90min 7.7 [SD 1.2] vs. 8.9 [SD 1.1] [P<.001]). During the second stage of labour, pain was lower in pregnant women undergoing a water birth (NRS HG 8.2 [SD 1.2], n=50; NRS CG 9.5 [SD 0.5], n=89 [P<.001]). Relative to the use of analgesia, in the CG 30 (33.7%) pregnant women requested epidural analgesia vs. 24 (21.1%) pregnant women in HG (P=.09). The neonatal parameters after water birth were not modified compared to those born out of water. The use of hydrotherapy reduces pain during labour, and during second stage in women who undergo a water birth and the demand for analgesia decreases in multiparous pregnant women. No adverse effects were seen in infants born under water. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Improving postoperative tonsillectomy pain management in children--a double blinded randomised control trial of a patient analgesia information sheet.

PubMed

Bailey, Lucas; Sun, Jing; Courtney, Mark; Murphy, Paul

2015-05-01

To evaluate paediatric post-tonsillectomy pain management using oxycodone when a specific analgesia information sheet is included with standard postoperative information. Oxycodone information sheets were randomly allocated to half the study children's post-tonsillectomy information pack. The trial was double-blinded to the surgeon, anaesthetist, nursing and administrative staff. Parents and children completed the pain assessment on day 3, 5 and 7. On day 10 the parents completed a questionnaire. A postoperative analgesia information sheet provides for higher satisfaction and knowledge for parents using oxycodone (p<0.001) and children have improved postoperative pain control, most significantly at day 5 (p<0.05). Parent assessment of the child's analgesia was superior with the oxycodone information sheet, most significantly at day 3 and 7 post operatively (p<0.05). There is also a positive correlation between the parents' observed pain score and children's self reported pain score, with a low correlation efficient level observed (p<0.001). Information sheets are useful in education and use of postoperative analgesia. The primary objective to explore the efficacy of the information sheet has proved to be successful in this setting. Given risks of opioid analgesia, it is recommended that postoperative information sheets be given to all parents, to provide for improved analgesia control and safe management of children in the postoperative period. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Is Local Infiltration Analgesia Superior to Peripheral Nerve Blockade for Pain Management After THA: A Network Meta-analysis.

PubMed

Jiménez-Almonte, José H; Wyles, Cody C; Wyles, Saranya P; Norambuena-Morales, German A; Báez, Pedro J; Murad, Mohammad H; Sierra, Rafael J

2016-02-01

Local infiltration analgesia and peripheral nerve blocks are common methods for pain management in patients after THA but direct head-to-head, randomized controlled trials (RCTs) have not been performed. A network meta-analysis allows indirect comparison of individual treatments relative to a common comparator; in this case placebo (or no intervention), epidural analgesia, and intrathecal morphine, yielding an estimate of comparative efficacy. We asked, when compared with a placebo, (1) does use of local infiltration analgesia reduce patient pain scores and opioid consumption, (2) does use of peripheral nerve blocks reduce patient pain scores and opioid consumption, and (3) is local infiltration analgesia favored over peripheral nerve blocks for postoperative pain management after THA? We searched six databases, from inception through June 30, 2014, to identify RCTs comparing local infiltration analgesia or peripheral nerve block use in patients after THA. A total of 35 RCTs at low risk of bias based on the recommended Cochrane Collaboration risk assessment tool were included in the network meta-analysis (2296 patients). Primary outcomes for this review were patient pain scores at rest and cumulative opioid consumption, both assessed at 24 hours after THA. Because of substantial heterogeneity (variation of outcomes between studies) across included trials, a random effect model for meta-analysis was used to estimate the weighted mean difference (WMD) and 95% CI. The gray literature was searched with the same inclusion criteria as published trials. Only one unpublished trial (published abstract) fulfilled our criteria and was included in this review. All other studies included in this systematic review were full published articles. Bayesian network meta-analysis included all RCTs that compared local infiltration analgesia or peripheral nerve blocks with placebo (or no intervention), epidural analgesia, and intrathecal morphine. Compared with placebo, local

Pain Management of Malignant Psoas Syndrome Under Epidural Analgesia During Palliative Radiotherapy.

PubMed

Ota, Takayo; Makihara, Masaru; Tsukuda, Hiroshi; Kajikawa, Ryuji; Inamori, Masayuki; Miyatake, Nozomi; Tanaka, Noriko; Tokunaga, Masahiro; Hasegawa, Yoshikazu; Tada, Takuhito; Fukuoka, Masahiro

2017-06-01

Malignant psoas syndrome is a rare malignant condition presenting as lumbosacral plexopathy and painful fixed flexion of the hip. Metastasis to the psoas muscle is observed, which damages the nerve bundles in the lumbosacral plexuses. The syndrome presents as refractory lower back pain with several other neurological symptoms. The pain is difficult to control because it is a mixture of nociceptive and neuropathic pain, which indicates that treatment requires a versatile approach. The authors report a case of severe back pain caused by metastasis to the psoas muscle of advanced gastric cancer in a patient who underwent palliative radiotherapy under epidural analgesia. Despite conventional analgesics and subcutaneous oxycodone, he had difficulties in maintaining supine position because of the back pain and had a problem to receive radiotherapy, which required him to stay still in the same position during the treatment. By epidural analgesia, he could remain in supine position and complete radiotherapy without increasing opioid administration. His back pain was improved after the radiotherapy. Epidural analgesia is an effective treatment choice for a patient who is unable to keep the position during palliative radiotherapy.

Liposomal Bupivacaine Use in Transversus Abdominis Plane Blocks Reduces Pain and Postoperative Intravenous Opioid Requirement After Colorectal Surgery.

PubMed

Stokes, Audrey L; Adhikary, Sanjib D; Quintili, Ashley; Puleo, Frances J; Choi, Christine S; Hollenbeak, Christopher S; Messaris, Evangelos

2017-02-01

Enhanced recovery protocols frequently use multimodal postoperative analgesia to improve postoperative outcomes in patients undergoing colorectal surgery. The purpose of this study was to evaluate liposomal bupivacaine use in transversus abdominis plane blocks on postoperative pain scores and opioid use after colorectal surgery. This was a retrospective cohort study comparing outcomes between patients receiving nonliposomal anesthetic (n = 104) and liposomal bupivacaine (n = 303) blocks. The study was conducted at a single tertiary care center. Patients included those identified within an institutional database as inpatients undergoing colorectal procedures between 2013 and 2015 who underwent transversus abdominis plane block for perioperative analgesia. The study measured postoperative pain scores and opioid requirements. Patients receiving liposomal bupivacaine had significantly lower pain scores for the first 24 to 36 postoperative hours. Pain scores were similar after 36 hours. The use of intravenous opioids among the liposomal bupivacaine group decreased by more than one third during the hospitalization (99.1 vs 64.5 mg; p = 0.040). The use of ketorolac was also decreased (49.0 vs 18.3 mg; p < 0.001). In subgroup analysis, the decrease in opioid use was observed between laparoscopic and robotic procedures but not with laparotomies. No significant differences were noted in the use of oral opioids, acetaminophen, or ibuprofen. Postoperative length of stay and total cost were decreased in the liposomal bupivacaine group but did not achieve statistical significance. The study was limited by its retrospective, single-center design and heterogeneity of block administration. Attenuated pain scores observed with liposomal bupivacaine use were associated with significantly lower intravenous opioid and ketorolac use, suggesting that liposomal bupivacaine-containing transversus abdominis plane blocks are well aligned with the opioid-reducing goals of many enhanced

LOCAL PERIARTICULAR ANALGESIA IN TOTAL KNEE ARTHROPLASTY

PubMed Central

Sadigursky, David; Simões, Daniel Pereira; de Albuquerque, Raphael Araújo; Silva, Monize Zórnio; Fernandes, Rogério Jamil Carneiro; Colavolpe, Paulo Oliveira

2017-01-01

ABSTRACT Objective: To evaluate the use of infiltration of periarticular analgesic agents intraoperatively in total knee arthroplasty (TKA), with regard to benefits, reduction of pain, opioid consumption, improvement of range of motion and early ambulation. Methods: To analyze the benefits of periarticular drug infiltration, the patients submitted to TKA were evaluated, being separated into two groups. One group received the local periarticular infiltration protocol containing 0.5% bupivacaine (400mg/20ml), 1/1000 epinephrine (0.3ml), triamcinolone hexacetonide (20mg/1ml), clonidine (150mcg/1ml) and 20 ml of saline (0.9% SS) and, the other group underwent conventional intravenous analgesia. The results were compared and the variables analyzed were age, sex, BMI, comorbidities, postoperative complications, pain, functional capacity, range of motion, transfusion and rescue opioids for analgesia. Results: The mean age of the patients was 68 years and most were female and presented involvement of the left knee. Postoperatively, patients who had received periarticular infiltration showed improvement of pain as well as functional capacity. Conclusion: The analysis of data obtained demonstrated that the periarticular infiltration of analgesic agents is significantly effective for pain control and functional recovery.Level of Evidence II, Prospective Comparative Study. PMID:28642656

[The role of the somatosensory cortex in the development of reflex analgesia].

PubMed

Kukushkin, M L; Reshetniak, V K; Durinian, R A

1986-06-01

The effects of reflex stimulation on the changes of nociception thresholds in animals before and after ablation of the somatosensory cortex were studied in behavioural experiments on adult cats. Electroacupuncture stimulation (EAP) was shown to increase nociception thresholds at all levels of the conventional scale. The ablation of both the first (S1) and the second (S2) somatosensory cortex led to EAP inefficiency at the side opposite to the ablation. Partial lesion of the lateral and suprasylvian gyri, used as control, did not affect the efficiency of reflex analgesia. It is concluded that somatosensory areas of the cortex, especially 2, are involved in reflex analgesia.

Breast-feeding problems after epidural analgesia for labour: a retrospective cohort study of pain, obstetrical procedures and breast-feeding practices.

PubMed

Volmanen, P; Valanne, J; Alahuhta, S

2004-01-01

Various clinical practices have been found to be associated with breast-feeding problems. However, little is known about the effect of pain, obstetrical procedures and analgesia on breast-feeding behaviour. We designed a retrospective study with a questionnaire concerning pain, obstetrical procedures and breast-feeding practices mailed to 164 primiparae in Lapland. Altogether 99 mothers (60%) returned completed questionnaires that could be included in the analysis, which was carried out in two steps. Firstly, all accepted questionnaires were grouped according to the success or failure to breast-feed fully during the first 12 weeks of life. Secondly, an ad hoc cohort study was performed on the sub-sample of 64 mothers delivered vaginally. As many as 44% of the 99 mothers reported partial breast feeding or formula feeding during the first 12 weeks. Older age of the mother, use of epidural analgesia and the problem of "not having enough milk" were associated with the failure to breast-feed fully. Caesarean section, other methods of labour analgesia and other breast-feeding problems were not associated with partial breast feeding or formula feeding. In the sub-sample, 67% of the mothers who had laboured with epidural analgesia and 29% of the mothers who laboured without epidural analgesia reported partial breast feeding or formula feeding (P = 0.003). The problem of "not having enough milk" was more often reported by those who had had epidural analgesia. Further studies conducted prospectively are needed to establish whether a causal relationship exists between epidural analgesia and breast-feeding problems.

Antenatal education for childbirth-epidural analgesia.

