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Sample records for ketorolac para analgesia

  1. [Ketorolac vs metamizol preemptive analgesia in children].

    PubMed

    Peñuelas-Acuña, Juana; Oriol-López, S Alejandra; Hernández-Bernal, Clara E; Castelazo Arredondo, J Antonio

    2003-01-01

    Preventive analgesia produced by ketorolac and metamizol was evaluated during a prospective study randomized in two groups. One hundred twenty children were included aged from 3 to 6 years who underwent surgery by different procedures. Analgesic dose was applied 15 min prior to surgery by intravenous (i.v.) via. Technique used was inhaled general anesthesia; use of opioids was avoided. Pain evaluation at the end of surgery (and during the following 48 to 72 h) as well as bleeding time, platelet count, and alterations in white blood cell count were dependent variables. As soon as patients arrived in the recovery room, pain was measured by modified McGrath scales and the chromatic EVA. In ketorolac group, 40% of children showed no pain and 55% presented mild to moderate pain (1-6). In metamizol group, 40% of children referred no pain, while 55% evaluated pain as minimal to moderate. Analgesia produced by both drugs presented no significant statistical diference (p > 0.5). Troughout followup, maximum pain referred had a values of 6 and 7, respectively, for ketorolac and metamizol. Fifteen min after analgesic dose, pain was referred as 3 and 4. No alterations were observed in bleeding time, platelet count, and white blood cell count. We conclude that both analgesics prevent hyperalgesia during post-surgical period. PMID:19753721

  2. Ketorolac

    MedlinePlus

    ... such as ketorolac may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may ... like coffee grounds, blood in the stool, or black and tarry stools.Ketorolac may cause kidney failure. ...

  3. A Comparative Efficacy of Propacetamol and Ketorolac in Postoperative Patient Controlled Analgesia

    PubMed Central

    Heo, Bong Ha; Park, Ji Hun; Choi, Jung Il; Kim, Woong Mo; Lee, Hyoung Gon; Cho, Soo Young

    2015-01-01

    Background Ketorolac has been used as a postoperative analgesia in combination with opioids. However, the use of ketorolac may produce serious side effects in vulnerable patients. Propacetamol is known to induce fewer side effects than ketorolac because it mainly affects the central nervous system. We compared the analgesic effects and patient satisfaction levels of each drug when combined with fentanyl patient-controlled analgesia (PCA). Methods The patients were divided into two groups, each with n = 46. The patients in each group were given 60 mg of ketorolac or 2 g of propacetamol (mixed with fentanyl) for 10 minutes. The patients were then given 180 mg of ketorolac or 8 g of propacetamol (mixed with fentanyl and ramosetron) through PCA. We assessed the visual analogue pain scale (VAS) at the time point immediately before administration (baseline) and at 15, 30, and 60 minutes, and 24 hours after administration. Also, the side effects of each regimen and each patient's degree of satisfaction were assessed. Results There was a significant decline in the VAS score in both groups (P < 0.05). However, there were no significant differences in the VAS scores between the groups at each time point. Satisfaction scores between the groups showed no significant difference. Conclusions The efficacy of propacetamol is comparable to that of ketorolac in postoperative PCA with fentanyl. PMID:26175881

  4. Epidural hematoma after thoracic epidural analgesia in a patient treated with ketorolac, mefenamic acid, and naftazone: a case report

    PubMed Central

    Jeon, Dae Geun; Kim, Seok-Kon; Kim, Juri

    2014-01-01

    A 26-year-old male undergoing thoracotomy and bleeding control received a preoperative thoracic epidural for postoperative analgesia. On the fifth postoperative day, paralysis of both lower limbs occurred and urgent magnetic resonance imaging showed massive anterior epidural hematoma. During laminectomy and decompression, platelet dysfunction was diagnosed and preoperative non-steroidal anti-inflammatory drugs medications were supposed to the cause of platelet dysfunction. After infusion of ten units of platelet concentrate, coagulopathy was improved. We should be more careful to drugs with antiplatelet effect when using regional analgesia. PMID:24729848

  5. Ketorolac Ophthalmic

    MedlinePlus

    ... swelling and redness (inflammation) that can occur after cataract surgery. Ketorolac is in a class of medications ... eyes four times a day. For inflammation after cataract surgery, one drop is usually instilled in the ...

  6. 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 ...

  7. Ketorolac Nasal Spray

    MedlinePlus

    ... Ketorolac is in a class of medications called NSAIDs. It works by stopping the body's production of ... you are allergic to ketorolac, aspirin or other NSAIDs such as ibuprofen (Advil, Motrin) or naproxen (Aleve, ...

  8. Ketorolac Nasal Spray

    MedlinePlus

    ... such as ketorolac may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may ... like coffee grounds, blood in the stool, or black and tarry stools.Ketorolac may cause an increased ...

  9. Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain.

    PubMed

    Forbes, J A; Butterworth, G A; Burchfield, W H; Beaver, W T

    1990-01-01

    One-hundred twenty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive oral doses of ketorolac tromethamine 10 mg, aspirin 650 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia. Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia, and significantly superior to acetaminophen-codeine for measures of total effect. The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours. Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery. Differences among the active medications were trivial for the postoperative days 1-6 analyses. The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin. PMID:2082317

  10. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management.

    PubMed

    Gillis, J C; Brogden, R N

    1997-01-01

    Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with strong analgesic activity. The analgesic efficacy of ketorolac has been extensively evaluated in the postoperative setting, in both hospital inpatients and outpatients, and in patients with various other acute pain states. After major abdominal, orthopaedic or gynaecological surgery or ambulatory laparoscopic or gynaecological procedures, ketorolac provides relief from mild to severe pain in the majority of patients and has similar analgesic efficacy to that of standard dosages of morphine and pethidine (meperidine) as well as less frequently used opioids and other NSAIDs. The analgesic effect of ketorolac may be slightly delayed but often persists for longer than that of opioids. Combined therapy with ketorolac and an opioid results in a 25 to 50% reduction in opioid requirements, and in some patients this is accompanied by a concomitant decrease in opioid-induced adverse events, more rapid return to normal gastrointestinal function and shorter stay in hospital. In children undergoing myringotomy, hernia repair, tonsillectomy, or other surgery associated with mild to moderate pain, ketorolac provides comparable analgesia to morphine, pethidine or paracetamol (acetaminophen). In the emergency department, ketorolac attenuates moderate to severe pain in patients with renal colic, migraine headache, musculoskeletal pain or sickle cell crisis and is usually as effective as frequently used opioids, such as morphine and pethidine, and other NSAIDs and analgesics. Subcutaneous administration of ketorolac reduces pain in patients with cancer and seems particularly beneficial in pain resulting from bone metastases. The acquisition cost of ketorolac is greater than that of morphine or pethidine; however, in a small number of studies, the higher cost of ketorolac was offset when treatment with ketorolac resulted in a reduced hospital stay compared with alternative opioid therapy. The tolerability profile of

  11. Ketorolac Administration Does Not Delay Early Fracture Healing in a Juvenile Rat Model

    PubMed Central

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

    2014-01-01

    . Clinical Relevance The absence of inhibitory effects of ketorolac on early juvenile rat fracture healing supports the clinical practice of utilizing NSAIDs for analgesia in children with long bone fractures. PMID:23653032

  12. 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 Central

    Isiordia-Espinoza, Mario-Alberto; Martinez-Rider, Ricardo; Perez-Urizar, Jose

    2016-01-01

    Background 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. Material and Methods 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. Results Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. Conclusions According to the VAS and AUC 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. Key words:Ketorolac, tramadol, third molar surgery, pain, preemptive analgesia. PMID:27475688

  13. Rocuronium-induced withdrawal movement: influence of ketorolac or a combination of lidocaine and ketorolac pretreatment

    PubMed Central

    Jeon, Younghoon; Ha, Jae Hyun; Lee, Jeong-Eun; Lee, Hyung-Chul; Ryu, Taeha

    2013-01-01

    Background Pain on injection of rocuronium is a common clinical problem. We compared the efficacy of lidocaine, ketorolac, and the 2 in combination as pretreatment for the prevention of rocuronium-induced withdrawal movement. Methods For this prospective, randomized, placebo-controlled, double-blind study a total of 140 patients were randomly allocated to one of 4 treatment groups to receive intravenously placebo (saline), lidocaine (20 mg), ketorolac (10 mg), or both (n = 35 for each group), with venous occlusion. The tourniquet was released after 2 min and anesthesia was performed using 5 mg/kg thiopental sodium followed by 0.6 mg/kg rocuronium. The withdrawal response was graded on a 4-point scale in a double-blind manner. Results The overall incidence of withdrawal movements after rocuronium was 34.3% with lidocaine (P = 0.001), 40% with ketorolac (P = 0.004), and 8.6% with both (P < 0.001), compared with 74.3% with placebo. There was a significantly lower incidence of withdrawal movements in patients receiving the lidocaine/ketorolac combination than in those receiving lidocaine or ketorolac alone (P = 0.009 and 0.002, respectively). The incidence of moderate to severe withdrawal movements was 14.3% with lidocaine, 17.2% with ketorolac, and 2.9% with lidocaine/ketorolac combination, as compared to 45.7% with the placebo. There was no significant difference in withdrawal movement between the lidocaine group and the ketorolac group. Conclusions Ketorolac pretreatment had an effect comparable to that of lidocaine in attenuating rocuronium-induced withdrawal movements and the lidocaine/ketorolac combination pretreatment, compared with lidocaine or ketorolac alone, effectively reduced withdrawal movements during rocuronium injection. PMID:23372882

  14. Comparative Evaluation of Preemptive Analgesic Effect of Injected Intramuscular Diclofenac and Ketorolac after Third Molar Surgery- A Randomized Controlled Trial

    PubMed Central

    Mony, Deepthi; Kulkarni, Deepak

    2016-01-01

    Introduction Analgesia pre-emptively administered effect-ively aid in management of pain. Pre-emptive analgesia is anti-nociceptive treatment which prevents altered central sensitization of afferent inputs. Aim To compare and evaluate the pre-emptive analgesic efficacy of preoperatively administered ketorolac and diclofenac for controlling postoperative pain after third molar surgery. Materials and Methods A total of 50 patients with symmetrically impacted third molars were divided into two groups, 30mg intramuscular injection of ketorolac and 75 mg diclofenac sodium were used in the respective groups. The visual analogue scale was used to assess post operative pain for three days and the patients were also evaluated for the number of rescue analgesia. Results The data was statistically evaluated with paired t- test. The maximum time taken for pain perception for Group A Ketoralac was 5.48 hrs and Group B Diclofenac sodium was 4.9 hrs and p=0.235 which was not significant. The mean number of tablets taken by the patients in the first three post operative days was 3.24 in Group A i.e., Ketorolac and 4.04 in Group B i.e., Diclofenac sodium. The values were compared using the paired t test. The p value = 0.004, which was significant. Conclusion Ketoralac showed better pre-emptive analgesic effect for post-operative pain management after third molar extraction. The immediate post-operative pain free period provided by both ketorolac and diclofenac by intramuscular route was same. PMID:27504398

  15. Effective analgesia after bilateral tubal ligation.

    PubMed

    Wittels, B; Faure, E A; Chavez, R; Moawad, A; Ismail, M; Hibbard, J; Principe, D; Karl, L; Toledano, A Y

    1998-09-01

    To evaluate the analgesic efficacy of local anesthetic infiltration, 20 parturients scheduled for elective minilaparotomy and bilateral tubal ligation with either spinal or epidural anesthesia participated in this prospective, randomized, controlled, double-blind trial. All patients received intravenous (iv) metoclopramide 10 mg and ketorolac 60 mg intraoperatively, as well as preincisional infiltration of the infraumbilical skin incision with 0.5% bupivacaine. Infiltration of bilateral uterine tubes and mesosalpinx was performed either with 0.5% bupivacaine (n = 10) or isotonic sodium chloride solution (n = 10). Intravenous meperidine (25 mg every 3 minutes as needed) was given to treat pain in the postanesthesia care unit (PACU). The total amount of meperidine administered in the PACU was significantly larger in the saline group than in the bupivacaine group. Pain scores at 30, 45, 60, 75, and 90 minutes postoperatively and on the 7th postoperative day were significantly lower in the bupivacaine group than in the saline group. During tubal ligation, infiltration of uterine tubes and mesosalpinx with 0.5% bupivacaine significantly enhanced analgesia both immediately postoperatively and on the 7th postoperative day compared with infiltration with sodium chloride. In conclusion, this study proved that during bilateral tubal ligation with either spinal or epidural anesthesia, preemptive analgesia using iv ketorolac, iv metoclopramide, and infiltration of the incised skin and uterine tubes with 0.5% bupivacaine can eliminate pain, nausea, vomiting, or cramping and maintain good analgesia for 7 days postoperatively. PMID:9728841

  16. Ketorolac

    MedlinePlus

    ... heartburn, vomit that is bloody or looks like coffee grounds, blood in the stool, or black and tarry ... stools vomit that is bloody or looks like coffee grounds drowsiness slowed breathing or fast, shallow breathing coma ( ...

  17. Ketorolac: a parenteral nonsteroidal antiinflammatory drug.

    PubMed

    Resman-Targoff, B H

    1990-11-01

    Ketorolac tromethamine is a pyrrolo-pyrrole nonsteroidal antiinflammatory drug (NSAID) with potent analgesic effects when administered intramuscularly for the treatment of acute pain. Ketorolac is well absorbed and has a rapid onset of action. Maximum plasma concentrations are achieved in 45-50 minutes and peak analgesic effects in about one to two hours following intramuscular injection. Ketorolac is more than 99 percent bound to plasma proteins and has a mean apparent volume of distribution of 0.11-0.25 L/kg. About 91 percent of a dose is excreted in urine, mostly as inactive metabolites, and approximately 6 percent is eliminated in feces. The elimination half-life, approximately four to six hours, increases in elderly patients and those with renal impairment. Its analgesic effectiveness was similar or superior to that of morphine, meperidine, or pentazocine in single-dose studies of patients with postoperative pain or renal colic and greater than that of placebo in patients with chronic cancer pain. The adverse effects are generally mild to moderate, self-limiting, and similar to those seen with other prostaglandin inhibitors. Ketorolac has a reversible inhibitory effect on platelet aggregation. It can cause dose-related gastric ulcerations, even when administered parenterally. Ketorolac is a promising parenteral alternative to oral NSAIDs and a nonnarcotic alternative to opioid analgesics. Additional multiple-dose studies are needed to more clearly define its place in therapy. PMID:2275236

  18. Evaluation of analgesic efficacy of bromfenac sodium ophthalmic solution 0.09% versus ketorolac tromethamine ophthalmic solution 0.5% following LASEK or Epi-LASIK

    PubMed Central

    Wang, Xiao Jing; Wong, Sze H; Givergis, Roshan; Chynn, Emil W

    2011-01-01

    Background To evaluate the analgesic efficacy of bromfenac sodium ophthalmic solution 0.09% compared with ketorolac tromethamine ophthalmic solution 0.5% in laser epithelial keratomileusis (LASEK) or epithelial keratomileusis (epi-LASEK), sometimes referred to as epi-LASIK. Methods Eighty eyes (from 40 patients, 18 men and 22 women) undergoing bilateral simultaneous LASEK or epi-LASEK were randomized to receive ketorolac in one eye and bromfenac in the other. Mean age was 33.13 ± 9.34 years. One drop of bromfenac or ketorolac was instilled in each eye 15 minutes and one minute prior to surgery, and two and four hours following surgery. Patients were instructed to instill the medications on-label each day through postoperative day 4. The subjects completed pain and visual blurriness assessments from day of surgery to postoperative day 4. Uncorrected visual acuity was tested on postoperative days 1 and 6. Results For each of the five days, pain scores for bromfenac-treated eyes were significantly less than that for ketorolac-treated eyes (P < 0.01). Of the 40 patients, 32 (80%) said bromfenac provided better postoperative analgesia than ketorolac. There was no statistically significant difference in visual blurriness scores between the two groups (P > 0.1). Uncorrected visual acuity did not vary significantly between the treatment groups (P > 0.1). No serious adverse events were noted. Conclusion Bromfenac is subjectively superior to ketorolac in reducing postoperative pain following LASEK or epi-LASEK. The subjects tolerated the drugs well with no serious adverse outcomes and no difference in uncorrected visual acuity. PMID:22034570

  19. Local infiltration analgesia is not improved by postoperative intra-articular bolus injections for pain after total hip arthroplasty

    PubMed Central

    Andersen, Karen V; Nikolajsen, Lone; Daugaard, Henrik; Andersen, Niels T; Haraldsted, Viggo; Søballe, Kjeld

    2015-01-01

    Background and purpose — The effect of postoperative intra-articular bolus injections after total hip arthroplasty (THA) remains unclear. We tested the hypothesis that intra-articular bolus injections administered every 6 hours after surgery during the first 24 hours would significantly improve analgesia after THA. Patients and methods — 80 patients undergoing THA received high-volume local infiltration analgesia (LIA; 200 mg ropivacaine and 30 mg ketorolac) followed by 4 intra-articular injections with either ropivacaine (100 mg) and ketorolac (15 mg) (the treatment group) or saline (the control group). The intra-articular injections were combined with 4 intravenous injections of either saline (treatment group) or 15 mg ketorolac (control group). All patients received morphine as patient-controlled analgesia (PCA). The primary outcome was consumption of intravenous morphine PCA and secondary outcomes were consumption of oral morphine, pain intensity, side effects, readiness for hospital discharge, length of hospital stay, and postoperative consumption of analgesics at 3, 6, and 12 weeks after surgery. Results — There were no statistically significant differences between the 2 groups regarding postoperative consumption of intravenous morphine PCA. Postoperative pain scores during walking were higher in the treatment group from 24–72 hours after surgery, but other pain scores were similar between groups. Time to readiness for hospital discharge was longer in the treatment group. Other secondary outcomes were similar between groups. Interpretation — Postoperative intra-articular bolus injections of ropivacaine and ketorolac cannot be recommended as analgesic method after THA. PMID:26312445

  20. 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. PMID:24481782

  1. A double-blind placebo-controlled comparison of a novel formulation of intravenous diclofenac and ketorolac for postoperative third molar extraction pain.

    PubMed

    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

  2. Analgesia after liver transplantation

    PubMed Central

    Milan, Zoka

    2015-01-01

    This article addresses postoperative analgesia in patients with end-stage liver disease who have undergone liver transplantation (LT). Postoperative analgesia determines how patients perceive LT. Although important, this topic is underrepresented in the current literature. With an increased frequency of fast tracking in LT, efficient intra- and postoperative analgesia are undergoing changes. We herein review the current literature, compare the benefits and disadvantages of the therapeutic options, and make recommendations based on the current literature and clinical experience. PMID:26413222

  3. Post-operative intravenous patient-controlled analgesic efficacy of morphine with ketorolac versus nefopam after laparoscopic gynecologic surgery: a randomized non-inferiority trial

    PubMed Central

    Yoon, Ji-Uk; Cheon, Ji-Hyun; Choi, Yoon-Mi; Ri, Hyun-Su; Baik, Seong-Wan

    2016-01-01

    Background Nefopam is a non-opioid non-steroidal centrally acting analgesic. This study was conducted to assess the analgesic efficacy of intravenous patient-controlled analgesia (IV-PCA) using nefopam alone, compared with a combination of morphine and ketorolac, after laparoscopic gynecologic surgery. Methods Sixty patients undergoing laparoscopic gynecologic surgery received IV-PCA. Group A (n = 30) received IV-PCA with a combination of morphine 60 mg and ketorolac 180 mg, while group B (n = 30) received nefopam 200 mg (basal rate 1 ml/h, bolus 1 ml, and lockout time 15 min for both). The primary outcome evaluated was analgesic efficacy using the visual analogue scale (VAS). Other evaluated outcomes included the incidence rate of postoperative nausea and vomiting (PONV), patient satisfaction of pain control, percentage of patients requiring additional opioids, and incidence rate of postoperative adverse effects. Results Group B was not inferior to group A in relation to the VAS in the post-anesthesia care unit, and at 12, 24, and 48 h after surgery (mean difference [95% confidence interval], 0.50 [–0.43 to 1.43], -0.30 [-1.25 to 0.65], -0.05 [-0.65 to 0.55], and 0.10 [-0.55 to 0.75], respectively). The incidence rate of nausea was lower in group B than in group A at 12 and 24 h after surgery (P = 0.004 and P = 0.017, respectively). There were no significant differences in the other outcomes between groups. Conclusions IV-PCA using nefopam alone has a non-inferior analgesic efficacy and produces a lower incidence of PONV in comparison with IV-PCA using a combination of morphine and ketorolac after laparoscopic gynecologic surgery. PMID:27066208

  4. Risk of Acute Kidney Injury After Primary and Revision Total Hip Arthroplasty and Total Knee Arthroplasty Using a Multimodal Approach to Perioperative Pain Control Including Ketorolac and Celecoxib.

    PubMed

    Warth, Lucian C; Noiseux, Nicolas O; Hogue, Matthew H; Klaassen, Alison L; Liu, Steve S; Callaghan, John J

    2016-01-01

    Safe and effective perioperative analgesia is instrumental to patient satisfaction and decreasing LOS after TJA. We evaluated rates of acute kidney injury (AKI) in primary and revision TJA using a multimodal pain control regimen including scheduled celecoxib and PRN ketorolac. Postoperative AKI was identified in 43/903 (4.8%) of 903 of patients with adequate preoperative renal function. Those who developed AKI had significantly increased LOS (P < .01), were older, more obese, and more likely to have diabetes (P < .05). With a protocol incorporating NSAIDs in patients without evidence of preoperative renal impairment, there is a 4.8% rate of AKI, which is 2.7 times higher than the reported literature. Acute postoperative kidney injury was significantly correlated with increased LOS and has important patient safety and healthcare-related cost implications. PMID:26377377

  5. Pharmacokinetics of ketorolac tromethamine in horses after intravenous, intramuscular, and oral single-dose administration.

    PubMed

    Bianco, A W; Constable, P D; Cooper, B R; Taylor, S D

    2016-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine-sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5-mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady-state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti-inflammatory properties of KT in horses. PMID:26416348

  6. Local Infiltration Analgesia reduces pain and hospital stay after primary TKA: randomized controlled double blind trial.

    PubMed

    Vaishya, Raju; Wani, Ajaz Majeed; Vijay, Vipul

    2015-12-01

    Postoperative analgesia following Total Knee Arthroplasty (TKA) with the use of parenteral opioids or epidural analgesia can be associated with important side effects. Good perioperative analgesia facilitates faster rehabilitation, improves patient satisfaction, and may reduce the hospital stay. We investigated the analgesic effect of a locally injected mixture of drugs, in a double blinded RCT in 80 primary TKA. They were randomized either to receive a periarticular mixture of drugs containing bupivacaine, ketorolac, morphine, and adrenalline or to receive normal saline. Visual analog scores (VAS) for pain (at rest and during activity) and for patient satisfaction and range of motion were recorded postoperatively. The patients who had received the periarticular injection used significantly less the Patient Controlled Analgesia (PCA) after the surgery as compared to the control group. In addition, they had lower VAS for pain during rest and activity and higher visual analog scores for patient satisfaction 72 hours postoperatively. No major complication related to the drugs was observed. Intraoperative periarticular injection with multimodal drugs following TKA can significantly reduce the postoperative pain and hence the requirements for PCA and hospital stay, with no apparent risks. PMID:26790796

  7. A double-blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic.

    PubMed

    Oosterlinck, W; Philp, N H; Charig, C; Gillies, G; Hetherington, J W; Lloyd, J

    1990-04-01

    The efficacy of a single dose of intramuscular ketorolac 10 mg or 90 mg was compared with pethidine 100 mg in a randomized double-blind study in 121 patients reporting at least moderate pain due to renal colic. Pain was assessed before drug administration, and then at 1 hour and 12 hours after the dose. Sedation was also assessed at these times, and additionally at the 12 hour assessment the time of the next analgesic dose was recorded. At 1 hour after dosing, pain scores had decreased in all groups; the largest decrease was seen in the ketorolac 90 mg group. The difference in the decrease was significant between the two ketorolac groups, but the differences between ketorolac and pethidine were not significant. Fewer patients in the ketorolac 90 mg group (17%) required a further dose of analgesic within 10 hours than in either the ketorolac 10 mg group (39%) or the pethidine 100 mg group (47%). The difference between ketorolac 90 mg and pethidine 100 mg was statistically significant. At both assessment times the proportion of patients with no sedation was higher in the two ketorolac groups than in the pethidine group. The overall incidence of adverse events was low with all drugs, notably so for the occurrence of vomiting after ketorolac. The results of the study show that intramuscular ketorolac is efficacious in the treatment of renal colic. PMID:2341581

  8. Epidural analgesia in obstetrics.

    PubMed

    Tan, T K

    1998-03-01

    An ideal analgesic for labour would preferably be non-invasive, as effective as spinals and epidurals without their attendant complications and is safe to mother and child and should not complicate the labour process. Analgesia for labouring women ranges from the use of opioid injections to invasive methods, chiefly epidural injections. Each has its advantages and drawbacks. This article provides a review of analgesic methods and techniques for labouring women. It focuses mainly on the role of epidurals, how it is utilised by anaesthetists and the differing methods of drug delivery through the epidural route. It discusses various concoctions of local anaesthetics and adjuvants used. The epidural route is probably the most effective and most commonly used invasive route for achieving analgesia during labour. Local anaesthetics of varying concentrations are administered as intermittent boluses or as a continuous infusion. Adjuvant drugs are able to enhance the quality and duration of the analgesia. Opioids including fentanyl and sufentanil, and clonidine are discussed. The use of patient-controlled epidural analgesia and combined spinal-epidural analgesia are reviewed. Ambulatory or mobile epidurals are increasingly popular. They are known to improve maternal satisfaction because of preservation of motor power. Ambulation may help with cervical dilatation and engagement, and abolition of backpain, among other advantages. This article describes the methods of establishing mobile epidurals and offers guidelines on safe ambulation and contraindications to its use. PMID:9663317

  9. Single-dose intramuscular ketorolac versus diclofenac for pain management in renal colic.

    PubMed

    Stein, A; Ben Dov, D; Finkel, B; Mecz, Y; Kitzes, R; Lurie, A

    1996-07-01

    A double-blind controlled study was designed to compare the effective- ness of a single intramuscular dose of 60 mg ketorolac with that of 75 mg diclofenac in the treatment of renal colic and to monitor side effects. Fifty-seven patients completed the study, 27 in the ketorolac group and 30 in the diclofenac group. Effectiveness of treatment was monitored by pain relief reported on a 4-point verbal scale at different time points. At 60 minutes 77.8% and 86.6% (P = 0.4) of patients, and at 120 minutes 81.5% and 96.6% (P = .1 5) of patients, reported significant pain relief following ketorolac and diclofenac doses, respectively. Both groups had an equal 92% significant pain relief at discharge from the emergency department. Both drugs were well tolerated by the patients. Ketorolac therefore, seems as effective as diclofenac in the treatment of renal colic. PMID:8768161

  10. 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

  11. Ethanol-induced analgesia

    SciTech Connect

    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 produce 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.

  12. Analgesia in Obstetrics

    PubMed Central

    Heesen, M.; Veeser, M.

    2012-01-01

    Background: An effective relief of labour pain has become an important part of obstetric medicine. Therefore regional nerve blocks, systemic analgesic and non-pharmacologic techniques are commonly used. This review article gives a summary of pathophysiology and anatomy of labour pain as well as advantages, disadvantages, risks and adverse reactions of analgesic techniques in newborns and parturients. Methods: We performed a selective literature search in Medline via PubMed using the search-terms “Analgesia” and “Obstetrics”. We also included the current guidelines of the German Society for Anesthesiology and Intensive Care Medicine. Results: PDA and CSE are safe techniques for the relief of labour pain if contraindications are excluded. The risk for instrumental delivery but not for caesarean section is increased under neuraxial analgesia. PDA and CSE should be performed in an early stage of labour using low doses of local anaesthetics if possible. It is not necessary to wait for a defined cervical dilatation before starting neuraxial analgesia. Anesthesiologists and obstetricians should inform patients as soon as possible before the situation of stress during labour. Systemic opioid analgesia is a possible alternative for neuraxial techniques. Because of possible side effects systemic remifentanil analgesia should only be performed under continuous monitoring. Several nonpharmacologic methods can also relieve labour pain, but results of studies about their effectiveness are inconsistent. PMID:25264376

  13. Comparison of the effects of intra-articular sole ropivacaine and combined ketorolac and ropivacaine for pain control after knee arthroscopy surgery

    PubMed Central

    Rokhtabnak, Faranak; Ale Bouyeh, Mahmood Reza; Seyed Siamdust, Alireza; Aghajani, Marjan

    2015-01-01

    Introduction: Effective pain relief is important after arthroscopic knee surgery to permit initiation of daily activities of life. This study is performed in order to investigate the effect of multi-model therapy for pain control after surgery. This clinical, randomized and double-blind trial is conducted on patients who get knee arthroscopy surgery. Methods: Of these patients, 40 were divided into two groups by Block Randomization method: 1 − sole ropivacaine group (150 mg); 2 − combined ketorolac (30 mg); and ropivacain (150 mg) group. These drugs were injected intra-articularly at the end of knee arthroscopic surgery. The first consequence including measurement of pain severity after entrance to recovery room and 2, 4, 8, 12, 18 and 24 hours after surgery were evaluated according to the visual analogue pain score. The second consequence, including nausea, vomiting and sedation, was assessed by expert nurses in the recovery room and surgery part according to nausea and vomiting scale and Ramsay sedation scale, respectively. Results: All groups had excellent analgesia at 0 and 4 hours, postoperatively. Group-combined ketorolac and ropivacaine had significantly lower visual analogue pain score as well as higher sedative scale at 8, 12, 18 and 24 hours after surgery at rest and during movement compared with the other group (p < 0.05). Moreover, there was no statistical difference between groups in regard of nausea and vomiting. Conclusion: Addition of ketolorac to ropivacaine intra-articularly in arthroscopic knee surgery enhances analgesic efficacy of local anaesthetics and cause more sedation after surgery. PMID:26516571

  14. 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. PMID:27169518

  15. Compatibility of ketorolac tromethamine injection with common infusion fluids and administration sets.

    PubMed

    Floy, B J; Royko, C G; Fleitman, J S

    1990-05-01

    The compatibility of ketorolac tromethamine injection with commonly used i.v. infusion solutions and administration set components was evaluated. The infusion solutions tested were 0.9% sodium chloride injection, 5% dextrose injection, 0.9% sodium chloride and 5% dextrose injection, Plasma-Lyte A pH 7.4 injection, Ringer's injection, and lactated Ringer's injection. The ketorolac tromethamine admixture concentration studied was 30 mg/50 mL for all solutions. Admixtures were stored in polyvinyl chloride bags and glass bottles at room temperature under fluorescent light and sampled at 0, 6, 24, and 48 hours. Chemical compatibility was determined by high-performance liquid chromatography, and physical compatibility was determined by visual analysis, counting of subvisible particles by HIAC, and pH measurements. Adsorption of ketorolac tromethamine to i.v. administration set components was also evaluated. Ketorolac tromethamine exhibited excellent physical and chemical stability in all six infusion solutions tested. No degradation of drug, formation of particulates, or adsorption to containers or infusion tubing was noted at any concentration for any of the solutions. After the solutions were mixed, the pH remained essentially unchanged. Ketorolac tromethamine injection was physically and chemically stable when mixed with a variety of commonly used infusion solutions and was not adsorbed to administration set components or to glass or polyvinyl chloride containers. PMID:2337102

  16. Intravitreal ketorolac for the treatment of chronic cystoid macular edema after cataract surgery

    PubMed Central

    Tsilimbaris, Miltiadis K; Tsika, Chrysanthi; Kymionis, George D

    2016-01-01

    Purpose To report two cases of chronic postoperative cystoid macular edema, resistant to topical therapy, treated with consecutive intravitreal injections of ketorolac tromethamine. Methods Four daily intravitreal injections of 500 μg/0.05 mL of ketorolac were given to each patient. Complete clinical examination and OCT were performed before every injection, 1, 2, 3 weeks, and 1, 3, and 6 months after the last injection. Fluorescein angiography was performed at baseline examination, 1, 3, and 6 months after the last injection. Results In both cases, the edema regressed and visual acuity increased. At 6 months after the last injection, the leakage was significantly reduced at the fluorescein angiography. Discussion Both cases responded favorably to the consecutive intravitreal administration of ketorolac tromethamine. The long-lasting remission of the macular edema in these chronic cases underlines the therapeutic potential of these agents when delivered intravitreally. PMID:26929630

  17. 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. PMID:25899151

  18. 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

  19. The Effect of Perioperative Ketorolac on the Clinical Failure Rate of Meniscal Repair

    PubMed Central

    Proffen, Benedikt L.; Nielson, Jason H.; Zurakowski, David; Micheli, Lyle J.; Curtis, Christine; Murray, Martha M.

