naloxone and Pain--Postoperative

Long-acting neuraxial opioids such as morphine and diamorphine, administered via spinal or epidural routes, are staple components of a multimodal approach to postoperative analgesia following cesarean delivery. The widespread use of neuraxial opioids is due largely to their significant analgesic efficacy and favorable safety profile. The most common side effects of neuraxial opioids are pruritus, nausea and vomiting. These symptoms appear to be dose-related. The most serious complication of neuraxial opioids is respiratory depression, which occurs in 0-0.9% of cases. Hypothermia has also been reported in association with neuraxial morphine use at cesarean delivery. This article will review recent advances in prophylaxis, treatment and monitoring of the side effects of long-acting neuraxial opioids.

Topics: Analgesics, Opioid; Cesarean Section; Female; Humans; Hypothermia; Morphine; Naloxone; Pain, Postoperative; Postoperative Nausea and Vomiting; Pregnancy; Pruritus; Respiratory Insufficiency; Serotonin Antagonists

To determine whether postoperative administration of low-dose intravenous naloxone decreases the incidence of postoperative nausea and vomiting (PONV) and its impact on postoperative opioid requirements and pain scores.. Meta-analysis of nine randomized controlled trials.. A total of 946 adult and pediatric patients who received low-dose intravenous naloxone for 24 hours after various surgeries.. Systemic literature searches of the Cochrane Central Register of Controlled Trials, Evidence-Based Medicine Reviews, PubMed, and Ovid MEDLINE databases were conducted. Among the relevant studies, data extraction and bias assessment determined the trials for inclusion in this meta-analysis. Nine randomized controlled trials met inclusion criteria. Naloxone demonstrated a reduced risk of postoperative nausea (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.67-0.95, p=0.01) in a pooled analysis of eight of the nine studies. However, naloxone did not decrease the risk of postoperative vomiting in a collective assessment of all nine trials (RR 0.83, 95% CI 0.63-1.09, p=0.18). Subgroup analysis of continuous-infusion naloxone found further reductions in nausea and vomiting, but these findings were limited to 186 of the 946 patients. Three studies recorded antiemetic doses and found an overall dose reduction (RR 0.64, 95% CI 0.42-0.96, p=0.03). Compared with controls, naloxone prophylaxis of PONV did not significantly change cumulative postoperative opioid needs (mean difference 0.29 mg, 95% CI -3.55 to 4.13 mg, p=0.88) among five trials, nor visual analog scale pain scores (mean difference -0.11, 95% CI -0.26 to 0.05, p=0.18) in six studies.. This pooled analysis of data suggests that low-dose naloxone plays no role in preventing PONV, while exhibiting no significant effects on postoperative opioid needs and pain scores. The reduction demonstrated in postoperative nausea did not translate into decreases in postoperative vomiting.

Topics: Analgesics, Opioid; Humans; Infusions, Intravenous; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Postoperative Nausea and Vomiting; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic

In Australia and New Zealand, in parallel with other developed countries, the number of patients prescribed opioids on a long-term basis has grown rapidly over the last decade. The burden of chronic pain is more widely recognised and there has been an increase in the use of opioids for both cancer and non-cancer indications. While the prevalence of illicit opioid use has remained relatively stable, the diversion and abuse of prescription opioids has escalated, as has the number of individuals receiving methadone or buprenorphine pharmacotherapy for opioid addiction. As a result, the proportion of opioid-tolerant patients requiring acute pain management has increased, often presenting clinicians with greater challenges than those faced when treating the opioid-naïve. Treatment aims include effective relief of acute pain, prevention of drug withdrawal, assistance with any related social, psychiatric and behavioural issues, and ensuring continuity of long-term care. Pharmacological approaches incorporate the continuation of usual medications (or equivalent), short-term use of sometimes much higher than average doses of additional opioid, and prescription of non-opioid and adjuvant drugs, aiming to improve pain relief and attenuate opioid tolerance and/or opioid-induced hyperalgesia. Discharge planning should commence at an early stage and may involve the use of a 'Reverse Pain Ladder' aiming to limit duration of additional opioid use. Legislative requirements may restrict which drugs can be prescribed at the time of hospital discharge. At all stages, there should be appropriate and regular consultation and liaison with the patient, other treating teams and specialist services.