PubMed

Cutajar, Lisa; Cyna, Allan M

2018-05-07

The language structures used by antenatal educators have not been previously researched in the context of antenatal childbirth classes. Epidural analgesia for labour is a common, and a frequently asked about, component of antenatal education for parents in hospitals providing maternity care. We aimed to identify the way information is described and presented by childbirth educators to assess content and determine which language structures such as metaphor, suggestion, information and storytelling are utilized. This observational study of antenatal education was conducted at a single tertiary referral center for maternity care in Western Sydney, Australia. All three childbirth educators agreed to be video recorded whilst providing information to parents during antenatal classes. Audio data was subsequently transcribed and then analysed by two researchers, independently categorising the various language structures and types of information provided. For the purposes of the current study, data concerning a single topic was used for the analysis-'epidural analgesia for labour'. Language structures used were highly variable between educators, as was the content and time taken for the information being provided. Our findings represent a first attempt to identify baseline information used in the clinical setting of antenatal education in order to categories communication structures used. This study has identified areas for further improvements and consistency in the way educators provide information to parents and has important implications for future midwifery practice, education and research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rodent analgesia: Assessment and therapeutics.

PubMed

Flecknell, Paul

2018-02-01

Current use of analgesics to control procedure-related pain in laboratory rodents is unacceptably low. Almost all currently available analgesics were developed in small rodents, prior to use in man, so that safety and efficacy data in laboratory assays are available. Greater use of analgesics would be encouraged by critical evaluation of the potential interactions of these compounds with the outcomes of specific research studies. As in other species, effective post-procedural analgesia requires reliable 'cage-side' methods of assessing pain. Recent advances in pain assessment should lead to both more extensive and more effective use of analgesics in these species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analgesia induced by morphine microinjected into the nucleus raphe magnus: effects on tonic pain.

PubMed

Dualé, Christian; Sierralta, Fernando; Dallel, Radhouane

2007-07-01

One of the possible sites of action of the analgesic effect of morphine is the Nucleus Raphe Magnus, as morphine injected into this structure induces analgesia in transient pain models. In order to test if morphine in the Nucleus Raphe Magnus is also analgesic in a tonic pain model, 5 microg of morphine or saline (control) were microinjected into the Nucleus Raphe Magnus of the rat. Analgesic effects were assessed following nociceptive stimulation using transient heating of the tail (phasic pain) and subcutaneous orofacial injection of 1.5 % formalin (tonic pain). While morphine was strongly analgesic for the tail-flick response (p <0.0001 compared to control), analgesia on the response to formalin was also observed for both early (p = 0.007) and late responses (p = 0.02). However, the response to formalin was not completely blunted. These results suggest that the Nucleus Raphe Magnus is not the exclusive site of action of morphine-induced analgesia in clinical conditions.

Comparison between a disposable and an electronic PCA device for labor epidural analgesia.

PubMed

Sumikura, Hiroyuki; van de Velde, Marc; Tateda, Takeshi

2004-01-01

The aims of the present study were (1) to investigate if a disposable patient-controlled analgesia (PCA) device can be used for labor analgesia and (2) to evaluate the device by midwives and parturients. Forty healthy parturients were divided into two groups and received combined spinal epidural analgesia for labor pain relief. Following intrathecal administration of 3 mg ropivacaine and 1.5 microg sufentanil, either a disposable PCA device (Coopdech Syrinjector; Daiken Medical, Osaka, Japan) or an electronic PCA device (IVAC PCAM PCA Syringe Pump; Alaris, Basingstoke, UK) was connected to the epidural catheter, and 0.15% ropivacaine with sufentanil 0.75 microg/ml was used for continuous infusion and PCA. For an electronic PCA device, continuous infusion rate, bolus dose, lockout time, and hourly limit were set at 4 ml/h, 3 ml, 15 min, and 16 ml, respectively. For a disposable PCA device, continuous infusion rate, bolus dose, and an hourly limit were set at 4 ml/h, 3 ml, and 16 ml, respectively, but lockout function was not available. No differences were observed between the groups concerning demographic data, obstetric data, and outcome of labor. Anesthetic requirements (disposable, 9.7 +/- 4.7 ml/h; electronic, 8.2 +/- 4.0 ml/h) and VAS score during the delivery (disposable, 26 +/- 25; electronic, 21 +/- 22) were similar between the groups. Midwives praised the disposable PCA device as well as the electronic one. The present results imply that the disposable PCA device can be an alternative to the electronic PCA device for labor analgesia.

[Frequency of colonization and isolated bacteria from the tip of the epidural catheter implanted for postoperative analgesia].

PubMed

Stabille, Débora Miranda Diogo; Filho, Augusto Diogo; Mandim, Beatriz Lemos da Silva; Araújo, Lúcio Borges de; Mesquita, Priscila Miranda Diogo; Jorge, Miguel Tanús

2015-01-01

The increased use of epidural analgesia with catheter leads to the need to demonstrate the safety of this method and know the incidence of catheter colonization, inserted postoperatively for epidural analgesia, and the bacteria responsible for this colonization. From November 2011 to April 2012, patients electively operated and maintained under epidural catheter for postoperative analgesia were evaluated. The catheter tip was collected for semiquantitative and qualitative microbiological analysis. Of 68 cultured catheters, six tips (8.8%) had positive cultures. No patient had superficial or deep infection. The mean duration of catheter use was 43.45hours (18-118) (p=0.0894). The type of surgery (contaminated or uncontaminated), physical status of patients, and surgical time showed no relation with the colonization of catheters. Microorganisms isolated from the catheter tip were Staphylococcus aureus, Pseudomonas aeruginosa and Sphingomonas paucimobilis. Postoperative epidural catheter analgesia, under this study conditions, was found to be low risk for bacterial colonization in patients at surgical wards. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

[Study on the preemptive analgesia effects of both the parecoxib sodium and the pentazocine in patients undergoing nasal endoscopic surgery].

PubMed

Kong, Yonggang; Yang, Xilin

2014-09-01

To evaluate the preemptive analgesia effects of both the parecoxib sodium and the pentazocine in patients undergoing nasal endoscopic surgery. In the randomized, double blind, controlled study, 120 patients undergoing septoplasty were divided into 3 groups (n = 40): group A received parecoxib 40 mg by muscle injection 30 min before the operation; group B received pentazocine 30 mg; group C received an equal volume of saline. The preemptive analgesia effect was evaluated with VAS scores which recorded at different time points. The proportion of participants using rescue analgesia after the operation were recorded as additional measures of preemptive analgesia. Intra-operative as well as the postoperative pain scores were less in the group A and group B than in the control group. Fewer participants required rescue medication after operation with parecoxib as well as pentazocine than placebo. However there were no difference in the preemptive effects between the group A and group B. Administration of both the parecoxib and pentazocine before the nasal endoscopic surgery can provide preemptive analgesia without serious adverse side effects that deserves popularization in the clinic.

Requests and usage of epidural analgesia in grand-grand multiparous and similar-aged women with lesser parity: prospective observational study.

PubMed

Ioscovich, Alexander; Fadeev, Angelika; Rivilis, Alina; Elstein, Deborah

2011-11-01

Epidural analgesia in older and multiparous women has been associated with risks. The aim of this study was to compare epidural analgesia use for labor/delivery in grand-grand multiparous women (GGMP; ≥10 births) relative to that in similar-aged women with lesser parity. This was a prospective observational study of advanced age gravida. All laboring women in a six-month period admitted to a tertiary Israeli center were included if they were advanced age (≥36 years old) with one to two previous births (Low parity; n=128) or four to five previous births (Medium parity; n=181), and all GGMP (any age; n=187). Primary outcome was comparison of requests for and use of epidural analgesia for labor/delivery. There were no significant differences across parity groups in percent of gravida requesting or receiving epidural analgesia (46.5-59.4%). Time from admission to epidural administration (range mean times: 168-187 min) and from advent of epidural to delivery (range mean times: 155-160 min) were comparable across parity groups. Use of other analgesia (5.8-8%) was not significantly different. Requests for and use of epidural analgesia was comparable in older gravida and was not correlated with parity. Mean times from presentation to epidural administration, mean cervical dilatation at epidural initiation, and mean time from performing of epidural to delivery were comparable across groups.

Regional analgesia for improvement of long-term functional outcome after elective large joint replacement.

PubMed

Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

2015-08-13

Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low.Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) - 2.23 to 10.21; P value = 0.21, 3 studies, 140 participants, very low quality evidence).We did not

Regional analgesia for improvement of long-term functional outcome after elective large joint replacement

PubMed Central

Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

2015-01-01

Background Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. Objectives To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. Search methods We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. Selection criteria We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. Data collection and analysis We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. Main results We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low. Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) �

Neuraxial labor analgesia is not an independent predictor of perineal lacerations after vaginal delivery of patients with intrauterine fetal demise.

PubMed

Lee, J H; Peralta, F M; Palatnik, A; Gaupp, C L; McCarthy, R J

2017-11-01

The role of neuraxial labor analgesia in perineal trauma following live births is controversial, and no studies have assessed the association in women delivering an intrauterine fetal demise. We evaluated the relationship between neuraxial labor analgesia and perineal laceration in these patients. This was a retrospective case-control study of women with a diagnosis of fetal death after 20weeks of gestation, a vaginal delivery, and an Apgar score of 0 at delivery, during the period from January 2007 through December 2015. The presence of a perineal laceration and its severity, graded from grade I to IV based on the 2014 American College of Obstetricians and Gynecologists guidelines, was recorded. A total of 329/422 (78%) patients received neuraxial, and 93/422 (22%) non-neuraxial, labor analgesia. A perineal laceration occurred in 23% in the neuraxial versus 10% in the non-neuraxial analgesia group, a difference of 13% (95% CI of difference 4% to 20%, P=0.005). After adjusting for confounder bias, greater birthweight (OR 4.22, 95% CI 3.00 to 5.92, P<0.001) and lower parity (OR 0.44, 95% CI 0.24 to 0.82, P=0.009), but not neuraxial analgesia (OR 1.29, 95% CI 0.47 to 3.57, P=0.61) were independent predictors of perineal laceration. The maintenance concentration of bupivacaine did not affect the rate of perineal injury. Neuraxial labor analgesia does not appear to be an independent risk for a perineal laceration in patients with intrauterine fetal demise. Our data suggests that the use of neuraxial analgesia should not raise concern about increased rates of perineal injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pectoral Fascial (PECS) I and II Blocks as Rescue Analgesia in a Patient Undergoing Minimally Invasive Cardiac Surgery.

PubMed

Yalamuri, Suraj; Klinger, Rebecca Y; Bullock, W Michael; Glower, Donald D; Bottiger, Brandi A; Gadsden, Jeffrey C

Patients undergoing minimally invasive cardiac surgery have the potential for significant pain from the thoracotomy site. We report the successful use of pectoral nerve block types I and II (Pecs I and II) as rescue analgesia in a patient undergoing minimally invasive mitral valve repair. In this case, a 78-year-old man, with no history of chronic pain, underwent mitral valve repair via right anterior thoracotomy for severe mitral regurgitation. After extubation, he complained of 10/10 pain at the incision site that was minimally responsive to intravenous opioids. He required supplemental oxygen because of poor pulmonary mechanics, with shallow breathing and splinting due to pain, and subsequent intensive care unit readmission. Ultrasound-guided Pecs I and II blocks were performed on the right side with 30 mL of 0.2% ropivacaine with 1:400,000 epinephrine. The blocks resulted in near-complete chest wall analgesia and improved pulmonary mechanics for approximately 24 hours. After the single-injection blocks regressed, a second set of blocks was performed with 266 mg of liposomal bupivacaine mixed with bupivacaine. This second set of blocks provided extended analgesia for an additional 48 hours. The patient was weaned rapidly from supplemental oxygen after the blocks because of improved analgesia. Pectoral nerve blocks have been described in the setting of breast surgery to provide chest wall analgesia. We report the first successful use of Pecs blocks to provide effective chest wall analgesia for a patient undergoing minimally invasive cardiac surgery with thoracotomy. We believe that these blocks may provide an important nonopioid option for the management of pain during recovery from minimally invasive cardiac surgery.