    2014-01-01

    Background: There has been recent interest in the effect of nonsteroidal anti-inflammatory medications on musculoskeletal healing. No studies have yet addressed the effect of these medications on meniscal healing. Hypothesis: The administration of ketorolac in the perioperative period will result in higher rates of meniscal repair clinical failure. Study design: Cohort study; Level of evidence, 3. Methods: A total of 110 consecutive patients underwent meniscal repair at our institution between August 1998 and July 2001. Three patients were lost to follow-up, and the remaining 107 (mean age, 15.9 ± 4.4 years) had a minimum 5-year follow-up (mean follow-up, 5.5 years). Thirty-two patients (30%) received ketorolac perioperatively. The primary outcome measure was reoperation for continued symptoms of meniscal pathology. Asymptomatic patients were evaluated by the International Knee Documentation Committee (IKDC) Subjective Knee Form, Short Form–36 (SF-36) Health Survey, and Knee Outcome Osteoarthritis Score (KOOS). Results: Kaplan-Meier survivorship revealed no difference in reoperation rates with and without the administration of perioperative ketorolac (P = .95). There was an overall failure rate of 35% (37/107 patients), with a 34% failure rate in patients receiving ketorolac (11/32 patients). Multivariable Cox regression confirmed that age, duration of symptoms, meniscal tear type, fixation technique, concurrent anterior cruciate ligament repair, and ketorolac usage did not have an impact on the rate of failure (P > .05 for all; ketorolac use, P > .50). Female sex (P = .04) and medial location (P = .01) were predictive of an increased risk for reoperation. Conclusion: Failure of meniscal repair was not altered with the administration of perioperative ketorolac. Further work studying the effects of longer term anti-inflammatory use after meniscal repair is necessary before stating that this class of medications has no effect on meniscal healing. Clinical

  20. 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. PMID:26206334

  1. 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. PMID:26666104

  2. Perioperative effects of oral ketorolac and acetaminophen in children undergoing bilateral myringotomy.

    PubMed

    Watcha, M F; Ramirez-Ruiz, M; White, P F; Jones, M B; Lagueruela, R G; Terkonda, R P

    1992-09-01

    Prophylactic administration of analgesics before surgery can decrease the intraoperative anaesthetic requirement and decrease pain during the early postoperative period. In a double-blind, placebo-controlled study involving 90 healthy ASA physical status I or II children undergoing bilateral myringotomy, we compared the postoperative analgesic effects of oral acetaminophen and ketorolac, when administered 30 min before induction of anaesthesia. Patients were randomized to receive saline (0.1 ml.kg-1), acetaminophen (10 mg.kg-1) or ketorolac (1 mg.kg-1) diluted in cherry syrup to a total volume of 5 ml. Anaesthesia was induced and maintained with halothane and nitrous oxide via a face mask. Postoperative pain was assessed by a blinded observer using an objective pain scale. The three study groups were similar with respect to demographic data, duration of anaesthesia and surgery, induction behaviour, oxygen saturation, incidence of postoperative emesis and, recovery times. The ketorolac group had lower postoperative pain scores and required less frequent analgesic therapy in the early postoperative period compared with the acetaminophen and placebo groups. In contrast, there were no differences in pain scores or analgesic requirements between the acetaminophen and the placebo groups. We conclude that the preoperative administration of oral ketorolac, but not acetaminophen, provided better postoperative pain control than placebo in children undergoing bilateral myringotomy. PMID:1394752

  3. The Effects of Paracetamol, Ketorolac, and Paracetamol Plus Morphine on Pain Control after Thyroidectomy

    PubMed Central

    Lee, Sun Yeul; Lee, Eun Ha; Han, Kyu Cheol; Ko, Young Kwon

    2010-01-01

    Background The aim of this study was to compare the efficacy of ketorolac, paracetamol, and paracetamol plus morphine on pain relief after thyroidectomy. Methods Eighty patients were randomly allocated to one of the 4 groups: normal saline (group C), ketorolac 30 mg (group K), paracetamol 1 g (group P), and paracetamol 700 mg plus morphine 3 mg (group PM). Each regimen was administered intravenously (IV) 30 min. before the end of surgery. If pain was not relieved, patients received an IV bolus of pethidine hydrochloride 25 mg. Pain intensity using a visual analogue scale (VAS) was recorded at 0.5, 1, 2, 4, and 6 hr after the end of surgery. Results VAS at 0.5 and 1 hr after the end of surgery were significantly lower in group K, group P, and group PM than in group C (P < 0.05). The number of patients receiving pethidine hydrochloride at 0.5 and 1 hr after the end of surgery was significantly lower in group K, group P, and group PM than in group C (P < 0.05). There was no significant difference among the groups in the incidences of adverse events associated with study medications and patient satisfaction (P > 0.05). Conclusions Paracetamol 1 g IV possesses a similar analgesic efficacy to ketorolac 30 mg IV after thyroidectomy. Paracetamol may represent an alternative to ketorolac for pain prevention after mildly to moderately painful surgery in situations where the use of NSAIDs is unsuitable. PMID:20556214

  4. 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). PMID:7603299

  5. Lipid Nanocapsule-Based Gels for Enhancement of Transdermal Delivery of Ketorolac Tromethamine

    PubMed Central

    Varshosaz, Jaleh; Hajhashemi, Valiollah; Soltanzadeh, Sindokht

    2011-01-01

    Previous reports show ineffective transdermal delivery of ketorolac by nanostructured lipid carriers (NLCs). The aim of the present work was enhancement of transdermal delivery of ketorolac by another colloidal carriers, lipid nanocapsules (LNCs). LNCs were prepared by emulsification with phase transition method and mixed in a Carbomer 934P gel base with oleic acid or propylene glycol as penetration enhancers. Permeation studies were performed by Franz diffusion cell using excised rat abdominal skin. Aerosil-induced rat paw edema model was used to investigate the in vivo performance. LNCs containing polyethylene glycol hydroxyl stearate, lecithin in Labrafac as the oily phase, and dilution of the primary emulsion with 3.5-fold volume of cold water produced the optimized nanoparticles. The 1% Carbomer gel base containing 10% oleic acid loaded with nanoparticles enhanced and prolonged the anti-inflammatory effects of this drug to more than 12 h in Aerosil-induced rat paw edema model. PMID:22175029

  6. Characterization and treatment of postsurgical dental implant pain employing intranasal ketorolac.

    PubMed

    Bockow, Rebecca; Korostoff, Jonathan; Pinto, Andres; Hutcheson, Matthew; Secreto, Stacey A; Bodner, Laura; Hersh, Elliot V

    2013-09-01

    The intensity and duration of pain following surgical placement of dental implants has not been well studied. Thus, the aim of this open-label study was to characterize the nature of postsurgical pain following the placement of one to three implants. The secondary goal was to explore the analgesic efficacy and tolerability of intranasal ketorolac in this patient population. Following implant surgery, postoperative pain was rated moderate or severe in 25/28 patients (89 percent), requiring prn analgesic dosing for up to 3 days in 14/25 individuals (56 percent). Intranasal ketorolac displayed an analgesic onset within 20 minutes, a duration of at least 6 hours, and was well tolerated by the cohort with brief stinging of the nasal mucosa reported by 9/25 individuals (36 percent). PMID:24564610

  7. Parenteral opioids for labor analgesia.

    PubMed

    Campbell, David C

    2003-09-01

    Labor pain relief is an important aspect of women's health that has historically been neglected. Epidural analgesia is the only consistently effective method of labor pain relief and has recently undergone substantial improvements to address the concerns of both parturients and obstetric care providers. With increased physician awareness, these recent advances are becoming more widely accepted and routinely available for all laboring parturients. Unfortunately, an increasing number of women are presenting to maternity wards with an absolute contraindication to epidural labor analgesia. The present review will provide an outline of the recent developments in parenteral analgesic options which complement modern epidural analgesic techniques. Protocols for the initiation of "state-of-the-art" parenteral analgesic techniques are provided as a guide to facilitate effective, modern, parenteral labor analgesia. PMID:12972743

  8. A double-blind study of the efficacy of topical ketorolac tromethamine gel in the treatment of ankle sprain, in comparison to placebo and etofenamate.

    PubMed

    Diebschlag, W; Nocker, W; Bullingham, R

    1990-01-01

    In a double-blind, placebo-controlled study the efficacy and safety of topical ketorolac tromethamine were assessed in the reduction of inflammation and pain due to ankle sprain. Ketorolac 2% gel was compared with etofenamate and placebo (ketorolac vehicle) in a 15-day study. Patients attended for visits on days 1 (admission), 2, 3, 4, 8, and 15 of the study. Measurements of efficacy were ankle volume, pain measured on visual analogue scales (VAS) and verbal rating of pain. Safety was assessed by volunteered adverse events and vital signs. A total of 37 patients was admitted to the study of whom 13 received ketorolac, 12 placebo, and 12 etofenamate. One patient receiving ketorolac was lost to follow-up on day 15 owing to an unrelated accident. The remaining 36 patients completed the study. Ketorolac was significantly better than placebo in reducing the volume of the injured ankle based on the maximum, the area under the curve, and the day 15 percentage changes in ankle volume. Results for etofenamate were similar to those for ketorolac for all three variables and there were no significant differences between the active treatments. Reductions in VAS pain at rest were more marked in the ketorolac group than either of the other groups at all visits. On day 4 the differences between ketorolac and each of the other groups were statistically significant. Reductions in VAS pain on movement were also greatest for the ketorolac group at all visits. The differences between ketorolac and each of the other groups achieved statistical significance on days 4 and 8, but were marginal in terms of significance on day 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2105985

  9. The clinical utility of new combination phenylephrine/ketorolac injection in cataract surgery.

    PubMed

    Lawuyi, Lola Elizabeth; Gurbaxani, Avinash

    2015-01-01

    The maintenance of mydriasis throughout cataract extraction surgery and the control of ocular inflammation are crucial for successful surgical outcomes. The development of miosis during cataract surgery compromises the visualization of the surgical field and working space for surgeons. This may lead to complications that include posterior capsular tear and associated vitreous loss, longer surgical time, and postoperative inflammation. Postoperative inflammation is often uncomfortable and frustrating for patients. It causes pain, redness, and photophobia. This compromises the best-uncorrected vision following surgery and often leads to multiple clinic visits. This article examines the literature published on the current treatments used to manage mydriasis, pain, and inflammation in cataract extraction surgery. Combination phenylephrine/ketorolac injection offers an exciting new class of medication for use in cataract surgery. With the recent approval of Omidria™ (combination of phenylephrine 1% and ketorolac 0.3%) by the US Food and Drug Administration (FDA) for intraocular use, we review the clinical utility of this new combination injection in cataract surgery. PubMed, MEDLINE, and conference proceedings were searched for the relevant literature using a combination of the following search terms: cataract extraction surgery, pupil dilation (mydriasis), miosis, phenylephrine, ketorolac, Omidria™, intracameral mydriatic. Relevant articles were reviewed and their references checked for further relevant literature. All abstracts were reviewed and full texts retrieved where available. PMID:26203214

  10. The use of intravenous ketorolac for the treatment of renal colic in the emergency department.

    PubMed

    Larsen, L S; Miller, A; Allegra, J R

    1993-05-01

    The objective of this study was to report the authors' experience using intravenous ketorolac (Syntex Laboratories, Palo Alto, CA) as an analgesic in the treatment of renal colic in a convenience sample at three suburban community hospital emergency departments. Twenty-five patients with renal colic were participants. Pregnant women, patients with a history of renal or hepatic impairment, bleeding diathesis, active peptic ulcer disease, or hypersensitivity to aspirin or nonsteroidal antiinflammatory drugs (NSAID) were excluded. Ketorolac 30 mg administered intravenously during a 1-minute period, and the following parameters were monitored at times 0, 5, 10, 20, 30, and 60 minutes: pain on a scale of 0 to 10, pulse rate, blood pressure, and adverse side effects. A total of 25 patients were included in our series. Initially, they had a median pain score of 9 with an interquartile range of 1. Thereafter, the median pain scores and (interquartile ranges) were 8 (three) at 5 minutes, 5 (four) at 10 minutes, 2 (four) at 20 minutes, 1 (three) at 30 minutes, and 0 (one) at 60 minutes. There were no adverse side effects observed in any patients. Therefore, it can be concluded that intravenous ketorolac is an effective analgesic agent for the control of pain in patients with renal colic. PMID:8489656

  11. The clinical utility of new combination phenylephrine/ketorolac injection in cataract surgery

    PubMed Central

    Lawuyi, Lola Elizabeth; Gurbaxani, Avinash

    2015-01-01

    The maintenance of mydriasis throughout cataract extraction surgery and the control of ocular inflammation are crucial for successful surgical outcomes. The development of miosis during cataract surgery compromises the visualization of the surgical field and working space for surgeons. This may lead to complications that include posterior capsular tear and associated vitreous loss, longer surgical time, and postoperative inflammation. Postoperative inflammation is often uncomfortable and frustrating for patients. It causes pain, redness, and photophobia. This compromises the best-uncorrected vision following surgery and often leads to multiple clinic visits. This article examines the literature published on the current treatments used to manage mydriasis, pain, and inflammation in cataract extraction surgery. Combination phenylephrine/ketorolac injection offers an exciting new class of medication for use in cataract surgery. With the recent approval of Omidria™ (combination of phenylephrine 1% and ketorolac 0.3%) by the US Food and Drug Administration (FDA) for intraocular use, we review the clinical utility of this new combination injection in cataract surgery. PubMed, MEDLINE, and conference proceedings were searched for the relevant literature using a combination of the following search terms: cataract extraction surgery, pupil dilation (mydriasis), miosis, phenylephrine, ketorolac, Omidria™, intracameral mydriatic. Relevant articles were reviewed and their references checked for further relevant literature. All abstracts were reviewed and full texts retrieved where available. PMID:26203214

  12. Evaluation of the antipyretic effect of ketorolac, acetaminophen, and placebo in endotoxin-induced fever.

    PubMed

    Vargas, R; Maneatis, T; Bynum, L; Peterson, C; McMahon, F G

    1994-08-01

    The authors studied the antipyretic effect of three intramuscular doses of ketorolac (15, 30, and 60 mg), acetaminophen 650 mg PO, and placebo in healthy male volunteers using an endotoxin-induced fever model. In this double-blind, double-dummy, parallel study, subjects were assigned randomly with equal probability to one of the above treatment groups. Thirty minutes after study medication administration, a 20 unit per kilogram dose of reference standard endotoxin (RSE) was administered intravenously, and temperature was determined every 15 minutes for an 8-hour period. Compared with placebo, all active treatment groups demonstrated a statistically significant reduction in both adjusted area under the temperature-by-time curve (AAUC) and the maximum increase over baseline temperature (dTmax). Furthermore, the 30 mg intramuscular dose of ketorolac demonstrated approximately the same antipyretic activity as the 650 mg oral dose of acetaminophen, and there was a statistically significant dose response across the three ketorolac doses studied (P < .0001). The majority of side effects reported during this study were symptoms associated with fever, including chills, headache, myalgia, and dizziness, all of which are effects of RSE. The frequency of side effects tended to be less in the treatment groups with the greatest antipyretic activity. PMID:7962674

  13. 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. PMID:25787064

  14. Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan.

    PubMed

    Li, Chenxi; Li, Chunyan; Liu, Zheshuo; Li, Qiuhong; Yan, Xueying; Liu, Yu; Lu, Weiyue

    2014-10-20

    The objective of this study was to construct a new in situ gel system based on the combination of poloxamer 407 and carrageenan (carrageenan-poloxamer 407 hydrogel, CPH) for intranasal delivery of ketorolac tromethamine. CPH showed potassium ion concentration - dependent erosion characteristics which ensured slow erosion in aqueous environment containing potassium ion at the physiological level. Loading with ketorolac tromethamine influenced erosion, drug release and thermosensitive properties of CPH. CPH containing 15% ketorolac tromethamine showed suitable gelation temperature (near 35°C) and in vitro sustained release profiles. Pharmacokinetic study of intranasal CPH containing 15% ketorolac tromethamine in rats demonstrated enhanced absolute bioavailability (68.8 ± 23.3%) and prolonged mean residence time (8.8 ± 3.5h) in comparison with the intranasal solution group (24.8 ± 13.8%, 3.9 ± 0.6h). Nasal ciliotoxicity evaluation on an in situ toad palate model preliminarily showed the safety of CPH for intranasal use. All results suggested the potential of CPH as a new sustained - release platform for the intranasal delivery of ketorolac tromethamine. PMID:25138250

  15. Music does not reduce alfentanil requirement during patient-controlled analgesia (PCA) use in extracorporeal shock wave lithotripsy for renal stones.

    PubMed

    Cepeda, M S; Diaz, J E; Hernandez, V; Daza, E; Carr, D B

    1998-12-01

    To evaluate the impact of music on opioid requirements and pain levels during renal lithotripsy using alfentanil patient-controlled analgesia (PCA), we conducted a prospective, blinded, randomized controlled trial. Patients undergoing lithotripsy were instructed in PCA use and asked to rate their anxiety and select their preferred type of music. They were then premedicated with morphine and ketorolac and randomly allocated into two groups. Group 1 (n = 97) had music started 10 min before the procedure and maintained until 10 min after its conclusion. Group 2 (n = 96) had music begun at the conclusion of lithotripsy and continued for 10 min. Pain intensity, alfentanil requirement, side effects, quality of analgesia, patient satisfaction, and acceptance of the technique were evaluated. Demographics, alfentanil requirement, pain levels, side effects, quality of analgesia, and patient satisfaction were similar in both groups. The addition of music did not provide any benefit. This result raises the possibility that some nonpharmacologic therapies have minimal impact in settings where the painful stimulus is moderate to severe and adequate pharmacotherapy is available. PMID:9879163

  16. [Influence of simulated microgravity on the threshold of pain sensitivity in humans with single dose of ketorolac].

    PubMed

    Baranov, M V; Kovalev, A S; Perfilov, D F; Chernogorov, R V; Repenkova, L G

    2015-01-01

    The data supporting the influence of simulated microgravity effects on pain sensitivity were obtained in the series of experiments involving human. In conditions of antiorthostatic hypokinesia (ANOH) and immersion revealed no reduction in pain sensitivity in the morning, which is typical for normal conditions. Ketorolac has no effect on pain sensitivity, when determining the pain threshold (PT) by method of thermoalgometry. However, the conditions of simulated microgravity substantially alter the pharmacokinetics of ketorolac, increasing the rate of absorption of the drug and reduce its relative bioavailability and retention time in the blood plasma. This may require changes in pain therapy schemes in space flight. PMID:26571803

  17. Placebo analgesia: understanding the mechanisms

    PubMed Central

    Medoff, Zev M; Colloca, Luana

    2015-01-01

    SUMMARY Expectations of pain relief drive placebo analgesia. Understanding how expectations of improvement trigger distinct biological systems to shape therapeutic analgesic outcomes has been the focus of recent pharmacologic and neuroimaging studies in the field of pain. Recent findings indicate that placebo effects can imitate the actions of real painkillers and promote the endogenous release of opioids and nonopioids in humans. Social support and observational learning also contribute to placebo analgesic effects. Distinct psychological traits can modulate expectations of analgesia, which facilitate brain pain control mechanisms involved in pain reduction. Many studies have highlighted the importance and clinical relevance of these responses. Gaining deeper understanding of these pain modulatory mechanisms has important implications for personalizing patient pain management. PMID:25806903

  18. Epidural optogenetics for controlled analgesia

    PubMed Central

    Bonin, Robert P; Wang, Feng; Desrochers-Couture, Mireille; Ga¸secka, Alicja; Boulanger, Marie-Eve; Côté, Daniel C

    2016-01-01

    Background Optogenetic tools enable cell selective and temporally precise control of neuronal activity; yet, difficulties in delivering sufficient light to the spinal cord of freely behaving animals have hampered the use of spinal optogenetic approaches to produce analgesia. We describe an epidural optic fiber designed for chronic spinal optogenetics that enables the precise delivery of light at multiple wavelengths to the spinal cord dorsal horn and sensory afferents. Results The epidural delivery of light enabled the optogenetic modulation of nociceptive processes at the spinal level. The acute and repeated activation of channelrhodopsin-2 expressing nociceptive afferents produced robust nocifensive behavior and mechanical sensitization in freely behaving mice, respectively. The optogenetic inhibition of GABAergic interneurons in the spinal cord dorsal horn through the activation of archaerhodopsin also produced a transient, but selective induction of mechanical hypersensitivity. Finally, we demonstrate the capacity of optogenetics to produce analgesia in freely behaving mice through the inhibition of nociceptive afferents via archaerhodopsin. Conclusion Epidural optogenetics provides a robust and powerful solution for activation of both excitatory and inhibitory opsins in sensory processing pathways. Our results demonstrate the potential of spinal optogenetics to modulate sensory behavior and produce analgesia in freely behaving animals. PMID:27030718

  19. Pharmacogenomic considerations in opioid analgesia

    PubMed Central

    Vuilleumier, Pascal H; Stamer, Ulrike M; Landau, Ruth

    2012-01-01

    Translating pharmacogenetics to clinical practice has been particularly challenging in the context of pain, due to the complexity of this multifaceted phenotype and the overall subjective nature of pain perception and response to analgesia. Overall, numerous genes involved with the pharmacokinetics and dynamics of opioids response are candidate genes in the context of opioid analgesia. The clinical relevance of CYP2D6 genotyping to predict analgesic outcomes is still relatively unknown; the two extremes in CYP2D6 genotype (ultrarapid and poor metabolism) seem to predict pain response and/or adverse effects. Overall, the level of evidence linking genetic variability (CYP2D6 and CYP3A4) to oxycodone response and phenotype (altered biotransformation of oxycodone into oxymorphone and overall clearance of oxycodone and oxymorphone) is strong; however, there has been no randomized clinical trial on the benefits of genetic testing prior to oxycodone therapy. On the other hand, predicting the analgesic response to morphine based on pharmacogenetic testing is more complex; though there was hope that simple genetic testing would allow tailoring morphine doses to provide optimal analgesia, this is unlikely to occur. A variety of polymorphisms clearly influence pain perception and behavior in response to pain. However, the response to analgesics also differs depending on the pain modality and the potential for repeated noxious stimuli, the opioid prescribed, and even its route of administration. PMID:23226064

  20. Comparison of the effects of acetaminophen to ketorolac when added to lidocaine for intravenous regional anesthesia

    PubMed Central

    Ko, Myoung Jin; Cheong, Soon Ho; Shin, Chee Mahn; Kim, Young Jae; Choe, Young Kyun; Lee, Kun Moo; Lim, Se Hun; Kim, Young Hwan; Cho, Kwang Rae; Lee, Sang Eun

    2010-01-01

    Background This study was done to evaluate the effect on pain relief when acetaminophen was added to lidocaine for intravenous regional anesthesia (IVRA). Methods Sixty patients undergoing hand or forearm surgery received IVRA were assigned to three groups: Group C received 0.5% lidocaine diluted with 0.9% normal saline to a total volume of 40 ml (n = 20), Group P received 0.5% lidocaine diluted with intravenous acetaminophen 300 mg to a total volume of 40 ml (n = 20) and Group K received 0.5% lidocaine diluted with 0.9% normal saline plus ketorolac 10 mg made up to a total volume of 40 ml (n = 20). Sensory block onset time, tourniquet pain onset time, which was defined as the time from tourniquet application to fentanyl administration for relieving tourniquet pain and amount of analgesic consumption during surgery were recorded. Following deflation of tourniquet sensory recovery time, postoperative pain and quantity of analgesic uses in post-anesthesia care unit were assessed. Results Sensory block onset time was shorter in Group P compared to Group C (P < 0.05). Tourniquet pain onset time was delayed in Group P when compared with group C (P < 0.05). Postoperative pain and analgesic consumption were reduced in Group P and Group K compared to Group C (P < 0.001). Conclusions The addition of acetaminophen to lidocaine for IVRA shortens the onset time of sensory block and delays tourniquet pain onset time, but not with ketorolac. Both acetaminophen and ketorolac reduce postoperative pain and analgesic consumption. PMID:20508792

  1. Postoperative Pain and Intravenous Patient-Controlled Analgesia-Related Adverse Effects in Young and Elderly Patients

    PubMed Central

    Koh, Jae Chul; Lee, Jinae; Kim, So Yeon; Choi, Sumin; Han, Dong Woo

    2015-01-01

    Abstract In this retrospective analysis of 10,575 patients who used fentanyl-based intravenous patient-controlled analgesia (IV-PCA) after surgery, we evaluated difference between young and elderly patients on their characteristic of adverse effects. We reviewed the data collected from the patients who were provided IV-PCA for pain control following elective surgery under either general or spinal anesthesia between September 2010 and March 2014. Postoperative pain, incidence of PCA-related adverse effects, and risk factors for the need of rescue analgesics and antiemetics for postoperative 48 hours were analyzed. Pain intensity (numerical rating scale [NRS]) at postoperative 6 to 12 hours (4.68 vs 4.58, P < 0.01) and incidence of nausea or vomiting (23.8% vs 20.6%, P < 0.001) were higher in young patients, while incidence of PCA discontinuation (9.9% vs 11.5%, P < 0.01) and sedation (0.1% vs 0.7%, P < 0.001) was higher in elderly patients. Despite larger fentanyl dose used, a greater proportion of young patients required rescue analgesics (53.8% vs 47.9%, P < 0.001) while addition of ketorolac was effective in reducing postoperative pain. Despite lower incidence of postoperative nausea and vomiting (PONV), a larger proportion of elderly patients required rescue antiemetics (10.1% vs 12.2%, P < 0.001) while addition of ramosetron was effective in reducing PONV. In conclusion, when fentanyl-based IV-PCA is used for postoperative pain control, a larger proportion of young patients may require rescue analgesics while elderly patients may require more rescue antiemetics. The addition of ketorolac or ramosetron to the PCA of young and elderly patients can be effective to prevent rescue analgesics or antiemetics use. PMID:26559296

  2. Indomethacin and ketorolac given preoperatively are equally effective in reducing early postoperative pain after laparoscopic cholecystectomy

    PubMed Central

    Forse, Allan; El-Beheiry, Hossam; Butler, Patrick O.; Pace, Ronald F.

    1996-01-01

    Objective To evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on pain after laparoscopic cholecystectomy. Design A prospective, randomized, placebo-controlled, double-blind study. Setting A university hospital. Patients Fifty-two patients with cholelithiasis but without known allergy to one of the study drugs, history of bleeding, peptic ulcer disease, known cardiac, lung or renal disease, abnormal liver function or use of opiates or NSAIDs within 2 weeks before operation. Patients were assigned to one of three groups, and treatment was randomized by placing the drugs in sealed, numbered envelopes. Intervention Administration of the NSAIDs ketorolac, intramuscularly, or indomethacin, rectally, before laparoscopic cholecystectomy. Main Outcome Measures Postoperative pain scored on a visual analogue scale and by nurse assessment, total dose of fentanyl citrate given, and nausea or emesis. Results Patients in the placebo group reported significantly more pain than either NSAID group (p < 0.05) and were reported as having significantly more pain by the nurses (p < 0.05). These patients were subsequently treated with a higher mean postoperative dose of fentanyl citrate than either NSAID group (p < 0.05). Furthermore, the placebo group reported more nausea and emesis (p < 0.05). There was no significant difference in any of the parameters measured between the ketorolac or indomethacin group. Conclusions The data demonstrate that the NSAIDs ketolorac and indomethacin, administered preoperatively, decrease early postoperative pain and nausea after laparoscopic cholecystectomy and are equally efficacious in producing these results. PMID:8599787

  3. An evaluation of obstetrical analgesia.

    PubMed

    FIST, H S

    1954-02-01

    Relief of pain and safety of mother and child are fundamentals in obstetrical analgesia. Elimination of those drugs which are ineffective or dangerous is the best guide to proper medication. Morphine, codeine, or similar opium derivatives should be avoided as they depress fetal respiration. Barbiturates have the same fault, despite their popularity. Demerol in small dosage is safe and effective. Scopolamine yields excellent results with safety. Magnesium sulfate potentiates and reinforces the action of scopolamine and involves no danger. This combination of drugs may be used by any competent general practitioner in the home or hospital. PMID:13126811

  4. Postoperative analgesia in elderly patients.

    PubMed

    Falzone, Elisabeth; Hoffmann, Clément; Keita, Hawa

    2013-02-01

    Elderly people represent the fastest-growing segment of our society and undergo surgery more frequently than other age groups. Effective postoperative analgesia is essential in these patients because inadequate pain control after surgery is associated with adverse outcomes in elderly patients. However, management of postoperative pain in older patients may be complicated by a number of factors, including a higher risk of age- and disease-related changes in physiology and disease-drug and drug-drug interactions. Physiological changes related to aging need to be carefully considered because aging is individualized and progressive. Assessment of pain management needs to include chronological age, biological age with regard to renal, liver and cardiac functions, and the individual profile of pathology and prescribed medications. In addition, ways in which pain should be assessed, particularly in patients with cognitive impairment, must be considered. Cognitively intact older patients can use most commonly used unidimensional pain scales such as the visual analogue scale (VAS), verbal rating scale (VRS), numeric rating scale (NRS) and facial pain scale (FPS). VRS and NRS are the most appropriate pain scales for the elderly. In older patients with mild to moderate cognitive impairment, the VRS is a better tool. For severe cognitively impaired older patients, behavioural scales validated in the postoperative context, such as Doloplus-2 or Algoplus, are appropriate. For postoperative pain treatment, most drugs (e.g. paracetamol, nonsteroidal anti-inflammatory drugs, nefopam, tramadol, codeine, morphine, local anaesthetics), techniques (e.g. intravenous morphine titration, subcutaneous morphine, intravenous or epidural patient-controlled analgesia, intrathecal morphine, peripheral nerve block) and strategies (e.g. anticipated intraoperative analgesia or multimodal analgesia) used for acute pain management can be used in older patients. However, in view of pharmacokinetic

  5. [Combined spinal and epidural analgesia in urology].

    PubMed

    Bovianska, N

    1995-01-01

    Combined spinal and epidural analgesia is a new concept in the field of regional anesthesia. It combines the positive qualities of spinal and epidural analgesia, and is performed by the "needle-in-needle" technique, described in the paper. This type of analgesia is practically implemented in the Clinical Center of Urology over the past few months, and shows encouraging results. This is a report on clinical experience had with 10 combined analgesia procedures, running a course free of any complications against the background of stable hemodynamics and respiration of the patients. The block induced is with 4-hour duration, and lends itself to prolongation through an epidural catheter. This renders the method variable and suited for postoperative analgesia too. The Espokan set technical devices used make puncture of the spinal-epidural space readily practicable. PMID:8648963

  6. [Pneumoencephalotomography under diaz-analgesia and narco-analgesia].