Topics: Acute Disease; Analgesics; Analgesics, Opioid; Animals; Australia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Tolerance; Humans; Hyperalgesia; Illicit Drugs; Methadone; Naloxone; Narcotic Antagonists; Narcotics; New Zealand; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Pain, Postoperative; Patient Discharge; Preoperative Care; Substance Withdrawal Syndrome

Pentazocine can be a useful analgesic agent for the management of acute dental pain. It has both central and peripheral opioid activity. In clinical trials, analgesic compounds containing pentazocine have been shown to effectively relieve moderate-to-severe pain. It is an appropriate analgesic for the codeine-sensitive patient. Because of a change in formulation, the potential for abuse has been minimized. Although there is a possibility that the drug may have a psychotomimetic effect, the incidence is low and should not preclude use. Analgesic compounds containing pentazocine are clinically appropriate for the management of surgically induced dental pain.

Topics: Analgesics; Drug Combinations; Facial Pain; Humans; Naloxone; Pain, Postoperative; Pentazocine; Receptors, Opioid; Tooth Extraction; Toothache

Topics: Endorphins; Fentanyl; Humans; Hydrocortisone; Intraoperative Period; Morphine; Naloxone; Pain; Pain, Postoperative; Physical Exertion; Postoperative Period; Stress, Physiological; Stress, Psychological; Surgical Procedures, Operative

Opioid-induced nausea and vomiting are common side effects of patient-controlled intravenous analgesia (PCIA). This study aimed to explore the inhibitory effect of a naloxone admixture on the incidence of sufentanil-induced postoperative nausea and vomiting (PONV).. A total of 132 Uyghur American Society of Anesthesiologists I and II patients scheduled to undergo elective gynecological laparoscopic surgery were recruited; among these, 120 patients were enrolled and randomly allocated into 4 groups: patients receiving PCIA but no naloxone were included in the control group (group A); patients receiving PCIA with a low-dose naloxone admixture at 0.2 μg·kg-1·h-1 were included in group B; patients receiving PCIA with naloxone admixture at 0.4 μg·kg-1·h-1 were included in group C; patients receiving PCIA with naloxone admixture at 0.6 μg·kg-1·h-1 were included in group D. All patients were administered sufentanil at 0.04 kg-1·h-1, butorphanol at 2 kg-1·h-1, and dexmedetomidine at 0.08 kg-1·h-1 using a PCIA device within 2 days of surgery. The occurrence of nausea and vomiting, visual analogue scores for pain intensity, mean arterial pressure, heart rate, oxygen saturation, pruritus, lethargy, respiratory depression, etc, was recorded at 2, 8, 12, 24, and 48 hours postoperatively.. There was a significant difference in the PONV scores between the groups at 8, 12, and 24 hours after surgery (P < 0.01). At 8 and 12 hours, the score of group C/D was significantly lower than that of group A/B (P < 0.01). At 24 hours after surgery, the PONV score of group B/C/D was significantly lower than that of group A (P < 0.01). No significant difference was observed in the general data and visual analogue scores for postoperative pain between the 4 groups.. Naloxone admixture administered at 0.4 to 0.6 μg·kg-1·h-1 can exert an effective inhibitory effect on the incidence and intensity of PONV in gynecological laparoscopic surgery.

Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Laparoscopy; Naloxone; Pain, Postoperative; Postoperative Nausea and Vomiting; Sufentanil

Topics: Adult; Aged; Analgesics, Opioid; Biliary Tract Surgical Procedures; Digestive System Diseases; Female; Humans; Incidence; Infusions, Intravenous; Injections, Spinal; Liver; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Respiratory Insufficiency; Young Adult

The analgesic efficacy of oxycodone prolonged-release (PR) combined with naloxone PR (OXN) in postoperative pain management is recognized, however, few studies have examined the efficacy of OXN on pain relief and bowel function following hysterectomy. This study compared the effect of OXN vs. standard treatment for post-operative pain management and bowel function following hysterectomy.. This randomized prospective study included 83 women who underwent laparoscopic/laparotomic hysterectomy. General anesthesia was induced by propofol (1.5-2 mg/kg), fentanyl (50-100 μg) and rocuronium (0.6-1 mg/kg) and maintained with sevoflurane (MAC 0.8-1) and fentanyl (1-2 μg/kg). Intraoperative analgesia was performed with ketorolac (30 mg), paracetamol (1 g) and morphine (0.1 mg/kg). Postoperative analgesia in the control group (N.=41) included morphine (0.2-0.4 mg/kg/day), whereas the OXN (N.=42) group only received oxycodone (10 mg)/naloxone (5 mg) for the first 48 hours. As rescue analgesic, both groups received paracetamol (3 mg). Bowel Function Index (BFI) and pain numeric rating scales (NRS) were measured at day 0, 1, 2, 3, 5 and 7, whereas vital parameters, rescue medication and side effects were recorded for the first three days only.. Bowel function indices were significantly improved in OXN-treated patients at all time points compared to morphine-treated patients. Mean static pain NRS was significantly decreased at day 2 and day 3 and dynamic pain NRS at day 3 in the OXN group. Side effects, rescue analgesic and antiemetics were more frequent in the control group.. Improved pain control, bowel function and reduced side effects were observed with OXN compared to morphine in patients who underwent hysterectomy.