Assessment of buprenorphine, carprofen, and their combination for postoperative analgesia in olive baboons (Papio anubis).

PubMed

Allison, Sarah O; Halliday, Lisa C; French, Jeffrey A; Novikov, Dmitri D; Fortman, Jeffrey D

2007-05-01

This study compared the efficacy of buprenorphine, carprofen, and a combination of the 2 analgesics in female baboons. Physiologic and behavioral parameters were assessed at baseline and postoperatively for 6 d by use of continuous noninvasive physiologic monitoring and twice-daily videotaping. Prior to surgery, all animals received a pre-emptive dose of either 0.01 mg/kg buprenorphine intramuscularly, 2.2 mg/kg carprofen intramuscularly, or a combination of 0.01 mg/kg buprenorphine and 2.2 mg/kg carprofen intramuscularly. All animals in the carprofen (n = 4) and buprenorphine+carprofen (n = 4) treatment groups appeared to have sufficient analgesia. Three of 4 animals in the buprenorphine group had adequate analgesia. The fourth animal had an elevated heart rate and spent less time standing during the postoperative period. In this study, the use of carprofen or a combination of carprofen plus buprenorphine provided more reliable postoperative analgesia than buprenorphine alone.

Peripheral nerve catheters and local anesthetic infiltration in perioperative analgesia.

PubMed

Merritt, Christopher K; Mariano, Edward R; Kaye, Alan David; Lissauer, Jonathan; Mancuso, Kenneth; Prabhakar, Amit; Urman, Richard D

2014-03-01

Peripheral nerve catheters (PNCs) and local infiltration analgesia (LIA) represent valuable options for controlling perioperative pain. PNCs have been increasingly utilized to provide both surgical anesthesia and prolonged postoperative analgesia for a wide variety of procedures. PNCs can be more technically challenging to place than typical single-injection nerve blocks (SINB), and familiarity with the indications, contraindications, relevant anatomy, and appropriate technical skills is a prerequisite for the placement of any PNC. PNCs include risks of peripheral nerve injury, damage to adjacent anatomic structures, local anesthetic toxicity, intravascular injection, risks associated with motor block, risks of unnoticed injury to the insensate limb, and risks of sedation associated with PNC placement. In addition to these common risks, there are specific risks unique to each PNC insertion site. LIA strategies have emerged that seek to provide the benefit of targeted local anesthesia while minimizing collateral motor block and increasing the applicability of durable local anesthesia beyond the extremities. LIA involves the injection and/or infusion of a local anesthetic near the site of surgical incision to provide targeted analgesia. A wide variety of techniques have been described, including single-injection intraoperative wound infiltration, indwelling wound infusion catheters, and the recent high-volume LIA technique associated with joint replacement surgery. The efficacy of these techniques varies depending on specific procedures and anatomic locations. The recent incorporation of ultra-long-acting liposomal bupivacaine preparations has the potential to dramatically increase the utility of single-injection LIA. LIA represents a promising yet under-investigated method of postoperative pain control. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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.

Thoracic epidural analgesia in donor hepatectomy: An analysis.

PubMed

Koul, Archna; Pant, Deepanjali; Rudravaram, Swetha; Sood, Jayashree

2018-02-01

The purpose of this study is to analyze whether supplementation of general anesthesia (GA) with thoracic epidural analgesia (TEA) for right lobe donor hepatectomy is a safe modality of pain relief in terms of changes in postoperative coagulation profile, incidence of epidural catheter-related complications, and timing of removal of epidural catheter. Retrospective analysis of the record of 104 patients who received TEA for right lobe donor hepatectomy was done. Platelet count, international normalized ratio, alanine aminotransferase, and aspartate aminotransferase were recorded postoperatively until the removal of the epidural catheter. The day of removal of the epidural catheter and visual analogue scale (VAS) scores were also recorded. Any complication encountered was documented. Intraoperatively, central venous pressure (CVP), hemodynamic variables, and volume of intravenous fluids infused were also noted. Statistical analysis was performed by using SPSS statistical package, version 17.0 (SPSS Inc. Chicago, IL). Continuous variables were presented as mean ± standard deviation. A total of 90% of patients had mean VAS scores between 1 and 4 in the postoperative period between days 1 and 5. None of the patients had a VAS score above 5. Although changes in coagulation status were encountered in all patients in the postoperative period, these changes were transient and did not persist beyond postoperative day (POD) 5. There was no delay in removal of the epidural catheter, and the majority of patients had the catheter removed by POD 4. There was no incidence of epidural hematoma. Aside from good intraoperative and postoperative analgesia, TEA in combination with balanced GA and fluid restriction enabled maintenance of low CVP and prevention of hepatic congestion. In conclusion, vigilant use of TEA appears to be safe during donor hepatectomy. Living liver donors should not be denied efficient analgesia for the fear of complications. Liver Transplantation 24 214

Paramedic attitudes regarding prehospital analgesia.

PubMed

Walsh, Brooks; Cone, David C; Meyer, Emily M; Larkin, Gregory L

2013-01-01

Although pain is a major reason why patients summon emergency medical services (EMS), prehospital medical providers administer analgesic agents at inappropriately low rates. One possible reason is the role of EMS provider attitudes. This study was conducted to elicit attitudes that may act as impediments or deterrents to administering analgesia in the prehospital environment. A qualitative methodology was employed. We recruited experienced paramedics, with at least one year of full-time fieldwork, from a variety of agencies in New England. We sought to include a balance of rural and urban as well as both private and hospital-based agencies. Participants at each site were selected through purposive sampling. A semistructured discussion guide was designed to elicit the paramedics' past experiences with administering analgesia, as well as reflections on their role in the care of patients in pain. Both interviews and focus groups were conducted. These sessions were recorded and transcribed verbatim. The transcripts were topic-analyzed and iteratively coded by two independent investigators utilizing the constant comparative method of Glaser and Strauss' Grounded Theory; coding ambiguities were resolved by consensus. Through a series of conceptual mapping and iterative code refinement, themes and domains were generated. Fifteen paramedics from five EMS agencies in three New England states were recruited. Major themes were: 1) a reluctance to administer opioids to patients without significant objective signs (e.g., deformity, hypertension); 2) a preoccupation with potential malingering; 3) ambivalence about the degree of pain control to target or to expect (e.g., aiming to "take the edge off"); 4) a fear of masking diagnostic symptoms; and 5) an aversion to aggressive dosing of opioids (e.g., initial doses of morphine did not exceed 5 mg). A number of potentially modifiable attitudinal barriers to appropriate pain management were revealed.

The hydrolysis kinetics of monobasic and dibasic aminoalkyl esters of ketorolac.

PubMed

Qandil, Amjad M; Jamhawi, Noor M; Tashtoush, Bassam M; Al-Ajlouni, Ahmad M; Idkaidek, Nasir M; Obaidat, Aiman A

2013-09-01

Six aminoethyl and aminobutyl esters of ketorolac containing 1-methylpiperazine (MPE and MPB), N-acetylpiperazine (APE and APB) or morpholine (ME and MB), were synthesized and their hydrolysis kinetics were studied. The hydrolysis was studied at pH 1 to 9 (for MPE, APE and ME) and pH 1 to 8 (for MPB, APB and MB) in aqueous phosphate buffer (0.16 M) with ionic strength (0.5 M) at 37°C. Calculation of k(obs), construction of the pH-rate profiles and determination of the rate equations were performed using KaleidaGraph® 4.1. The hydrolysis displays pseudo-first order kinetics and the pH-rate profiles shows that the aminobutyl esters, MPE, APB and MB, are the most stable. The hydrolysis of the ethyl esters MPE, APE and ME, depending on the pH, is either fast and catalyzed by the hydroxide anion or slow and uncatalyzed for the diprotonated, monoprotonated and nonprotonated forms. The hydrolysis of the butyl esters showed a similar profile, albeit it was also catalyzed by hydronium cation. In addition, the hydroxide anion is 105 more effective in catalyzing the hydrolysis than the hydronium cation. The hydrolysis pattern of the aminoethyl esters is affected by the number and pKa of its basic nitrogen atoms. The monobasic APE and ME, show a similar hydrolysis pattern that is different than the dibasic MPE. The length of the side chain and the pKa of the basic nitrogen atoms in the aminoethyl moiety affect the mechanism of hydrolysis as the extent of protonation at a given pH is directly related to the pKa.

Effects of Epidural Labour Analgesia in Mother and Foetus.

PubMed

Deshmukh, Varsha Laxmikant; Ghosh, Shaswatee S; Yelikar, Kanan A; Gadappa, Shreeniwas N

2018-04-01

Aim of study was to determine effect of epidural analgesia on progress of labour and mode of delivery, to find out its complications in labour and puerperium and to evaluate neonatal outcome in terms of APGAR score. The present study was conducted in Department of Obstetrics and Gynaecology at Government Medical College Aurangabad over period of 2 years from June 2014 to June 2016 after taking approval from institutional ethical board. Hundred low-risk primigravidas were included in the study, 50 women received epidural analgesia for relief of labour pain at 3-4 cm and 50 women served as control. The important  outcome  FACTORS studied were the following : (1) duration of active phase of I stage, and II stage, (2) mode of delivery, (3) APGAR scores, (4) untoward reactions and intrapartum complications, (5) overall satisfaction of the mother. The operative delivery rates were not significantly different in both the groups (8% in the control group and 6% in the study group: p value NS, i.e. > 0.05). The duration of first stage (our study showed no significant difference in the duration of first stage in both the study and control groups p value > 0.05) and second stage of labour ( p value NS > 0.05) and the need for oxytocin were comparable in the two groups. The side effects observed were minimal. It has given excellent pain relief and improved neonatal outcome (5 min). EA is associated with rates of vaginal delivery (88 v/s 84%) and LSCS rate (8 v/s 6%) which are comparable with control group. Epidural analgesia is a very promising, safe and effective method of pain relief. No major complications and a good APGAR score make it a good option of care in modern obstetrics.

The contribution of suggestibility and expectation to placebo analgesia phenomenon in an experimental setting.

PubMed

De Pascalis, Vilfredo; Chiaradia, Carmela; Carotenuto, Eleonora

2002-04-01

This study reports how placebo analgesia was produced by conditioning whereby the intensity of electric stimulation was surreptitiously reduced in order to examine the contribution of psychological factors of suggestibility and expectancy on placebo analgesia. This strategy was used in order to manipulate expectancy for pain reduction. The magnitudes of the placebo effects were estimated after a manipulation procedure and during experimental trials in which stimulus intensities were reset to original baseline levels. Individual differences in suggestibility, verbal expectancy for drug efficacy and manipulation procedure for pain reduction were tested as possible mediators of placebo analgesia. The following dependent variables were measured: (a) subjective expectancy for drug efficacy in pain relief, (b) expected pain intensity and unpleasantness, (c) concurrent pain intensity and unpleasantness and (d) remembered pain intensity and unpleasantness. Statistically significant placebo effects on sensory and affective measures of pain were obtained independently of the extent of the surreptitious lowering of stimulus strength during manipulation trials. The pairing of placebo administration with painful stimulation was sufficient to produce a generalized placebo analgesic effect. However, verbal expectancy for drug efficacy and individual differences in suggestibility were found to contribute significantly to the magnitude of placebo analgesia. The highest placebo effect was shown by the most pronounced reductions in pain ratings in highly suggestible subjects who received suggestions presumed to elicit high expectancy for drug efficacy. The results also demonstrated that placebo effects established on remembered pain were at least twice as great as those obtained on concurrent placebo effects. This was mainly because baseline pain was remembered as being much more intense than it really was. Moreover, remembered placebo effects, like the concurrent placebo effects

Pharmacokinetics of buprenorphine following constant rate infusion for postoperative analgesia in dogs undergoing ovariectomy.