    PubMed

    Bergeron, J L; Renou, A M; Boulard, G; Vernhiet, J; Nicod, J

    1978-01-01

    The authors reported 92 observations of anesthesia for gaseous encephalotomography interest the adult. The contrast produce is air. 49 under diazanalgesia and myoresolution. Diazepam, +Fentanyl, pancuronium bromide N2O to 60 p. 100. 25 under diazanalgesia and myoresolution. Diazepam, +Fentanyl, succinylcholine, N2O to 60 p. 100. 18 under narco-analgesia and myoresolution. +Fentyl, pancuronium bromide N2O to 60 p. 100. The conditions of the study are described in the first part. The results and their analysis permit the appreciation of: - the patient confort, the quality of the examination; -the respect of the hemodynamics for this examination, reputed to be "difficult"; -the immediatly noticeable diminution of side effects; -the absence of side effects; -the justification and interesting of the control ventilation; -the quality of waking up. In the conclusion the authors underline the interest of their different techniques and the possibility of using them in operations in sitting position in neurosurgery, and all important chirurgical intervention. PMID:677506

  7. Comparison of Preoperative Topical Dexamethasone Phosphate Versus Ketorolac Tromethamine in Maintaining Intraoperative Mydriasis During Small Incision Cataract Surgery

    PubMed Central

    Sharma, Hans Raj; Sharma, Rajni; Singh, Amrita

    2016-01-01

    Introduction Intraoperative miosis is one of the many challenges which a surgeon can face during cataract surgery. It may lead to impaired view and difficulty in delivering the nucleus. Also, it increases the chances of more serious intraoperative and postoperative complications. Therefore, maintaining adequate pupillary dilatation is of utmost importance during cataract surgery. Aim To study the efficacy of topical dexamethasone phosphate (0.1%) and topical ketorolac tromethamine (0.4%) in maintaining pupillary dilatation during cataract surgery. Materials and Methods A total of 200 patients were studied. These were randomly divided into two groups of 100 each. Group1 was given topical dexamethasone phosphate (0.1%) and Group 2, topical ketorolac tromethamine (0.4%). Medications were started 1-day before surgery in the form of one drop to be instilled every 6 hours. Pupillary diameter was measured in the horizontal meridian; 4 readings were taken - before making the incision, after nucleus delivery, following cortical clean-up and after Intraocular Lens (IOL) implantation. Results The two drugs showed no statistically significant difference in pupillary diameter at the commencement of surgery (p=0.435). The difference between the two drugs was statistically significant, for the mean pupillary diameter which changed from the start of surgery to after cortical clean-up. At this stage, ketorolac group showed a tendency towards larger mean pupillary diameter than dexamethasone group (6.70 ± 0.85mm and 6.32 ± 0.84mm, respectively, p=0.002). Again, ketorolac group patients had larger pupillary diameter after IOL implantation than dexamethasone group patients (the mean was 6.16± 0.97mm and 5.75 ± 0.73mm, respectively, p=0.001). Conclusion Both ketorolac tromethamine (0.4%) and dexamethasone phosphate (0.1%) are effective in maintaining adequate mydriasis during cataract surgery, but the comparative analysis of the two drugs concludes that, ketorolac is definitely a

  8. Guideline Implementation: Moderate Sedation/Analgesia.

    PubMed

    Fencl, Jennifer L

    2016-05-01

    Moderate sedation/analgesia is practiced in a variety of settings and delivered by a variety of health care providers, with a goal of reducing the patient's anxiety and discomfort during diagnostic and therapeutic procedures. The updated AORN "Guideline for care of the patient receiving moderate sedation/analgesia" provides guidance on RN administration of moderate sedation/analgesia within the scope of nursing practice as defined by the state boards of nursing. The guideline addresses patient selection and assessment, staffing for the procedure, patient monitoring, medication administration, and criteria for postoperative discharge. This article focuses on key points of the guideline to promote safe care throughout the perioperative continuum for a patient receiving moderate sedation/analgesia. Perioperative RNs should review the complete guideline for additional information and for guidance when writing and updating policies and procedures. PMID:27129752

  9. Procedural sedation and analgesia in pediatric patients

    PubMed Central

    Mahajan, Charu; Dash, Hari Hara

    2014-01-01

    A spectrum of conditions requires sedation and analgesia in pediatric population. Ineffective treatment of pain may result in physiological and behavioral responses that can adversely affect the developing nociceptive system. The recognition of pain in children can be facilitated by different pain scales. This article reviews the procedural sedation and analgesia (PSA) practices in children along with pharmacology of the drugs used for this purpose. PMID:24891893

  10. Patient-controlled epidural analgesia for labor.

    PubMed

    Halpern, Stephen H; Carvalho, Brendan

    2009-03-01

    Patient-controlled epidural analgesia (PCEA) for labor was introduced into clinical practice 20 yr ago. The PCEA technique has been shown to have significant benefits when compared with continuous epidural infusion. We conducted a systematic review using MEDLINE and EMBASE (1988-April 1, 2008) of all randomized, controlled trials in parturients who received PCEA in labor in which one of the following comparisons were made: background infusion versus none; ropivacaine versus bupivacaine; high versus low concentrations of local anesthetics; and new strategies versus standard strategies. The outcomes of interest were maternal analgesia, satisfaction, motor block, and the incidence of unscheduled clinician interventions. A continuous background infusion improved maternal analgesia and reduced unscheduled clinician interventions. Larger bolus doses (more than 5 mL) may provide better analgesia compared with small boluses. Low concentrations of bupivacaine or ropivacaine provide excellent analgesia without significant motor block. Many strategies with PCEA can provide effective labor analgesia. High volume, dilute local anesthetic solutions with a continuous background infusion appear to be the most successful strategy. Research into new delivery strategies, such as mandatory programmed intermittent boluses and computerized feedback dosing, is ongoing. PMID:19224805

  11. Ketorolac Ophthalmic

    MedlinePlus

    ... is in a class of medications called nonsteroidal anti-inflammatory drugs (NSAIDs). It works by stopping the release ... blood thinners') such as warfarin (Coumadin); aspirin; nonsteroidal anti-inflammatory agents, such as celecoxib (Celebrex), diclofenac (Voltaren), etodolac ( ...

  12. Ketorolac Injection

    MedlinePlus

    ... heartburn, vomit that is bloody or looks like coffee grounds, blood in the stool, or black and tarry ... stools vomit that is bloody or looks like coffee grounds drowsiness hives rash itching difficulty swallowing difficulty breathing, ...

  13. A double-blind, placebo-controlled randomized comparison of pre and postoperative administration of ketorolac and tramadol for dental extraction pain

    PubMed Central

    Mishra, Hitesh; Khan, Farhan Ahmad

    2012-01-01

    Objective: To compare the analgesic efficacy and safety of single-dose oral ketorolac and tramadol administered pre and postoperatively for dental extraction pain. Materials and Methods: 74 patients undergoing third molar extraction (impacted or other causes) were recruited into the study, over a period of 1 year. The patients were divided into six groups and they were given ketorolac (20 mg), tramadol (100 mg), or placebo either preoperatively or postoperatively (half an hour before or half an hour after the procedure). Placebo was glucose powder filled in empty capsule. Pain assessment was done using a modified Verbal Rating Scale (VRS) at 30 min, 2, 4, and 6 h after the procedure. A record of whether rescue analgesic (ibuprofen 400 mg) was taken during the 6 h study period, along with the time it was taken, was made. Record of any adverse effects experienced by the patient was also kept. Maximum pain scores for each of the six study groups, over the 6 h study period, were noted. Results: Ketorolac and tramadol were significantly better than placebo in relieving molar tooth extraction pain. Postoperative administration of tramadol was found to be more efficacious than preoperative administration in relieving the pain, whereas the preoperative administration of ketorolac was better than its postoperative administration. Conclusion: This study demonstrated that tramadol is equally effective to ketorolac in relieving pain in the first 6 h after molar extraction and therefore can be tried in patients who are intolerant to nonsteroidal anti-inflammatory drugs. PMID:22557747

  14. Pain analgesia among adolescent self-injurers.

    PubMed

    Glenn, Jeffrey J; Michel, Bethany D; Franklin, Joseph C; Hooley, Jill M; Nock, Matthew K

    2014-12-30

    Although non-suicidal self-injury (NSSI) involves self-inflicted physical harm, many self-injurers report feeling little or no pain during the act. Here we test: (1) whether the pain analgesia effects observed among adult self-injurers are also present among adolescents, and (2) three potential explanatory models proposing that habituation, dissociation, and/or self-criticism help explain the association between NSSI and pain analgesia among adolescents. Participants were 79 adolescents (12-19 years) recruited from the community who took part in a laboratory-based pain study. Results revealed that adolescent self-injurers have a higher pain threshold and greater pain endurance than non-injurers. Statistical mediation models revealed that the habituation and dissociation models were not supported; however, a self-critical style does mediate the association between NSSI and pain analgesia. The present findings extend earlier work by highlighting that a self-critical style may help to explain why self-injurers exhibit pain analgesia. Specifically, the tendency to experience self-critical thoughts in response to stressful events may represent a third variable that increases the likelihood of both NSSI and pain analgesia. Prospective experimental studies are needed to replicate and tease apart the direction of these associations, and may provide valuable leads in the development of effective treatments for this dangerous behavior problem. PMID:25172611

  15. Epidural analgesia, neonatal care and breastfeeding.

    PubMed

    Zuppa, Antonio Alberto; Alighieri, Giovanni; Riccardi, Riccardo; Cavani, Maria; Iafisco, Alma; Cota, Francesco; Romagnoli, Costantino

    2014-01-01

    The objective of our study is to evaluate the correlation between epidural analgesia during labor, start of breastfeeding and type of maternal-neonatal care.Two different assistance models were considered: Partial and Full Rooming-in.In this cohort study, 2480 healthy infants were enrolled, 1519 in the Partial Rooming-in group and 1321 in the Full Rooming-in group; 1223 were born to women subjected to epidural analgesia in labor.In case of Partial Rooming-in the rate of exclusive or prevailing breastfeeding is significant more frequent in newborns born to mothers who didn't receive analgesia. Instead, in case of Full Rooming-in the rate of exclusive or prevailing breastfeeding is almost the same and there's no correlation between the use or not of epidural analgesia.The good start of lactation and the success of breastfeeding seems to be guaranteed by the type of care offered to the couple mother-infant, that reverses any possible adverse effects of the use of epidural analgesia in labor. PMID:25432659

  16. 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

  17. Acupuncture for analgesia in veterinary medicine.

    PubMed

    Fry, Lindsey M; Neary, Susan M; Sharrock, Joseph; Rychel, Jessica K

    2014-06-01

    Acupuncture for analgesia is growing rapidly in popularity with veterinarians and pet owners. This article summarizes the mechanisms of analgesia derived from acupuncture and reviews current literature on the topic. Areas covered include the local effects at area of needle insertion, systemic effects secondary to circulating neurotransmitters and changes in cell signaling, central nervous system effects including the brain and spinal cord, and myofascial trigger point and pathology treatment. Clinical applications are discussed and suggested in each section. When used by appropriately trained professionals, acupuncture offers a compelling and safe method for pain management in our veterinary patients and should be strongly considered as a part of multimodal pain management plans. PMID:25454374

  18. Potentiation of morphine analgesia by caffeine.

    PubMed Central

    Misra, A. L.; Pontani, R. B.; Vadlamani, N. L.

    1985-01-01

    Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation. PMID:4005485

  19. Potentiation of morphine analgesia by caffeine.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1985-04-01

    Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation. PMID:4005485

  20. Enhancement of ketorolac tromethamine permeability through rat skin using penetration enhancers: An ex-vivo study

    PubMed Central

    Kumar, Pawan; Singh, Shailendra Kumar; Mishra, Dina Nath; Girotra, Priti

    2015-01-01

    Introduction: Ketorolac tromethamine (KT), a nonsteroidal anti-inflammatory drug, when given orally causes gastrointestinal disturbances. Its transdermal drug delivery may reduce such side effects associated with them. The present investigation was aimed at evaluating the efficiency of various penetration enhancers for improved permeation of KT through the skin. Materials and Methods: A concentration of 1 mg/mL of the drug solution with enhancers was used to evaluate diffusion through the rat skin using a Franz diffusion cell assembly. 20 different penetration enhancers were selected for this study. Results: Saturated fatty acids like stearic and palmitic acid were found to increase the permeation rate of the drug to a great extent whereas unsaturated fatty acid viz. oleic acid exhibited maximum permeation. Increase in permeability efficiency of various penetration enhancers was observed in the following order: Oleic acid > stearic acid > palmitic acid > isopropyl myristate > tween 80 > span 80 > span 40 > span 20 > l-limonene > l-menthol > fenchone > α-pinene > urea > dimethyl sulfoxide (DMSO) > triton X-100 > tween 20 > dimethyl formamide > acetone > control > citric acid > ascorbic acid. Ascorbic acid and citric acid had no effect on permeation rate. Conclusion: The results revealed that the permeation of KT through the skin can maximally be enhanced using oleic acid-an unsaturated fatty acid. PMID:26258055

  1. Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation

    PubMed Central

    Abou el Ela, Amal El Sayeh F.; Hassan, Maha A.; El- Maraghy, Dalia A.

    2013-01-01

    The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet. PMID:25161380

  2. Comparison of the anti-inflammatory effect of dexamethasone and ketorolac in the extractions of third molars.

    PubMed

    Paiva-Oliveira, Janayna Gomes; Bastos, Paulo Roberto Haidamus Oliveira; Cury Pontes, Elenir R J; da Silva, Júlio César Leite; Delgado, Jéssica Andréa Berto; Oshiro-Filho, Nelson Talatoci

    2016-06-01

    This double-blind, split-mouth, and randomized study was aimed to compare the efficacy of dexamethasone and ketorolac tromethamine, through the evaluation of pain, edema, and limitation of mouth opening. Thirty-four individuals aged 18-26 years, having bilateral mandibular third molars, in a similar position, were selected. Two different surgical procedures were performed on the same individual by the single surgeon. For an extraction, the individual received 1 capsule of 10 mg ketorolac tromethamine 1 h before surgery and every 8 h for 2 days. For the extraction of the contralateral side, the individual received 1 capsule of 8 mg dexamethasone 1 h before surgery and 1 placebo capsule every 8 h for 2 days. Sodium metamizol, 500 mg, was given as rescue medication in postoperative. Pain was assessed by the Visual Box Scale-11 points (BS-11) at 24 h postoperative. Edema (metric measurement) and the maximum mouth opening (interincisal) were recorded in the pre-operative, 24 h, 48 h, 72 h and 7 days postoperatively. The results showed that both therapeutic treatments used were effective in the postoperative, and there were no statistically significant differences between the groups for the pain and edema variables. However, for the limitation of mouth opening, 24 h and 7 days postoperatively, the dexamethasone group had a lower limitation of mouth opening, behaving better than the ketorolac for this variable in these periods. Due also to the higher margin of safety, the use of dexamethasone as a single dose becomes a more suitable alternative for use in routine surgical extractions of third molars. PMID:26572899

  3. [A rare complication of labor epidural analgesia].

    PubMed

    Vazin, Mojgan Hosseini

    2008-06-16

    This case describes a patient who developed a complete right hemiparesis with ptosis of eyelid, trigeminus and facial paresis following a routine epidural analgesia for labor. A subdural deposit of the local anaesthetic might be the cause of these symptoms. The pathogenesis of these symptoms as well as the diagnoses and treatment of the condition is discussed. PMID:18565319

  4. Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles.

    PubMed

    Fathalla, Zeinab M A; Khaled, Khaled A; Hussein, Amal K; Alany, Raid G; Vangala, Anil

    2016-01-01

    The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0 ± 2.4 nm to 257.2 ± 18.6 nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10 mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p < 0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT. PMID:26407208

  5. Nasal delivery of analgesic ketorolac tromethamine thermo- and ion-sensitive in situ hydrogels.

    PubMed

    Li, Xin; Du, Lina; Chen, Xu; Ge, Pingju; Wang, Yu; Fu, Yangmu; Sun, Haiyan; Jiang, Qingwei; Jin, Yiguang

    2015-07-15

    Ketorolac tromethamine (KT) was potent to treat moderate to moderately severe pains. However, KT solutions for nasal delivery lost quickly from the nasal route. Thermo- and ion-sensitive in-situ hydrogels (ISGs) are appropriate for nasal drug delivery because the intranasal temperature maintains ∼37 °C and nasal fluids consist of plentiful cations. In this study, a novel nasal thermo- and ion-sensitive ISG of KT was prepared with thermo-sensitive poloxamer 407 (P407) and ion-sensitive deacetylated gellan gum (DGG). The optimal formulation of the KT ISG consisted of 3% (w/v) DGG and 18% (w/v) P407 and its viscosity was up to 7.63 Pas at 37 °C. Furthermore, penetration enhancers and bacterial inhibitors were added and their fractions in the ISG were optimized based on transmucosal efficiencies and toxicity on toad pili. Sulfobutyl ether-β-cyclodextrin of 2.5% (w/v) and chlorobutanol of 0.5% (w/v) were chosen as the penetration enhancer and the bacterial inhibitor, respectively. The Fick's diffusion and dissolution of KT could drive it continuous release from the dually sensitive ISG according to the in vitro investigation. Two methods, writhing frequencies induced by acetic acid and latency time of tails retracting from hot water, were used to evaluate the pharmacodynamics of the KT ISG on the mouse models. The writhing frequencies significantly decreased and the latency time of tail retracting was obviously prolonged (p<0.05) for the KT ISG compared to the control. The thermo- and ion-sensitive KT ISG had appropriate gelation temperature, sustained drug release, improved intranasal absorption, obvious pharmacodynamic effect, and negligible nasal ciliotoxicity. It is a promising intranasal analgesic formulation. PMID:25957699

  6. Efficacy of Intrathecal Morphine Combined with Intravenous Analgesia versus Thoracic Epidural Analgesia after Gastrectomy

    PubMed Central

    Lee, Jae Hoon; Park, Jin Ha; Kil, Hae Keum; Choi, Seung Ho; Noh, Sung Hoon

    2014-01-01

    Purpose Epidural analgesia has been the preferred analgesic technique after major abdominal surgery. On the other hand, the combined use of intrathecal morphine (ITM) and intravenous patient controlled analgesia (IVPCA) has been shown to be a viable alternative approach for analgesia. We hypothesized that ITM combined with IVPCA is as effective as patient controlled thoracic epidural analgesia (PCTEA) with respect to postoperative pain control after conventional open gastrectomy. Materials and Methods Sixty-four patients undergoing conventional open gastrectomy due to gastric cancer were randomly allocated into the intrathecal morphine combined with intravenous patient-controlled analgesia (IT) group or patient-controlled thoracic epidural analgesia (EP) group. The IT group received preoperative 0.3 mg of ITM, followed by postoperative IVPCA. The EP group preoperatively underwent epidural catheterization, followed by postoperative PCTEA. Visual analog scale (VAS) scores were assessed until 48 hrs after surgery. Adverse effects related to analgesia, profiles associated with recovery from surgery, and postoperative complications within 30 days after surgery were also evaluated. Results This study failed to demonstrate the non-inferiority of ITM-IVPCA (n=29) to PCTEA (n=30) with respect to VAS 24 hrs after surgery. Furthermore, the IT group consumed more fentanyl than the EP group did (1247.2±263.7 µg vs. 1048.9±71.7 µg, p<0.001). The IT group took a longer time to ambulate than the EP group (p=0.021) and had higher incidences of postoperative ileus (p=0.012) and pulmonary complications (p=0.05) compared with the EP group. Conclusion ITM-IVPCA is not as effective as PCTEA in patients undergoing gastrectomy, with respect to pain control, ambulation, postoperative ileus and pulmonary complications. PMID:24954344

  7. 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

  8. Analgesia for patients with advanced disease: 2

    PubMed Central

    Hall, E; Sykes, N

    2004-01-01

    The first article in this series explored epidemiology and patterns of pain in advanced disease, non-pharmacological treatments, and the use of opioids to manage pain. This second article examines the use of non-opioid drugs and anaesthetic interventions for pain relief in advanced disease. It also discusses an approach to managing analgesia in dying patients and finally looks at future developments. PMID:15082837

  9. Novel delivery systems for postoperative analgesia.

    PubMed

    Palmer, Pamela P; Royal, Mike A; Miller, Ronald D

    2014-03-01

    Moderate-to-severe postoperative pain is usually controlled using a multimodal approach, including opioids. Intravenously administered patient-controlled analgesia (IV PCA) with opioids, popular for over 40 years, enables patients to control their level of analgesia and has advantages over a nurse-administered approach, including more satisfied patients and improved pain relief. Unfortunately, IV PCA has drawbacks such as device programming errors, medication prescribing errors, pump malfunction, limitations on patient mobility, IV patency issues, and transmission of infection. Furthermore, the setup of an infusion pump is often complex, time-consuming, and requires witnessed confirmation. Complicating IV PCA is the problem of commonly used compounds, morphine and hydromorphone, having significantly reduced brain/effector-site permeability and active metabolites, both of which create the risk of delayed adverse events. Novel patient-controlled modalities that incorporate rapid effector site-permeating opioids and non-invasive routes of administration offer great promise to enhance both patient and caregiver experiences with postoperative analgesia systems. PMID:24815968

  10. Patient controlled analgesia with remifentanil versus epidural analgesia in labour: randomised multicentre equivalence trial

    PubMed Central

    Bloemenkamp, Kitty W; Franssen, Maureen T; Papatsonis, Dimitri N; Hajenius, Petra J; Hollmann, Markus W; Woiski, Mallory D; Porath, Martina; van den Berg, Hans J; van Beek, Erik; Borchert, Odette W H M; Schuitemaker, Nico; Sikkema, J Marko; Kuipers, A H M; Logtenberg, Sabine L M; van der Salm, Paulien C M; Oude Rengerink, Katrien; Lopriore, Enrico; van den Akker-van Marle, M Elske; le Cessie, Saskia; van Lith, Jan M; Struys, Michel M; Mol, Ben Willem J; Dahan, Albert; Middeldorp, Johanna M

    2015-01-01

    Objective To determine women’s satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. Design Multicentre randomised controlled equivalence trial. Setting 15 hospitals in the Netherlands. Participants Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data. Intervention Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour. Main outcome measures Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome. Results 1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The

  11. 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

  12. Validated spectrophotometric and chromatographic methods for simultaneous determination of ketorolac tromethamine and phenylephrine hydrochloride.

    PubMed

    Belal, T S; El-Kafrawy, D S; Mahrous, M S; Abdel-Khalek, M M; Abo-Gharam, A H

    2016-07-01

    This work describes five simple and reliable spectrophotometric and chromatographic methods for analysis of the binary mixture of ketorolac tromethamine (KTR) and phenylephrine hydrochloride (PHE). Method I is based on the use of conventional Amax and derivative spectrophotometry with the zero-crossing technique where KTR was determined using its Amax and (1)D amplitudes at 323 and 341nm respectively, while PHE was determined by measuring the (1)D amplitudes at 248.5nm. Method II involves the application of the ratio spectra derivative spectrophotometry. For KTR, 12μg/mL PHE was used as a divisor and the (1)DD amplitudes at 265nm were plotted against KTR concentrations; while - by using 4μg/mL KTR as divisor - the (1)DD amplitudes at 243.5nm were found proportional to PHE concentrations. Method III depends on ratio-difference measurement where the peak to trough amplitudes between 260 and 284nm were measured and correlated to KTR concentration. Similarly, the peak to trough amplitudes between 235 and 260nm in the PHE ratio spectra were recorded. For method IV, the two compounds were separated using Merck HPTLC sheets of silica gel 60 F254 and a mobile phase composed of chloroform/methanol/ammonia (70:30:2, by volume) followed by densitometric measurement of KTR and PHE spots at 320 and 278nm respectively. Method V depends on HPLC-DAD. Effective chromatographic separation was achieved using Zorbax eclipse plus C8 column (4.6×250mm, 5μm) with a mobile phase consisting of 0.05M o-phosphoric acid and acetonitrile (50:50, by volume) at a flow rate 1mL/min and detection at 313 and 274nm for KTR and PHE respectively. Analytical performance of the developed methods was statistically validated according to the ICH guidelines with respect to linearity, ranges, precision, accuracy, detection and quantification limits. The validated spectrophotometric and chromatographic methods were successfully applied to the simultaneous analysis of KTR and PHE in synthetic mixtures

  13. Patient-controlled oral analgesia versus nurse-controlled parenteral analgesia after caesarean section: a randomised controlled trial.

    PubMed

    Bonnal, A; Dehon, A; Nagot, N; Macioce, V; Nogue, E; Morau, E

    2016-05-01

    We assessed the effectiveness of early patient-controlled oral analgesia compared with parenteral analgesia in a randomised controlled non-inferiority trial of women undergoing elective caesarean section under regional anaesthesia. Seventy-seven women received multimodal paracetamol, ketoprofen and morphine analgesia. The woman having patient-controlled oral analgesia were administered four pillboxes on the postnatal ward containing tablets and instructions for self-medication, the first at 7 h after the spinal injection and then three more at 12-hourly intervals. Pain at rest and on movement was evaluated using an 11-point verbal rating scale at 2 h and then at 6-hourly intervals for 48 h. The pre-defined non-inferiority limit for the difference in mean pain scores (patient-controlled oral analgesia minus parenteral) was one. The one-sided 95% CI of the difference in mean pain scores was significantly lower than one at all time-points at rest and on movement, demonstrating non-inferiority of patient-controlled oral analgesia. More women used morphine in the patient-controlled oral analgesia group (22 (58%)) than in the parenteral group (9 (23%); p = 0.002). The median (IQR [range]) number of morphine doses in the patient-controlled oral analgesia group was 2 (1-3 [1-7]) compared with 1 (1-1 [1-2]); p = 0.006) in the parenteral group. Minor drug errors or omissions were identified in five (13%) women receiving patient-controlled oral analgesia. Pruritus was more frequent in the patient-controlled oral analgesia group (14 (37%) vs 6 (15%) respectively; p = 0.03), but no differences were noted for other adverse events and maternal satisfaction. After elective caesarean section, early patient-controlled oral analgesia is non-inferior to standard parenteral analgesia for pain management, and can be one of the steps of an enhanced recovery process. PMID:26931110

  14. Control of acute pain after major abdominal surgery in 585 patients given tramadol and ketorolac by intravenous infusion.

    PubMed

    Pieri, M; Meacci, L; Santini, L; Santini, G; Dollorenzo, R; Sansevero, A

    2002-01-01

    The aim of this study was to assess the efficacy and safety of postoperative pain relief using tramadol and ketorolac in continuous intravenous infusion. The 585 patients included in the study underwent major surgery according to a protocol involving the parenteral administration of 100 mg tramadol approximately 40 min before the end of surgery. This was followed by the continuous intravenous infusion of 600 mg tramadol and 180 mg ketorolac diluted with physiological solution to a total volume of 96 ml. Delivery was carried out using an elastomeric pump or a syringe pump and administered over a 48-hour period at a constant rate of 2 ml/h. Any further doses consisted of 100 mg tramadol up to a maximum of 300 mg over a 24-h period. Pain was assessed on a verbal numeric scale (VNS). For each patient the intensity of pain was assessed both at rest and on movement (coughing, deep breathing, movement of lower limbs). At the scheduled times (T0-T72, every 6 h), the following parameters were evaluated: hemodynamic stability; respiratory function; the appearance of any side effects; the level of sedation; and the need for any further doses of analgesic. The analysis of the data obtained showed the good quality of postoperative pain relief achieved: pain intensity at rest was, on average, always below VNS level 3, while during movement it always had an average VNS level of 3-4. The only side effects found with any frequency were nausea (22.6%) and vomiting (8.5%); hemodynamic and respiratory parameters remained stable. The method adopted was of limited cost and was well accepted by both patients and staff. On the basis of the data obtained, it is possible to affirm that the post-operative pain protocol proposed is effective, safe, without significant side effects, and of limited cost. Therefore, it is the first choice protocol for our operating unit after major abdominal surgery. PMID:12224377

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

    PubMed Central

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

    2011-01-01

    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 μg/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. PMID:24309316

  16. Formulation and pharmacokinetics of colon-specific double-compression coated mini-tablets: Chronopharmaceutical delivery of ketorolac tromethamine.

    PubMed

    Vemula, Sateesh Kumar

    2015-08-01

    The present study is designed and significantly planned to study the effect of double-compression coating on core mini-tablets to attain the chronopharmaceutical delivery of ketorolac tromethamine to colon. Double-compression coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. From the in vitro drug release studies, F6 tablets was considered as the optimized formulation, which retarded the drug release in stomach and small intestine (3.51 ± 0.15% in 5h) and progressively released to colon (99.82 ± 0.69% in 24h). The release process followed supercase-II transport with zero order release kinetics. Similarity factor calculated from stability studies was found to be 84.73. From the pharmacokinetic evaluation, the immediate release core mini-tablets reached peak plasma concentration (Cmax of 4532.68 ± 28.14 ng/ml) at 2h Tmax and colon targeted tablets showed Cmax=3782.29 ± 17.83 ng/ml at 12h Tmax. The area under the curve and mean resident time of core mini-tablets were found to be 11,278.26 ± 132.67 ng-h/ml and 3.68 h respectively while 17,324.48 ± 56.32 ng-h/ml and 10.39 h for compression coated tablets. Hence the development of double-compression coated tablets is a promising way to gain the chronopharmaceutical delivery of ketorolac tromethamine to colon. PMID:26056929

  17. Abdominoplasty with procedural sedation and analgesia.

    PubMed

    Rosenberg, M H; Palaia, D A; Bonanno, P C

    2001-05-01

    The ability to perform abdominal cosmetic surgery in the ambulatory setting provides a more comfortable environment for the patient, ease of scheduling for the physician, and decreased costs. Avoiding the use of general anesthesia allows for quicker recovery, shorter length of hospital stay, and decreased rate of postoperative complications. The authors report 106 consecutive abdominoplasties, including fascial plication when indicated, using local anesthesia, with procedural sedation and analgesia. All procedures were performed with an anesthesiologist providing intraoperative monitoring of the patients. Their protocol uses procedural sedation and analgesia, which results in a depressed level of consciousness, but allows the patient to maintain airway control independently and continuously. The results of this approach were measured in terms of procedure time, length of hospital stay, rate of complications, total recovery time, and the level of patient satisfaction. Between January 1996 and January 1999, 106 patients underwent abdominoplasty (performed by one of the authors) under local anesthesia with procedural sedation and analgesia. All patients had an American Society of Anesthesiologists status of 1 to 3, and underwent a full abdominoplasty, including fascial plication. In 26% of the patients, allied procedures were also performed, most commonly liposuction or augmentation mammaplasty. The mean age in this series was 45 years, and all patients were available for follow-up at least 1 year after surgery. The mean operative time was 135 minutes, recovery room time was 68 minutes, and all patients were ambulatory. There were no surgical complications, including flap loss or wound dehiscence, and no complications related to anesthesia (cardiac, deep vein thrombosis, fat emboli, pulmonary embolism, etc.). Because paralytic agents were not used, none of the patients required catheterization postoperatively. Patients were generally pleased with the results of

  18. Spinal analgesia for advanced cancer patients: an update.

    PubMed

    Mercadante, Sebastiano; Porzio, Giampiero; Gebbia, Vittorio

    2012-05-01

    In the nineties, spinal analgesia has been described as an useful means to control pain in advanced cancer patients. The aim of this review was to update this information with a systematic analysis of studies performed in the last 10 years. 27 papers pertinent with the topic selected for review were collected according to selection criteria. Few studies added further information on spinal analgesia in last decade. Despite a lack of a clinical evidence, spinal analgesia with a combination of opioids, principally morphine, and local anesthetics may allow to achieve analgesia in patients who had been intensively treated unsuccessfully with different trials of opioids. Some adjuvant drugs such as clonidine, ketamine, betamethasone, meperidine, and ziconotide may be promising agents, but several problems have to be solved before they can be used in the daily practice. In complex pain situations, spinal analgesia should not be negated to cancer patients, and oncologists should address this group of patients to other specialists. PMID:21684173

  19. Characterization of forced degradation products of ketorolac tromethamine using LC/ESI/Q/TOF/MS/MS and in silico toxicity prediction.