Topics: Analgesics, Opioid; Chronic Pain; Constipation; Delayed-Action Preparations; Drug Combinations; Female; Humans; Hysterectomy; Naloxone; Oxycodone; Pain, Postoperative; Prospective Studies

Despite advances in pain management, several patients continue to experience severe acute pain after lumbar spine surgery. The aim of this study was to assess the safety and effectiveness of single ultra-low-dose intrathecal (IT) naloxone in combination with IT morphine for reducing pain intensity, pruritus, nausea, and vomiting in patients undergoing lumbar laminectomy with spinal fusion.. In this double-blind trial, patients scheduled for lumbar laminectomy with spinal fusion were randomly assigned to receive single ultra-low-dose IT naloxone (20 μg) and IT morphine (0.2 mg) (group M+N) or IT morphine (0.2 mg) alone (group M). The severity of postoperative pain, pruritus and nausea, and frequency of vomiting were assessed at recovery from anesthesia and, subsequently, at 1, 3, 6, 12, and 24 hours postoperatively using an 11-point (0-10) visual analogue scale.. A total of 77 patients completed the study, and there were significant differences in postoperative pain, pruritus, and nausea visual analogue scale between the groups (P<0.05). After adjusting for body mass index and surgery duration, IT naloxone administration reduced the pain score (coefficient=1.84; 95% confidence interval [CI], 1.05-2.63; P<0.001), and the scores of pruritus and nausea (coefficient=0.9; 95% CI, 0.44-1.37; P<0.001 and coefficient=0.71; 95% CI, 0.12-1.31; P=0.02, respectively) compared with IT morphine alone. No serious adverse effects were observed.. The addition of ultra-low-dose IT naloxone to IT morphine provides excellent postoperative pain management and effectively controls pruritus and nausea in patients undergoing laminectomy with spinal fusion.

Topics: Adult; Aged; Analgesia, Patient-Controlled; Double-Blind Method; Female; Humans; Injections, Spinal; Laminectomy; Lumbar Vertebrae; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Postoperative Complications; Postoperative Nausea and Vomiting; Pruritus; Spinal Fusion

Thoracic epidural analgesia (TEA) enhances recovery after bowel surgery. Early postoperative prolonged-release oral formulation of oxycodone or oxycodone/naloxone is potentially useful as a second analgesic step to reduce the duration of TEA. We hypothesized that oxycodone would decrease the duration of TEA and combined with naloxone preserve gastrointestinal function. Ninety patients undergoing open cystectomy and urinary diversion were enrolled in this randomized double-blind, three-arm, parallel-group, placebo-controlled single-center trial between September 2015 and February 2017. Exclusion criteria were known allergy to oxycodone/naloxone, pulmonary diseases, hepatopathy, and analgesics nonnaïve patients. From postoperative day 3, patients received batches with oxycodone, oxycodone/naloxone, or placebo every 12 hours (n = 30 in each arm). Reduction of the epidural drug infusion rate was attempted with the goal to maintain a pain intensity <3 at rest and <5 (numeric rating score) at mobilization during 6 hours. Primary endpoint was duration of TEA and secondary endpoint return of gastrointestinal function. The median duration of TEA did not differ between patients treated with oxycodone/naloxone (6.7 [range 3.1-10.3] days), oxycodone (7.0 [3.0-9.1]), or placebo (6.4 [3.1-8.4]); P = 0.88. Time to the first defecation was prolonged in the oxycodone group compared to the placebo group (difference 22.48 hours ±8.95; P = 0.037). In the oxycodone group, we found 8/30 patients with ileus (27%) compared to 2/28 (7%) in the oxycodone/naloxone group and to 2/30 (7%) in the placebo group; (P = 0.031). Oxycodone, with or without naloxone, did not reduce the duration of TEA. Oxycodone alone led to a delayed return of bowel function, whereas the combination was not different from placebo.