PubMed

Barbarossa, Andrea; Rambaldi, Julie; Giunti, Massimo; Zaghini, Anna; Cunto, Marco; Zambelli, Daniele; Valgimigli, Simond; Santoro, Francesco; Romagnoli, Noemi

2017-05-01

To investigate the pharmacokinetics of buprenorphine and its main active metabolite, norbuprenorphine, after administration of an intravenous loading dose followed by constant rate infusion (CRI) in dogs. Prospective, clinical study. A total of seven healthy dogs undergoing elective ovariectomy. Buprenorphine was administered as a loading dose (intravenous bolus of 15 μg kg -1 ) followed by CRI (2.5 μg kg -1 hour -1 for 6 hours). Moreover, intraoperative analgesia was supplemented by an intramuscular carprofen (4 mg kg -1 ) injection, administered prior to surgery, and by lidocaine, administrated through subcutaneous infiltration and through a splash on the ovarian vascular pedicle during surgery. Pain and sedation were scored for all animals throughout the 24-hour study period and rescue analgesia was administered when a visual analogue scale score was > 40 mm. Blood samples were collected from a jugular catheter at regular intervals, and plasma concentrations of buprenorphine and norbuprenorphine were determined by a validated liquid chromatography-tandem mass spectrometry method. Buprenorphine showed a two-compartment kinetic profile. Maximum concentration was 23.92 ± 8.64 ng mL -1 at 1 minute (maximum time); elimination half-life was 41.87 ± 17.35 minutes; area under the curve was 486.68 ± 125.66 minutes ng -1 mL -1 ; clearance was 33.61 ± 13.01 mL minute -1 kg -1 , and volume of distribution at steady state was 1.77 ± 0.50 L kg -1 . In no case was rescue analgesia required. Norbuprenorphine resulted below the lower limit of quantification in almost all samples. The results suggest that a buprenorphine CRI can be a useful tool for providing analgesia in postoperative patients, considering its minor side effects and the advantages of a CRI compared to frequent boluses. The negligible contribution of norbuprenorphine to the therapeutic effect was confirmed. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary

Etoricoxib - preemptive and postoperative analgesia (EPPA) in patients with laparotomy or thoracotomy - design and protocols

PubMed Central

2010-01-01

Background and Objective Our objective was to report on the design and essentials of the Etoricoxib protocol- Preemptive and Postoperative Analgesia (EPPA) Trial, investigating whether preemptive analgesia with cox-2 inhibitors is more efficacious than placebo in patients who receive either laparotomy or thoracotomy. Design and Methods The study is a 2 × 2 factorial armed, double blinded, bicentric, randomised placebo-controlled trial comparing (a) etoricoxib and (b) placebo in a pre- and postoperative setting. The total observation period is 6 months. According to a power analysis, 120 patients scheduled for abdominal or thoracic surgery will randomly be allocated to either the preemptive or the postoperative treatment group. These two groups are each divided into two arms. Preemptive group patients receive etoricoxib prior to surgery and either etoricoxib again or placebo postoperatively. Postoperative group patients receive placebo prior to surgery and either placebo again or etoricoxib after surgery (2 × 2 factorial study design). The Main Outcome Measure is the cumulative use of morphine within the first 48 hours after surgery (measured by patient controlled analgesia PCA). Secondary outcome parameters include a broad range of tests including sensoric perception and genetic polymorphisms. Discussion The results of this study will provide information on the analgesic effectiveness of etoricoxib in preemptive analgesia and will give hints on possible preventive effects of persistent pain. Trial registration NCT00716833 PMID:20504378

The impact of long-lasting preemptive epidural analgesia before total hip replacement on the hormonal stress response. A prospective, randomized, double-blind study.

PubMed

Al Oweidi, Abdelkarim S; Klasen, Joachim; Al-Mustafa, Mahmoud M; Abu-Halaweh, Sami A; Al-Zaben, Khaled R; Massad, Islam M; Qudaisat, Ibrahim Y

2010-06-01

Recent studies suggest that preemptive analgesia may be effective in reducing postoperative pain. One physiologic explanation may be interference with the endogenous opioid response. We investigated whether long-lasting preoperative preemptive analgesia may have an effect on the hormonal stress response after total hip replacement. 42 patients scheduled for elective hip replacement for coxarthrosis were randomized to receive, on the day before the operation, either 5 ml*h(-1) ropivacaine 0.2% (study group, n = 21) or 5 ml*h(-1) saline (control group, n = 21). Postoperative analgesia was achieved in both groups by patient-controlled epidural analgesia (PCEA) with ropivacaine 0.2%. The main outcome measure was the concentration of authentic beta-endorphin [1-31] in plasma up to 4 days after surgery. Additional parameters included concentrations of adrenocorticotrope hormone and cortisol. Both groups were comparable concerning preoperative parameters and pain scores. Epidural blocks were sufficient in all patients for operative analgesia. Preemptive analgesia was performed for 11-20 hours in both groups and led to significantly decreased pain scores before surgery. Preemptive analgesia with epidural ropivacaine did not lead to decreased concentrations of beta-endorphin [1-31] before the start of surgery or in the postoperative period. Furthermore, no differences could be detected in the time course of beta-endorphin and adrenocorticotrope hormone after surgery. However, cortisol concentrations differed significantly between groups before the operation, but showed a comparable rise after surgery. Differences in postoperative pain after preemptive analgesia do not seem to be due to an altered endogenous opioid response.

Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter

PubMed Central

Li, Yuting; Liu, Xing; Liu, Chang; Kang, Jiuhong; Yang, Jingyu; Pei, Gang; Wu, Chunfu

2009-01-01

Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance. PMID:19399231

Comparison of morphine and carprofen administered alone or in combination for analgesia in dogs undergoing ovariohysterectomy.

PubMed

Dzikiti, T B; Joubert, K E; Venter, L J; Dzikiti, L N

2006-09-01

In this study the analgesic efficacy of the pure agonistic opioid morphine and the cyclo-oxygenase type-2-selective carprofen were compared since there is no previous specific comparative study for these two common analgesics. Forty-five bitches undergoing elective ovariohysterectomy were randomly assigned to one of three groups; receiving morphine 0.4 mg/kg bodyweight pre-operatively and 0.2 mg/kg every 4-6 hours thereafter (Morphine group), receiving a once-off carprofen 4 mg/kg injection (Carprofen group) or receiving both morphine and carprofen (MorphCarp group). The dogs were premedicated with acepromazine 0.01 mg/kg and induced with either thiopentone 5-10 mg/kg or propofol 4-6 mg/kg. General anaesthesia was maintained with halothane in oxygen. The degree of pain was assessed over a 24-hour period under blinded conditions using a pain scale modified from the University of Melbourne pain scale and the Glasgow composite pain tool. Physiological parameters such as respiratory rate, pulse rate and body temperature were also assessed over the same time period. There was no significant difference in pain-scores and thus analgesia offered by the three analgesia protocols at any assessment point across the three groups, but there were differences within groups across time points. Baseline total pain-scores were lower than scores at all post-operative points within all three groups. Both morphine and carprofen provided good analgesia without any obvious adverse effects. This study indicates that at the dosages indicated above, carprofen administered on its own produces analgesia equal to that produced by morphine and that the two drugs administered together do not produce better analgesia than either drug administered on its own.

Local infiltration of analgesia and sciatic nerve block provide similar pain relief after total knee arthroplasty.

PubMed

Tanikawa, Hidenori; Harato, Kengo; Ogawa, Ryo; Sato, Tomoyuki; Kobayashi, Shu; Nomoto, So; Niki, Yasuo; Okuma, Kazunari

2017-07-11

Although femoral nerve block provides satisfactory analgesia after total knee arthroplasty (TKA), residual posterior knee pain may decrease patient satisfaction. We conducted a randomized controlled trial to clarify the efficacy of the sciatic nerve block (SNB) and local infiltration of analgesia with steroid (LIA) regarding postoperative analgesia after TKA, when administrated in addition to femoral nerve block (FNB). Seventy-eight patients were randomly allocated to the two groups: concomitant administration of FNB and SNB or FNB and LIA. The outcome measures included post-operative pain, passive knee motion, C-reactive protein level, time to achieve rehabilitation goals, the Knee Society Score at the time of discharge, patient satisfaction level with anesthesia, length of hospital stay, surgical time, and complications related to local anesthesia. The patients in group SNB showed less pain than group LIA only on postoperative hours 0 and 3. Satisfactory postoperative analgesia after TKA was also achieved with LIA combined with FNB, while averting the risks associated with SNB. The influence on progress of rehabilitation and length of hospital stay was similar for both anesthesia techniques. The LIA offers a potentially safer alternative to SNB as an adjunct to FNB, particularly for patients who have risk factors for sciatic nerve injury.

Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial.

PubMed

Lockwood, Geoff G; Cabreros, Leilani; Banach, Dorota; Punjabi, Prakash P

2017-10-01

Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg -1 .hr -1 ) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l -1 . There were no adverse events as a consequence of the study. Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. ISRCTN13424423 ( https://www.isrctn.com ).

Penthrox alone versus Penthrox plus periprostatic infiltration of local analgesia for analgesia in transrectal ultrasound-guided prostate biopsy.

PubMed

Huang, Sean; Pepdjonovic, Lana; Konstantatos, Alex; Frydenberg, Mark; Grummet, Jeremy

2016-03-01

The objective of this study was to compare pain intensity in patients undergoing transrectal ultrasound (TRUS)-guided biopsy of the prostate with Penthrox alone compared with Penthrox plus periprostatic infiltration of local analgesia (PILA). Seventy-two subjects participated in this study after receiving appropriate education. Forty-two patients self-administered inhaled Penthrox (3 mL methoxyflurane) alone for analgesia (Group A), followed by 30 patients who self-administered Penthrox and received PILA with 5 mL of 2% lignocaine. All subjects had TRUS biopsy performed. Immediately after the procedure, patients were asked to rate their pain intensity using a numerical verbal rating scale from 0 to 10. Baseline characteristics of the two groups were similar. Patients in Group B reported significantly lower post TRUS biopsy median pain intensity of 2 (1-3) compared with Group A subjects who reported a median post TRUS biopsy pain intensity of 3 (2-5) (P = 0.014). A total of 72 men underwent TRUS-guided biopsy. All patients indicated they would be happy to have another TRUS-guided prostate biopsy in the future. Our study shows that Penthrox plus PILA shows promise as an efficacious and easily tolerated analgesic technique for outpatient TRUS biopsy, keeping resource use to a minimum. Planning for a multi-centre, double-blind randomized control trial comparing Penthrox plus PILA with PILA alone is presently underway. © 2015 Royal Australasian College of Surgeons.

5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha-adrenoceptor antagonists in rats.

PubMed Central

Archer, T.; Danysz, W.; Jonsson, G.; Minor, B. G.; Post, C.