    PubMed

    Kalariya, Pradipbhai D; Raju, B; Borkar, Roshan M; Namdev, Deepak; Gananadhamu, S; Nandekar, Prajwal P; Sangamwar, Abhay T; Srinivas, R

    2014-05-01

    Ketorolac, a nonsteroidal anti-inflammatory drug, was subjected to forced degradation studies as per International Conference on Harmonization guidelines. A simple, rapid, precise, and accurate high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (LC/ESI/Q/TOF/MS/MS) method has been developed for the identification and structural characterization of stressed degradation products of ketorolac. The drug was found to degrade in hydrolytic (acidic, basic, and neutral), photolytic (acidic, basic, and neutral solution), and thermal conditions, whereas the solid form of the drug was found to be stable under photolytic conditions. The method has shown adequate separation of ketorolac tromethamine and its degradation products on a Grace Smart C-18 (250 mm × 4.6 mm i.d., 5 µm) column using 20 mM ammonium formate (pH = 3.2): acetonitrile as a mobile phase in gradient elution mode at a flow rate of 1.0 ml/min. A total of nine degradation products were identified and characterized by LC/ESI/MS/MS. The most probable mechanisms for the formation of degradation products have been proposed on the basis of a comparison of the fragmentation of the [M + H](+) ions of ketorolac and its degradation products. In silico toxicity of the drug and degradation products was investigated by using topkat and derek softwares. The method was validated in terms of specificity, linearity, accuracy, precision, and robustness as per International Conference on Harmonization guidelines. PMID:24809899

  20. Analgesia for people with acute ankle sprain.

    PubMed

    Carter, David; Amblum-Almer, Jeshni

    2015-04-01

    Around 302,000 people with soft-tissue ankle injuries present to UK emergency departments every year (Ferran and Maffulli 2006). These patients are generally treated conservatively with analgesia, ice, compression and elevation, and rest. There is some discussion in the literature about whether or not people with these injuries should be treated with non-steroidal anti-inflammatory drugs (NSAIDs), with some authors claiming that the inflammatory response following injury is part of the healing process and should not be halted. This article examines the literature on the efficacy of administering NSAIDs as the first-line drug management for ankle sprain. It also considers cost of treatment, prescribing practice and contraindications of NSAIDs. PMID:25854742

  1. Behavioral evidence for an opiate pituitary mechanism subserving conditioned analgesia.

    PubMed

    Gaiardi, M; Bartoletti, M; Gubellini, C; Bacchi, A; Babbini, M

    1983-09-01

    The effect of a naloxone or a dexamethasone pretreatment on the conditioned analgesia resulting from the exposure of rats to an experimental chamber repeatedly paired with a grid shock was investigated. Shock induced disruption of bar pressing activity was taken as a behavioral measure of pain responsiveness. It was found that a 6, but not a 3, mg/kg dose of naloxone i.p. is hyperalgesic in unconditioned rats and effectively antagonizes conditioned analgesia. Dexamethasone (up to a dose of 2 + 1 mg/kg i.p. 23 and 1 h prior) did not alter the pain responsiveness of unconditioned rats, but caused a dose dependent suppression of conditioned analgesia. These results are discussed in terms of an opiate pituitary mechanism subserving conditioned analgesia. PMID:6314229

  2. [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. PMID:26596028

  3. Labor Epidural Analgesia and Breastfeeding: A Systematic Review.

    PubMed

    French, Cynthia A; Cong, Xiaomei; Chung, Keun Sam

    2016-08-01

    Despite widespread use of epidural analgesia during labor, no consensus has been reached among obstetric and anesthesia providers regarding its effects on breastfeeding. The purpose of this review was to examine the relationship between labor epidural analgesia and breastfeeding in the immediate postpartum period. PubMed, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature were searched for articles published in 1990 or thereafter, using the search term breastfeeding combined with epidural, labor epidural analgesia, labor analgesia, or epidural analgesia Of 117 articles, 23 described empirical studies specific to labor epidural analgesia and measured a breastfeeding outcome. Results were conflicting: 12 studies showed negative associations between epidural analgesia and breastfeeding success, 10 studies showed no effect, and 1 study showed a positive association. Most studies were observational. Of 3 randomized controlled studies, randomization methods were inadequate in 2 and not evaluable in 1. Other limitations were related to small sample size or inadequate study power; variation and lack of information regarding type and dosage of analgesia or use of other intrapartum interventions; differences in timing, definition, and method of assessing breastfeeding success; or failure to consider factors such as mothers' intention to breastfeed, social support, siblings, or the mother's need to return to work or school. It is also unclear to what extent results are mediated through effects on infant neurobehavior, maternal fever, oxytocin release, duration of labor, and need for instrumental delivery. Clinician awareness of factors affecting breastfeeding can help identify women at risk for breastfeeding difficulties in order to target support and resources effectively. PMID:27121239

  4. Novel stereoselective high-performance liquid chromatographic method for simultaneous determination of guaifenesin and ketorolac enantiomers in human plasma.

    PubMed

    Maher, Hadir M; Al-Taweel, Shorog M; Alshehri, Mona M; Alzoman, Nourah Z

    2014-10-01

    A novel method was developed for the simultaneous determination of guaifenesin (GUA) and ketorolac tromethamine (KET) enantiomers in plasma samples. Since GUA probably increases the absorption of coadministered drugs (e.g., KET), it would be extremely important to monitor KET plasma levels for the purpose of dose adjustment with a subsequent decrease in the side effects. Enantiomeric resolution was achieved on a polysaccharide-based chiral stationary phase, amylose-2, as a chiral selector under the normal phase (NP) mode and using ornidazole (ORN) as internal standard. This innovative method has the advantage of the ease and reliability of sample preparation for plasma samples. Sample clean-up was based on simply using methanol for protein precipitation followed by direct extraction of drug residues using ethanol. Both GUA and KET enantiomers were separated using an isocratic mobile phase composed of hexane/isopropanol/trifluoroacetic acid, 85:15:0.05 v/v/v. Peak area ratios were linear over the range 0.05-20 µg/mL for the four enantiomers S (+) GUA, R (-) GUA, R (+) KET, and S (-) KET. The method was fully validated according to the International Conference on Harmonization (ICH) guidelines in terms of system suitability, specificity, accuracy, precision, robustness, and solution stability. Finally, this procedure was innovative to apply the rationale of developing a chiral high-performance liquid chromatography (HPLC) procedure for the simultaneous quantitative analysis of drug isomers in clinical samples. PMID:25043279

  5. 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

  6. 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

  7. Epidural analgesia is superior to local infiltration analgesia in children with cerebral palsy undergoing unilateral hip reconstruction

    PubMed Central

    Kjeldgaard Pedersen, Line; Nikolajsen, Lone; Rahbek, Ole; Uldall Duch, Birgitte; Møller-Madsen, Bjarne

    2016-01-01

    Background and purpose — Treatment of postoperative pain in children with cerebral palsy (CP) is a major challenge. We investigated the effect of epidural analgesia, high-volume local infiltration analgesia (LIA), and an approximated placebo control on early postoperative pain in children with CP who were undergoing unilateral hip reconstruction. Patients and methods — Between 2009 and 2014, we included 18 children with CP. The first part of the study was a randomized double-blind trial with allocation to either LIA or placebo for postoperative pain management, in addition to intravenous or oral analgesia. In the second part of the study, the children were consecutively included for postoperative pain management with epidural analgesia in addition to intravenous or oral analgesia. The primary outcome was postoperative pain 4 h postoperatively using 2 pain assessment tools (r-FLACC and VAS-OBS) ranging from 0 to 10. The secondary outcome was opioid consumption over the 21-h study period. Results — The mean level of pain 4 h postoperatively was lower in the epidural group (r-FLACC: 0.7; VAS-OBS: 0.6) than in both the LIA group (r-FLACC: 4.8, p = 0.01; VAS-OBS: 5.2, p = 0.02) and the placebo group (r-FLACC: 5.2, p = 0.01; VAS-OBS: 6.5, p < 0.001). Corrected for body weight, the mean opioid consumption was lower in the epidural group than in the LIA group and the placebo group (both p < 0.001). Interpretation — Epidural analgesia is superior to local infiltration analgesia for early postoperative pain management in children with cerebral palsy who undergo unilateral hip reconstruction. PMID:26541479

  8. Randomized clinical trial of local infiltration plus patient-controlled opiate analgesia vs. epidural analgesia following liver resection surgery

    PubMed Central

    Revie, Erica J; McKeown, Dermot W; Wilson, John A; Garden, O James; Wigmore, Stephen J

    2012-01-01

    Objectives Epidural analgesia is recommended for the provision of analgesia following major abdominal surgery. Continuous local anaesthetic wound infiltration may be an effective alternative. A prospective randomized trial was undertaken to compare these two methods following open liver resection. The primary outcome was length of time required to fulfil criteria for discharge from hospital. Methods Patients undergoing open liver resection were randomized to receive either epidural (EP group) or local anaesthetic wound infiltration plus patient-controlled opiate analgesia (WI group) for the first 2 days postoperatively. All other care followed a standardized enhanced recovery protocol. Time to fulfil discharge criteria, pain scores, physical activity measurements and complications were recorded. Results Between August 2009 and July 2010, 65 patients were randomized to EP (n= 32) or WI (n= 33). The mean time required to fulfil discharge criteria was 4.5 days (range: 2.5–63.5 days) in the WI group and 6.0 days (range: 3.0–42.5 days) in the EP group (P= 0.044). During the first 48 h following surgery, pain scores were significantly lower in the EP group both at rest and on movement. Resting pain scores within both groups were rated as mild (range: 0–3). There was no significant difference between the groups in time to first mobilization or overall complication rate (48.5% in the WI group vs. 58.1% in the EP group; P= 0.443). Conclusions Local anaesthetic wound infiltration combined with patient-controlled opiate analgesia reduces the length of time required to fulfil criteria for discharge from hospital compared with epidural analgesia following open liver resection. Epidural analgesia provides superior analgesia, but does not confer benefits in terms of faster mobilization or recovery. PMID:22882198

  9. Epidural analgesia is superior to local infiltration analgesia in children with cerebral palsy undergoing unilateral hip reconstruction.

    PubMed

    Kjeldgaard Pedersen, Line; Nikolajsen, Lone; Rahbek, Ole; Uldall Duch, Birgitte; Møller-Madsen, Bjarne

    2016-04-01

    Background and purpose - Treatment of postoperative pain in children with cerebral palsy (CP) is a major challenge. We investigated the effect of epidural analgesia, high-volume local infiltration analgesia (LIA), and an approximated placebo control on early postoperative pain in children with CP who were undergoing unilateral hip reconstruction. Patients and methods - Between 2009 and 2014, we included 18 children with CP. The first part of the study was a randomized double-blind trial with allocation to either LIA or placebo for postoperative pain management, in addition to intravenous or oral analgesia. In the second part of the study, the children were consecutively included for postoperative pain management with epidural analgesia in addition to intravenous or oral analgesia. The primary outcome was postoperative pain 4 h postoperatively using 2 pain assessment tools (r-FLACC and VAS-OBS) ranging from 0 to 10. The secondary outcome was opioid consumption over the 21-h study period. Results - The mean level of pain 4 h postoperatively was lower in the epidural group (r-FLACC: 0.7; VAS-OBS: 0.6) than in both the LIA group (r-FLACC: 4.8, p = 0.01; VAS-OBS: 5.2, p = 0.02) and the placebo group (r-FLACC: 5.2, p = 0.01; VAS-OBS: 6.5, p < 0.001). Corrected for body weight, the mean opioid consumption was lower in the epidural group than in the LIA group and the placebo group (both p < 0.001). Interpretation - Epidural analgesia is superior to local infiltration analgesia for early postoperative pain management in children with cerebral palsy who undergo unilateral hip reconstruction. PMID:26541479

  10. Continuous shoulder analgesia via an indwelling axillary brachial plexus catheter.

    PubMed

    Reuben, S S; Steinberg, R B

    2000-09-01

    Continuous interscalene brachial plexus blockade can provide anesthesia and analgesia in the shoulder region. Difficulty accessing the interscalene space and premature displacement of interscalene catheters may preclude their use in certain situations. We present two case reports in which a catheter was advanced from the axilla along the brachial plexus sheath to the interscalene space to provide continuous cervicobrachial plexus analgesia. In the first case report, previous neck surgery made the anatomic landmarks for performing an interscalene block very difficult. An epidural catheter was advanced from the axillary brachial plexus sheath to the interscalene space under fluoroscopic guidance. This technique provided both intraoperative analgesia for shoulder surgery as well as 24-hour postoperative analgesia by an infusion of 0.125% bupivacaine. In the second case report, a catheter was inserted in a similar fashion from the axillary to the interscalene space to provide 14 days of continuous analgesia in the management of complex regional pain syndrome. We have found that this technique allows us to secure the catheter more easily than with the traditional interscalene approach and thus prevents premature dislodgment. This approach may be a suitable alternative when either an interscalene or an infraclavicular catheter may not be inserted. PMID:11090734

  11. Epidural and opioid analgesia following the Nuss procedure

    PubMed Central

    Walaszczyk, Malgorzata; Knapik, Piotr; Misiolek, Hanna; Korlacki, Wojciech

    2011-01-01

    Summary Background Parents have the right to decide on behalf of their children and deny consent to regional anaesthesia. The investigators decided to investigate quality of postoperative analgesia in adolescents undergoing epidural and opioid analgesia following the Nuss procedure. Material/Methods The study subjects were 61 adolescents aged 11–18 years who underwent pectus excavatum repair with the Nuss procedure. Patients were divided into epidural (n=41) and opioid (n=20) groups, depending on their parents’ consent to epidural catheter insertion. Intraoperatively, 0.5% epidural ropivacaine with fentanyl or intermittent intravenous injections of fentanyl were used. Postoperative analgesia was achieved with either epidural infusion of 0.1% ropivacaine with fentanyl, or subcutaneous morphine via an intraoperatively inserted “butterfly” cannula. Additionally, both groups received metamizol and paracetamol. Primary outcome variables were postoperative pain scores (Numeric Rating Scale and Prince Henry Hospital Pain Score). Secondary outcome variables included hemodynamic parameters, additional analgesia and side effects. Results Heart rate and blood pressure values in the postoperative period were significantly higher in the opioid group. Pain scores requiring intervention were noted almost exclusively in the opioid group. Conclusions Denial of parental consent to epidural analgesia following the Nuss procedure results in significantly worse control of postoperative pain. Our data may be useful when discussing with parents the available anaesthetic techniques for exceptionally painful procedures. PMID:22037752

  12. NOP receptor mediates anti-analgesia induced by agonist-antagonist opioids.

    PubMed

    Gear, R W; Bogen, O; Ferrari, L F; Green, P G; Levine, J D

    2014-01-17

    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 ∼90min 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 U69593 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 J-113397, 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

  13. Multimodal Analgesia in the Hip Fracture Patient.

    PubMed

    Fabi, David W

    2016-05-01

    Hip fracture is one of the most common injuries among the elderly and, because the population is aging, it is expected to remain a major clinical challenge and public health problem for the foreseeable future. The clinical importance of early mobilization and prompt participation in physical therapy after hip fracture surgery is now widely recognized. Because postoperative pain can impair mobility and delay physical therapy, much attention is now being paid to finding more effective ways of controlling pain after hip fracture. Oversedation with opioid drugs inhibits communication between the patient and the health care team, can delay ambulation and rehabilitation therapy, and may increase the probability of the patient requiring a skilled nursing facility, which adds further cost to the overall health care system. Multiple pain pathways contribute to the perception of postoperative pain, and although opioids are highly effective in blocking nociceptive pain through inhibition of the mu receptors, they do not block other pain pathways. Multimodal analgesia involves the use of several anesthetic and analgesic modalities that are strategically combined to block pain perception at different sites in the peripheral and central nervous systems. This balanced, multifaceted approach provides more effective control of postoperative pain than opioid drugs alone, allows lower doses of opioids to be used as part of the multimodal regimen (thereby reducing the risk of opioid-related adverse events and complications), and may facilitate more rapid recovery and improve certain outcome measures related to recovery time. One prospective randomized study evaluating the clinical value of multimodal pain management in elderly patients undergoing bipolar hip hemiarthroplasty found that a multimodal regimen, including preemptive pain medication and intraoperative periarticular injections, reduced pain on postoperative days 1 and 4, and reduced overall opioid use. This article describes

  14. Microspheres and tablet in capsule system: A novel chronotherapeutic system of ketorolac tromethamine for site and time specific delivery

    PubMed Central

    Shahi, Priya; Kumari, Neeraj; Pathak, Kamla

    2015-01-01

    The objective of the present work was to develop a novel delivery system of ketorolac tromethamine (KT) for dual pulse release based on microspheres and tablet in capsule system (MATICS) as a treatment modality for rheumatoid arthritis. The design consisted of an impermeable hard gelatin capsule body, in which a core tablet was (second pulse) placed in the bottom and sealed with a hydrogel plug (HP2). The body was locked with enteric coated cap filled with KT microspheres (first pulse). The microspheres for first pulse were selected by screening the formulations (M1–M6), and M1 with least particle size of 96.38 ± 0.05 μm, highest drug loading of 25.10% ± 0.28% and maximum CDR of 89.32% ± 0.21% was adjudged as the best formulation. The HP2 tablet was selected based on its capability for maintaining a lag period of 6 h. The selection criterion of the second pulse (core tablet: T3) was its disintegration time of 4.02 ± 0.53 min and CDR of 99.10% ± 0.32% in 30 min. All the optimized formulations were assembled in accordance with the proposed design to form pulsatile MATICS and evaluated for in vitro release. MATICS displayed delayed sustained CDR of 80.15% in 8 h from the first pulse (microspheres) after a lag time of 2 h, followed by 97.05% KT release from second pulse (core tablet) in simulated colonic fluid within 10 h. Conclusively, in vitro pulsatile release was a rational combination of delayed sustained and immediate release of KT that has the potential to combat the pain at night and morning stiffness. Incorporation of two pulses in one system offers a reduction in dose frequency and better pain management. PMID:26258058

  15. [Current approaches to the analgesia of spontaneous child birth].

    PubMed

    Neĭmark, M I; Geronimus, V Iu

    2007-01-01

    The authors have compared various modes of spontaneous labor. Prolonged epidural infusion of naropine in combination with fentanyl has been found to cause a less motor block and therefore it may be used in the late first-to-second period of labor. Adequate analgesia ensures a smooth course of the second labor period and promotes the reduction in its duration and the correction of central hemodynamic and hormonal homeostastic disorders. The administration of moradol provides adequate analgesia of the first labor period, prevention, and elimination of abnormal labor activity, without exerting a depressive effect on maternal and neonatal respiration, which makes it possible to consider this procedure as an alternative mode of labor pain relief if there are contraindications to epidural analgesia. PMID:18330019

  16. Liposomal extended-release bupivacaine for postsurgical analgesia

    PubMed Central

    Lambrechts, Mark; O’Brien, Michael J; Savoie, Felix H; You, Zongbing

    2013-01-01

    When physicians consider which analgesia to use postsurgery, the primary goal is to relieve pain with minimal adverse side effects. Bupivacaine, a commonly used analgesic, has been formulated into an aqueous suspension of multivesicular liposomes that provide long-lasting analgesia for up to 72 hours, while avoiding the adverse side effects of opioids. The increased efficacy of liposomal extended-release bupivacaine, compared to bupivacaine hydrochloride, has promoted its usage in a variety of surgeries including hemorrhoidectomy, bunionectomy, inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty. However, like other bupivacaine formulations, the liposomal extended-release bupivacaine does have some side effects. In this brief review, we provide an update of the current knowledge in the use of bupivacaine for postsurgical analgesia. PMID:24043932

  17. CLASSICAL CONDITIONING AND PAIN: CONDITIONED ANALGESIA AND HYPERALGESIA

    PubMed Central

    Miguez, Gonzalo; Laborda, Mario A.; Miller, Ralph R.

    2013-01-01

    This article reviews situations in which stimuli produce an increase or a decrease in nociceptive responses through basic associative processes and provides an associative account of such changes. Specifically, the literature suggests that cues associated with stress can produce conditioned analgesia or conditioned hyperalgesia, depending on the properties of the conditioned stimulus (e.g., contextual cues and audiovisual cues vs. gustatory and olfactory cues, respectively) and the proprieties of the unconditioned stimulus (e.g., appetitive, aversive, or analgesic, respectively). When such cues are associated with reducers of exogenous pain (e.g., opiates), they typically increase sensitivity to pain. Overall, the evidence concerning conditioned stress-induced analgesia, conditioned hyperalagesia, conditioned tolerance to morphine, and conditioned reduction of morphine analgesia suggests that selective associations between stimuli underlie changes in pain sensitivity. PMID:24269884

  18. 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. PMID:20529986

  19. The neuroanatomy of sexual dimorphism in opioid analgesia.

    PubMed

    Loyd, Dayna R; Murphy, Anne Z

    2014-09-01

    The influence of sex has been neglected in clinical studies on pain and analgesia, with the vast majority of research conducted exclusively in males. However, both preclinical and clinical studies indicate that males and females differ in both the anatomical and physiological composition of central nervous system circuits that are involved in pain processing and analgesia. These differences influence not only the response to noxious stimuli, but also the ability of pharmacological agents to modify this response. Morphine is the most widely prescribed opiate for the alleviation of persistent pain in the clinic; however, it is becoming increasingly clear that morphine is less potent in women compared to men. This review highlights recent research identifying neuroanatomical and physiological dimorphisms underlying sex differences in pain and opioid analgesia, focusing on the endogenous descending pain modulatory circuit. PMID:24731947

  20. The Neuroanatomy of Sexual Dimorphism in Opioid Analgesia

    PubMed Central

    Loyd, Dayna R.; Murphy, Anne Z.

    2014-01-01

    The influence of sex has been neglected in clinical studies on pain and analgesia, with the vast majority of research conducted exclusively in males. However, both preclinical and clinical studies indicate that males and females differ in both the anatomical and physiological composition of central nervous system circuits that are involved in pain processing and analgesia. These differences influence not only the response to noxious stimuli, but also the ability of pharmacological agents to modify this response. Morphine is the most widely prescribed opiate for the alleviation of persistent pain in the clinic; however, it is becoming increasingly clear that morphine is less potent in women compared to men. This review highlights recent research identifying neuroanatomical and physiological dimorphisms underlying sex differences in pain and opioid analgesia, focusing on the endogenous descending pain modulatory circuit. PMID:24731947

  1. Potentiation of morphine analgesia by subanesthetic doses of pentobarbital.

    PubMed

    Pontani, R B; Vadlamani, N L; Misra, A L

    1985-03-01

    Pentobarbital pretreatment reportedly either inhibits, enhances or has no effect on morphine analgesia. The effect of subanesthetic doses of sodium pentobarbital (8-12 mg kg-1, SC) delivered via a delivery system on analgesia of morphine (5 mg kg-1, SC or 1 mg kg-1, IV) acutely administered 45 min after the sodium pentobarbital pellet implantation was assessed using the warm water (55 degrees C)-induced tail-withdrawal reflex in male Wistar rats. Significant potentiation of morphine analgesia was observed in sodium pentobarbital as compared to the placebo-pelleted animals. Pharmacokinetic or dispositional factors were not involved in this potentiation, which was possibly due to the activation of the descending inhibitory control pathways of nociceptive spinal tail-withdrawal reflex by a combined interaction of two drugs at spinal and supraspinal sites of action, that mediate opiate antinociception. PMID:3991755

  2. Role of Epidural and Patient-Controlled Analgesia in Site-Specific Laparoscopic Colorectal Surgery

    PubMed Central

    Kamiński, Jan P.; Pai, Ajit; Ailabouni, Luay; Marecik, Slawomir J.; Prasad, Leela M.; Abcarian, Herand

    2014-01-01

    Background and Objectives: Limited data are available comparing epidural and patient-controlled analgesia in site-specific colorectal surgery. The aim of this study was to evaluate 2 modes of analgesia in patients undergoing laparoscopic right colectomy (RC) and low anterior resection (LAR). Methods: Prospectively collected data on 433 patients undergoing laparoscopic or laparoscopic-assisted colon surgery at a single institution were retrospectively reviewed from March 2004 to February 2009. Patients were divided into groups undergoing RC (n = 175) and LAR (n = 258). These groups were evaluated by use of analgesia: epidural analgesia, “patient-controlled analgesia” alone, and a combination of both. Demographic and perioperative outcomes were compared. Results: Epidural analgesia was associated with a faster return of bowel function, by 1 day (P < .001), in patients who underwent LAR but not in the RC group. Delayed return of bowel function was associated with increased operative time in the LAR group (P = .05), patients with diabetes who underwent RC (P = .037), and patients after RC with combined analgesia (P = .011). Mean visual analogue scale pain scores were significantly lower with epidural analgesia compared with patient-controlled analgesia in both LAR and RC groups (P < .001). Conclusion: Epidural analgesia was associated with a faster return of bowel function in the laparoscopic LAR group but not the RC group. Epidural analgesia was superior to patient-controlled analgesia in controlling postoperative pain but was inadequate in 28% of patients and needed the addition of patient-controlled analgesia. PMID:25419110

  3. DHEA administration modulates stress-induced analgesia in rats.

    PubMed

    Cecconello, Ana Lúcia; Torres, Iraci L S; Oliveira, Carla; Zanini, Priscila; Niches, Gabriela; Ribeiro, Maria Flávia Marques

    2016-04-01

    An important aspect of adaptive stress response is the pain response suppression that occurs during or following stress exposure, which is often referred to as acute stress-induced analgesia. Dehydroepiandrosterone (DHEA) participates in the modulation of adaptive stress response, changing the HPA axis activity. The effect of DHEA on the HPA axis activity is dependent on the state and uses the same systems that participate in the regulation of acute stress-induced analgesia. The impact of DHEA on nociception has been studied; however, the effect of DHEA on stress-induced analgesia is not known. Thus, the aim of the present study was to evaluate the effect of DHEA on stress-induced analgesia and determine the best time for hormone administration in relation to exposure to stressor stimulus. The animals were stressed by restraint for 1h in a single exposure and received treatment with DHEA by a single injection before the stress or a single injection after the stress. Nociception was assessed with a tail-flick apparatus. Serum corticosterone levels were measured. DHEA administered before exposure to stress prolonged the acute stress-induced analgesia. This effect was not observed when the DHEA was administered after the stress. DHEA treatment in non-stressed rats did not alter the nociceptive threshold, suggesting that the DHEA effect on nociception is state-dependent. The injection of DHEA had the same effect as exposure to acute stress, with both increasing the levels of corticosterone. In conclusion, acute treatment with DHEA mimics the response to acute stress indexed by an increase in activity of the HPA axis. The treatment with DHEA before stress exposure may facilitate adaptive stress response, prolonging acute stress-induced analgesia, which may be a therapeutic strategy of interest to clinics. PMID:26852948

  4. Improvement of 'dynamic analgesia' does not decrease atelectasis after thoracotomy.

    PubMed

    Boisseau, N; Rabary, O; Padovani, B; Staccini, P; Mouroux, J; Grimaud, D; Raucoules-Aimé, M

    2001-10-01

    There is still controversy concerning the beneficial aspects of 'dynamic analgesia' (i.e. pain while coughing or moving) on the reduction of postoperative atelectasis. In this study, we tested the hypothesis that thoracic epidural analgesia (TEA) prevents these abnormalities as opposed to multimodal analgesia with i.v. patient controlled analgesia (i.v. PCA) after thoracotomy. Fifty-four patients undergoing thoracotomy (lung cancer) were randomly assigned to one of the two groups. Clinical respiratory characteristics, arterial blood gas, and pulmonary function tests (forced vital capacity and forced expiratory volume in 1 s) were obtained before surgery and on the next 3 postoperative days. Atelectasis was compared between the two groups by performing computed tomography (CT) scan of the chest at day 3. Postoperative respiratory function and arterial blood gas values were reduced compared with preoperative values (mean (SD) FEV1 day 0: 1.1 (0.3) litre; 1.3 (0.4) litre) but there was no significant difference between groups at any time. PCA and TEA provided a good level of analgesia at rest (VAS day 0: 21 (15/100); 8 (9/100)), but TEA was more effective for analgesia during mobilization (VAS day 0: 52 (3/100); 25 (17/100)). CT scans revealed comparable amounts of atelectasis (expressed as a percentage of total lung volume) in the TEA (7.1 (2.8)%) and in the i.v. PCA group (6.71 (3.2)%). There was no statistical difference in the number of patients presenting with at least one atelectasis of various types (lamellar, plate, segmental, lobar). PMID:11878725

  5. Nitrous oxide/oxygen analgesia in emergency care.

    PubMed

    McKinnon, K D; Culver, D; Prno, J M

    1980-01-01

    A method of analgesia relatively new to North American emergency care involves the use of a homogeneous gas composed of 50% nitrous oxide and 50% oxygen (Entonox). The gas is administered by the patient, who holds the Entonox apparatus mask to his face and triggers gas flow by exerting negative inspiratory pressure (-1 cm. H(2)O). Worthwhile analgesia (i.e. marked or partial pain relief) was achieved in 95% of 110 emergency department patients experiencing significant pain from various sources. PMID:21297843

  6. Nitrous Oxide/Oxygen Analgesia In Emergency Care

    PubMed Central

    McKinnon, Kent D. L.; Culver, Denis; Prno, John M.

    1980-01-01

    A method of analgesia relatively new to North American emergency care involves the use of a homogeneous gas composed of 50% nitrous oxide and 50% oxygen (Entonox). The gas is administered by the patient, who holds the Entonox apparatus mask to his face and triggers gas flow by exerting negative inspiratory pressure (−1 cm. H2O). Worthwhile analgesia (i.e. marked or partial pain relief) was achieved in 95% of 110 emergency department patients experiencing significant pain from various sources. ImagesFig. 3 PMID:21297843

  7. Validated Stability-indicating Reverse-phase Ultra-performance Liquid Chromatography Method for Simultaneous Determination of Sodium Methylparaben, Sodium Propylparaben and Ketorolac Tromethamine in Topical Dosage Forms

    PubMed Central

    Roy, C.; Chakrabarty, J.; Modi, P. B.

    2013-01-01

    A sensitive, fast, and stability-indicating isocratic reverse-phase ultra-performance liquid chromatography method was developed and validated for quantitative simultaneous determination of sodium methylparaben, sodium propylparaben and ketorolac tromethamine in topical dosage forms. Separation of all peaks was achieved by using acquity ethylene bridged hybrid C18 (50×2.1 mm, 1.7 μ) as stationary phase, mobile phase used was triethylamine buffer (pH 2.5):tetrahydrofuran:methanol (665:35:300, v/v/v) with isocratic mode at a flow rate of 0.40 ml/min. All component were detected at 252 nm with 10 min run time. The described method was found to be linear in the concentration range of 248-744 μg/ml for ketorolac tromethamine, 20.8-62.4 μg/ml for sodium methylparaben and 2.38-7.13 μg/ml for sodium propylparaben with correlation coefficients more than 0.999. Method was validated in terms of specificity, linearity, accuracy, precision, solution stability, filter equivalency, and robustness as per International Conference on Harmonization guideline. Formulation was exposed to the stress conditions of peroxide, acid, base, thermal, and photolytic degradation and proven all components were well separated in the presence of degradants. PMID:24019569

  8. Comparison of relative oxycodone consumption in surgical pleth index-guided analgesia versus conventional analgesia during sevoflurane anesthesia

    PubMed Central

    Won, Young Ju; Lim, Byung Gun; Lee, So Hyun; Park, Sangwoo; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon

    2016-01-01

    Abstract Background: The surgical pleth index (SPI) is proposed for titration of analgesic drugs during general anesthesia. Several reports have investigated the effect of SPI on the consumption of opioids including remifentanil, fentanyl, and sufentanil during anesthesia, but there are no reports about oxycodone. We aimed to investigate intravenous oxycodone consumption between SPI-guided analgesia and conventional analgesia practices during sevoflurane anesthesia in patients undergoing thyroidectomy. Methods: Forty-five patients undergoing elective thyroidectomy were randomly assigned to an SPI group (SPI-guided analgesia group, n = 23) or a control group (conventional analgesia group, n = 22). Anesthesia was maintained with sevoflurane to achieve bispectral index values between 40 and 60. In the SPI group, oxycodone 1 mg was administered intravenously at SPI values over 50; in the control group, oxycodone 1 mg was administered intravenously at the occurrence of tachycardia or hypertension event. Intraoperative oxycodone consumption and extubation time were recorded. The number of hemodynamic and somatic movement events was recorded, as were postoperative pain and recovery scores. Results: Patients’ characteristics were comparable between the groups. Intraoperative oxycodone consumption in the SPI group was significantly lower than the control group (3.5 ± 2.4 vs 5.1 ± 2.4 mg; P = 0.012). Extubation time was significantly shorter in the SPI group (10.6 ± 3.5 vs 13.4 ± 4.6 min; P = 0.026). Hemodynamic and somatic movement events during anesthesia were comparable between the groups, as were numeric rating scales for pain and modified Aldrete scores at postanesthesia care unit. Conclusions: SPI-guided analgesia reduces intravenous oxycodone consumption and extubation time compared with conventional analgesia based on clinical parameters during sevoflurane anesthesia in patients undergoing thyroidectomy. PMID:27583920

  9. Epidural morphine analgesia in Guillain Barré syndrome.

    PubMed Central

    Genis, D; Busquets, C; Manubens, E; Dávalos, A; Baró, J; Oterino, A

    1989-01-01

    Severe pain is a frequent symptom in the Guillain Barré syndrome and can be intense, long lasting and with no response to the usual analgesics, including parenteral opiates. Epidural analgesia using morphine chloride in low doses has satisfactorily relieved pain in this disease in nine patients. PMID:2795070

  10. Effect of epidural analgesia on the primary cesarean rate.

    PubMed

    Gribble, R K; Meier, P R

    1991-08-01

    There is some concern that providing parturients with epidural analgesia increases the likelihood of cesarean delivery. Because of the widespread interest in cesarean rates and the expanding use of epidural analgesia, we believed that this contention should be assessed. Hospital records were reviewed to determine the primary cesarean rate for 1084 parturients who delivered at our institution during 15 months in which there was a 24-hour "on demand" epidural service. This was compared with our primary cesarean rate during 15 months in which epidural analgesia was not available, even on physician request. Because of the characteristics of our institution, this control group consisted of patients from the same population base managed by the same eight obstetricians using the same management techniques. For patients in labor, the primary cesarean rate overall was 9.0% before and 8.2% after the epidural service began (P = .626). When subpopulations based on parity and indication for cesarean delivery were studied, there were no significant changes in the cesarean rate. These results demonstrate that the availability of on-demand epidural analgesia for patients in labor did not increase the primary cesarean rate, either in the aggregate or for any of the subpopulations studied. PMID:2067767

  11. Mechanisms of acupuncture analgesia for clinical and experimental pain.

    PubMed

    Staud, Roland; Price, Donald D

    2006-05-01

    There is convincing evidence that acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting, as well as postoperative dental pain. Less convincing data support AP's efficacy for chronic pain conditions, including headache, fibromyalgia and low back pain. There is no evidence that AP is effective in treating addiction, insomnia, obesity, asthma or stroke deficits. AP seems to be efficacious for alleviating experimental pain by increasing pain thresholds in human subjects and it appears to activate analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes some time to develop and to resolve. Furthermore, repetitive use of AP analgesia can result in tolerance that demonstrates cross-tolerance with morphine. However, it appears that not all forms of AP are equally effective for providing analgesia. In particular, electro-AP seems to best deliver stimuli that activate powerful opioid and nonopioid analgesic mechanisms. Thus, future carefully controlled clinical trials using adequate electro-AP may be able to provide the necessary evidence for relevant analgesia in chronic pain conditions, such as headache, fibromyalgia, irritable bowel syndrome and low back pain. PMID:16734514

  12. Multimodal analgesia for perioperative pain in three cats.

    PubMed

    Steagall, Paulo V M; Monteiro-Steagall, Beatriz P

    2013-08-01

    Adequate pain relief is usually achieved with the simultaneous use of two or more different classes of analgesics, often called multimodal analgesia. The purpose of this article is to highlight the use of perioperative multimodal analgesia and the need to individualize the treatment plan based on the presenting condition, and to adjust it based on the response to analgesia for a given patient. This case series presents the alleviation of acute pain in three cats undergoing different major surgical procedures. These cases involved the administration of different classes of analgesic drugs, including opioids, non-steroidal anti-inflammatory drugs, tramadol, ketamine, gabapentin and local anesthetics. The rationale for the administration of analgesic drugs is discussed herein. Each case presented a particular challenge owing to the different cause, severity, duration and location of pain. Pain management is a challenging, but essential, component of feline practice: multimodal analgesia may minimize stress while controlling acute perioperative pain. Individual response to therapy is a key component of pain relief in cats. PMID:23382595

  13. Analgesia and sedation for children undergoing burn wound care.

    PubMed

    Bayat, Ahmad; Ramaiah, Ramesh; Bhananker, Sanjay M

    2010-11-01

    Standard care of burn wounds consists of cleaning and debridement (removing devitalized tissue), followed by daily dressing changes. Children with burns undergo multiple, painful and anxiety-provoking procedures during wound care and rehabilitation. The goal of procedural sedation is safe and efficacious management of pain and emotional distress, requiring a careful and systematic approach. Achieving the best results needs understanding of the mechanisms of pain and the physiologic changes in burn patients, frequent evaluation and assessment of pain and anxiety, and administration of suitable pharmacological and nonpharmacological therapies. Pharmacological therapies provide the backbone of analgesia and sedation for procedural pain management. Opioids provide excellent pain control, but they must be administered judiciously due to their side effects. Sedative drugs, such as benzodiazepines and propofol, provide excellent sedation, but they must not be used as a substitute for analgesic drugs. Ketamine is increasingly used for analgesia and sedation in children as a single agent or an adjuvant. Nonpharmacological therapies such as virtual reality, relaxation, cartoon viewing, music, massage and hypnosis are necessary components of procedural sedation and analgesia for children. These can be combined with pharmacological techniques and are used to limit the use of drugs (and hence side effects), as well as to improve patient participation and satisfaction. In this article, we review the pathophysiologic changes associated with major thermal injury in children, the options available for sedation and analgesia for wound care procedures in these children and our institutional guidelines for procedural sedation. PMID:20977331

  14. Sensitivity of quantitative sensory models to morphine analgesia in humans

    PubMed Central

    Olesen, Anne Estrup; Brock, Christina; Sverrisdóttir, Eva; Larsen, Isabelle Myriam; Drewes, Asbjørn Mohr

    2014-01-01

    Introduction Opioid analgesia can be explored with quantitative sensory testing, but most investigations have used models of phasic pain, and such brief stimuli may be limited in the ability to faithfully simulate natural and clinical painful experiences. Therefore, identification of appropriate experimental pain models is critical for our understanding of opioid effects with the potential to improve treatment. Objectives The aim was to explore and compare various pain models to morphine analgesia in healthy volunteers. Methods The study was a double-blind, randomized, two-way crossover study. Thirty-nine healthy participants were included and received morphine 30 mg (2 mg/mL) as oral solution or placebo. To cover both tonic and phasic stimulations, a comprehensive multi-modal, multi-tissue pain-testing program was performed. Results Tonic experimental pain models were sensitive to morphine analgesia compared to placebo: muscle pressure (F=4.87, P=0.03), bone pressure (F=3.98, P=0.05), rectal pressure (F=4.25, P=0.04), and the cold pressor test (F=25.3, P<0.001). Compared to placebo, morphine increased tolerance to muscle stimulation by 14.07%; bone stimulation by 9.72%; rectal mechanical stimulation by 20.40%, and reduced pain reported during the cold pressor test by 9.14%. In contrast, the more phasic experimental pain models were not sensitive to morphine analgesia: skin heat, rectal electrical stimulation, or rectal heat stimulation (all P>0.05). Conclusion Pain models with deep tonic stimulation including C fiber activation and and/or endogenous pain modulation were more sensitive to morphine analgesia. To avoid false negative results in future studies, we recommend inclusion of reproducible tonic pain models in deep tissues, mimicking clinical pain to a higher degree. PMID:25525384

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

    PubMed Central

    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

  16. Evaluating Femoral-Sciatic Nerve Blocks, Epidural Analgesia, and No Use of Regional Analgesia in Dogs Undergoing Tibia-Plateau-Leveling-Osteotomy.

    PubMed

    Boscan, Pedro; Wennogle, Sara

    2016-01-01

    This is a retrospective study evaluating femoral-sciatic nerve blocks (FSBs), epidural analgesia, and non-regional analgesia (NRA) in dogs undergoing tibia-plateau-leveling-osteotomy surgery. Thirty-five records met the criteria for each of the FSB and epidural analgesia groups. Seventeen anesthesia records met the criteria for the NRA or control group. The parameters reported were: isoflurane vaporizer setting, rescue analgesia/anesthesia drugs received, heart rate, systolic blood pressure, and recovery quality (0-4, with 0 being poor and 4 being good). Rescue analgesia-anesthesia during surgery was performed with either fentanyl, ketamine, or propofol. A larger percentage of dogs in the NRA group required rescue analgesia during surgery. The FSB group had a higher recovery quality with median (95% confidence interval of four (±0.3) when compared to two (±0.8) in NRA (p < 0.01). No difference between groups was observed on any other parameter reported. As part of a multimodal analgesia approach for tibia-plateau-leveling-osteotomy surgery, the use of femoral and sciatic nerves blocks with bupivacaine appears to be an alternative technique to help with analgesia and anesthesia during surgery. PMID:26808436

  17. [A double-blind study of the analgesic efficacy in kidney colic of the combination of dipyrone and spasmolytic with ketorolac trometamol].

    PubMed

    Martín Carrasco, C; Rodríguez Vázquez, M; Palacios Garciá, R

    1993-11-01

    We conducted a double-blind study in 34 patients to compare the analgesic efficacy in acute renal colic using 2.5 g dipyrone combined with a spasmolytic agent and 30 mg ketorolac tromethamine, diluted in 100 ml saline solution and injected intravenously. Clinical criteria and the observation of red cells in urine were used for the diagnosis. The intensity of the pain and its development were measured using visual analogue scales (VAS) and a scale of items showing patient improvement. The side effects were spontaneously mentioned by the patients and elicited by direct questioning. It can be confirmed with a beta error of 0.10 that the analgesic effect obtained by both treatments is similar. Nevertheless, the combination of dipyrone and spasmolytic produces more side effects, possibly due to the spasmolytic agent. PMID:8304789

  18. pH-sensitive interpenetrating polymer network microspheres of poly(vinyl alcohol) and carboxymethyl cellulose for controlled release of the nonsteroidal anti-inflammatory drug ketorolac tromethamine.

    PubMed

    Kondolot Solak, Ebru; Er, Akın

    2016-05-01

    In this study, we aimed to produce pH-sensitive microspheres for the controlled release of the nonsteroidal anti-inflammatory drug, ketorolac tromethamine (KT). For this purpose, an interpenetrating polymer network (IPN) of microspheres of poly(vinyl alcohol) (PVA)/sodium carboxymethyl cellulose (NaCMC) were prepared, based on different formulations using glutaraldehyde (GA) (0.66 M) and hydrochloric acid (HCl) (3%, v/v). The preparation conditions of the microspheres were optimized by considering the percentage of entrapment efficiency and swelling capacity of the microspheres, and their release data. The effects of PVA and NaCMC ratio on the release of KT for over a period of 6 h, at three pH values (1.2, 6.8, and 7.4), have been discussed. PMID:25619756

  19. Intraoperative Dexmedetomidine Promotes Postoperative Analgesia in Patients After Abdominal Colectomy

    PubMed Central

    Ge, Dong-Jian; Qi, Bin; Tang, Gang; Li, Jin-Yu

    2015-01-01

    Abstract Surgery-induced acute postoperative pain may lead to prolonged convalescence. The present study was designed to investigate the effects of intraoperative dexmedetomidine on postoperative analgesia following abdominal colectomy surgeries. Eighty patients scheduled for abdominal colectomy surgery under general anesthesia were divided into 2 groups, which were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS). During surgery, patients in the PRD group had a lower bispectral index (BIS) value, which indicated a deeper anesthetic state, and a higher sedation score right after extubation than patients in the PRS group. During the first 24 hours post surgery, PRD patients consumed less morphine in patient-controlled analgesia (PCA) and had a lower score in the visual analog scale (VAS) testing than their controls from the PRS group. Intraoperative administration of dexmedetomidine appears to promote the analgesic property of morphine-based PCA in patients after abdominal colectomy. PMID:26376397

  20. Suckling- and sucrose-induced analgesia in human newborns.

    PubMed

    Blass, E M; Watt, L B

    1999-12-01

    This experiment had three goals: 1. To identify the basis of sucking-induced analgesia in healthy, term, newborn humans undergoing the painful, routine, procedure of heel lance and blood collection. 2. To evaluate how taste-induced and sucking-induced analgesias combine to combat pain. 3. To determine whether facial grimacing was an accurate index of diminished pain, or whether it was linked to tissue trauma. We report that: 1. Sucking an unflavored pacifier was analgesic when and only when suck rate exceeded 30 sucks/min. 2. The combination of sucrose and nonnutritive sucking was remarkably analgesic; we saw no behavioral indication in nine of the ten infants that the heel lance had even occurred. 3. Grimacing was reduced to almost naught by procedures that essentially eliminated crying and markedly reduced heart rate during the blood harvesting procedure. PMID:10568870

  1. Acupuncture Anesthesia and Analgesia for Clinical Acute Pain in Japan

    PubMed Central

    2008-01-01

    Acupuncture anesthesia has been practiced in China since about 1960. In Japan, Hyodo reported 30 cases of acupuncture anesthesia in 1972. However, from around 1980, the direction of acupuncture investigations turned from anesthesia to analgesia. Acupuncture analgesia is presently considered a way to activate the body's endogenous analgesic system. Recently, with the rise of acupuncture as one of the most well known CAM therapies, acupuncture or moxibustion treatment has been reported for both acute and chronic pain. Even so, few clinical reports and original articles have been reported in Japan. This review illustrates how acupuncture is being used in Japan for acute pain such as surgical operations, post- operative pain (POP), neuropathic pain, pain associated with teeth extractions and after the extraction of impacted wisdom teeth. PMID:18604250

  2. CNS Animal fMRI imaging in Pain and Analgesia

    PubMed Central

    Borsook, David; Becerra, Lino

    2010-01-01

    Animal imaging of brain systems offers exciting opportunities to better understand the neurobiology of pain and analgesia. Overall functional studies have lagged behind human studies as a result of technical issues including the use of anesthesia. Now that many of these issues have been overcome including the possibility of imaging awake animals, there are new opportunities to study whole brain systems neurobiology of acute and chronic pain as well as analgesic effects on brain systems de novo (using pharmacological MRI) or testing in animal models of pain. Understanding brain networks in these areas may provide new insights into translational science, and use neural networks as a “language of translation” between preclinical to clinical models. In this review we evaluate the role of functional and anatomical imaging in furthering our understanding in pain and analgesia. PMID:21126534

  3. Pleasure-related analgesia activates opioid-insensitive circuits.

    PubMed

    Kut, Elvan; Candia, Victor; von Overbeck, Jan; Pok, Judit; Fink, Daniel; Folkers, Gerd

    2011-03-16

    Recent findings suggest that pain and pleasure share common neurochemical circuits, and studies in animals and humans show that opioid-mediated descending pathways can inhibit or facilitate pain. We explored the role of endogenous opioid neurotransmission in pleasure-related analgesia. μ-Opioidergic activity was blocked with 0.2 mg/kg naloxone to assess its effects on hedonic responses to pleasant emotional pictures (International Affective Picture System) and its modulating effects on heat pain tolerance. Naloxone did not alter subjective and autonomous reactions to pleasure induction or overall mood of participants. In addition, pleasure-related increases in pain tolerance persisted after reversal of endogenous μ-opioidergic neurotransmission. Subjective pain intensity and unpleasantness ratings increased after naloxone administration. These findings suggest that, in addition to opioid-sensitive circuits, mainly opioid-insensitive pain-modulating circuits are activated during pleasure-related analgesia. PMID:21411655

  4. Inserting epidural patient controlled analgesia into a peripheral venous line.

    PubMed

    2016-01-01

    A case is reported from the Safety Reporting System in Anaesthesia and Resuscitation database. The event occurred in a patient undergoing abdominal surgery in whom an epidural catheter was inserted for analgesia. After the intervention, the patient was transferred to the recovery unit where the patient controlled analgesia (PCA) is programmed. Due to an error, the PCA was connected to a peripheral venous line, which was detected early without harm to the patient. Communication and analysis of this incident served to introduce a new drug delivery protocol through PCA pumps, including the obligation to prescribe the PCA in the electronic system, a dual computerised check immediately before connecting PCA, labelling the medication bag as well as the proximal and distal lines, standardisation of daily visits to patients, and monthly monitoring of results. PMID:27062173

  5. CNS animal fMRI in pain and analgesia.

    PubMed

    Borsook, David; Becerra, Lino

    2011-04-01

    Animal imaging of brain systems offers exciting opportunities to better understand the neurobiology of pain and analgesia. Overall functional studies have lagged behind human studies as a result of technical issues including the use of anesthesia. Now that many of these issues have been overcome including the possibility of imaging awake animals, there are new opportunities to study whole brain systems neurobiology of acute and chronic pain as well as analgesic effects on brain systems de novo (using pharmacological MRI) or testing in animal models of pain. Understanding brain networks in these areas may provide new insights into translational science, and use neural networks as a "language of translation" between preclinical to clinical models. In this review we evaluate the role of functional and anatomical imaging in furthering our understanding in pain and analgesia. PMID:21126534

  6. Post-operative epidural analgesia: effects on lung volumes.

    PubMed

    Wahba, W M; Don, H F; Craig, D B

    1975-07-01

    A study was undertaken to assess the role of post-operative pain in reducing Functional Residual Capacity (FRC) and Vital Capacity (VC). The efficacy of post-operative epidural analgesia in reversing these changes was measured in eight subjects after upper abdominal operations. With pain, FRC and VC were 78 per cent and 37 per cent of control respectively. Following epidural analgesia, the values were 84 per cent and 55 per cent. These figures indicate the pain component in the post-operative reduction of these two lung capacities. This partial restoration may be of value in the prevention of post-operative pulmonary complications by avoiding closure of small airways during tidal breathing and by increasing the effectiveness of deep breathing and coughing in the removal of secretions and the reversal of atelectasis. PMID:1095163

  7. Two opioid forms of stress analgesia: studies of tolerance and cross-tolerance.

    PubMed

    Terman, G W; Lewis, J W; Liebeskind, J C

    1986-03-12

    We have previously reported that stress analgesia sensitive to and insensitive to opiate antagonists can be differentially produced in rats by varying the severity or temporal pattern of inescapable footshock. In these studies, we give further evidence for the opioid and non-opioid bases of these paradigms of stress analgesia. We find that naloxone-sensitive analgesia demonstrates tolerance with repeated stress and cross-tolerance with morphine, whereas naloxone-insensitive analgesia demonstrates neither of these characteristics. Moreover, different forms of opioid, but not non-opioid, stress analgesia manifest cross-tolerance with each other. These data are discussed in terms of the similarities and differences between two forms of opioid stress analgesia. PMID:3955348

  8. Stereospecific potentiation of opiate analgesia by cocaine: predominant role of noradrenaline.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1987-01-01

    Cocaine hydrochloride (50 mg) pellets implanted subcutaneously in male Wistar rats potentiated the analgesia of morphine, levorphanol, methadone and buprenorphine as measured by the tail-withdrawal test. Potentiated opiate analgesia was abolished by naloxone and further enhanced by desipramine and phenoxybenzamine. Yohimbine, alpha-methyl p-tyrosine, haloperidol, zimelidine, methysergide, p-chlorophenylalanine produced no significant effect on potentiated opiate analgesia. Pseudo-cocaine (dextro-cocaine), which is several-fold less potent than cocaine as an inhibitor of noradrenaline and dopamine reuptake in the CNS, had no significant effect on opiate analgesia. Analgesia produced by low doses of baclofen, a GABA agonist, was also not potentiated by cocaine. This study suggests a predominant role for noradrenaline in the stereospecific potentiation of opiate analgesia by cocaine. PMID:3822492

  9. Preemptive analgesia: the prevention of neurogenous orofacial pain.

    PubMed Central

    Foreman, P. A.

    1995-01-01

    Chronic neurogenous pain is often an extremely difficult condition to manage. In the orofacial region, trauma from injury or dental procedures may lead to the development of severe neuralgic pains and major distress to the patient. Clinical and experimental evidence suggests that the use of adequate preemptive regional anesthesia, systemic analgesia, and the avoidance of repeated, painful stimuli may reduce the incidence of this problem. PMID:8934952

  10. Multimodal analgesia versus traditional opiate based analgesia after cardiac surgery, a randomized controlled trial

    PubMed Central

    2014-01-01

    Background To evaluate if an opiate sparing multimodal regimen of dexamethasone, gabapentin, ibuprofen and paracetamol had better analgesic effect, less side effects and was safe compared to a traditional morphine and paracetamol regimen after cardiac surgery. Methods Open-label, prospective randomized controlled trial. 180 patients undergoing cardiac procedures through median sternotomy, were included in the period march 2007- August 2009. 151 patients were available for analysis. Pain was assessed with the 11-numeric rating scale (11-NRS). Results Patients in the multimodal group demonstrated significantly lower average pain scores from the day of surgery throughout the third postoperative day. Extensive nausea and vomiting, was found in no patient in the multimodal group but in 13 patients in the morphine group, p < 0.001. Postoperative rise in individual creatinine levels demonstrated a non-significant rise in the multimodal group, 33.0±53.4 vs. 19.9±48.5, p = 0.133. Patients in the multimodal group suffered less major in-hospital events in crude numbers: myocardial infarction (MI) (1 vs. 2, p = 0.54), stroke (0 vs. 3, p = 0.075), dialysis (1 vs. 2, p = 0.54), and gastrointestinal (GI) bleeding (0 vs. 1, p = 0.31). 30-day mortality was 1 vs. 2, p = 0.54. Conclusions In patients undergoing cardiac surgery, a multimodal regimen offered significantly better analgesia than a traditional opiate regimen. Nausea and vomiting complaints were significantly reduced. No safety issues were observed with the multimodal regimen. Trial registration Clinicaltrials.gov identifier: NCT01966172 PMID:24650125

  11. Phorbol ester suppression of opioid analgesia in rats

    SciTech Connect

    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 marked 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.

  12. Mediation of opioid analgesia by a truncated 6-transmembrane GPCR

    PubMed Central

    Lu, Zhigang; Xu, Jin; Rossi, Grace C.; Majumdar, Susruta; Pasternak, Gavril W.; Pan, Ying-Xian

    2015-01-01

    The generation of potent opioid analgesics that lack the side effects of traditional opioids may be possible by targeting truncated splice variants of the μ-opioid receptor. μ-Opioids act through GPCRs that are generated from the Oprm1 gene, which undergoes extensive alternative splicing. The most abundant set of Oprm1 variants encode classical full-length 7 transmembrane domain (7TM) μ-opioid receptors that mediate the actions of the traditional μ-opioid drugs morphine and methadone. In contrast, 3-iodobenzoyl-6β-naltrexamide (IBNtxA) is a potent analgesic against thermal, inflammatory, and neuropathic pain that acts independently of 7TM μ-opioid receptors but has no activity in mice lacking a set of 6TM truncated μ-opioid receptor splice variants. Unlike traditional opioids, IBNtxA does not depress respiration or result in physical dependence or reward behavior, suggesting it acts through an alternative μ-opioid receptor target. Here we demonstrated that a truncated 6TM splice variant, mMOR-1G, can rescue IBNtxA analgesia in a μ-opioid receptor–deficient mouse that lacks all Oprm1 splice variants, ablating μ-opioid activity in these animals. Intrathecal administration of lentivirus containing the 6TM variant mMOR-1G restored IBNtxA, but not morphine, analgesia in Oprm1-deficient animals. Together, these results confirm that a truncated 6TM GPCR is both necessary and sufficient for IBNtxA analgesia. PMID:26011641

  13. Depressed mood, anxiety, and the use of labor analgesia.

    PubMed

    Pettersson, Fatimah Dabo; Hellgren, Charlotte; Nyberg, Fred; Åkerud, Helena; Sundström-Poromaa, Inger

    2016-02-01

    Relatively little is known about mental health and labor pain. The aim of this study was to assess if self-rated antenatal depressed mood and anxiety are associated with pain-related behaviors and self-reported labor pain. We also wanted to replicate our previous finding of altered labor pain behavior in carriers of a specific guanosine triphosphate cyclohydrolase 1 gene (GCH1) haplotype. Ninety-nine women in gestational weeks 37 to 40 filled out questionnaires on depression and anxiety symptoms and later rated their labor pain by use of visual analog scales. Each subject was also genotyped for GCH1. Following adjustment for relevant confounders, women who arrived early to the delivery unit (cervical dilation <5 cm) had a significantly higher antenatal Montgomery-Åsberg Depression Rating Scale (MADRS-S) score, p < 0.05, than late arrivers (cervical dilation >5 cm). Women with increased Spielberger State-Trait Anxiety Inventory (STAI-T) scores reported higher self-rated pain prior to labor analgesia, p < 0.05, than women with low STAI-T scores. No association between the GCH1 pain-protective haplotype and cervical dilation was found, but a previously demonstrated association with increased use of second-line analgesia was confirmed. Depressed mood during pregnancy is associated with early arrival to the delivery department, whereas antenatal anxiety is associated with increased self-rated pain prior to labor analgesia. PMID:26392364

  14. 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

  15. [Questionnaires on patient-controlled analgesia to the nursing staff in the surgical ward].

    PubMed

    Inoue, S; Satoh, M; Suzuki, H; Shimohata, K; Fukuda, H; Seo, N

    2001-10-01

    Thirty-one nurses in the surgical ward engaged in delivering postoperative analgesia using patient-controlled analgesia (PCA) were asked to complete questionnaires on postoperative analgesia and PCA. Ninety-seven per cent of respondents agreed that the postoperative analgesia is beneficial for postoperative recovery, and answered that the desirable goal in postoperative analgesia is "no pain at rest". Not only "pain at movement" or "pain on coughing", but also "decreased conscious level while analgesia is achieved" were selected as undesirable conditions during postoperative course. Although no one had learned the concept of PCA in their nursing schools, 94 per cent of respondents approved PCA as a method for postoperative analgesia. Seventy seven per cent responded that PCA is effective in the pain relief during position change, pulmonary physiotherapy and induced early ambulation. In addition, 65 per cent of respondents chose PCA as a method for postoperative analgesia when they receive thoraco-abdominal surgery. On the other hand, some problems on pain management using PCA, such as taking care of patients' ambulation with carrying a PCA pump, extra time for instruction of PCA and extra support for patients' psychological state were listed. In conclusion, these results suggest that PCA is accepted as an excellent method for postoperative analgesia among our nurses in the surgical ward, and education in postoperative pain management including PCA is required in nursing school as well as after graduation. PMID:11712354

  16. 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...

  17. 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... (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...

  18. 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...

  19. 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... (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...

  20. 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...

  1. 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. PMID:26376025

  2. Gender specificity of sucrose induced analgesia in human adults.

    PubMed

    Bhattacharjee, Manasi; Bhatia, Renu; Mathur, Rashmi

    2007-01-01

    Sweet, palatable substances such as sucrose are reported to calm infants undergoing routine investigative procedures. The analgesic effect persists in pre pubertal children and adults with a hint of gender dependent variation in the analgesic response. The present study was therefore designed to explore gender specificity of sucrose induced analgesia in adult volunteers utilizing the nociceptive flexion reflex, an objective tool for pain assessment. Nociceptive flexion reflex was recorded, both before and after (up to 15 min) ingestion of 100 ml of 25% sucrose solution in 6 male and 6 female volunteers. In the male volunteers the maximum amplitude of the response was 20.8 +/- 7.7 microV before sucrose ingestion and 22.6 +/- 9.1 microV, 6.6 +/- 0.7 microV, 6.2 +/- 1.1 microV, 7.5 +/- 0.9 microV at 0, 5, 10 and 15 minutes post sucrose ingestion respectively. In female volunteers, the maximum amplitude of the response was 33.7 +/- 17.7 microV before sucrose ingestion and 43.6 +/- 17.2 microV, 7.1 +/- 1.2 microV, 25.9 +/- 16.1 microV, 50.6 +/- 16.3 microV at the same time intervals post sucrose ingestion. The maximum amplitude values were significantly lower in the males at 10 and 15 minutes after sucrose ingestion (P < 0.05). This is the first objective report of gender specificity in sucrose induced analgesia in adult humans. The gender dependent variation in sucrose induced analgesia is prolonged in male (15 min) and short lived in female (5 min) volunteers. This knowledge may have important implications in pain management. PMID:18476396

  3. The elusive rat model of conditioned placebo analgesia.

    PubMed

    McNabb, Christopher T; White, Michelle M; Harris, Amber L; Fuchs, Perry N

    2014-10-01

    Recent research on human placebo analgesia has suggested the need for rodent models to further elucidate the neural substrates of the placebo effect. This series of 3 experiments therefore was performed in an attempt to develop a model of placebo analgesia in rats. In each study, female Sprague-Dawley rats received an L5 spinal nerve ligation to induce a neuropathic pain condition. Each rat then underwent a 4-day conditioning procedure in which an active analgesic drug or its vehicle (unconditioned stimulus) was associated with the following cues (conditioned stimuli): novel testing room (environmental), vanilla scent cue (olfactory), dim incandescent lighting (visual), restraint procedure/injection (tactile), and time of day and injection-test latency (temporal). The analgesics for each experiment were as follows: Experiment 1 used 90 mg/kg gabapentin, experiment 2 used 3mg/kg loperamide hydrochloride, and experiment 3 used 6 mg/kg morphine sulfate. On the following test day, half of the animals received the opposite treatment, resulting in 4 conditioning manipulations: drug/drug, drug/vehicle, vehicle/drug, and vehicle/vehicle. Nociceptive thresholds were assessed with the mechanical paw withdrawal threshold test each day after the conditioning procedure. In all 3 experiments, no significant differences were detected on test day between control and placebo groups, indicating a lack of a conditioned placebo analgesic response. Our results contrast with prior research that implies the existence of a reliable and robust response to placebo treatment. We conclude that placebo analgesia in rats is not particularly robust and that it is difficult to achieve using conventional procedures and proper experimental design. PMID:25026214

  4. Doubtful effect of continuous intraarticular analgesia after total knee arthroplasty

    PubMed Central

    Ali, Abdulemir; Sundberg, Martin; Hansson, Ulrik; Malmvik, Johan; Flivik, Gunnar

    2015-01-01

    Background and purpose Local infiltration analgesia (LIA) is well established for effective postoperative pain relief in total knee arthroplasty (TKA). To prolong the effect of LIA, infusion pumps with local intraarticular analgesia can be used. We evaluated the effect of such an infusion pump for the first 48 h postoperatively regarding pain, knee function, length of stay (LOS) in hospital, and complications. Patients and methods 200 patients received peroperative LIA and a continuous intraarticular elastomeric infusion pump set at 2 mL/h. The patients were randomized either to ropivacaine (7.5 mg/mL) or to NaCl (9 mg/mL) in the pump. Visual analog scale (VAS) pain (0–100 mm), analgesic consumption, side effects of medicine, range of motion (ROM), leg-raising ability, LOS, and complications during the first 3 months were recorded. Results On the first postoperative day, the ropivacaine group had lower VAS pain (33 vs. 40 at 12 noon and 36 vs. 43 at 8 p.m.; p = 0.02 and 0.03, respectively), but after that all recorded variables were similar between the groups. During the first 3 months, the ropivacaine group had a greater number of superficial and deep surgical wound infections (11 patients vs. 2 patients, p = 0.02). There were no other statistically significant differences between the groups. Interpretation Continuous intraarticular analgesia (CIAA) with ropivacaine after TKA has no relevant clinical effect on VAS pain and does not affect LOS, analgesic consumption, ROM, or leg-raising ability. There may, however, be a higher risk of wound-healing complications including deep infections. PMID:25428755

  5. Effect of magnesium infusion on thoracic epidural analgesia

    PubMed Central

    Gupta, Sampa Dutta; Mitra, Koel; Mukherjee, Maitreyee; Roy, Suddhadeb; Sarkar, Aniruddha; Kundu, Sudeshna; Goswami, Anupam; Sarkar, Uday Narayan; Sanki, Prakash; Mitra, Ritabrata

    2011-01-01

    Introduction: Patients of lung volume reduction surgery (LVRS) having an ASA status III or more are likely to be further downgraded by surgery to critical levels of pulmonary function. Aim: To compare the efficacy of thoracic epidural block with (0.125%) bupivacaine, fentanyl combination and (0.125%) bupivacaine, fentanyl combination with adjunctive intravenous magnesium infusion for the relief of postoperative pain in patients undergoing LVRS. Methods: Patients were operated under general anesthesia. Thirty minutes before the anticipated completion of skin closure in both groups, (Group A and Group B) 7 ml of (0.125%) bupivacaine calculated as 1.5 ml/thoracic segment space for achieving analgesia in dermatomes of T4, T5, T6, T7, and T8 segments, along with fentanyl 50 μg (0.5 ml), was administered through the catheter, activating the epidural block, and the time was noted. Thereafter, in patients of Group A, magnesium sulfate injection 30 mg/kg i.v. bolus was followed by infusion of magnesium sulfate at 10 mg/kg/hr and continued up to 24 hours. Group B was treated as control. Results and Analysis: A significant increase in the mean and maximum duration of analgesia in Group A in comparison with Group B (P<0.05) was observed. Total epidural dose of fentanyl and bupivacaine required in Group A was significantly lower in comparison with Group B in 24 hours. Discussion: Requirement of total doses of local anesthetics along with opioids could be minimized by magnesium infusion; therefore, the further downgradation of patients of LVRS may be prevented. Conclusion: Intravenous magnesium can prolong opioid-induced analgesia while minimizing nausea, pruritus, and somnolence. PMID:21655018

  6. Butorphanol in labour analgesia: A prospective cohort study

    PubMed Central

    Halder, Ajay; Agarwal, Rachana

    2013-01-01

    Objective Parenteral opioids can be administered with ease at a very low cost with high efficacy as labour analgesia. However, there are insufficient data available to accept the benefits of parenteral opioids over other proven methods of labour analgesia. Butorphanol, a new synthetic opioid, has emerged as a promising agent in terms of efficacy and a better safety profile. This study investigates the effect of butorphanol as a labour analgesia to gather further evidence of its safety and efficacy to pave the way for its widespread use in low resource settings. Material and Methods One hundred low risk term consenting pregnant women were recruited to take part in a prospective cohort study. Intramuscular injections of butorphanol tartrate 1 mg (Butrum 1/2mg, Aristo, Mumbai, India) were given in the active phase of labour and repeated two hourly. Pain relief was noted on a 10-point visual pain analogue scale (VPAS). Obstetric and neonatal outcome measures were mode of delivery, duration of labour, Apgar scores at 1 and 5 minutes and Neonatal Intensive Care Unit admissions. Collected data were analysed for statistically significant pain relief between pre- and post-administration VPAS scores and also for the incidence of adverse outcomes. Results Pain started to decrease significantly within 15 minutes of administration and reached the nadir (3.08 SD0.51) at the end of two hours. The pain remained below four on the VPAS until the end of six hours and was still significantly low after eight hours. The incidence of adverse outcomes was low in the present study. Conclusion Butorphanol is an effective parenteral opioid analgesic which can be administered with reasonable safety for the mother and the neonate. The study has the drawback of lack of control and small sample size. PMID:24592110

  7. Postpartum septic sacroiliitis coincident with labour epidural analgesia.

    PubMed

    Mulvey, J M

    2008-11-01

    A 22-year-old woman presented to hospital 10 days after emergency caesarean section with severe back pain, fever tachycardia and a raised C-reactive protein. She had received labour epidural analgesia and was investigated for an epidural abscess. After repeat magnetic resonance imaging she was ultimately diagnosed with septic sacroiliitis. Although an uncommon cause of back pain, pregnancy-associated sacroiliitis should be considered in the differential diagnosis of post-epidural back pain, as the presentation and symptoms of an epidural infection and sacroiliitis are similar. We recommend imaging to include the sacroiliac joints when considering the diagnosis of an epidural collection. PMID:19115661

  8. Imaging-guided hyperstimulation analgesia in low back pain.

    PubMed

    Gorenberg, Miguel; Schwartz, Kobi

    2013-01-01

    Low back pain in patients with myofascial pain syndrome is characterized by painful active myofascial trigger points (ATPs) in muscles. This article reviews a novel, noninvasive modality that combines simultaneous imaging and treatment, thus taking advantage of the electrodermal information available from imaged ATPs to deliver localized neurostimulation, to stimulate peripheral nerve endings (Aδ fibers) and in turn, to release endogenous endorphins. "Hyperstimulation analgesia" with localized, intense, low-rate electrical pulses applied to painful ATPs was found to be effective in 95% patients with chronic nonspecific low back pain, in a clinical validation study. PMID:23847430

  9. Regional anaesthesia and analgesia on the front line.

    PubMed

    Scott, D M

    2009-11-01

    Deployment to a combat zone with the military poses many challenges to the anaesthetist. One of these challenges is the safe, rapid and comfortable initial wound management and repatriation of wounded combat soldiers to their home country or tertiary treatment facility for definitive care and rehabilitation. The current conflict in Afghanistan is associated with injury patterns that differ from wars such as Vietnam or Korea. This report describes the experience of an Australian military anaesthetist and the value of regional anaesthesia and analgesia for the care of the wounded combat soldier PMID:20014611

  10. 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.