1986-01-01

The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in the hot-plate and tail-flick tests, but not in the shock titration test. Intrathecal yohimbine showed a dose-related lowering of pain thresholds in saline and 5-MeODMT-treated animals. Phentolamine and prazosin produced normal dose-related curves in the hot-plate test and biphasic effects in the shock titration and tail-flick tests. These results demonstrate a functional interaction between alpha 2-adrenoceptors and 5-HT agonist-induced analgesia at a spinal level in rats. PMID:2877697

Assessment of Buprenorphine, Carprofen, and Their Combination for Postoperative Analgesia in Olive Baboons (Papio anubis)

PubMed Central

Allison, Sarah O; Halliday, Lisa C; French, Jeffrey A; Novikov, Dmitri D; Fortman, Jeffrey D

2010-01-01

This study compared the efficacy of buprenorphine, carprofen, and a combination of the 2 analgesics in female baboons. Physiologic and behavioral parameters were assessed at baseline and postoperatively for 6 d by use of continuous noninvasive physiologic monitoring and twice-daily videotaping. Prior to surgery, all animals received a pre-emptive dose of either 0.01 mg/kg buprenorphine intramuscularly, 2.2 mg/kg carprofen intramuscularly, or a combination of 0.01 mg/kg buprenorphine and 2.2 mg/kg carprofen intramuscularly. All animals in the carprofen (n = 4) and buprenorphine+carprofen (n = 4) treatment groups appeared to have sufficient analgesia. Three of 4 animals in the buprenorphine group had adequate analgesia. The fourth animal had an elevated heart rate and spent less time standing during the postoperative period. In this study, the use of carprofen or a combination of carprofen plus buprenorphine provided more reliable postoperative analgesia than buprenorphine alone. PMID:17487949

Excessive daytime sleepiness in patients on intrathecal analgesia for chronic pain.

PubMed

Demartini, Laura; Fanfulla, Francesco; Bonezzi, Cesare; Armiento, Luciana; Buonocore, Michelangelo

2015-01-01

Intrathecal (IT) drug administration is an advanced technique in pain treatment algorithm for patients poorly responsive to systemic pharmacological treatment or less invasive techniques. The aim is to improve analgesia lowering side effects; despite this premise, many side effects of long-term IT therapy have been described, mainly related to opioid administration. We observed, in some of the patients regularly followed for pump refills in our Pain Unit, the appearance of excessive daytime sleepiness (EDS) interfering with daily life and work activity; this study aims to investigate the incidence of EDS in patients on IT analgesia with opioid or non-opioid drugs and its possible relationship with respiratory problems during sleep. 21 patients on IT therapy for chronic pain answered the Epworth Sleepiness Scale (ESS). The incidence of EDS in patients receiving IT opioids was compared to a control group not receiving opioids. In 10 patients, who performed polysomnography (PSG) and maintenance of wakefulness test (MWT) for sleep complaints, we studied the relationship between PSG data and ESS scores and we verified the concordance of ESS and MWT results. 38% of the patients reported EDS, according to ESS data; all the patients with EDS were receiving an IT opioid. Even if some patients presented sleep apneas, we failed to correlate this data with daytime sleepiness. Subjective sleepiness is confirmed by the results of MWT. Our data demonstrate that EDS is a frequent and important side effect of IT analgesia and it seems related to opioids administration.

The Neuroanatomy of Sexual Dimorphism in Opioid Analgesia

DTIC Science & Technology

2014-04-13

2012 for review). Studies utilizing orofacial , somatosensory or visceral pain assays typically report that morphine produces a significantly greater...Review The neuroanatomy of sexual dimorphism in opioid analgesia Dayna R. Loyd a, Anne Z. Murphy b,⁎ a Pain Management Research Area, United States...online 13 April 2014 Keywords: Pain Periaqueductal gray Morphine Mu opioid receptor The influence of sex has been neglected in clinical studies on pain

beta-Endorphin-induced analgesia is inhibited by synthetic analogs of beta-endorphin.

PubMed

Nicolas, P; Hammonds, R G; Li, C H

1984-05-01

Competitive antagonism of human beta-endorphin (beta h-EP)-induced analgesia by synthetic beta h-EP analogs with high in vitro opiate receptor binding to in vivo analgesic potency ratio has been demonstrated. A parallel shift of the dose-response curve for analgesia to the right was observed when either beta h-EP or [ Trp27 ] -beta h-EP was coinjected with various doses of [Gln8, Gly31 ]-beta h-EP-Gly-Gly-NH2, [Arg9,19,24,28,29]-beta h-EP, or [ Cys11 ,26, Phe27 , Gly31 ]-beta h-EP. It was estimated that the most potent antagonist, [Gln8, Gly31 ]-beta h-EP-Gly-NH2, is at least 200 times more potent than naloxone.

beta-Endorphin-induced analgesia is inhibited by synthetic analogs of beta-endorphin.

PubMed Central

Nicolas, P; Hammonds, R G; Li, C H

1984-01-01

Competitive antagonism of human beta-endorphin (beta h-EP)-induced analgesia by synthetic beta h-EP analogs with high in vitro opiate receptor binding to in vivo analgesic potency ratio has been demonstrated. A parallel shift of the dose-response curve for analgesia to the right was observed when either beta h-EP or [ Trp27 ] -beta h-EP was coinjected with various doses of [Gln8, Gly31 ]-beta h-EP-Gly-Gly-NH2, [Arg9,19,24,28,29]-beta h-EP, or [ Cys11 ,26, Phe27 , Gly31 ]-beta h-EP. It was estimated that the most potent antagonist, [Gln8, Gly31 ]-beta h-EP-Gly-NH2, is at least 200 times more potent than naloxone. PMID:6328494

Maternal satisfaction as an outcome criterion in research on labor analgesia: data analysis from the recent literature.

PubMed

Dualé, Christian; Nicolas-Courbon, Aurélie; Gerbaud, Laurent; Lemery, Didier; Bonnin, Martine; Pereira, Bruno

2015-03-01

To investigate whether maternal satisfaction (MS) is taken into consideration as an outcome criterion in clinical research on analgesia for labor. A systematic review of articles reporting analgesia for labor from a panel of 17 influential journals was undertaken. A total of 116 articles were analyzed, including 282 within-study groups. The scope of MS, the type of outcome measure used, and the time of measurement were noted. Each available observation was assigned an ordinal value of MS (ordMS), according to data distribution. The factors influencing ordMS were identified by multivariable analysis. The methods used to assess MS were very variable, even within the different measurement tools reported. The weighted distribution of ordMS was 17.8%, 21.8%, 31.2%, and 29.3% for levels "poor," "fair," "good," and "excellent," respectively. In comparative studies, statistical differences for analgesia were related to statistical differences for MS (P<0.0001), but only the negative predictive value was high (0.87). Power to detect a difference in MS between treatment groups was low in general, but it influenced reporting of a significant difference for MS (P<0.0001). The obstetrical factors influencing ordMS were: the body mass index, the initial cervical dilatation, and the within-study percentage of nulliparous women. The techniques alternative to epidural analgesia negatively influenced ordMS. A standard and validated tool to assess MS in clinical research on analgesia for labor is still to be developed. Power should be improved by acting on sample sizes or sensitivity of the outcome.

Preemptive analgesia in rhegmatogenous retinal detachment surgery: is it effective?

PubMed

Mahfouz, Abdul Kader M; Nabawi, Khaled S

2002-10-01

To evaluate the efficacy of preemptive analgesia in surgical repair of retinal detachment (RD) using scleral buckle and cryopexy under general anesthesia. Thirty patients who were scheduled for rhegmatogenous RD surgical repair using scleral buckle and cryopexy and who were American Society of Anesthesiologists physical status I, II, or III were included in this study. The patients were randomly divided into two equal groups. The surgery was done under general anesthesia in both groups, but in Group 2, sub-Tenon anesthesia was given as preemptive analgesia after induction anesthesia and before start of surgery. Both groups were statistically comparable as regards patient age and weight and duration of anesthesia and surgery. The incidences of intraoperative oculocardiac reflex and postoperative vomiting were significantly lower in Group 2 compared with Group 1 (P < 0.001 and 0.0113, respectively). The time of first postoperative analgesic dose was significantly shorter in Group 1 (46.67 +/- 18.84 minutes) compared with Group 2 (162.67 +/- 29.391 minutes) (P < 0.001). The total analgesic consumption per 24 hours was significantly higher in Group 1 compared with Group 2 (P < 0.001). The time of discharge from the hospital was significantly shorter in Group 2 (8.8 +/- 2.704 hours) compared with Group 1 (12.4 +/- 3.481 hours) (P = 0.0018). The use of sub-Tenon block as preemptive analgesia after induction of general anesthesia and before the start of rhegmatogenous RD surgical repair was effective in reducing postoperative pain and analgesic requirements compared with an unblocked group. The use of sub-Tenon block was also effective in reducing intraoperative incidence of oculocardiac reflex and postoperative incidence of vomiting.

Stress antagonizes morphine-induced analgesia in rats

NASA Technical Reports Server (NTRS)

Vernikos, J.; Shannon, L.; Heybach, J. P.

1981-01-01

Exposure to restraint stress resulted in antagonism of the analgesic effect of administered morphine in adult male rats. This antagonism of morphine-induced analgesia by restraint stress was not affected by adrenalectomy one day prior to testing, suggesting that stress-induced secretion of corticosteroids is not critical to this antagonism. In addition, parenteral administration of exogenous adrenocorticotropin (ACTH) mimicked the effect of stress in antagonizing morphine's analgesic efficacy. The hypothesis that ACTH is an endogenous opiate antagonist involved in modulating pain sensitivity is supported.

Comparison of continuous interscalene block and subacromial infusion of local anesthetic for postoperative analgesia after open shoulder surgery.

PubMed

Baskan, Semih; Cankaya, Deniz; Unal, Hidayet; Yoldas, Burak; Taspinar, Vildan; Deveci, Alper; Tabak, Yalcin; Baydar, Mustafa

2017-01-01

This study compared the efficacy of continuous interscalene block (CISB) and subacromial infusion of local anesthetic (CSIA) for postoperative analgesia after open shoulder surgery. This randomized, prospective, double-blinded, single-center study included 40 adult patients undergoing open shoulder surgery. All patients received a standardized general anesthetic. The patients were separated into group CISB and group CSIA. A loading dose of 40 mL 0.25% bupivacaine was administered and patient-controlled analgesia was applied by catheter with 0.1% bupivacaine 5 mL/h throughout 24 h basal infusion, 2 mL bolus dose, and 20 min knocked time in both groups postoperatively. Visual analog scale (VAS) scores, additional analgesia need, local anesthetic consumption, complications, and side effects were recorded during the first 24 h postoperatively. The range of motion (ROM) score was recorded preoperatively and in the first and third weeks postoperatively. A statistically significant difference was determined between the groups in respect of consumption of local anesthetic, VAS scores, additional analgesia consumption, complications, and side effects, with lower values recorded in the CISB group. There were no significant differences in ROM scoring in the preoperative and postoperative third week between the two groups but there were significant differences in ROM scoring in the postoperative first week, with higher ROM scoring values in the group CISB patients. The results of this study have shown that continuous interscalene infusion of bupivacaine is an effective and safe method of postoperative analgesia after open shoulder surgery.

Transversus abdominis plane block as a component of multimodal analgesia for laparoscopic cholecystectomy.

PubMed

Oksar, Menekse; Koyuncu, Onur; Turhanoglu, Selim; Temiz, Muhyittin; Oran, Mustafa Cemil

2016-11-01

To evaluate and compare intercostal-iliac transversus abdominis plane (TAP) and oblique subcostal TAP (OSTAP) blocks for multimodal analgesia in patients receiving laparoscopic cholecystectomy. A prospective, randomized, double-blinded clinical study. Operating room, postoperative recovery area, and ward. In total, 60 laparoscopic cholecystectomy patients (43 women, 17 men, American Society of Anesthesiologists grades I-II) were enrolled from the general surgery department of our tertiary care center. The patients were assigned to 1 of the 3 groups. Group 1 received TAP blocks (n=20), group 2 received OSTAP blocks (n=20), and group 3 patients were used as controls and received patient-controlled analgesia (PCA) only (n=20). After the induction of anesthesia, blocks were performed bilaterally in study groups 1 and 2, using 20mL of lidocaine (5mg/mL). PCA with intravenous tramadol was routinely provided for all patients during the first 24hours. The intraoperative use of remifentanil, postoperative visual analog scale (VAS) scores, demand for PCA, and total analgesic consumption were recorded. The patients in the control group had greater analgesic demands and analgesic consumption than did those in groups 1 and 2. However, patients in the OSTAP group had lower VAS scores than did those in groups 1 and 3. The demand for analgesia was greater in the control group than in groups 1 and 2. Moreover, lower VAS scores were recorded in the OSTAP group than in groups 1 and 3 and were positively correlated with total PCA consumption among all patients. However, postoperative VAS scores were negatively correlated with the total intraoperative consumption of remifentanil at 24hours. TAP and OSTAP blocks improved postoperative analgesia in patients receiving laparoscopic cholecystectomy, which resulted in lower VAS scores and reduction in total analgesic consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

Continuous spinal labor analgesia for two deliveries in a parturient with severe subvalvular aortic stenosis.