  11. Local infiltration analgesia in hip and knee arthroplasty: an emerging technique.

    PubMed

    Dillon, John P; Brennan, Louise; Mitchell, David

    2012-04-01

    The optimal form of post-operative analgesia in hip and knee arthroplasty is still debated. Traditionally, patient-controlled analgesia and epidural anaesthesia were used. Potential side-effects such as nausea, confusion, urinary retention, hypotension and immobility have resulted in the emergence of newer techniques that limit opioid use. Peripheral nerve blockade provides excellent analgesia but limits patient ability to ambulate in the immediate post-operative period. Local infiltrative analgesia (LIA) is an emerging technique that has shown to provide superior analgesia, higher patient satisfaction and earlier discharge from hospital when compared to some of the more traditional methods. This review article highlights the advantages of LIA in hip and knee arthroplasty surgery. We describe the technique used, including additional measures that aid early ambulation and discharge from hospital in this cohort of patients. PMID:22696983

  12. Fentanyl versus tramadol with levobupivacaine for combined spinal-epidural analgesia in labor

    PubMed Central

    Chatrath, Veena; Khetarpal, Ranjana; Sharma, Sujata; Kumari, Pratibha; Sudha; Bali, Kusum

    2015-01-01

    Background: Neuraxial labor analgesia using new local anesthetics such as levobupivacaine has become very popular by virtue of the safety and lesser motor blockade caused by these agents. Combined spinal-epidural analgesia (CSEA) has become the preferred method for labor analgesia as it combines benefits of both spinal analgesia and flexibility of the epidural catheter. Adding opioids to local anesthetic drugs provide rapid onset and prolonged analgesia but may be associated with several maternal and fetal adverse effects. The purpose of this study is to compare fentanyl and tramadol used in CSEA in terms of duration of analgesia and frequency of the adverse fetomaternal outcome. Materials and Methods: A total of 60 primiparas with a singleton pregnancy in active labor were given CSEA after randomly allocating them in two groups of 30 each. Group I received intrathecal 2.5 mg levobupivacaine + 25 μg fentanyl followed by epidural top ups of 20 ml 0.125% solution of the same combination. Group II received 25 mg tramadol instead of fentanyl. Epidural top ups were given when parturient complained of two painful contractions (visual analogue scale ≥ 4). Data collected were demographic profile of the patients, analgesic qualities, side- effects and the fetomaternal outcome. Results: Patients in Group II had significantly prolonged analgesia (145 ± 9 minutes) than in Group I (95 ± 7 minutes). Patients receiving fentanyl showed rapid onset of analgesia, but there were more incidence of side-effects like shivering, pruritus, transient fetal bradycardia, hypotension, nausea and vomiting. Only side-effect in the tramadol group was nausea and vomiting. During labor, maternal satisfaction was excellent. Conclusions: Adding tramadol to local anesthetic provides prolonged analgesia with minimal side effects. Fentanyl, when used as adjuvant to local anesthetic, has a rapid onset of analgesia but has certain fetomaternal side-effects. PMID:26240543

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

    SciTech Connect

    Kooij, Sanne M. van der Moolenaar, Lobke M.; Ankum, Willem M.; Reekers, Jim A.; Mol, Ben Willem J.; Hehenkamp, Wouter J. K.

    2013-12-15

    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 analogue 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.

  14. [Fentanyl in peridural obstetrical analgesia. Evaluation after 4 years' use].

    PubMed

    Lévêque, C; Garen, C; Pathier, D; Mazuir, E; Maneglia, R; Janse-Marec, J; Cousin, M T

    1987-01-01

    7,500 deliveries occurred from the date of opening of the Maternity Hospital Jean-Rostand. 3,500 of these were conducted under epidural anaesthesia. At different stages prospective studies were carried out to recall the effect of adding fentanyl to bupivacaine when the epidural injection was made. A pharmacokinetic study. This shows that the levels in the mother and the fetus begin to coincide more with the number of doses that are given and pass from 0.3 after 50 micrograms have been administered to 0.5 after 100 micrograms have been administered and 0.7 after 150 micrograms have been administered. The fetal levels are far lower than those required to depress respiration. The half life of distribution through the circulation has been worked out at 4 minutes and the half for elimination of the drug at 460 minutes. The maternal levels show great fluctuations and late alterations. Analgesia is earlier, more complete and more prolonged when fentanyl is added. Fentanyl also masks irregularities. Undesirable effects such as tiredness, pruritus, nausea, vomiting and urinary retention occur infrequently and last only for short periods of time. No mother had respiratory depression. The doses of bupivacaine that had to be given were as a whole less when fentanyl was added. In 40% of cases it only required one injection to achieve analgesia throughout the whole labour. The length of labour and the number of caesarean operations carried out did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3584862

  15. [Perioperative analgesia with continuous peripheral nerve blocks in children].

    PubMed

    Dadure, C; Capdevila, X

    2007-02-01

    Recently, regional anaesthesia in children has generated increasing interest. But single injection techniques have a limited duration of postoperative analgesia. Then, continuous peripheral nerve blocks have taken an important position in the anaesthetic arsenal, allowing an effective, safe and prolonged postoperative pain management. As adults, indications for continuous peripheral nerve blocks depend on the analysis of individual benefits/risks ratio. Main indications are intense postoperative pain surgical procedures, with or without postoperative rehabilitation, and complex regional pain syndrome. Contraindications to these procedures are rather similar to those in adults, plus parental and/or children refusal. Continuous peripheral nerve blocks are usually performed under general anaesthesia or sedation in children, and require appropriate equipment in order to decrease the risk of nerve injury. New techniques, such as transcutaneous nerve stimulation or ultrasound guidance, appeared to facilitate nerve and plexus approach identification in paediatric patients. Nevertheless, continuous peripheral nerve block may theoretically mask a compartment syndrome after trauma surgical procedures. Finally, ropivacaine appears to be the most appropriate drug for continuous peripheral nerve blocks in children, requiring low flow rates and concentrations of local anaesthetic. These techniques may facilitate early ambulation by an improved pain management or even postoperative analgesia at home with disposable pumps. One might infer from the current review that excellent pain relief coupled with a reduction of side effects would contribute to improve the quality of life and to decrease the frequency of disabling behavioural modifications in children, sometimes psychologically injured by hospital stay and postoperative pain. PMID:17174518

  16. Preemptive Analgesia Does Not Reduce Pain or Improve Postoperative Functioning

    PubMed Central

    Grube, Jennifer O.; Damme-Sorenen, Jesse

    2004-01-01

    Objectives: To examine the effectiveness of preemptive analgesia in gynecologic laparoscopy patients. Methods: A double-blinded, randomized trial was performed from June 2000 to June 2001. Preoperatively, patients were randomly assigned to 0.25% bupivicaine or normal saline control. Following anesthetic induction, the study drug or a placebo was injected prior to the proposed incisions. Results: Of the 164 patients enrolled, 85 were randomized to the study group and 79 to the control. Age, surgery indication, and estimated blood loss did not vary significantly between groups. Overall mean pain score (± standard error of the mean) for study and control groups did not differ at 4 hours (3.2±0.3 vs 3.2±0.3) or at 24 hours (4.2±0.3 vs 4.2±0.3). Incisional pain scores also did not differ at 4 hours (3.0±0.3 vs 2.7±0.3) or at 24 hours (3.6±0.3 vs 3.6±0.3). Both groups were similar in activity limitation at 24 hours and oral narcotic consumption within 24 hours postoperatively. After stratifying surgery type for level of complexity, no difference was noted between groups. Multiple logistic regression analysis also noted no difference in outcomes. Conclusion: Preemptive analgesia in patients undergoing gynecologic laparoscopy does not reduce postoperative pain or decrease the time to return of normal activities. PMID:14974656

  17. Cytochrome P450 epoxygenase dependence of opioid analgesia: fluconazole does not interfere with remifentanil-mediated analgesia in human subjects.

    PubMed

    Oertel, B G; Vermehren, J; Huynh, T T; Doehring, A; Ferreiros, N; Zimmermann, M; Geisslinger, G; Lötsch, J

    2014-12-01

    Cytochrome P450 (CYP) inhibitors may reduce opioid analgesia by inhibiting CYP activity-dependent post-opioid receptor signaling pathways in the brain. This suggestion was predicated on observations of highly attenuated morphine antinociception in rodents after intracerebroventricular injection of fluconazole or carrying a neuron-specific deletion of the cytochrome P450 reductase. However, based on assessments of thermal and electrical pain tolerance, respiratory function, and side effects in 21 healthy volunteers, before and during steady-state concentrations of 1.5 and 3.0 ng/ml of remifentanil at the effect site (viz., the central nervous system), administration of 400 mg/day fluconazole for 8 days in a double-blind, placebo-controlled manner failed to attenuate opioid effects. Although CYP inhibitors such as fluconazole are unlikely to attenuate remifentanil analgesia in humans, extrapolation of the findings to other opioids is premature because differences among opioid effects, such as ligand-selective biased signaling at opioid receptors, leave the possibility that CYP-dependent opioid signaling in the brain might be limited to morphine and may not extend to remifentanil. PMID:25148377

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

    SciTech Connect

    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 was 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.

  19. Placebo conditioning and placebo analgesia modulate a common brain network during pain anticipation and perception

    PubMed Central

    Watson, Alison; El-Deredy, Wael; Iannetti, Gian Domenico; Lloyd, Donna; Tracey, Irene; Vogt, Brent A.; Nadeau, Valerie; Jones, Anthony K.P.

    2009-01-01

    The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. In the control session participants were explicitly told that the treatment was inactive. The sham treatment group reported a significant reduction in pain rating (p = 0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia. PMID:19523766

  20. Clonidine as an adjuvant for propranolol enhances its effect on infiltrative cutaneous analgesia in rats.

    PubMed

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

    2016-03-11

    Clonidine prolongs duration of analgesia when used as an adjunct to local anesthetics for infiltrative cutaneous analgesia, and propranolol produces local anesthesia. The purpose of the experiment was to evaluate clonidine as an adjuvant for propranolol on the quality and duration of cutaneous analgesia. A rat model of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick was employed to evaluate the cutaneous analgesic effect of propranolol combined with clonidine. The long-lasting local anesthetic bupivacaine was used as control. Cutaneous analgesia elicited by propranolol and bupivacaine was dose-dependent, and both propranolol (9.0μmol) and bupivacaine (1.8μmol) produced 100% nociceptive blockade. On an 50% effective dose (ED50) basis, the relative potency was bupivacaine [0.48 (0.42-0.55) μmol] greater than propranolol [2.27 (1.98-2.54) μmol] (p<0.01). Subcutaneous saline and clonidine (0.12μmol) did not produce cutaneous analgesia. The mixture of an ineffective-dose clonidine (0.12μmol) and a drug (propranolol or bupivacaine) at ED50 or ED95 increased the potency and extended the duration at producing cutaneous analgesia. The resulting data demonstrated that propranolol is less potent than bupivacaine as an infiltrative anesthetic. Clonidine as an adjuvant for propranolol or bupivacaine has a significant peripheral action in increasing the depth and duration of action on infiltrative cutaneous analgesia. PMID:26828301

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

    PubMed Central

    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. PMID:27335882

  2. Dexmedetomidine in Postoperative Analgesia in Patients Undergoing Hysterectomy

    PubMed Central

    Ren, Chunguang; Chi, Meiying; Zhang, Yanwei; Zhang, Zongwang; Qi, Feng; Liu, Zhong

    2015-01-01

    Abstract Both dexmedetomidine and sufentanil modulate spinal analgesia by different mechanisms, and yet no human studies are available on their combination for analgesia during the first 72 hours after abdominal hysterectomy. This CONSORT-prospective, randomized, double-blinded, controlled trial sought to evaluate the safety and efficacy of the combination of dexmedetomidine and sufentanil in intravenous patient-controlled analgesia (PCA) for 72 hours after abdominal hysterectomy. Ninety women undergoing total abdominal hysterectomy were divided into 3 equal groups that received sufentanil (Group C; 0.02 μg/kg/h), sufentanil plus dexmedetomidine (Group D1; 0.02 μg/kg/h, each), or sufentanil (0.02 μg/kg/h) plus dexmedetomidine (0.05 μg/kg/h) (Group D2) for 72 hours after surgery in this double-blinded, randomized study. The primary outcome measure was the postoperative sufentanil consumption, whereas the secondary outcome measures were pain intensity (visual analogue scale), requirement of narcotic drugs during the operation, level of sedation, Bruggrmann comfort scale, and concerning adverse effects. The postoperative sufentanil consumption was significantly lower in Groups D1 and D2 than in Group C during the observation period (P < 0.05), but lower in Group D2 than in Group D1 at 24, 48, and 72 hours after surgery (P < 0.05). The heart rate after intubation and incision was lower in Groups D1 and D2 than in Group C (P < 0.05). On arrival at the recovery room, Groups D1 and D2 had lower mean blood pressure than Group C (P < 0.05). The intraoperative requirement of sevoflurane was 30% lesser in Groups D1 and D2 than in Group C. The sedation levels were greater in Groups D1 and D2 during the first hour (P < 0.05). Compared with Groups C and D1, Group D2 showed lower levels of the overall incidence of nausea and vomiting (P < 0.05). Among the tested PCA options, the addition of dexmedetomidine (0.05 μg/kg/h) and sufentanil (0

  3. Postoperative analgesia after paediatric orchidopexy: evaluation of a bupivacaine-morphine mixture.

    PubMed

    Wolf, A R; Hughes, D; Wade, A; Mather, S J; Prys-Roberts, C

    1990-04-01

    The value of combining morphine with bupivacaine for caudal analgesia was investigated. Thirty children, undergoing orchidopexy, received a caudal block of 0.125% bupivacaine with or without morphine 0.05 mg kg-1. Analgesia, side-effects, ventilatory frequency and oxygen saturation (SaO2) were recorded after operation. None of the 15 patients receiving the bupivacaine-morphine mixture required post-operative opioids, whereas eight of 15 patients receiving bupivacaine alone needed additional opioid analgesia. The incidence of side effects after surgery was similar for the two groups and there was no detectable difference in ventilatory frequency or SaO2. PMID:1970738

  4. [Dexmedetomidine use for postoperative adrenergic analgesia and sedation in abdominal surgery].

    PubMed

    Gur'ianov, V A; Nosenko, M M; Gadzhibekov, N Ch; Ialich, A Iu; Aliautdin, R N; Tolmachev, G N

    2013-01-01

    Comparative study of postoperative analgesia and sedation with trimeperidine and dexmedetomidine and their effects on haemodynamics and vegetative nervous system was performed. Assessment of analgesia and sedation during vagotonia (first part of the study) and hypokinetic type of haemodynamics (second part of the study) was carried out with visual analogue scale (VAS) and Richmond scale. Results of the study showed that dexmedetomidine is more effective and safer than trimeperidine for analgesia and sedation in patients with spontaneous breathing after abdominal surgery. Dexmedetomidine use allows keeping optimal type of haemodynamics and vegetative nervous system parameters on first day of postoperative period. PMID:24749259

  5. Opioid and non-opioid mechanisms of stress analgesia: lack of cross-tolerance between stressors.

    PubMed

    Terman, G W; Lewis, J W; Liebeskind, J C

    1983-01-31

    Qualitatively different analgesic responses can be evoked in rats by exposure to prolonged, intermittent or brief, continuous footshock stress. These two forms of stress analgesia appear to be mediated by opioid and nonopioid pain-inhibitory substrates, respectively. The present study confirms our previous observation that tolerance develops to only the opioid form of stress analgesia and shows that cross-tolerance does not occur between the opioid and nonopioid forms. These data provide further evidence that independent mechanisms underlie opioid and nonopioid stress analgesia. PMID:6297681

  6. Glia: novel counter-regulators of opioid analgesia.

    PubMed

    Watkins, Linda R; Hutchinson, Mark R; Johnston, Ian N; Maier, Steven F

    2005-12-01

    Development of analgesic tolerance and withdrawal-induced pain enhancement present serious difficulties for the use of opioids for pain control. Although neuronal mechanisms to account for these phenomena have been sought for many decades, their bases remain unresolved. Within the past four years, a novel non-neuronal candidate has been uncovered that opposes acute opioid analgesia and contributes to development of opioid tolerance and tolerance-associated pain enhancement. This novel candidate is spinal cord glia. Glia are important contributors to the creation of enhanced pain states via the release of neuroexcitatory substances. New data suggest that glia also release neuroexcitatory substances in response to morphine, thereby opposing its effects. Controlling glial activation could therefore increase the clinical utility of analgesic drugs. PMID:16246435

  7. The role of epidural anesthesia and analgesia in postoperative outcome.

    PubMed

    Grass, J A

    2000-06-01

    There is increasing evidence to support the hypothesis that epidural anesthesia and analgesia (EAA) can improve surgical outcome by reducing postoperative morbidity and hastening recovery. Likely benefits include decreased incidence of cardiac complications in high-risk patients; lower incidence of pulmonary complications, specifically pneumonia, atelectasis, and hypoxemia in patients at risk for pulmonary complications; lower incidence of vascular graft occlusion after lower extremity revascularization; lower incidence of DVT and pulmonary embolus; suppression of the neuroendocrine stress response; and earlier return of gastrointestinal function. Nonetheless, large multicenter prospective randomized studies are required to more definitively assess the impact of EAA on morbidity and mortality, ICU time, length of hospitalization, and cost of healthcare. PMID:10935017

  8. [Obstetric anaesthesia and analgesia--new aspects from the literature].

    PubMed

    Wulf, Hinnerk

    2011-07-01

    This review summarises the current (and controversial) topics in the field of anaesthesia and analgesia in obstetrics. In the British report "Saving mothers' lives 2006-2008" it is shown that the direct causes of maternal deaths are as before mainly sepsis, preeclampsia and eclampsia, thrombosis, thromboembolisms, and amniotic fluid embolism as well as haemorrhagic complications. Deaths associated with anaesthesia still involve airway complications. In the "closed claims" in U.S. American statistics, in the meantime ones finds maternal and perinatal deaths and brain damage to be less frequent whereas liability claims due to nerve damage and back pain have increased, presumably as a result of the change away from the use of general anaesthesia to the use of regional anaesthesia in obstetrics. PMID:21815121

  9. Intravenous sub-anesthetic ketamine for perioperative analgesia

    PubMed Central

    Gorlin, Andrew W; Rosenfeld, David M; Ramakrishna, Harish

    2016-01-01

    Ketamine, an N-methyl-d-aspartate antagonist, blunts central pain sensitization at sub-anesthetic doses (0.3 mg/kg or less) and has been studied extensively as an adjunct for perioperative analgesia. At sub-anesthetic doses, ketamine has a minimal physiologic impact though it is associated with a low incidence of mild psychomimetic symptoms as well as nystagmus and double vision. Contraindications to its use do exist and due to ketamine's metabolism, caution should be exercised in patients with renal or hepatic dysfunction. Sub-anesthetic ketamine improves pain scores and reduces perioperative opioid consumption in a broad range of surgical procedures. In addition, there is evidence that ketamine may be useful in patients with opioid tolerance and for preventing chronic postsurgical pain. PMID:27275042

  10. Continuous Local Infiltration Analgesia after TKA: A Meta-Analysis.

    PubMed

    Keijsers, Renee; van den Bekerom, Michel; van Delft, Rogier; van Lotten, Manon; Rademakers, Maarten; Nolte, Peter A

    2016-05-01

    The analgesic effect of local infiltration analgesia (LIA) after total knee arthroplasty (TKA) has been reported to be less than 24 hours. The concept of continuous LIA (CLIA) has been developed to achieve prolonged analgesia by bolus injections or by pump infusion of analgesics. The purpose of this meta-analysis is to assess the effect of CLIA versus single-shot injection LIA (SLIA) and placebo on pain after TKA.A systematic search was performed in most relevant databases to identify all randomized controlled trials (RCTs) comparing intra-articular CLIA with SLIA or placebo for TKA. Primary outcome measures were visual analogue scale (VAS)-scores after 24, 48, and 72 hours at rest and during activity. Data were extracted for meta-analysis and pooled using Cochrane software. The results of comparable studies were pooled using the fixed effects model or random effects model.A total of 11 RCTs were included. Five articles were eligible for meta-analysis comparing CLIA versus placebo, involving 227 TKAs. VAS scores at rest 24 hours after surgery were in favor of CLIA with a decrease of pain scores of 46%. On the second and third postoperative day, the decrease in VAS scores was no longer significant. During activity VAS scores were also in favor of CLIA after 24 and 48 hours.Two studies were eligible for meta-analysis comparing CLIA versus SLIA. VAS scores at rest, 48 hours after surgery, were in favor of CLIA. CLIA can possibly provide a reduced pain perception for 24 hours postoperative at rest after performing a TKA. This effect may persist until 48 hours postoperative during activity. Due to the high level of heterogeneity no firm further conclusions can be drawn. PMID:26190787

  11. Diclofenac or paracetamol for analgesia in paediatric myringotomy outpatients.

    PubMed

    Tay, C L M; Tan, S

    2002-02-01

    This prospective, randomized, double-blind study compared the analgesic efficacy of oral diclofenac resinate 0.5 mg.kg(-1) with paracetamol 15 mg/kg(-1) for control of postoperative pain in paediatric patients for outpatient bilateral myringotomy and tube insertion. Paracetamol, the most commonly used oral analgesic for paediatric patients, was compared with a new palatable syrup formulation of diclofenac. Sixty-three ASA 1 orA SA 2 children aged one year and above were randomly assigned to receive diclofenac (Group A) or paracetamol (Group B). The study drug was given 30 to 60 minutes before induction of anaesthesia. Anaesthesia was induced with either inhalational sevoflurane or intravenous thiopentone. All subjects received intravenous fentanyl 1 microg/kg(-1) intraoperatively. Postoperative pain was assessed by a blinded observer using the CHEOPS score on eye-opening, and then at 10, 30 and 60 minutes. Children with a CHEOPS score > 7 received further fentanyl 1 microg x kg(-1). The number of cases requiring this "rescue" analgesia was recorded. Both groups were comparable in demographics, induction technique, duration of anaesthesia and time between premedication and induction of anaesthesia. Overall, CHEOPS scores were low for both groups at all times and did not differ between the groups at any time. Twenty per cent of the diclofenac group and 27% of the paracetamol group required rescue analgesia (not statistically significant). The efficacy of diclofenac 0.5 mg x kg(-1) and paracetamol 15 mg x kg(-1) as oral analgesic premedication for BMT was comparable in children receiving an anaesthetic which included intraoperative administration of fentanyl 1 microg x kg(-1). PMID:11939442

  12. [Treatment of postoperative pain by balanced spinal analgesia].

    PubMed

    Polati, E; Finco, G; Bartoloni, A; Rigo, V; Gottin, L; Pinaroli, A M; Barzoi, G

    1995-01-01

    Postoperative pain relief has the aim to provide patient subjective comfort, to inhibit neuroendocrine and metabolic responses to surgical injury and to enhance restoration of function by allowing the patient to breathe, cough, move more easily and to begin enteral nutrition. Opioid analgesics, independently from the route of administration, are unable to provide all this. In addition to spinal opioids other drugs, such as local anesthetics, alpha 2-agonists and cholinergic drugs, may produce an antinociceptive effect when administered by spinal route. All these drugs may be administered in combination between them, realising the so called "balanced spinal analgesia". The aim of this study is to analyse the available methods for the evaluation of pharmacological interactions, the types of interaction among different spinal antinociceptive drugs and the role of balanced spinal analgesia in the treatment of postoperative pain. Analysis of the presented data shows that the spinal synergism between opioids-local anesthetics and opioids-alpha 2-agonists can be useful in the treatment of postoperative pain, because these drug combinations are able to provide a satisfactory pain control at low doses with a reduction of the adverse effects. Furthermore, the combined use of opioids-local anesthetics proved to be effective also in abolishing postoperative incident pain and in inhibiting neuroendocrine and metabolic responses to surgical injury. Especially in high risk patients this is related to a better outcome. Finally, even if the synergism between cholinergic drugs with opioids or a2-agonists have been proved, at the moment their use in man by spinal route in the treatment of postoperative pain is not advisable. PMID:9480192

  13. Blockade of tolerance to morphine analgesia by cocaine.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1989-07-01

    Tolerance to morphine analgesia was induced in male Sprague-Dawley rats by s.c. implantation of a morphine base pellet (75 mg) on the first and second day and determining the magnitude of tolerance 72 h after the first implant by s.c. injection of a test dose of morphine (5 mg/kg). Implantation of a cocaine hydrochloride pellet (25 mg), concurrently with morphine pellets or of a cocaine hydrochloride (50 mg) pellet after the development of tolerance, blocked both the development and expression of morphine analgesic tolerance. In morphine-pelleted animals pretreatment for 3 days with desipramine or zimelidine or phenoxybenzamine but not haloperidol produced no significant morphine tolerance. Pretreatment with a combination of desipramine and zimelidine, however, was as effective as cocaine in blocking morphine tolerance. Alpha-Methyl-p-tyrosine methyl ester counteracted the effect of cocaine in blocking morphine tolerance and potentiated the tolerance development. Blockade of morphine tolerance by cocaine was reinforced and facilitated by pretreatment with fenfluramine or p-chlorophenylalanine ethyl ester and to a lesser extent by clonidine and haloperidol. Acute administration of fenfluramine or zimelidine or a combination of desipramine and zimelidine or alpha-methyl-p-tyrosine methyl ester or p-chlorophenylalanine ethyl ester did not significantly affect morphine analgesia. The study suggests an important role of the concomitant depletion of both central noradrenaline and serotonin in the blockade of morphine tolerance by cocaine and stresses the importance of the counter-balancing functional relationship between these two neurotransmitters in the central nervous system. PMID:2780065

  14. Evaluation of menstrual cycle effects on morphine and pentazocine analgesia

    PubMed Central

    Ribeiro-Dasilva, MC; Shinal, RM; Glover, T; Williams, RS; Staud, R; Riley, JL; Fillingim, RB

    2011-01-01

    Studies have demonstrated menstrual cycle influences on basal pain perception, but direct evidence of menstrual cycle influences on analgesic responses has not been reported in humans. Our aim was to determine whether the magnitude of morphine and pentazocine analgesia varied across the menstrual cycle. Sixty-five healthy women, 35 taking oral contraceptives (OC) and 30 normally cycling (NOC), underwent experimental pain assessment both before and after intravenous administration morphine (0.08 mg/kg) or pentazocine (0.5 mg/kg) compared to saline placebo. Both active drug and placebo were administered once during the follicular phase and once during the luteal phase. Measures of heat, ischemic and pressure pain sensitivity were obtained before and after drug administration. Change scores in pain responses were computed to determine morphine and pentazocine analgesic responses, and medication side effects were recorded. The data were analyzed using mixed-model ANOVAs. NOC women showed slightly greater heat pain sensitivity in the follicular vs. luteal phase, while the reverse pattern emerged for OC women (p=0.046). Also, OC women showed lower pressure pain thresholds compared to NOC women (p < .05). Regarding analgesic responses, NOC women showed greater morphine analgesia for ischemic pain during the follicular vs. the luteal phase (p=0.004). Likewise, side effects for morphine were significantly higher in NOC women in the follicular phase than in the luteal phase (p=0.02). These findings suggest that sex hormones may influence opioid responses; however, the effects vary across medications and pain modalities and are likely to be modest in magnitude. PMID:21239109

  15. [Maternal behavior toward her newborn infant. Potential modification by peridural analgesia or childbirth preparation].

    PubMed

    Wagner, A; Grenom, A; Pierre, F; Soutoul, J H; Fabre-Nys, C; Krebhiel, D

    1989-01-01

    The effects of sophrology and epidural analgesia on early relationship between the mother and her child were studied on a simple of 190 deliveries. The mothers were observed during and just after delivery. Mothers who had been separated from their child before the end of the observation were excluded from the study. The patients had the choice between epidural analgesia or prenatal care with sophrology. Participation to prenatal courses has statistically a positive effect on the relation between the mother and her child (p less than 0.01). Instead, epidural analgesia and posture have very limited effect on this factor. However, a trend to more interaction is found in multipari and patients who didn't choose epidural analgesia. PMID:2928660

  16. 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. PMID:9762758

  17. Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue.