PubMed

Hyuga, Shunsuke; Okutomi, Toshiyuki; Kato, Rie; Hosokawa, Yuki

2016-12-01

Various degrees of left ventricular outflow tract (LVOT) obstruction have been seen in patients with subvalvular aortic stenosis (SAS). Regional analgesia during labor for parturients with SAS is relatively contraindicated because it has a potential risk for hemodynamic instability due to sympathetic blockade as a result of vasodilation by local anesthetics. We thought continuous spinal analgesia (CSA) using an opioid and minimal doses of local anesthetic could provide more stable hemodynamic status. We demonstrate the management of a 28-year-old pregnant patient with SAS who received CSA for her two deliveries. For her first delivery (peak pressure gradient (∆P) between LV and aorta was approximately 55 mmHg), intrathecal fentanyl was used as a basal infusion, but we needed a small amount of bupivacaine to provide supplemental intrathecal analgesia as labor progressed. Although there were mild fluctuations in hemodynamics, she was asymptomatic. For her second delivery (∆P between LV and aorta was approximately 90 mmHg), minimal doses of continuous bupivacaine were used as a basal infusion. For her additional analgesic requests, bolus co-administration of fentanyl was effective. There were no fluctuations in her hemodynamics. Although her SAS in her second pregnancy was more severe than in the first, her hemodynamics exhibited less fluctuation during the second delivery with this method. In conclusion, CSA using fentanyl combined with minimal doses of bupivacaine provided satisfactory analgesia and stable hemodynamics in parturient with severe SAS.

Postoperative Analgesia with Intravenous Paracetamol and Dexmedetomidine in Laparoscopic Cholecystectomy Surgeries: A Prospective Randomized Comparative Study

PubMed Central

Sharma, Ridhima; Gupta, Raghav; Choudhary, Ripon; Singh Bajwa, Sukhminder Jit

2017-01-01

Background and Aim: Therapeutic use of nonopioid analgesic such as paracetamol (PCM) is an alternative to opioids, so to avoid the established side effects associated with opioids, PCM is commonly used due to its analgesic and antipyretic effects. Recently, dexmedetomidine has also emerged on the anesthesia front with a potential role of providing postoperative analgesia. The present study was conducted to compare and assess the quality and duration of analgesia with PCM and dexmedetomidine using visual analog scale (VAS). Methods: One hundred patients between the age of 18 and 60 years of the American Society of Anesthesiologists grade I and II undergoing laparoscopic cholecystectomy surgery were randomly allocated into two groups (n = 50). Each patient received either 1 g intravenous PCM, in 100 ml solution before incision (Group I), or i.v. dexmedetomidine 1 μg/kg as bolus over 10 min followed by infusion of 0.5 μg/kg/h (Group II). Postoperatively, the following parameters were observed: quality and duration of analgesia, hemodynamic parameters, time to the first dose of rescue analgesia, sedation, and any postoperative complication or side effects. Statistical analysis was carried out using an unpaired t-test for quantitative parameters and nonparametric data using Wilcoxon signed-rank test and Mann–Whitney U-test. Qualitative data were analyzed using Chi-square or Fishers' exact test. Results: Postoperative analgesic requirement significantly decreased (P = 0.001), with a lower score on VAS, better patient satisfaction scores, and Ramsay Sedation Score ranges from 3 to 5 (62%) in Group I. The incidence of nausea and vomiting, hypotension, and bradycardia was comparable in both the groups except shivering, which was found significantly less in Group II. Conclusion: Incorporation of dexmedetomidine as a part of multimodal analgesia provides better hemodynamic profile, analgesic, sedative, and amnesic properties along with negligible serious adverse effects

Improved Outcomes Associated with the Liberal Use of Thoracic Epidural Analgesia in Patients with Rib Fractures.

PubMed

Jensen, Courtney D; Stark, Jamie T; Jacobson, Lewis L; Powers, Jan M; Joseph, Michael F; Kinsella-Shaw, Jeffrey M; Denegar, Craig R

2017-09-01

Each year, more than 150,000 patients with rib fractures are admitted to US trauma centers; as many as 10% die. Effective pain control is critical to survival. One way to manage pain is thoracic epidural analgesia. If this treatment reduces mortality, more frequent use may be indicated. We analyzed the patient registry of a level II trauma center. All patients admitted with one or more rib fractures (N = 1,347) were considered. Patients who were not candidates for epidural analgesia (N = 382) were eliminated. Mortality was assessed with binary logistic regressions. Across the total population, mortality was 6.7%; incidence of pneumonia was 11.1%; mechanical ventilation was required in 23.8% of patients, for an average duration of 10.0 days; average stay in the hospital was 7.7 nights; and 49.7% of patients were admitted to the ICU for an average of 7.2 nights. Epidural analgesia was administered to 18.4% of patients. After matching samples for candidacy, patients who received epidurals were 3.7 years older, fractured 2.6 more ribs, had higher injury severity scores, and were more likely to present with bilateral fractures, flail segments, pulmonary contusions, hemothoraces, and pneumothoraces. Despite greater injury severity, mortality among these patients was lower (0.5%) than those who received alternative care (1.9%). Controlling for age, injury severity, and use of mechanical ventilation, epidural analgesia predicted a 97% reduction in mortality. Thoracic epidural analgesia associates with reduced mortality in rib fracture patients. Better care of this population is likely to be facilitated by more frequent reliance on this treatment. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Effects of parecoxib on analgesia benefit and blood loss following open prostatectomy: a multicentre randomized trial.

PubMed

Dirkmann, Daniel; Groeben, Harald; Farhan, Hassan; Stahl, David L; Eikermann, Matthias

2015-01-01

This multi-centre, prospective, randomized, double-blind, placebo-controlled study was designed to test the hypotheses that parecoxib improves patients' postoperative analgesia without increasing surgical blood loss following radical open prostatectomy. 105 patients (64 ± 7 years old) were randomized to receive either parecoxib or placebo with concurrent morphine patient controlled analgesia. Cumulative opioid consumption (primary objective) and the overall benefit of analgesia score (OBAS), the modified brief pain inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR-SDS), and perioperative blood loss (secondary objectives) were assessed. In each group 48 patients received the study medication for 48 hours postoperatively. Parecoxib significantly reduced cumulative opioid consumption by 24% (43 ± 24.1 mg versus 57 ± 28 mg, mean ± SD, p=0.02), translating into improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI-sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss was significantly higher at 24 hours following surgery in the parecoxib group (4.3 g⋅dL(-1) (3.6/4.9) versus (3.2 g⋅dL(-1) (2.4/4.95), p=0.02). Following major abdominal surgery, parecoxib significantly improves patients' perceived analgesia. Parecoxib may however increase perioperative blood loss. Further trials are needed to evaluate the effects of selective cyclooxygenase-2 inhibitors on blood loss. ClinicalTrials.gov Identifier: NCT00346268.

21 CFR 868.5160 - Gas machine for anesthesia or analgesia.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Gas machine for anesthesia or analgesia. 868.5160 Section 868.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5160 Gas machine for anesthesia...

21 CFR 868.5160 - Gas machine for anesthesia or analgesia.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gas machine for anesthesia or analgesia. 868.5160 Section 868.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5160 Gas machine for anesthesia...

[Brachial plexus. Anesthesia and analgesia].

PubMed

Schulz-Stübner, S

2003-07-01

This review explains the different approaches to the brachial plexus (posterior cervical, interscalene, supra- and infraclavicular, and axillary) and their advantages and disadvantages (indications, contraindications, and complications) for surgery and postoperative or chronic pain management. One of the focussed areas of this review is the use of continuous catheter techniques. Information about the most commonly used local anesthetics as well as adjuncts suggested in the literature is summarized. As essential components for the success of those techniques, organizational and documentation requirements are described. In summary, regional techniques for single shot or continuous block of the brachial plexus are an efficient and safe way of providing anesthesia and analgesia for surgery or pain in the region of the shoulder, arm, or hand.

[Comparison of clinical effectiveness of thoracic epidural and intravenous patient-controlled analgesia for the treatment of rib fractures pain in intensive care unit].

PubMed

Topçu, Ismet; Ekici, Zeynep; Sakarya, Melek

2007-07-01

The results of thoracic epidural and systemic patient controlled analgesia practice were evaluated retrospectively in patients with thoracic trauma. Patients who were admitted to the intensive care unit between 1997 and 2003, with a diagnosis of multiple rib fractures related to thoracic trauma were evaluated retrospectively. Data were recorded from 49 patients who met the following criteria; three or more rib fractures, initiation of PCA with I.V. phentanyl or thoracic epidural analgesia with phentanyl and bupivacaine. There were no significant differences between the groups concerning injury severity score. APACHE II score (8.1+/-1.6 and 9.2+/-1.7) and the number of rib fractures (4+/-1.1 and 6.8+/-2.7) were higher in thoracic epidural analgesia group (p<0.05). Pain scores of patients who received thoracic epidural analgesia were significantly lower as from 6th hour during whole therapy (p<0.05). Length of intensive care unit stay (15.6+/-5.9 and 12.1+/-4.4 day) was found to be shorter in thoracic epidural analgesia group (p<0.05). There were no differences between the groups regarding mechanical ventilation requirement, pulmonary and cardiac complications. We suggest that the use of thoracic epidural analgesia with infusion of local anesthetics and opioids are more appropriate as they provide more effective analgesia and shorten length of intensive care unit stay in chest trauma patients with more than three rib fractures who require intensive care.

Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a randomised controlled trial

PubMed Central

Pak, Linda Ma; Haroutounian, Simon; Hawkins, William G; Worley, Lori; Kurtz, Monika; Frey, Karen; Karanikolas, Menelaos; Swarm, Robert A; Bottros, Michael M

2018-01-01

Introduction Epidural analgesia provides an important synergistic method of pain control. In addition to reducing perioperative opioid consumption, the deliverance of analgesia into the epidural space, effectively creating a sympathetic blockade, has a multitude of additional potential benefits, from decreasing the incidence of postoperative delirium to reducing the development of persistent postsurgical pain (PPSP). Prior studies have also identified a correlation between the use of epidural analgesia and improved oncological outcomes and survival. The aim of this study is to evaluate the effect of epidural analgesia in pancreatic operations on immediate postoperative outcomes, the development of PPSP and oncological outcomes in a prospective, single-blind, randomised controlled trial. Methods The Epidurals in Pancreatic Resection Outcomes (E-PRO) study is a prospective, single-centre, randomised controlled trial. 150 patients undergoing either pancreaticoduodenectomy or distal pancreatectomy will be randomised to receive an epidural bupivacaine infusion following anaesthetic induction followed by continued epidural bupivacaine infusion postoperatively in addition to the institutional standardised pain regimen of hydromorphone patient-controlled analgesia (PCA), acetaminophen and ketorolac (intervention group) or no epidural infusion and only the standardised postoperative pain regimen (control group). The primary outcome was the postoperative opioid consumption, measured in morphine or morphine-equivalents. Secondary outcomes include patient-reported postoperative pain numerical rating scores, trend and relative ratios of serum inflammatory markers (interleukin (IL)-1β, IL-6, tumour necrosis factor-α, IL-10), occurrence of postoperative delirium, development of PPSP as determined by quantitative sensory testing, and disease-free and overall survival. Ethics and dissemination The E-PRO trial has been approved by the institutional review board. Recruitment began

Quality of analgesia in physician-operated telemedical prehospital emergency care is comparable to physician-based prehospital care - a retrospective longitudinal study.

PubMed

Lenssen, Niklas; Krockauer, Andreas; Beckers, Stefan K; Rossaint, Rolf; Hirsch, Frederik; Brokmann, Jörg C; Bergrath, Sebastian

2017-05-08

Acute pain is a common reason for summoning emergency medical services (EMS). Yet in several countries the law restricts opioid-based analgesia administration to physicians. Telemedical support of paramedics is a novel approach to enable timely treatment under the guidance of a physician. In this retrospective observational study, conducted in the EMS of Aachen, Germany, the analgesic quality and occurrence of adverse events were compared between telemedically-supported paramedics (July-December, 2014) and a historical control group (conventional on-scene EMS physicians; January-March, 2014). pain (initial numerical rating scale (NRS) ≥5) and/or performed analgesia. Telemedically-assisted analgesia was performed in 149 patients; conventional analgesia in 199 control cases. Teleconsultation vs. Initial NRS scores were 8.0 ± 1.5 and 8.1 ± 1.7. Complete NRS documentation was carried out in 140/149 vs. 130/199 cases, p < 0.0001. NRS scores were reduced by 4.94 ± 2.01 and 4.84 ± 2.28 (p = 0.5379), leading to mean NRS scores at emergency room arrival of 3.1 ± 1.7 vs. 3.3 ± 1.9 (p = 0.5229). No severe adverse events occurred in either group. Clinically relevant pain reduction was achieved in both groups. Thus, the concept of remote physician-based telemedically-delegated analgesia by paramedics is effective compared to analgesia by on-scene EMS physicians and safe.

Spinal analgesia and auditory functions: a comparison of two sizes of Quincke needle.

PubMed

Malhotra, S K; Iyer, B A; Gupta, A K; Raghunathan, M; Nakra, D

2007-01-01

Spinal anaesthesia may produce complications ranging from minor problems such as pain on injection, backache and urinary retention to more serious consequences such as post-dural puncture headache (PDPH), neurological complications like meningitis, cranial and peripheral nerve palsies and even cardiac arrest. Impaired auditory function is a relatively lesser-recognized complication of spinal analgesia. The objective of this study was to investigate the effects of spinal analgesia on vestibular dysfunction, using different sizes of the same type of spinal needle. The study included 30 ASA I patients who had received spinal analgesia for lower abdominal surgery. Pure tone audiometry was performed before surgery and on postoperative day 2. In addition, any patient with hearing impairment of >15 dB was scheduled to undergo electrocochleography. Hearing levels were measured from 250 Hz to 8 kHz. In group 1 (n=15), a 26gauge Quincke needle was used. In group 2 (n=15), a 23-gauge Quincke needle was used. Comparison of hearing thresholds showed a significant reduction in the hearing level (P<0.05) in 2 patients in group 2 but none in group 1. The use of a 23-gauge Quincke needle is associated with a greater reduction in the mean hearing level compared to a 26-gauge needle of the same type.

Labor Analgesia Consumption and Time to Neuraxial Catheter Placement in Women with a History of Surgical Correction for Scoliosis: A Case-Matched Study.

PubMed

Bauchat, Jeanette R; McCarthy, Robert J; Koski, Tyler R; Wong, Cynthia A

2015-10-01

Neuraxial analgesic techniques are the most effective form of labor analgesia. Small studies (9-21 patients), conducted 10 to 20 years ago, demonstrated successful neuraxial labor analgesia in only 50% to 66% of patients with surgical correction for scoliosis. Newer surgical techniques for scoliosis correction make the epidural space more accessible, but postsurgical changes may still alter the efficacy of neuraxial labor analgesia. The purpose of this prospective case-matched study was to compare hourly bupivacaine consumption and time to placement of neuraxial technique in laboring women with spinal instrumentation compared with women without previous back surgery. All women with previous spinal instrumentation surgery for scoliosis correction who requested neuraxial labor analgesia at Prentice Women's Hospital during the study period were approached. Control subjects were matched for anesthesiologist level of experience. The primary outcomes were bupivacaine consumption per hour of labor analgesia and time to placement of the neuraxial technique. Secondary outcomes included supplemental analgesia requirements and neuraxial analgesia failures and complications. Data from 41 women with surgical correction for scoliosis and 41 control subjects requesting neuraxial labor analgesia were analyzed. Obstetric and demographic characteristics of study participants were not different between groups. Median (interquartile range) hourly bupivacaine consumption was 15.2 mg/h (12.5-18.7) in the spinal instrumentation group and 14.2 mg/h (11.8-16.0) in the control group; the difference in medians was 1 mg/h (95% confidence interval [CI], -1.3 to 3.0; P = 0.38). The total bupivacaine consumption, number of manual reboluses, and number of subjects requiring greater bupivacaine concentrations did not differ between groups. Neuraxial analgesia failure occurred in 5 (12%) of women in the spinal instrumentation group but in none of the control patients (difference [95% CI], 12% [-0

Analysis and evaluation of the effectiveness of epidural analgesia and its relationship with eutocic or dystocic delivery.

PubMed

Sánchez-Migallón, V; Sánchez, E; Raynard, M; Miranda, A; Borràs, R M

Numerous studies have demonstrated the difference in the verbal rating scale with regard to obstructed labour and induced labour, so that obstructed labour and foetal macrosomia have been related to a greater sensation of pain during labour, particularly in the first stage. Even the epidural analgesia is linked to the need for instrumented or caesarean section due to foetal obstruction. The goal of the study is to analyze and evaluate the effectiveness of epidural analgesia in normal versus obstructed labour. One hundred and eighty pregnant women were included in an observational, analytical, longitudinal and prospective study, that was performed in the Obstetrics Department of the Hospital Universitario Dexeus. All the nulliparous or multiparous over 36 weeks of pregnancy, after 3cm of cervical dilatation in spontaneous or induced labor were included. All the patients were given epidural analgesia according to protocol. The basic descriptive methods were used for the univariate statistical analysis of the sample and the Mann-Whitney U test was used for the comparison of means between both groups. The correlations between variables were studied by means of the Spearman coefficient of correlation. The differences regarded as statistically significant are those whose P<.05. In our population there were no statistically significant differences in the effectiveness of epidural analgesia in normal versus obstructed labour. Patients who got epidural analgesia and had obstructed labors have the same degree of verbal rating scale as patients that do not had obstructed labors (P>.05). Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Subcutaneous infiltration of doxylamine on cutaneous analgesia in rats.

PubMed

Hung, Ching-Hsia; Shieh, Ja-Ping; Chiu, Chong-Chi; Wang, Jhi-Joung; Chen, Yu-Wen

2018-06-01

We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED 50 )), the relative potency was bupivacaine (0.41 (0.36-0.48) mmol)> doxylamine (7.39 (6.91-7.91)mmol) (p<0.01). On an equipotent basis (ED 25 , ED 50 and ED 75 ), subcutaneous doxylamine resulted in greater duration of action (p<0.01) than bupivacaine at producing cutaneous analgesia. The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Intraperitoneal bupivacaine with or without incisional bupivacaine for postoperative analgesia in dogs undergoing ovariohysterectomy.

PubMed

Kalchofner Guerrero, Karin S; Campagna, Ivo; Bruhl-Day, Rodolfo; Hegamin-Younger, Cecilia; Guerrero, Tomas G

2016-09-01

Intraperitoneal (IP) bupivacaine provides postoperative analgesia in dogs undergoing ovariohysterectomy (OHE) alone or in combination with incisional (INC) bupivacaine. This study investigated whether the combination of INC and IP bupivacaine is superior to IP bupivacaine alone. Prospective, randomized, blinded clinical study. Thirty-nine privately owned dogs undergoing OHE, aged 25 ± 23 months and weighing 11.8 ± 5.7 kg. Dogs were premedicated with acepromazine (0.05 mg kg(-1) ) and morphine (0.5 mg kg(-1) ) intramuscularly (IM); anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Carprofen (4 mg kg(-1) ) was administered subcutaneously (SC) after intubation. Bupivacaine (3 mg kg(-1) ) IP was administered before complete closure of the linea alba to all dogs. Dogs were randomly assigned into two groups: group B received bupivacaine (n = 20; 1 mg kg(-1) ) and group S received saline (n = 19; 0.2 mL kg(-1) ) INC as a subcutaneous 'splash' before skin closure. Postoperative analgesia was assessed with a dynamic interactive visual analogue scale, the short form of the Glasgow Composite Pain Scale, and mechanical nociceptive threshold (MNT) measurement at 0.5, 1, 2, 4, 6, 8, 12 and 20 hours after surgery by one blinded observer. Parametric data were tested using t-test; nonparametric data were analysed using the two-sample Wilcoxon test (p < 0.05). There was no significant difference between groups with regard to age, weight, surgical and anaesthetic duration, incision length, sedation and pain scores. MNT values decreased in both groups at all time points as compared with the baseline. No dog required rescue analgesia. No postoperative complications were observed. Bupivacaine IP and carprofen SC after morphine IM did provide satisfactory postoperative analgesia in dogs undergoing OHE with the anaesthetic protocol used. There appears to be no clinical advantage to adding bupivacaine INC. Neither protocol could

Effect of pre-emptive analgesia by continuous femoral nerve block on early postoperative cognitive function following total knee arthroplasty in elderly patients

PubMed Central

Deng, Li-Qin; Hou, Lei-Na; Song, Feng-Xiang; Zhu, Han-Yue; Zhao, Hai-Ying; Chen, Gang; Li, Jing-Jing

2017-01-01

To the best of our knowledge, the effect of pre-emptively blocking pain transmission on acute postoperative cognitive dysfunction (POCD) has not yet been assessed. Therefore, the present study aimed to investigate the effect of pre-emptive analgesia via a continuous femoral nerve block (CFNB) on postoperative pain and early cognitive function following total knee arthroplasty (TKA) surgery in elderly patients. CFNB was performed prior to TKA surgery in the pre-emptive analgesia group (n=30) and following TKA surgery in the control group (n=30). POCD was defined as a two-point reduction in the postoperative score compared with the preoperative score in the mini-mental state examination. The visual analog scale (VAS) was used to evaluate the intensity of pain at rest and during exercise. The intraoperative dose of remifentanil in the pre-emptive analgesia group was significantly lower than in the control group (P<0.01). In the preemptive analgesia group, VAS scores at three days post-surgery were lower than those in the control group (P<0.01). The incidence of POCD on the third postoperative day was slightly lower in the pre-emptive analgesia group compared with the control group. In conclusion, the results demonstrate that pre-emptive analgesia by CFNB may promote the recovery of early cognitive function following TKA in elderly patients. PMID:28413514

Effect of pre-emptive analgesia by continuous femoral nerve block on early postoperative cognitive function following total knee arthroplasty in elderly patients.