    PubMed

    Binder, Waltraud; Mousa, Shaaban A; Sitte, Nicolle; Kaiser, Myriam; Stein, Christoph; Schäfer, Michael

    2004-07-01

    Stress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose-dependent antinociception, reversible by alpha(1)-, alpha(2)- and beta(2)-antagonists. alpha(1)-, alpha(2)- and beta(2)-adrenergic receptors were demonstrated on beta-endorphin-containing immune cells and noradrenaline induced adrenergic receptor-specific release of beta-endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by micro - and delta-opioid antagonists as well as by anti-beta-endorphin. Stress-induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron-derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release beta-endorphin, which induces analgesia via activation of peripheral opioid receptors. PMID:15245482

  18. Early rehabilitation after anterior cruciate ligament reconstruction under regional analgesia: a case report.

    PubMed

    Al-Nasser, Bassam; Palacios, Jean Luc; Lapasset, Lionel; Hattée, Bernard; Leroy, Frédéric

    2004-02-01

    Patients undergoing major knee surgery may experience postoperative pain, which could be exacerbated by early postoperative continuous passive motion or active mobilization. This pain may result in poor functional recovery. Use of regional analgesia techniques to achieve more consistent pain relief and to facilitate rapid rehabilitation can play an important role in optimizing postoperative outcome after anterior cruciate ligament repair (ACLR). This case study concerns a 20-year-old male soldier, otherwise healthy, who underwent ACLR. We inserted a catheter in the fascia iliaca compartment and performed postoperative analgesia with low-concentration ropivacaine by using an elastomeric pump. The patient started early rehabilitation under fascia iliaca compartment analgesia. We discuss the case and the influence of regional analgesia techniques on postoperative and clinical outcomes. PMID:14966725

  19. Body region shocked need not critically define the neurochemical basis of stress analgesia.

    PubMed

    Cannon, J T; Terman, G W; Lewis, J W; Liebeskind, J C

    1984-12-10

    Both opioid and non-opioid forms of stress-induced analgesia have been demonstrated in rats, although the conditions leading to their selective activation are still being investigated. We have shown that variations in shock intensity, duration or temporal pattern can determine whether opioid or non-opioid stress analgesia occurs. Others have suggested that body region shocked is the critical determinant, analgesia from front paw shock being opioid and that from hind paw shock non-opioid. We now report that either opioid or non-opioid stress analgesia can be evoked from either front or hind paws depending only on footshock intensity when duration and temporal pattern are held constant. PMID:6525518

  20. Comparison of Perioperative Outcomes for Epidural versus Intravenous Patient-Controlled Analgesia after Radical Cystectomy

    PubMed Central

    Winer, Andrew G.; Sfakianos, John P.; Puttanniah, Vinay G.; Bochner, Bernard H.

    2016-01-01

    Background and Objectives Use of patient-controlled epidural analgesia after various operations has been associated with earlier return of bowel function and thus decrease the length of stay (LOS). The primary aim of this study was to compare LOS after radical cystectomy between patients who received epidural analgesia versus those who received intravenous patient controlled analgesia. Our secondary analysis included the assessment of other metrics such as total opioid requirements, pain scores, return of bowel function and complication rates between the two groups. Methods We conducted a retrospective review using the electronic medical records of 308 patients who underwent radical cystectomies at Memorial Sloan Kettering between 2006 and 2011. We aimed to understand if epidural analgesia was associated with a reduced length of stay compared to patient controlled intravenous opioid analgesia. We also aimed to identify performance improvements as a function of epidural analgesia status using various metrics such as pain management, bowel function return, and complication rates. We used both univariate and multivariable analyses to identify if epidural analgesia was associated with meaningful differences in the aforementioned metrics. Results Median age at radical cystectomy, body mass index, sex, ASA score, and T stage were similar for both groups. For our primary objective of LOS, we found no significant difference between the two cohorts (8 vs 7 days, p=0.2). Analysis of our secondary outcome measures revealed that epidural analgesia use was associated with less total opioid requirement for the first three post-operative days (p=0.0001). Additionally, epidural analgesia was found to be associated with improved post-operative pain scores compared to intravenous patient-controlled analgesia on post-operative days 1 (p=0.0001) and 2 (p=0.004), and there was a slight improvement on post-operative day 3, but this was not significant (p=0.77). In contrast, we found no

  1. Mediation of buprenorphine analgesia by a combination of traditional and truncated mu opioid receptor splice variants.

    PubMed

    Grinnell, Steven G; Ansonoff, Michael; Marrone, Gina F; Lu, Zhigang; Narayan, Ankita; Xu, Jin; Rossi, Grace; Majumdar, Susruta; Pan, Ying-Xian; Bassoni, Daniel L; Pintar, John; Pasternak, Gavril W

    2016-10-01

    Buprenorphine has long been classified as a mu analgesic, although its high affinity for other opioid receptor classes and the orphanin FQ/nociceptin ORL1 receptor may contribute to its other actions. The current studies confirmed a mu mechanism for buprenorphine analgesia, implicating several subsets of mu receptor splice variants. Buprenorphine analgesia depended on the expression of both exon 1-associated traditional full length 7 transmembrane (7TM) and exon 11-associated truncated 6 transmembrane (6TM) MOR-1 variants. In genetic models, disruption of delta, kappa1 or ORL1 receptors had no impact on buprenorphine analgesia, while loss of the traditional 7TM MOR-1 variants in an exon 1 knockout (KO) mouse markedly lowered buprenorphine analgesia. Loss of the truncated 6TM variants in an exon 11 KO mouse totally eliminated buprenorphine analgesia. In distinction to analgesia, the inhibition of gastrointestinal transit and stimulation of locomotor activity were independent of truncated 6TM variants. Restoring expression of a 6TM variant with a lentivirus rescued buprenorphine analgesia in an exon 11 KO mouse that still expressed the 7TM variants. Despite a potent and robust stimulation of (35) S-GTPγS binding in MOR-1 expressing CHO cells, buprenorphine failed to recruit β-arrestin-2 binding at doses as high as 10 µM. Buprenorphine was an antagonist in DOR-1 expressing cells and an inverse agonist in KOR-1 cells. Buprenorphine analgesia is complex and requires multiple mu receptor splice variant classes but other actions may involve alternative receptors. PMID:27223691

  2. TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain.

    PubMed

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

    2013-10-01

    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, although 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 that 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

  3. 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

  4. Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain

    PubMed Central

    Plapler, Pérola Grinberg; Scheinberg, Morton Aaron; Ecclissato, Christina da Cunha; Bocchi de Oliveira, Monalisa Fernanda; Amazonas, Roberto Bleuel

    2016-01-01

    Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. Objective The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity. Patients and methods In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. Results KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland–Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting. Conclusion KT is not inferior in efficacy and delivers faster pain relief than NA. PMID:27382251

  5. A comparison between subpleural patient-controlled analgesia by bupivacaine and intermittent analgesia in post-operative thoracotomy: A double-blind randomized clinical trial*

    PubMed Central

    Goharian, Vahid; Tabatabaee, Sayyed Abbas; MozafarHashemi, Sayyed; Mohajery, Gholamreza; Ramezani, Mohammad Arash; Shabani, Fatemeh; MotevalliEmami, Zahra

    2011-01-01

    BACKGROUND: The efficacy of subpleural analgesia to reduce postoperative pain intensity in patients after lateral thoracotomy is controversial. In this study, we demonstrated the efficacy of two types of subpleural analgesia. METHODS: This prospective, controlled, randomized, double-blind trial was performed in Department of Thoracic Surgery of Alzahra Hospital associated with Isfahan University of Medical Sciences from June 2009 until August 2010. After posterolateral thoracotomy and admission to the ICU, patients were randomly assigned into two groups of subpleural patient-controlled analgesia (SPCA) (0.02 cc/kg/h of 0.5% bupivacaine) and subpleural intermittent analgesia (SIA) (0.1cc/kg/6h of 0.5% bupivacaine). The data regarding age, sex, visual analog scale (VAS) (at 8, 16 and 24 hours after initiation of analgesia), morphine consumption, systemic adverse effects, length of ICU and hospital stay, complications, public health service (PHS) criteria, and cost was recorded. Data was analyzed by Mann-Whitney U-test, repeated measured test, chi-square test and the Fisher's exact test. A p < 0.05 was considered significant. RESULTS: The study population consisted of 90 patients. There were no significant differences in sex, age, weight, intraoperative analgesics, duration of one-lung ventilation, and adverse effects between the SPCA and SIA groups. Although pain scores were significantly reduced at 16 hours after the first subpleural instillation of bupivacaine 0.5% with patient-controlled analgesia, comparison between mean pain scores in the two groups at 8 and 24 hours after the first subpleural instillation of bupivacaine 0.5% revealed no significant difference. In addition, no significant difference was found in VAS scores at the three evaluated times (p < 0.05). CONCLUSIONS: Optimal use of SPCA bupivacaine for postoperative pain treatment is more effective in pain reduction than SIA bupivacaine. The consumption rate of opioid and bupivacaine was also decreased

  6. Bilateral interpleural versus lumbar epidural bupivacaine-morphine analgesia for upper abdominal surgery.

    PubMed

    Demian, Atef D; Wahba, Ashraf M; Atia, Emad M; Hussein, Sami H

    2003-10-01

    This randomized study was designed to compare the effectiveness of bilateral interpleural analgesia with lumbar epidural analgesia, on postoperative pain relief in upper abdominal surgery. The studied patients were randomely allocated into either interpleural group "IP" (n = 15) or epidural group "EP" (n = 15). In "IP" group, preanesthetic bilateral interpleural block was done using a mixture of bupivacaine 0.5% (0.8 mg/kg) and 2 mg morphine diluted to 50 ml saline for each side. In "EP" group, the same mixture-diluted in 20 ml saline-was injected in the epidural space (L2-3). The general anesthetic technique was the same in both groups. Hemodynamic, gasometric, verbal pain score (VPS) values and complications were compared in both techniques. Heart rate (HR) and mean arterial pressure (MAP) readings were in the accepted normal range in the perioperative period although significant lower readings were detected in "EP" group. No significant differences were displayed in blood gasometric variables between the two groups. There were considerable level of analgesia in both groups in the postoperative period although "EP" analgesia was superior to "IP". More pain free patients (9 versus 4) and significant lower consumption of nalbuphine were detected in "EP" group. The results of this study indicate that bilateral "IP" analgesia may offer a satisfactory analgesia for upper abdominal surgery when the use of other analgesic techniques may be contraindicated. PMID:14740589

  7. Naltrexone-sensitive analgesia following exposure of mice to 2450-MHz radiofrequency radiation.

    PubMed

    Maillefer, R H; Quock, R M

    1992-09-01

    To determine whether exposure to radiofrequency radiation (RFR) would induce sufficient thermal stress to activate endogenous opioid mechanisms, male Swiss Webster mice were exposed to 10, 15, and 20 mW/cm2 RFR in a 2450-MHz waveguide system for 10 min at specific absorption rates (SARs) of 23.7, 34.6, and 45.5 W/kg, respectively, then tested in the abdominal constriction paradigm. Confinement in the RFR exposure chamber alone did not appreciably alter body temperature but did appear to induce a stress-associated analgesia that was not blocked by naltrexone. Exposure of confined mice to RFR raised body temperature and further increased analgesia in an SAR-dependent manner. The high SAR-induced analgesia, but not the hyperthermia, was blocked 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 nonopioid mechanisms. PMID:1409913

  8. Potentiation of swim analgesia by D-amino acids in mice is genotype dependent.

    PubMed

    Panocka, I; Sadowski, B

    1990-12-01

    The effect of combined treatment with 125 mg/kg of D-phenylalanine plus 125 mg/kg of D-leucine (IP) on magnitude and duration of analgesia caused by 3 min swim at 20 degrees C was studied in mouse lines selectively bred for 20 generations toward high and low level of stress-induced analgesia. The D-amino acids administered 30 min prior to swimming increased postswim tail-flick latencies and prolonged antinociception more in the high analgesia line (HA) than in concomitantly bred unselected controls, but were not effective in the low analgesia line (LA). The potentiation of swim analgesia by D-amino acids was prevented by simultaneous administration of 1 mg/kg of naloxone hydrochloride which, given alone, antagonized the analgesia more in the HA line than in controls, but not in the LA line. The results are interpreted in terms of genetic differentiation of opioidergic transmission in the selectively bred mouse lines. PMID:2093164

  9. RSK2 Signaling in Medial Habenula Contributes to Acute Morphine Analgesia

    PubMed Central

    Darcq, Emmanuel; Befort, Katia; Koebel, Pascale; Pannetier, Solange; Mahoney, Megan K; Gaveriaux-Ruff, Claire; Hanauer, André; Kieffer, Brigitte L

    2012-01-01

    It has been established that mu opioid receptors activate the ERK1/2 signaling cascade both in vitro and in vivo. The Ser/Thr kinase RSK2 is a direct downstream effector of ERK1/2 and has a role in cellular signaling, cell survival growth, and differentiation; however, its role in biological processes in vivo is less well known. Here we determined whether RSK2 contributes to mu-mediated signaling in vivo. Knockout mice for the rsk2 gene were tested for main morphine effects, including analgesia, tolerance to analgesia, locomotor activation, and sensitization to this effect, as well as morphine withdrawal. The deletion of RSK2 reduced acute morphine analgesia in the tail immersion test, indicating a role for this kinase in mu receptor-mediated nociceptive processing. All other morphine effects and adaptations to chronic morphine were unchanged. Because the mu opioid receptor and RSK2 both show high density in the habenula, we specifically downregulated RSK2 in this brain metastructure using an adeno-associated-virally mediated shRNA approach. Remarkably, morphine analgesia was significantly reduced, as observed in the total knockout animals. Together, these data indicate that RSK2 has a role in nociception, and strongly suggest that a mu opioid receptor–RSK2 signaling mechanism contributes to morphine analgesia at the level of habenula. This study opens novel perspectives for both our understanding of opioid analgesia, and the identification of signaling pathways operating in the habenular complex. PMID:22218090

  10. The TGR5 receptor mediates bile acid–induced itch and analgesia

    PubMed Central

    Alemi, Farzad; Kwon, Edwin; Poole, Daniel P.; Lieu, TinaMarie; Lyo, Victoria; Cattaruzza, Fiore; Cevikbas, Ferda; Steinhoff, Martin; Nassini, Romina; Materazzi, Serena; Guerrero-Alba, Raquel; Valdez-Morales, Eduardo; Cottrell, Graeme S.; Schoonjans, Kristina; Geppetti, Pierangelo; Vanner, Stephen J.; Bunnett, Nigel W.; Corvera, Carlos U.

    2013-01-01

    Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide– and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases. PMID:23524965

  11. Postoperative pain relief using intermittent intrapleural analgesia following thoracoscopic anterior correction for progressive adolescent idiopathic scoliosis

    PubMed Central

    2013-01-01

    Background Thoracoscopic anterior scoliosis instrumentation is a safe and viable surgical option for corrective fusion of progressive adolescent idiopathic scoliosis (AIS) and has been performed at our centre on 205 patients since 2000. However, there is a paucity of literature reporting on or examining optimum methods of analgesia following this type of surgery. A retrospective study was designed to present the authors’ technique for delivering intermittent local anaesthetic boluses via an intrapleural catheter following thoracoscopic scoliosis surgery; report the pain levels that may be expected and any adverse effects associated with the use of intrapleural analgesia, as part of a combined postoperative analgesia regime. Methods Records for 32 patients who underwent thoracoscopic anterior correction for AIS were reviewed. All patients received an intrapleural catheter inserted during surgery, in addition to patient-controlled opiate analgesia and oral analgesia. After surgery, patients received a bolus of 0.25% bupivacaine every four hours via the intrapleural catheter. Patient’s perceptions of their pain control was measured using the visual analogue pain scale scores which were recorded before and after local anaesthetic administration and the quantity and time of day that any other analgesia was taken, were also recorded. Results 28 female and four male patients (mean age 14.5 ± 1.5 years) had a total of 230 boluses of local anaesthetic administered in the 96 hour period following surgery. Pain scores significantly decreased following the administration of a bolus (p < 0.0001), with the mean pain score decreasing from 3.66 to 1.83. The quantity of opiates via patient-controlled analgesia after surgery decreased steadily between successive 24 hours intervals after an initial increase in the second 24 hour period when patients were mobilised. One intrapleural catheter required early removal due to leakage; there were no other associated

  12. Perioperative analgesic effects of intravenous paracetamol: Preemptive versus preventive analgesia in elective cesarean section

    PubMed Central

    Hassan, Hossam Ibrahim Eldesuky Ali

    2014-01-01

    Background: Cesarean section (CS) is the one of the most common surgical procedure in women. There is preoperative stress effect before the delivery of the baby as (intubation and skin incision). There is acute postoperative pain, which may be progressed to chronic pain. All these perioperative stress effects need for various approach of treatment, which including systemic and neuraxial analgesia. The different analgesia modalities may affect and impair early interaction between mother and infant. Preemptive intravenous (I.V.) paracetamol (before induction) may reduce stress response before the delivery of the baby, intraoperative opioids and postoperative pain. Objectives: The aim of this study to compare between the administration of I.V. paracetamol as: Preemptive analgesia (preoperative) and preventive analgesia (at the end of surgery) as regards of hemodynamic, pain control, duration of analgesia, cumulative doses of intraoperative opioids and their related side-effects and to compare between two different protocols of postoperative analgesia and their cumulative doses. Patients and Methods: Sixty patients undergoing elective CS were randomly enrolled in this study and divided into two groups of 30 patients each. Group I: i.V. paracetamol 1 g (100 ml) was given 30 min before induction of anesthesia. Group II: i.V. paracetamol 1 g (100 ml) was given 30 min before the end of surgery. Heart rate, systolic blood pressure, diastolic blood pressure, and peripheral oxygen saturation were recorded. Postoperative pain was assessed by visual analog score. Postoperative pethidine was given by two different protocols: group I: 0.5 mg/kg was divided into 0.25 mg/kg intramuscular and 0.25 mg/kg I.V. Group II was given pethidine 0.5 mg/kg I.V. Doses of intraoperative fentanyl, postoperative pethidine, duration of paracetamol analgesic time, time to next analgesia, and side-effects of opioid were noted and compared. Result: Preemptive group had hemodynamic stability

  13. Multiple levels paravertebral block versus morphine patient-controlled analgesia for postoperative analgesia following breast cancer surgery with unilateral lumpectomy, and axillary lymph nodes dissection

    PubMed Central

    Fallatah, Summayah; Mousa, WF

    2016-01-01

    Background: Postoperative pain after breast cancer surgery is not uncommon. Narcotic based analgesia is commonly used for postoperative pain management. However, the side-effects and complications of systemic narcotics is a significant disadvantage. Different locoregional anesthetic techniques have been tried including, single and multiple levels paravertebral block (PVB), which seems to have a significant reduction in immediate postoperative pain with fewer side-effects. The aim of this study was to compare unilateral multiple level PVB versus morphine patient-controlled analgesia (PCA) for pain relief after breast cancer surgery with unilateral lumpectomy and axillary lymph nodes dissection. Materials and Methods: Forty patients scheduled for breast cancer surgery were randomized to receive either preoperative unilateral multiple injections PVB at five thoracic dermatomes (group P, 20 patients) or postoperative intravenous PCA with morphine (group M, 20 patients) for postoperative pain control. Numerical pain scale, mean arterial pressure, heart rate, Time to first analgesic demand, 24-h morphine consumption side-effects and length of hospital stay were recorded. Results: PVB resulted in a significantly more postoperative analgesia, maintained hemodynamic, more significant reduction in nausea and vomiting, and shorter hospital stay compared with PCA patients. Conclusion: Multiple levels PVB is an effective regional anesthetic technique for postoperative pain management, it provides superior analgesia with less narcotics consumption, and fewer side-effects compared with PCA morphine for patients with breast cancer who undergo unilateral lumpectomy, with axillary lymph nodes dissection. PMID:26955304

  14. Focused analgesia in waking and hypnosis: effects on pain, memory, and somatosensory event-related potentials.

    PubMed

    De Pascalis, Vilfredo; Cacace, Immacolata; Massicolle, Francesca

    2008-01-01

    Somatosensory event-related potentials (SERPs) to painful electric standard stimuli under an odd-ball paradigm were analyzed in 12 high hypnotizable (HH), 12 medium hypnotizable (MH), and 12 low hypnotizable (LH) subjects during waking, hypnosis, and a cued eyes-open posthypnotic condition. In each of these conditions subjects were suggested to produce an obstructive imagery of stimulus perception as a treatment for pain reduction. A No-Analgesia treatment served as a control in waking and hypnosis conditions. The subjects were required to count the number of delivered target stimuli. HH subjects experienced significant pain and distress reductions during posthypnotic analgesia as compared to hypnotic analgesia and between these two analgesic conditions as compared to the two control conditions. Outside of hypnosis, these subjects remembered less pain and distress levels than they reported during hypnotic and posthypnotic analgesia treatments. In contrast, for waking-analgesia treatment, HH subjects remembered similar pain and distress levels to those they reported concurrently with the stimulation. HH subjects, during hypnotic and posthypnotic analgesia treatments, detected a smaller number of target stimuli and displayed a significant amplitude reduction of the midline frontal and central N140 and P200 SERP components. No significant SERP differences were observed for these subjects between treatments in waking condition and between hypnotic and posthypnotic analgesic treatments. For the MH and LH subjects no significant N140 and P200 amplitude changes were observed among analgesic conditions as compared to control conditions. These amplitude findings are seen as indicating that hypnotic analgesia can affect earlier and later stages of stimulus processing. PMID:18023535

  15. Neurobiological studies of chronic pain and analgesia: Rationale and refinements.

    PubMed

    Fairbanks, Carolyn A; Goracke-Postle, Cory J

    2015-07-15

    Chronic pain is a complex condition for which the need for specialized research and therapies has been recognized internationally. This review summarizes the context for the international call for expansion of pain research to improve our understanding of the mechanisms underlying pain in order to achieve improvements in pain management. The methods for conducting sensory assessment in animal models are discussed and the development of animal models of chronic pain is specifically reviewed, with an emphasis on ongoing refinements to more closely mimic a variety of human pain conditions. Pharmacological correspondences between pre-clinical pain models and the human clinical experience are noted. A discussion of the 3Rs Framework (Replacement, Reduction, Refinement) and how each may be considered in pain research is featured. Finally, suggestions are provided for engaging principal investigators, IACUC reviewers, and institutions in the development of strong partnerships to simultaneously expand our knowledge of the mechanisms underlying pain and analgesia while ensuring the humane use of animals in research. PMID:25818751

  16. Tat-Mediated Peptide Intervention in Analgesia and Anesthesia

    PubMed Central

    Tao, Feng; Johns, Roger A.

    2010-01-01

    Membrane-permeable peptide carriers are attractive drug delivery tools. Among such carriers, the protein transduction domain (PTD) of the human immunodeficiency virus-type 1 Tat protein is most frequently used and has been successfully shown to deliver a large variety of cargoes. The Tat PTD can facilitate the uptake of large, biologically active molecules into mammalian cells, and recent studies have shown that it can mediate the delivery of different cargoes into tissues throughout a living organism. Given that the Tat PTD-mediated delivery is size-independent, this technology could make previously non-applicable large molecules usable to modulate biological function in vivo and treat human diseases. It is likely that the peptide carrier-mediated intracellular delivery process encompasses multiple mechanisms, but endocytic pathways are the predominant internalization routes. Tat PTD has been successfully used in preclinical models for the study of cancer, ischemia, inflammation, analgesia, and anesthesia. Our recent studies have shown that intraperitoneally injected fusion Tat peptide Tat-PSD-95 PDZ2 can be delivered into the spinal cord to dose-dependently disrupt protein-protein interactions between PSD-95 and NMDA receptors. This peptide significantly inhibits chronic inflammatory pain and reduces the threshold for halothane anesthesia. The ability of the Tat PTD to target any cell is advantageous in some respects. However, the drug delivery system will be more attractive if we can modify the Tat PTD to deliver cargo only into desired organs to avoid possible side effects. PMID:20711510

  17. RESULTS OF THE MEGAVERTEBRATE ANALGESIA SURVEY: ELEPHANTS AND RHINO.

    PubMed

    Kottwitz, Jack; Boothe, Matthew; Harmon, Roy; Citino, Scott B; Zuba, Jeffery R; Boothe, Dawn M

    2016-03-01

    An online survey utilizing Survey Monkey linked through the American Association of Zoo Veterinarians listserve examined current practices in megavertebrate analgesia. Data collected included drugs administered, dosing regimens, ease of administration, efficacy, and adverse events. Fifty-nine facilities (38 housing elephants, 33 housing rhinoceroses) responded. All facilities administered nonsteroidal anti-inflammatory drugs (NSAIDs), with phenylbutazone (0.25-10 mg/kg) and flunixin meglumine (0.2-4 mg/kg) being most common. Efficacy was reported as "good" to "excellent" for these medications. Opioids were administered to elephants (11 of 38) and rhinoceroses (7 of 33), with tramadol (0.5-3.0 mg/kg) and butorphanol (0.05-1.0 mg/kg) being most common. Tramadol efficacy scores were highly variable in both elephants and rhinoceroses. While drug choices were similar among institutions, substantial variability in dosing regimens and reported efficacy between and within facilities indicates the need for pharmacokinetic studies and standardized methods of analyzing response to treatment to establish dosing regimens and clinical trials to establish efficacy and safety. PMID:27010292

  18. Perioperative analgesia and the effects of dietary supplements.

    PubMed

    Abe, Andrew; Kaye, Alan David; Gritsenko, Karina; Urman, Richard D; Kaye, Adam Marc

    2014-06-01

    With over 50,000 dietary supplements available, resurgence in consumer interest over the past few decades has resulted in an explosion of use of these agents worldwide. Disillusionment with current medications and belief in "natural medicines" has resulted in a multibillion dollar industry. Active ingredients in a number of herbs are being tested for therapeutic potential, and some are efficacious, so herbal medicines cannot be dismissed. The prevalence of herbology is further encouraged by a relatively relaxed policy of the FDA regarding these compounds, which they consider foods. As herbal products are included in the "supplement" category, there is no existing protocol for standardization of these products. There are numerous examples of herbals that can adversely affect patient recovery and outcomes in anesthesia. The prudent anesthesia provider will make sure to obtain correct information as to accurate herbal usage of each patient and attempt to discontinue these products two to three weeks prior to the delivery of an anesthetic. Postoperative analgesia, bleeding, and level of sedation can be negatively impacted related to herbal products and herbal-drug interactions. Over 90 herbal products are associated with bleeding and this can be a specific problem intraoperatively or when considering placement of a regional anesthetic for postoperative pain management. PMID:24993438

  19. Sevoflurane for analgesia-testing a modified vaporiser for delivery.

    PubMed

    Miller, L A; Makins, H; Eltringham, R; Neighbour, R

    2015-07-01

    The Diamedica Sevoflurane Inhaler (Diamedica UK Ltd, Bratton Fleming, UK) (DSI) is a breathing system which includes a modification of an existing vaporiser (Diamedica Draw-over Vaporiser, Diamedica UK Ltd, Bratton Fleming, UK), to enable the delivery of 0.8% sevoflurane. Previous studies have suggested that self-administered sevoflurane at sub-anaesthetic concentration can provide useful pain relief during the first stage of labour and that it may be more effective than Entonox. Further research and potential clinical use have been impeded by the lack of a practical delivery system. In this study, the performance of two versions of the DSI (DSI-1 and DSI-2) was investigated. DSI-1 was tested over a range of minute volumes (1 to 30 l/min) and ambient temperatures (10°C to 40°C). The sevoflurane output increased unacceptably with rising ambient temperature, therefore the design was modified to create the DSI-2. The results from testing this revised version are also described. Mean sevoflurane output from the DSI-2 was found to be within a clinically acceptable range at the minute volumes tested (0.78% to 0.88%) and ambient temperatures tested (0.69% to 0.9%). Based upon these results, the authors propose to undertake further studies of sevoflurane analgesia using the DSI-2. PMID:26099767

  20. Augmentation of acetaminophen analgesia by the antihistamine phenyltoloxamine.

    PubMed

    Sunshine, A; Zighelboim, I; De Castro, A; Sorrentino, J V; Smith, D S; Bartizek, R D; Olson, N Z

    1989-07-01

    A double-blind, placebo-controlled, parallel-group study was performed to compare the analgesic activity of the combination of 650 mg acetaminophen plus 60 mg phenyltoloxamine citrate with that of 650 mg acetaminophen alone. Two hundred female inpatients who had severe pain associated with a recent episiotomy procedure were randomly assigned to receive a single dose of one of the two active treatments or a placebo. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard subjective scales for pain intensity and relief, a number of derived variables based on these data and two global measures. For essentially all measures, the two active treatments were significantly superior to the placebo control. The combination was significantly superior to acetaminophen alone for all analgesic measures including SPID, TOTAL, and global ratings. The results of this study demonstrate that 60 mg phenyltoloxamine produces significant augmentation of the analgesic activity of 650 mg acetaminophen in postepisiotomy pain. PMID:2569485

  1. [Pediatric patient sedation and analgesia for diagnostic medical procedures].

    PubMed

    Kadosaki, Mamoru

    2014-08-01

    There is an increasing demand for anesthesiologists to work outside the operating room in order to provide general anesthesia or monitored sedation for a variety of medical investigations or procedures in infants and children. The concept that treatment should be a pain- and stress-free experience is now well accepted, and this has placed additional responsibilities on anesthesiologists. We describe pediatric anesthesia and monitored sedation for diagnostic medical procedures. Children requiring a painful procedure and prolonged examination should be provided with optimal sedation and analgesia. The child should be monitored with standard ASA monitors. In the case of medical procedures such as gastrointestinal endoscopy, transesophageal echocardiography, and cardiac catheterization, general endotracheal anesthesia with neuromuscular block is recommended. Several short-acting anesthetic drugs, including sevoflurane, propofol, remifentanil, and rocuronium, have become available in Japan, and the safety and efficacy of pediatric general anesthesia for diagnostic medical procedures have improved. Infants who require a noninvasive and short examination may not be provided with anesthetics. The feed and wrap method is recommended. Satisfactory immobilization of the child during noninvasive medical procedures, including magnetic resonance imaging, may be achieved by intravenous sedation or general anesthesia. Monitored intravenous sedation using propofol is the most widely used for healthy children; general anesthesia with a laryngeal mask airway or endotracheal intubation and controlled ventilation is required for a critically ill child. PMID:25669029

  2. The effects of low-dose ketamine on the analgesia nociception index (ANI) measured with the novel PhysioDoloris™ analgesia monitor: a pilot study.

    PubMed

    Bollag, Laurent; Ortner, Clemens M; Jelacic, Srdjan; Rivat, Cyril; Landau, Ruth; Richebé, Philippe

    2015-04-01

    The PhysioDoloris™ analgesia monitor assesses nociception effects on the autonomic nervous system by analyzing changes in heart rate variability (HRV). This non-invasive device analyses ECG signals and determines the analgesia nociception index (ANI), allowing for quantitative assessment of the analgesia/nociception balance in anesthetized patients. Ketamine, an analgesic adjuvant with sympathomimetic properties, has been shown to improve perioperative pain management. The purpose of this pilot study was to evaluate whether low-dose ketamine, due to its intrinsic effect on the sino-atrial node, affects HRV and, therefore, interferes with ANI measurements. This pilot study included 20 women undergoing abdominal hysterectomies. Anesthesia and analgesia were maintained with sevoflurane and fentanyl respectively, in a standardized manner. Five minutes after intubation, 0.5 μg kg(-1) of intravenous (i.v.) ketamine was administered. ANI, bispectral index (BIS), heart rate and blood pressure were recorded from the induction of anesthesia until 5 min after skin incision. There was not any significant decrease in mean (±SD) ANI values after intubation (2.11±20.11, p=0.35) or i.v. ketamine administration (1.31±15.26, p=0.28). The mean (±SD) reduction in ANI values after skin incision was statistically significant (13.65±15.44, p=0.01), which is consistent with increased nociception. A single i.v. bolus of 0.5 μg kg(-1) ketamine did not influence the ANI values of 20 women under standardized general anesthesia conditions and absent noxious stimulation. These results suggest that the ANI derived from the PhysioDoloris™ analgesia monitor is feasible under such clinical conditions. PMID:25062948

  3. [The modulation of cerebral cortex and subcortical nuclei on NRM and their role in acupuncture analgesia].