PubMed

Deng, Li-Qin; Hou, Lei-Na; Song, Feng-Xiang; Zhu, Han-Yue; Zhao, Hai-Ying; Chen, Gang; Li, Jing-Jing

2017-04-01

To the best of our knowledge, the effect of pre-emptively blocking pain transmission on acute postoperative cognitive dysfunction (POCD) has not yet been assessed. Therefore, the present study aimed to investigate the effect of pre-emptive analgesia via a continuous femoral nerve block (CFNB) on postoperative pain and early cognitive function following total knee arthroplasty (TKA) surgery in elderly patients. CFNB was performed prior to TKA surgery in the pre-emptive analgesia group (n=30) and following TKA surgery in the control group (n=30). POCD was defined as a two-point reduction in the postoperative score compared with the preoperative score in the mini-mental state examination. The visual analog scale (VAS) was used to evaluate the intensity of pain at rest and during exercise. The intraoperative dose of remifentanil in the pre-emptive analgesia group was significantly lower than in the control group (P<0.01). In the preemptive analgesia group, VAS scores at three days post-surgery were lower than those in the control group (P<0.01). The incidence of POCD on the third postoperative day was slightly lower in the pre-emptive analgesia group compared with the control group. In conclusion, the results demonstrate that pre-emptive analgesia by CFNB may promote the recovery of early cognitive function following TKA in elderly patients.

Linking pain and the body: neural correlates of visually induced analgesia.

PubMed

Longo, Matthew R; Iannetti, Gian Domenico; Mancini, Flavia; Driver, Jon; Haggard, Patrick

2012-02-22

The visual context of seeing the body can reduce the experience of acute pain, producing a multisensory analgesia. Here we investigated the neural correlates of this "visually induced analgesia" using fMRI. We induced acute pain with an infrared laser while human participants looked either at their stimulated right hand or at another object. Behavioral results confirmed the expected analgesic effect of seeing the body, while fMRI results revealed an associated reduction of laser-induced activity in ipsilateral primary somatosensory cortex (SI) and contralateral operculoinsular cortex during the visual context of seeing the body. We further identified two known cortical networks activated by sensory stimulation: (1) a set of brain areas consistently activated by painful stimuli (the so-called "pain matrix"), and (2) an extensive set of posterior brain areas activated by the visual perception of the body ("visual body network"). Connectivity analyses via psychophysiological interactions revealed that the visual context of seeing the body increased effective connectivity (i.e., functional coupling) between posterior parietal nodes of the visual body network and the purported pain matrix. Increased connectivity with these posterior parietal nodes was seen for several pain-related regions, including somatosensory area SII, anterior and posterior insula, and anterior cingulate cortex. These findings suggest that visually induced analgesia does not involve an overall reduction of the cortical response elicited by laser stimulation, but is consequent to the interplay between the brain's pain network and a posterior network for body perception, resulting in modulation of the experience of pain.

Analgesic efficacy of lidocaine and multimodal analgesia for chest tube removal: A randomized trial study1

PubMed Central

Pinheiro, Valdecy Ferreira de Oliveira; da Costa, José Madson Vidal; Cascudo, Marcelo Matos; Pinheiro, Ênio de Oliveira; Fernandes, Maria Angela Ferreira; de Araujo, Ivonete Batista

2015-01-01

Objective: to assess the analgesic efficacy of subcutaneous lidocaine and multimodal analgesia for chest tube removal following heart surgery. Methods: sixty volunteers were randomly allocated in two groups; 30 participants in the experimental group were given 1% subcutaneous lidocaine, and 30 controls were given a multimodal analgesia regime comprising systemic anti-inflammatory agents and opioids. The intensity and quality of pain and trait and state anxiety were assessed. The association between independent variables and final outcome was assessed by means of the Chi-squared test with Yates' correction and Fisher's exact test. Results: the groups did not exhibit significant difference with respect to the intensity of pain upon chest tube removal (p= 0.47). The most frequent descriptors of pain reported by the participants were pressing, sharp, pricking, burning and unbearable. Conclusion: the present study suggests that the analgesic effect of the subcutaneous administration of 1% lidocaine combined with multimodal analgesia is most efficacious. PMID:26625989

Comparison of epidural morphine versus intramuscular morphine for postoperative analgesia.

PubMed

Baftiu, Nehat; Hadri, Burhan; Mustafa, Aziz

2010-01-01

To compare effects and side effects or complications of epidural versus intramuscularly administered morphine for relieve of postoperative pain. In the first group (epidural) analgesia is achieved by application of morphine through epidural catheter. To the amount of morphine is added physiological solution until 10 ml of total volume of the mixture is achieved. This mixture is given to 150 patients, by epidural route before the exit from the operation room. Epidural catheter is removed after 48 hours. Second group (intramuscular) analgesia is realized by application of 10 mg of morphine by intramuscular route. Morphine is injected at the end of surgery. Pain is assessed with combination of verbal categorical scale and visual analog scale. Verbal categorical scale used is 8 points scale and contains words of Tursky: 0 no pain, 1 very low pain, 2 week pain, 3 mild pain, 4 moderate pain, 5 strong pain, 6 severe pain, 7 untolerated pain. Awareness is assed during first 24 hours. For this Reynolds 4 points scale is used: awaked 1, somnolent 2, sleepy 3, deep sleep 4. Pain assessed by visual analog scale (VAS) is 15.17-29.62 in the epidural group patients versus 26.39-70.83 in intramuscular group. Variation of respiration rate in both groups is not significant 22.21 +/- 4.23 and 23.98 +/- 2.72 in minute, in epidural and intramuscular morphine groups, respectively. PaCO2 and PaO2 values are similar without significant variation 35.34 +/- 4.72 mmHg in the epidural morphine group and 31.3 +/- 3.21 mmHg in intramuscular morphine group. Epidural administration of morphine provides better analgesia in quality, since it is deeper, longer in duration and with less inhibitory supra-spinal actions when compared to intramuscular administered morphine.

The Effect of the Time of Injection of Intrathecal Analgesia on the Length of Early and Advanced Labor

DTIC Science & Technology

1999-10-01

Recommendations for future studies include a prospective randomized clinical trial to examine the effect of the timing of intrathecal narcotic...population and in clinical practice. Friedman (1978) Intrathecal Analgesia 7 however, does provide averages and upper statistical limits for the first and...morphine into the subarchnoid space of rats produced potent analgesia (Wang, 1977). These effects were then clinically applied in man for the relief of

Hypnotic analgesia reduces brain responses to pain seen in others.

PubMed

Braboszcz, Claire; Brandao-Farinelli, Edith; Vuilleumier, Patrik

2017-08-29

Brain responses to pain experienced by oneself or seen in other people show consistent overlap in the pain processing network, particularly anterior insula, supporting the view that pain empathy partly relies on neural processes engaged by self-nociception. However, it remains unresolved whether changes in one's own pain sensation may affect empathic responding to others' pain. Here we show that inducing analgesia through hypnosis leads to decreased responses to both self and vicarious experience of pain. Activations in the right anterior insula and amygdala were markedly reduced when participants received painful thermal stimuli following hypnotic analgesia on their own hand, but also when they viewed pictures of others' hand in pain. Functional connectivity analysis indicated that this hypnotic modulation of pain responses was associated with differential recruitment of right prefrontal regions implicated in selective attention and inhibitory control. Our results provide novel support to the view that self-nociception is involved during empathy for pain, and demonstrate the possibility to use hypnotic procedures to modulate higher-level emotional and social processes.

Bacterial infection in deep paraspinal muscles in a parturient following epidural analgesia.

PubMed

Yang, Ying-Wei; Chen, Wei-Ting; Chen, Jui-Yuan; Lee, She-Chin; Chang, Yi; Wen, Yeong-Ray

2011-06-01

We report a case of paraspinal muscle infection shortly after epidural analgesia for labor pain in a nulliparous parturient who was subjected to emergent Cesarean section because of fetal distress. Epidural morphine was administered for 3 days for postoperative pain control. She began to have constant lower back pain on postpartum Day 4. Magnetic resonance image study revealed a broad area of subcutaneous edema with a continuum along the catheter trajectory deep to the paraspinal muscles. An injection-related bacterial infection was suspected; the patient was treated with intravenous antibiotics and was soon cured uncomplicatedly. Epidural analgesia is effective to control labor pain and, in general, it is safe. However, the sequelae of complicated infection may be underestimated. We herein report a case complicated by iatrogenic infection, discuss the causes, and give suggestions for prevention. Copyright © 2011. Published by Elsevier B.V.

Effects of Epidural Labor Analgesia With Low Concentrations of Local Anesthetics on Obstetric Outcomes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Wang, Ting-Ting; Sun, Shen; Huang, Shao-Qiang

2017-05-01

Low concentrations of local anesthetics (LCLAs) are increasingly popular for epidural labor analgesia. The effects of epidural analgesia with low concentrations of anesthetics on the duration of the second stage of labor and the instrumental birth rate, however, remain controversial. A systematic review was conducted to compare the effects of epidural analgesia with LCLAs with those of nonepidural analgesia on obstetric outcomes. The databases of PubMed, Embase, and the Cochrane controlled trials register were independently searched by 2 researchers, and randomized controlled trials that compared epidural labor analgesia utilizing LCLAs with nonepidural analgesia were retrieved. The primary outcomes were the duration of the second stage of labor and the instrumental birth rate; secondary outcomes included the cesarean delivery rate, the spontaneous vaginal delivery rate, and the duration of the first stage of labor. Ten studies (1809 women) were included. There was no significant difference between groups in the duration of the second stage of labor (mean difference = 5.71 minutes, 95% confidence interval [CI], -6.14 to 17.83; P = .36) or the instrumental birth rate (risk ratio [RR] = 1.52, 95% CI, 0.97-2.4; P = .07). There was no significant difference between groups in the cesarean delivery rate (RR = 0.8, 95% CI, 0.6-1.05; P = .11), the spontaneous vaginal delivery rate (RR = 0.98, 95% CI, 0.91-1.06; P = .62), or the duration of the first stage of labor (mean difference = 17.34 minutes, 95% CI, -5.89 to 40.56; P = .14). Compared with nonepidural analgesia, epidural analgesia with LCLAs is not associated with a prolonged duration of the second stage of labor or an increased instrumental birth rate. The results of this meta-analysis are based on small trials of low quality. These conclusions require confirmation by large-sample and high-quality trials in the future.

Local infiltration analgesia is comparable to femoral nerve block after anterior cruciate ligament reconstruction with hamstring tendon graft: a randomised controlled trial.

PubMed

Kristensen, Pia Kjær; Pfeiffer-Jensen, Mogens; Storm, Jens Ole; Thillemann, Theis Muncholm

2014-02-01

Arthroscopic anterior cruciate ligament (ACL) reconstruction is a painful procedure requiring intensive postoperative pain management. Femoral nerve block is widely used in ACL surgery. However, femoral nerve block does not cover the donor site of the hamstring tendons. Local infiltration analgesia is a simple technique that has proven effective in postoperative pain management after total knee arthroplasty. Further, local infiltration analgesia covers the donor site and is associated with few complications. It was hypothesised that local infiltration analgesia at the donor site and wounds would decrease pain and opioid consumption after ACL reconstruction with hamstring tendon graft. Sixty patients undergoing primary ACL surgery with hamstring tendon graft were randomised to receive either local infiltration analgesia or femoral nerve block. Pain was scored on the numeric rating scale, and use of opioid, range of motion and adverse effects were assessed at the postoperative recovery unit (0 h), 3, 24 and 48 h, postoperatively. There were no significant differences between the groups in pain intensity or total opioid consumption at any of the follow-up points. Further, there were no differences between groups concerning side effects and range of motion. Local infiltration analgesia and femoral nerve block are similar in the management of postoperative pain after ACL reconstruction with hamstring tendon graft. Until randomised studies have investigated femoral nerve block combined with infiltration at the donor site, we recommend local infiltration analgesia in ACL reconstruction with hamstring tendon graft.