    PubMed

    Liu, X

    1996-01-01

    The vast research have demonstrated that the acupuncture analgesia is effected through a physiological mechanism brought about by the nervous system, particularly the central nervous system. We combined the acupuncture effects and theory of channels and collaterals with the new advance of pain neurophysiology, and centred attention on nucleus raphe magnus (NRM), that is one of the origins of the important descending inhibitory pathways of the intrinsic analgesic systems in brain. The unit discharges of NRM neurons and their nociceptors/ph responses were recorded extracellularly with glass microelectrode at 1495 neurons on 634 wastar rats. The modulation of cerebral cortex, the head of N. caudatum (NCa), N. Accumbens (N. Ac), N lateral habenular (NHa) and Periaquaeductal gray matter (PAG) on NRM and their role in acupuncture analgesia were studied by central locational stimulation, lesion and microinjection. The result were as follows: 1. The most NRM neurons could respond to noxious stimulation of tail tip with increasing or decreasing firing rate. Electroacupuncture (EA) at "Zusanli" could activate the NRM neuron, increasing discharges, and inhibit their nociceptive responses, producing analgesia. 2. The activity of NRM neuron was modulated by PAG, NAc, and NCa. Stimulation at one of them can activate neuron of NRM, increasing firing rate, and induce analgesia. When the lesion or microinjection naloxone were made in PAG, NAc or NCa, EA analgesia could be weakened or lost, even the nociceptive responses might be increased. It is suggest that the nuclei participated in EA analgesia with their endogenous opiate like substance, and were playing an important role. It is also indicated that the electroacupuncture was used on the patients with some nuclei lesion or pathological changes should be careful to avoid making patients feel more painful. 3. Somatosensory area II (Sm II) of cerebral cortex participated in EA analgesia. The analgesic effects of EA at "Zusanli

  4. Dose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans.

    PubMed

    Gear, Robert W; Gordon, Newton C; Miaskowski, Christine; Paul, Steven M; Heller, Philip H; Levine, Jon D

    2003-11-01

    The analgesic effect of kappa partial agonist opioids (i.e. nalbuphine, pentazocine and butorphanol) is significantly greater in women. Recent evidence suggests that this sexual dimorphism may result from a naloxone-sensitive anti-analgesic effect that is activated along with, and summates with, the analgesic effect of these agents, resulting in decreased analgesia or increased pain. For example, nalbuphine (5 mg) produces profound anti-analgesia (i.e. enhanced pain) in men, but addition of a low dose of the opioid receptor antagonist naloxone (0.4 mg, opioid antagonist) induces significant analgesia in men and enhances nalbuphine analgesia in women. To further delineate the dose-dependent relationship of nalbuphine and naloxone, we recently evaluated the effect of a lower dose of nalbuphine (2.5 mg) with and without naloxone (0.4 mg) on dental postoperative pain. In women, nalbuphine alone induced modest short duration analgesia, which was antagonized by the addition of naloxone. In men, this dose of nalbuphine alone did not produce analgesia or anti-analgesia, and naloxone did not alter the response to nalbuphine. Thus, it appeared that the 2.5 mg dose of nalbuphine was not sufficient to induce anti-analgesia while the 0.4 mg dose of naloxone was able to antagonize the analgesic effect of nalbuphine, at least in women. In the current study, we tested the hypothesis that an important determinant of naloxone enhancement of nalbuphine analgesia is the dose ratio of nalbuphine to naloxone. Since a dose ratio of 12.5:1 (i.e. 5 mg nalbuphine:0.4 mg naloxone) resulted in analgesic enhancement, but a dose ratio of 6.25:1 (2.5 mg:0.4 mg) did not, we tested the same, lower, dose of nalbuphine (2.5 mg) in combination with a lower dose of naloxone (0.2 mg) to maintain the 12.5:1 dose ratio. This lower dose of naloxone significantly prolonged the analgesic effect of nalbuphine in both men and women, suggesting that the anti-analgesic effect of nalbuphine is present in both

  5. Intracameral phenylephrine and ketorolac injection (OMS302) for maintenance of intraoperative pupil diameter and reduction of postoperative pain in intraocular lens replacement with phacoemulsification

    PubMed Central

    Lindstrom, Richard L; Loden, James C; Walters, Thomas R; Dunn, Steven H; Whitaker, J Steven; Kim, Terry; Demopulos, Gregory A; Tjia, Khiun

    2014-01-01

    Background The purpose of this study was to evaluate the effect of OMS302 on intraoperative pupil diameter and early postoperative ocular pain when administered during intraocular lens replacement surgery. Methods Four hundred and six patients (406 study eyes; 202 in the OMS302 group and 204 in the placebo group) were entered into this randomized, double-masked, placebo-controlled, multicenter Phase III study, which was conducted at 15 centers in the USA and the Netherlands. The patients received OMS302 (60.75 mM phenylephrine HCl and 11.25 mM ketorolac tromethamine) or placebo in irrigation solution during intraocular lens replacement. No other changes in procedure were required. Coprimary endpoints were change in pupil diameter over time from surgical baseline to end of procedure and patient-reported ocular pain during the first 12 hours postoperatively. Secondary endpoints included additional measures of pupil diameter and postoperative pain. Results OMS302 was superior to placebo in maintaining intraoperative mydriasis, preventing miosis, and reducing postoperative pain. The weighted mean (standard error) difference (OMS302 – placebo) in change in the area under the curve from baseline for pupil diameter was 0.590 ([0.049]; 95% confidence interval 0.494 to 0.686; P<0.0001). For ocular pain scores, the weighted mean (standard error) difference was −4.580 ([1.192]; 95% confidence interval −6.917 to 2.244; P=0.0002). All secondary efficacy results favored OMS302. Specifically, analyses supporting prevention of miosis (patients with ≥6 mm pupil diameter at completion of cortical clean-up and those with <6 mm diameter at any time during surgery) were significant for OMS302 (95.9% versus 77.0% and 9.2% versus 38.0%, respectively; P<0.0001 for each endpoint). OMS302 was well tolerated and not associated with any unexpected adverse events. Conclusion OMS302 maintained mydriasis, prevented miosis, and reduced early postoperative pain when administered in

  6. Improving analgesia in fractured neck of femur with a standardised fascia iliaca block protocol

    PubMed Central

    Watson, Paul; Rugonfalvi-Kiss, Szabolcs

    2016-01-01

    Fractured neck of femur (NOF) causes significant morbidity and pain for patients; adequate analgesia is an essential component of patient centred care. Patients experiencing greater pain during treatment for fractured NOF are slower to mobilise and have poorer health-related quality of life. NICE guidance suggests considering adding nerve blocks if paracetamol and opioids do not provide sufficient preoperative pain relief. We set out to audit pain levels in this group of patients in a small District General Hospital and to develop a protocol to improve analgesia provision if required. We identified that patients waiting a long time for fixation of fractured NOF could benefit from safe, effective analgesia by way of fascia iliaca compartment block (FICB). We drew up a protocol and held training sessions bringing about a culture change to provide an excellent standard of analgesia for these patients. Most patients reported much better levels of analgesia post-block and junior doctors felt more empowered. Further developments considered are training of senior ED nurses to administer FICB (in keeping with the AAGBI position statement) and a fascia iliaca catheter placement service. PMID:27239308

  7. Analgesia induced by isolated bovine chromaffin cells implanted in rat spinal cord.

    PubMed

    Sagen, J; Pappas, G D; Pollard, H 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. PMID:3463981

  8. Post-ictal analgesia: involvement of opioid, serotoninergic and cholinergic mechanisms.

    PubMed

    Coimbra, N C; Castro-Souza, C; Segato, E N; Nora, J E; Herrero, C F; Tedeschi-Filho, W; Garcia-Cairasco, N

    2001-01-12

    The neural mechanisms involved in post-ictal analgesia remain to be elucidated. Pentylenetetrazol (PTZ) is used experimentally to induce seizure in animal subjects. This non-competitive antagonist blocks GABA-mediated Cl(-) flux. The aim of this work is to study the neurochemical basis of the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test, in eight rats per group. Convulsions were followed by significant increase in the tail-flick latencies (TFL), at least for 30 min of the post-ictal period. Peripheral administration of naloxone (5 mg/kg and 10 mg/kg), atropine (1 mg/kg and 5 mg/kg), methysergide (1 mg/kg and 5 mg/kg) and ketanserine (1 mg/kg and 2 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls. However, while naloxone antagonized analgesia 15 and 25 min post convulsions, the other drugs caused a blockade of the post-ictal analgesia in a relatively greater period of time. These results indicate that endogenous opioids, serotonin and acetylcholine may be involved in post-ictal analgesia. PMID:11150491

  9. Baseline reward circuitry activity and trait reward responsiveness predict expression of opioid analgesia in healthy subjects

    PubMed Central

    Wanigasekera, Vishvarani; Lee, Michael C.; Rogers, Richard; Kong, Yazhuo; Leknes, Siri; Andersson, Jesper; Tracey, Irene

    2012-01-01

    Variability in opioid analgesia has been attributed to many factors. For example, genetic variability of the μ-opioid receptor (MOR)-encoding gene introduces variability in MOR function and endogenous opioid neurotransmission. Emerging evidence suggests that personality trait related to the experience of reward is linked to endogenous opioid neurotransmission. We hypothesized that opioid-induced behavioral analgesia would be predicted by the trait reward responsiveness (RWR) and the response of the brain reward circuitry to noxious stimuli at baseline before opioid administration. In healthy volunteers using functional magnetic resonance imaging and the μ-opioid agonist remifentanil, we found that the magnitude of behavioral opioid analgesia is positively correlated with the trait RWR and predicted by the neuronal response to painful noxious stimuli before infusion in key structures of the reward circuitry, such as the orbitofrontal cortex, nucleus accumbens, and the ventral tegmental area. These findings highlight the role of the brain reward circuitry in the expression of behavioral opioid analgesia. We also show a positive correlation between behavioral opioid analgesia and opioid-induced suppression of neuronal responses to noxious stimuli in key structures of the descending pain modulatory system (amygdala, periaqueductal gray, and rostral–ventromedial medulla), as well as the hippocampus. Further, these activity changes were predicted by the preinfusion period neuronal response to noxious stimuli within the ventral tegmentum. These results support the notion of future imaging-based subject-stratification paradigms that can guide therapeutic decisions. PMID:23045652

  10. Effects of continuous fascia iliaca compartment blocks for postoperative analgesia in patients with hip fracture

    PubMed Central

    Nie, Hongling; Yang, Ya-Xiong; Wang, Yang; Liu, Yong; Zhao, Bin; Luan, Bo

    2015-01-01

    BACKGROUND: Effective analgesia is essential for the postoperative care of orthopedic patients. OBJECTIVES: To evaluate the efficacy of continuous fascia iliaca compartment block (FIB) as postoperative analgesia after hip fracture surgery, and to compare FIB with patient-controlled intravenous analgesia (PCIA) using fentanyl for 48 h postoperatively. METHODS: Patients with hip fractures who were scheduled for open reduction and internal fixation surgery using the antirotation proximal femoral nail technique were randomly assigned to the FIB or PCIA groups. Postoperative pain was assessed using a numeral rating scale at 2 h, 4 h, 6 h, 12 h, 24 h and 48 h after analgesia was started. Delirium, postoperative nausea and vomiting (PONV), and pruritus were also monitored. RESULTS: Patients in the FIB group reported less pain than those in the PCIA group (P=0.039, d=−0.3). The change in pain scores over time was similar between the two groups. There were six patients with PONV and five patients with pruritus in the PCIA group, while no PONV or pruritus was noticed in the FIB group (P=0.013). Ten (19.6%) patients in the FIB group and three (5.7%) patients in the PCIA group developed postoperative delirium (P=0.032, d=0.77). CONCLUSION: Continuous FIB is a safe and effective technique for postoperative analgesia after hip fracture surgery, making it an option for pain management in elderly patients with hip fractures. PMID:26125194

  11. 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

    2016-05-01

    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. PMID:27019034

  12. Effects of multimodal analgesia on the success of mouse embryo transfer surgery.

    PubMed

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

    2011-07-01

    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

  13. 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.

  14. Comparison of tapentadol with tramadol for analgesia after cardiac surgery

    PubMed Central

    Iyer, Srinivas Kalyanaraman; Mohan, Gokulakrishnan; Ramakrishnan, Sivakumar; Theodore, Sanjay

    2015-01-01

    Background: Tapentadol is a relatively new analgesic. We decided to compare it with tramadol for their various effects after cardiac surgery. Setting: A study in a tertiary care hospital. Materials and Methods: Sixty adults undergoing cardiac surgery were divided into 2 groups of 30 each by computerized random allotment (Group X = tapentadol 50 mg oral and Group Y = tramadol 100 mg oral). Informed Consent and Institutional Ethics Committee approval were obtained. The patients were given either drug X or drug Y after extubation in this single blinded study, wherein the data collectors and analyzers were blinded to the study. All patients received oral paracetamol qds and either drug X or drug Y tds. The pain score was noted on a Visual Analog Scale before each drug dose, 3 h later and on coughing. Heart rate, respiratory rate, and blood pressure were recorded before the drug dose and 3 h later. Postoperative nausea or vomiting (PONV), temperature, and modified Glasgow Coma Scale readings were recorded. The above readings were obtained for 6 doses (up to 48 h after extubation). Statistics: t-test, Pearson Chi-square test, Fisher exact test, and Mantel–Haenszel test were used for statistics. Results: Tapentadol group patients had significantly better analgesia 3 h after the drug and “on coughing” than tramadol group. The difference in their effects on blood creatinine levels, temperature, hemodynamics, oxygen saturation, and respiratory rate were not clinically significant. Tapentadol produced lesser drowsiness and lesser vomiting than tramadol. Conclusions: Tapentadol, due to its norepinephrine reuptake inhibition properties, in addition to mu agonist, is a better analgesic than tramadol and has lesser PONV. PMID:26139740

  15. Ethnic differences in the use of intrapartum epidural analgesia

    PubMed Central

    2012-01-01

    Background Obstetric epidural analgesia (EA) is widely applied, but studies have reported that its use may be less extensive among immigrant women or those from minority ethnic groups. Our aim was to examine whether this was the case in our geographic area, which contains an important immigrant population, and if so, to describe the different components of this phenomenon. Methods Cross-sectional observational study. Setting: general acute care hospital, located in Marbella, southern Spain. Analysis of computer records of deliveries performed from 2004 to 2010. Comparison of characteristics of deliveries according to the mothers’ geographic origins and of vaginal deliveries noting whether EA was received, using univariate and bivariate statistical analysis and multiple logistic regression (MLR). Results A total of 21,034 deliveries were recorded, and 37.4% of these corresponded to immigrant women. EA was provided to 61.1% of the Spanish women and to 51.5% of the immigrants, with important variations according to geographic origin: over 52% of women from other European countries and South America received EA, compared with around 45% of the African women and 37% of the Asian women. These differences persisted in the MLR model after adjusting for the mother's age, type of labor initiation, the weight of the neonate and for single or multiple gestation. With the Spanish patients as the reference category, all the other countries of origin presented lower probabilities of EA use. This was particularly apparent for the patients from Asia (OR 0.38; 95%CI 0.31-0.46), Morocco (OR 0.49; 95%CI 0.43-0.54) and other Africa (OR 0.55; 95%CI 0.37-0.81). Conclusions We observed a different use of EA in vaginal deliveries, according to the geographic origin of the women. The explanation for this involves a complex set of factors, depending both on the patient and on the healthcare staff. PMID:22818255

  16. Effects of regional analgesia on stress responses to pediatric surgery.

    PubMed

    Wolf, Andrew R

    2012-01-01

    Invasive surgery induces a combination of local response to tissue injury and generalized activation of systemic metabolic and hormonal pathways via afferent nerve pathways and the central nervous system. The local inflammatory responses and the parallel neurohumoral responses are not isolated but linked through complex signaling networks, some of which remain poorly understood. The magnitude of the response is broadly related to the site of injury (greater in regions with visceral pain afferents such as abdomen and thorax) and the extent of the trauma. The changes include alterations in metabolic, hormonal, inflammatory, and immune systems that can be collectively termed the stress response. Integral to the stress responses are the effects of nociceptive afferent stimuli on systemic and pulmonary vascular resistance, heart rate, and blood pressure, which are a combination of efferent autonomic response and catecholamine release via the adrenal medulla. Therefore, pain responses, cardiovascular responses, and stress responses need to be considered as different aspects of a combined bodily reaction to surgery and trauma. It is important at the outset to understand that not all components of the stress response are suppressed together and that this is important when discussing different analgesic modalities (i.e. opioids vs regional anesthesia). For example, in terms of the use of fentanyl in the infant, the dose required to provide analgesia (1-5 mcg·kg(-1)) is less than that required for hemodynamic stability in response to stimuli (5-10 mcg·kg(-1)) (1) and that this in turn is less than that required to suppress most aspects of the stress response (25-50 mcg·kg(-1)) (2). In contrast to this considerable dose dependency, central local anesthetic blocks allow blockade of the afferent and efferent sympathetic pathways at relatively low doses resulting in profound suppression of hemodynamic and stress responses to surgery. PMID:21999144

  17. A double-blind randomised comparison of intravenous patient-controlled remifentanil with intramuscular pethidine for labour analgesia.

    PubMed

    Ng, T K T; Cheng, B C P; Chan, W S; Lam, K K; Chan, M T V

    2011-09-01

    In a prospective, double-blind, randomised controlled trial, we compared the efficacy of patient-controlled analgesia using remifentanil (25-30 μg per bolus) with intramuscular pethidine (50-75 mg) for labour analgesia in 69 parturients. Parturients receiving patient-controlled analgesia reported less pain than those receiving intramuscular pethidine throughout the study period (p < 0.001), with maximal reduction in visual analogue pain score at 2 h after commencement of analgesia (mean (SD) 20 (17) in the patient-controlled analgesia group and 36 (22) in the intramuscular pethidine group. The median (95% CI) time to the first request for rescue analgesics was significantly longer with patient-controlled analgesia (8.0 (6.8-9.2) h) compared with intramuscular pethidine (4.9 (3.8-5.4) h, p < 0.001). Maternal satisfaction scores were also higher with remifentanil compared with intramuscular pethidine (p= 0.001). There was no report of sedation, aponea or oxygen desaturation in either group, and Apgar scores were similar between groups. We conclude that patient-controlled analgesia with remifentanil provides better labour analgesia and maternal satisfaction than intramuscular pethidine. At this dose, maternal and fetal side effects were uncommon. PMID:21707564

  18. The opioid/nonopioid nature of stress-induced analgesia and learned helplessness.

    PubMed

    Maier, S F; Sherman, J E; Lewis, J W; Terman, G W; Liebeskind, J C

    1983-01-01

    Exposure to a variety of stressors produces a subsequent analgesic reaction. This stress-induced analgesia (SIA) is sometimes opioid in nature (reversed by opiate antagonists and cross-tolerant with morphine) and sometimes nonopioid. Both 30 min of intermittent footshock and 60-80 five-sec tailshocks have been shown to produce opioid SIA, whereas 3 min of continuous footshock and 5-40 tailshocks produce nonopioid SIA. We report that both of the opioid SIA procedures produce a learned helplessness effect as assessed by shuttlebox escape acquisition and an analgesia that is reinstatable 24 hr. later. The nonopioid procedures produce neither a learned helplessness effect nor a reinstatable analgesia. It is argued that these data implicate the learning of uncontrollability in the activation of opioid systems. PMID:6682435

  19. The effect of a combination of rectal diclofenac and caudal bupivacaine on postoperative analgesia in children.

    PubMed

    Gadiyar, V; Gallagher, T M; Crean, P M; Taylor, R H

    1995-09-01

    Both caudal anaesthesia and non-steroidal anti-inflammatory drugs have been used in the management of postoperative pain in children. The aim of the present study was to evaluate the combination of caudal analgesia and rectally administered diclofenac in the treatment of pain following minor surgery in children. Thirty-nine, ASA grade 1 or 2, children undergoing inguinal or penoscrotal surgery were randomly assigned to receive either a caudal block using 0.125% bupivacaine with adrenaline or a similar caudal block in combination with rectally administered diclofenac 1 mg.kg-1. Children given a caudal block alone were more likely to need analgesia in the first 24 h postoperatively. It would appear that the combination of a caudal block and rectal diclofenac in children undergoing minor lower abdominal surgery reduces the need for subsequent analgesia. PMID:7573879

  20. 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

  1. Fluoroscopically guided tunneled trans-caudal epidural catheter technique for opioid-free neonatal epidural analgesia.

    PubMed

    Franklin, Andrew D; Hughes, Elisabeth M

    2016-06-01

    Epidural analgesia confers significant perioperative advantages to neonates undergoing surgical procedures but may be very technically challenging to place using a standard interlaminar loss-of-resistance to saline technique given the shallow depth of the epidural space. Thoracic epidural catheters placed via the caudal route may reduce the risk of direct neural injury from needle placement, but often pose higher risks of infection and/or improper positioning if placed without radiographic guidance. We present a detailed method of placing a fluoroscopically guided, tunneled transcaudal epidural catheter, which may reduce both of these risks. The accuracy and precision of this technique often provides adequate analgesia to allow for opioid-free epidural infusions as well as significant reductions in systemic opioids through the perioperative period. Opioid-free analgesia using a regional anesthetic technique allows for earlier extubation and reduced perioperative sedation, which may have a less deleterious neurocognitive effect on the developing brain of the neonate. PMID:26896945

  2. A Comparison of Patient Controlled Epidural Analgesia With Intravenous Patient Controlled Analgesia for Postoperative Pain Management After Major Gynecologic Oncologic Surgeries: A Randomized Controlled Clinical Trial

    PubMed Central

    Moslemi, Farnaz; Rasooli, Sousan; Baybordi, Ali; Golzari, Samad E.J.

    2015-01-01

    Background: Postoperative pain after major open gynecologic surgeries requires appropriate pain management. Objectives: This study aimed at comparing perioperative patient controlled epidural analgesia (PCEA) and patient controlled intravenous analgesia (PCA) after gynecologic oncology surgeries. Patients and Methods: In this clinical trial study, 90 patients with American society of anesthesiologists (ASA) class I or II scheduled for gynecologic oncologic surgeries were randomly allocated to two groups (45 patients each group) to receive: patient-controlled epidural analgesia with bupivacaine and fentanyl (PCEA group), or patient controlled intravenous analgesia (IV PCA group) with fentanyl, pethidine and ondansetron. Postoperative pain was assessed over 48 hours using the visual analog scale (VAS). The frequency of rescue analgesia was recorded. Occurrence of any concomitant events such as nausea, vomiting, ileus, purities, sedation and respiratory complications were recorded postoperatively. Results: There were no statistically significant differences in demographic data including; age, weight, ASA physical status, duration of surgery, intraoperative bleeding, and the amount of blood transfusion (P > 0.05), between the two studied groups. Severity of postoperative pain was not significantly different between the two groups (P > 0.05); however, after first patient mobilization, pain was significantly lower in the epidural group than the IV group (P < 0.001). There was no significant difference between the two groups regarding the incidence of complications such as nausea, vomiting, purities or ileus (P > 0.05). Nevertheless, the incidence and severity of sedation was significantly higher in the IV group (P < 0.001). Respiratory depression was higher in the IV group than the epidural group; this difference, however, was not significant (P = 0.11). In the epidural group, only 10 patients (22.2%) had mild and transient lower extremities parenthesis. Conclusions

  3. Role of C-fibers in pain and morphine induced analgesia/hyperalgesia in rats

    PubMed Central

    Alizadeh, Zahra; Behnam-Rassouli, Morteza; Hosseini, Shirin

    2014-01-01

    Background Usual dosage of morphine (10 mg/kg) induces analgesia and ultra-low dose (ULD) of morphine (1 µg/kg); hyperalgesia, and C-fibers are also bearing µ-opioid receptors; here the importance of C-fibers on pain and morphine induced analgesia/hyperalgesia is questioned and investigated using pain evaluation methods and infant capsaicin treating for C-fibers lesioning. Methods Wistar male rats (200-250 grams) were assigned to three categories i.e. control, sham (receiving neonatal capsaicin vehicle) and c-lesion (receiving neonatal capsaicin), each one with three groups (n=7). They were injected intraperitoneally with single dosage of saline, 10 mg/kg or 1 µg/kg morphine, respectively. Thermal pain threshold was evaluated using the tail flick test before and 30 minutes after the injections. Chemical pain was assessed using the formalin test (FT) 30 minutes after the administrations. Results Results indicated that thermal (P < 0.001) and chemical pains in both neurogenic and inflammatory phases of FT (P < 0.05) were reduced in C-lesion animals. In the C-normal and C-lesion animals, 10 mg/kg morphine exerted analgesia both in thermal (P < 0.001) and two phases of FT (P < 0.01), but it was more potent in C-lesion animals (P < 0.05). Although ULD of morphine in C-normal animals produced hyperalgesic effect in thermal and chemical pains (P < 0.001), in C-lesion animals, it produced analgesia (P < 0.05) at the neurogenic phase of FT. Conclusion Results can raise the C-fibers involvement for a significant portion of nociceptive transmission, because C-lesioning potentiated morphine induced analgesia and eliminated ULD of morphine induced hyperalgesia. Therefore C and Aδ fibers can be involved in morphine analgesia; while, just C-fibers are possibly responsible for only presynaptically hyperalgesic/excitatory action of ULD in morphine. PMID:24800043

  4. Inhibiting Spinal Neuron-Astrocytic Activation Correlates with Synergistic Analgesia of Dexmedetomidine and Ropivacaine

    PubMed Central

    Cui, Yuan-Yuan; Dong, Yu-Lin; Chen, Guo-Zhong; Wang, Wen

    2014-01-01

    Background This study aims to identify that intrathecal (i.t.) injection of dexmedetomidine (Dex) and ropivacaine (Ropi) induces synergistic analgesia on chronic inflammatory pain and is accompanied with corresponding “neuron-astrocytic” alterations. Methods Male, adult Sprague-Dawley rats were randomly divided into sham, control and i.t. medication groups. The analgesia profiles of i.t. Dex, Ropi, and their combination detected by Hargreaves heat test were investigated on the subcutaneous (s.c.) injection of complete Freund adjuvant (CFA) induced chronic pain in rat and their synergistic analgesia was confirmed by using isobolographic analysis. During consecutive daily administration, pain behavior was daily recorded, and immunohistochemical staining was applied to investigate the number of Fos-immunoreactive (Fos-ir) neurons on hour 2 and day 1, 3 and 7, and the expression of glial fibrillary acidic protein (GFAP) within the spinal dorsal horn (SDH) on day 1, 3, 5 and 7 after s.c. injection of CFA, respectively, and then Western blot to examine spinal GFAP and β-actin levels on day 3 and 7. Results i.t. Dex or Ropi displayed a short-term analgesia in a dose-dependent manner, and consecutive daily administrations of their combination showed synergistic analgesia and remarkably down-regulated neuronal and astrocytic activations indicated by decreases in the number of Fos-ir neurons and the GFAP expression within the SDH, respectively. Conclusion i.t. co-delivery of Dex and Ropi shows synergistic analgesia on the chronic inflammatory pain, in which spinal “neuron-astrocytic activation” mechanism may play an important role. PMID:24658263

  5. Comparison of continuous epidural infusion and programmed intermittent epidural bolus in labor analgesia

    PubMed Central

    Lin, Yunan; Li, Qiang; Liu, Jinlu; Yang, Ruimin; Liu, Jingchen

    2016-01-01

    Background This study aims to investigate differences between continuous epidural infusion (CEI) and programmed intermittent epidural bolus (IEB) analgesia for the Chinese parturients undergoing spontaneous delivery and to approach their safety to parturients and neonates. Methods Two hundred healthy American Society of Anesthesiologists class I or II, term (≥37 weeks’ gestation), nulliparous women who requested analgesia for labor were recruited. Epidural analgesia was initiated with a solution of 0.15% ropivacaine 10 mL and maintained with 0.1% ropivacaine mixed with sufentanil 0.3 μg/mL by CEI at a rate of 5 mL/h combined with a patient-controlled epidural analgesia (PCEA) bolus of 5 mL of ropivacaine sufentanil mixture or IEB of 5 mL of ropivacaine sufentanil mixture combined with a PCEA bolus of 5 mL of ropivacaine sufentanil mixture. The lockout interval was 20 minutes in each arm between the CEI and the IEB group. After 20 minutes of first dosage, visual analog scale (VAS) score was obtained every 60 minutes. The maternal and fetal outcome and total consumption of analgesic solution were compared. Results There was no difference in demographic characteristics, duration of first and second stages, delivery methods, sensory block, fetal Apgar scores, and the maternal outcomes between the CEI and IEB groups. There was a significant difference in VAS scores and epidural ropivacaine total consumption between the two groups (IEB vs CEI: 51.27±9.61 vs 70.44±12.78 mg, P<0.01). Conclusion The use of programmed IEB mixed with PCEA improved labor analgesia compared to CEI mixed with PCEA, which could act as maintenance mode for epidural labor analgesia. PMID:27471390

  6. 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

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

    PubMed Central

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

    2016-01-01

    Background 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). Methods 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 1st and 3rd 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. Results 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). Conclusions Intravenous parecoxib in multimodal analgesia improves postoperative analgesia provided by TEA, relieves stress response after thoracotomy, and may restrain the development of chronic pain. PMID:27162662

  8. The association between negative affect and opioid analgesia in patients with discogenic low back pain.

    PubMed

    Wasan, Ajay D; Davar, Gudarz; Jamison, Robert

    2005-10-01

    Comprised mainly of depression, anxiety, and high neuroticism, psychopathology diminishes the effectiveness of many chronic pain treatments. But, it is not known if it is associated with diminished opioid analgesia in patients with chronic, noncancer pain. We tested the hypothesis that psychopathology diminishes opioid analgesia in patients with discogenic low back pain in 60 patients not on opioids in a double blind, placebo controlled, random crossover designed trial. Patients were stratified into three groups of psychological symptom severity (LOW, MOD, and HIGH), based on composite scores on depression, anxiety for pain, and neuroticism scales. Subjects were given intravenous morphine (4-6mg dosed by ideal body weight) and placebo in random order on separate visits, and completed serial pain ratings over three hours at each session. With 20 subjects per group, there were nonsignificant differences between groups in the distribution of age, gender, baseline pain (avg. 6.1/10), radicular pain, and morphine dose (5.0mg). For morphine analgesia, using a total pain relief calculation (TOTPAR), the LOW group had 65.1% TOTPAR vs. 41.0% in the HIGH group, P=.026. For placebo analgesia the LOW group had 7.7% TOTPAR vs. 23.5% in the HIGH group, P=.03. A morphine minus placebo analgesia calculation revealed 59.2% TOTPAR in the LOW group vs. 21.7% in the HIGH group, P=.0001. High levels of psychopathology are associated with diminished opioid analgesia in patients with discogenic low back pain. These results have implications for the prescription of oral opioids to patients with chronic low back pain and psychopathology. PMID:16154274

  9. Pupillary reflex measurement predicts insufficient analgesia before endotracheal suctioning in critically ill patients

    PubMed Central

    2013-01-01

    Introduction This study aimed to evaluate the pupillary dilatation reflex (PDR) during a tetanic stimulation to predict insufficient analgesia before nociceptive stimulation in the intensive care unit (ICU). Methods In this prospective non-interventional study in a surgical ICU of a university hospital, PDR was assessed during tetanic stimulation (of 10, 20 or 40 mA) immediately before 40 endotracheal suctionings in 34 deeply sedated patients. An insufficient analgesia during endotracheal suction was defined by an increase of ≥1 point on the Behavioral Pain Scale (BPS). Results A total of 27 (68%) patients had insufficient analgesia. PDR with 10 mA, 20 mA and 40 mA stimulation was higher in patients with insufficient analgesia (P <0.01). The threshold values of the pupil diameter variation during a 10, 20 and 40 mA tetanic stimulation to predict insufficient analgesia during an endotracheal suctioning were 1, 5 and 13% respectively. The areas (95% confidence interval) under the receiver operating curve were 0.70 (0.54 to 0.85), 0.78 (0.61 to 0.91) and 0.85 (0.721 to 0.954) with 10, 20 and 40 mA tetanic stimulations respectively. A sensitivity analysis using the Richmond Agitation Sedation Scale (RASS) confirmed the results. The 40 mA stimulation was poorly tolerated. Conclusions In deeply sedated mechanically ventilated patients, a pupil diameter variation ≥5% during a 20 mA tetanic stimulation was highly predictable of insufficient analgesia during endotracheal suction. A 40 mA tetanic stimulation is painful and should not be used. PMID:23883683

  10. Cognitive impairment is a risk factor for delayed analgesia in older people with long bone fracture: a multicenter exploratory study.

    PubMed

    Fry, Margaret; Arendts, Glenn; Chenoweth, Lynn; MacGregor, Casimir

    2014-08-27

    ABSTRACT Background: Older people who present to the emergency department (ED) often experience a significant delay to analgesia. This study compares the time to analgesia for cognitively impaired and cognitively intact older people diagnosed with a long bone fracture. Methods: The aim of the study was to determine if cognitive impairment is associated with a delayed analgesic response. A 12-month exploratory study, using patient data, was conducted across four EDs. Medical records of 264 patients with long bone fractures were randomly selected. Results: The majority of patients waited longer than 60 minutes for analgesia. The median time to analgesia was longer for the cognitively impaired (149 minutes) compared with cognitively intact (72 minutes; Mann-Whitney U test: p < 0.001). Conclusions: This study suggests that cognitive impairment is a significant risk factor for delayed analgesia response in the ED. PMID:25162158