Topics: Administration, Oral; Aged; Aged, 80 and over; Analgesia, Epidural; Analgesics, Opioid; Cystectomy; Double-Blind Method; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Oxycodone; Pain, Postoperative; Prospective Studies; Urinary Diversion

The purpose of this study was to determine whether oral prolonged-release oxycodone-naloxone combination (OXN) could provide equivalent analgesia and a side-effect profile similar to intravenous morphine patient-controlled analgesia (IVPCA) for the control of pain in the immediate postoperative period after total knee replacement (TKR).. All patients received a sciatic nerve block with 0.3% ropivacaine 15 mL, femoral nerve block with 0.5% ropivacaine 20 mL, spinal anesthesia and postoperative continuous femoral nerve infusion (ropivacaine 0.2% 4 mL/h). After surgery, patients were randomly allocated to receive either 10 +10 +5 mg controlled release OXN oral administration 12 hourly or IVPCA with morphine (2 mg bolus, no basal infusion). The primary outcome was the average rest and dynamic pain for the first 48 h postoperatively. Secondary outcomes were: post operative nausea vomiting (PONV) and the total morphine consumption.. OXN group experienced better pain control at rest during the first (0.89±1.54 vs. 1.27±1.82, P=0.0019) and second (1.03±1.69 vs. 1.65±2.05, P=0.0006) postoperative period. There was no statistically significant difference in pain score during movement between the two groups. The secondary outcome measures showed no significant differences in the total morphine consumption (12.04±1.1 vs. 11.46±3.7 mg, P=0.20) or PONV (0.6±0.8 vs. 0.8±1.0, P=0.40).. This study show that in the immediate postoperative period after TKR, the patients receiving oral prolonged-release OXN experienced the same to better pain control than those receiving morphine IVPCA, with a similar degree of PONV.

Topics: Administration, Oral; Aged; Analgesia; Analgesia, Patient-Controlled; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Delayed-Action Preparations; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Morphine; Naloxone; Oxycodone; Pain, Postoperative; Prospective Studies

Lumbar discectomy is one of the most commonly performed neurosurgical procedures. Many patients experience postoperative pain after lumbar discectomy. This study evaluated the effect of ultra-low-dose naloxone infusion on pain intensity after lumbar discectomy in individuals receiving patient-controlled analgesia (PCA) with morphine.. In a double-blind, randomized, controlled trial, a total of 80 patients scheduled for open discectomy was randomly assigned to receive naloxone (group N) or placebo (group P). After surgery, all patients were connected to a morphine PCA pump. Both groups received 500 mL of normal saline using a continuous infusion pump through a separate intravenous line for 24 hours. However, group N received a total dose of 0.25 μg/kg/h naloxone, which was added to the normal saline infusion. All patients were asked to grade the intensity of their pain, severity of nausea, vomiting, and pruritus on a 0 to 10 visual analog scale before being discharged from the postanesthesia care unit and at 1, 6, 12, and 24 hours postoperatively.. It was observed that both groups had a statistically significant (P<0.01) time trend difference for pain, nausea, and pruritus scores. A significant difference was found between the 2 groups in terms of intensity of pain, nausea, and pruritus, with the naloxone group experiencing a lower level in comparison with the placebo group. Moreover, the median (interquartile range) of morphine consumption after surgery for patients who received naloxone was 26 (24.25 to 28) mg, which is significantly (P<0.001) lower than for the placebo group, which had a median (interquartile range) of 34 (32 to 36) mg.. It is concluded that infusion of ultra-low-dose naloxone (0.25 μg/kg/h) along with morphine PCA can significantly reduce pain intensity, morphine consumption, and opioid-induced nausea and pruritus after lumbar discectomy.

Topics: Adult; Aged; Analgesia, Patient-Controlled; Analgesics, Opioid; Diskectomy; Double-Blind Method; Female; Humans; Infusions, Intravenous; Intervertebral Disc Displacement; Lumbar Vertebrae; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Pruritus

High post-operative pain scores after "minor" orthopedic/trauma surgery are in part attributed to inadequate prescription of opioid analgesics. Novel concepts aiming to achieve sufficient analgesia while minimizing opioid-related side effects by avoiding fluctuating plasma levels are based on perioperative oral administration of extended-release opioids beginning with the first dose pre-operatively. This is the first study to evaluate analgesic efficacy and side effect rates of extended-release tapentadol compared to oxycodone/naloxone following orthopedic/trauma surgery.. This randomized, observer-blinded, active-controlled prospective clinical trial had 2 co-primary endpoints: (1) Analgesic efficacy: Mean pain level on a numeric rating scale (NRS) from 0 to 10 during exercise over 5 days. (2) Safety: Side effect sum score of the following events: Nausea, vomiting, constipation, sedation, vertigo, somnolence. The study was powered to detect superiority of tapentadol for at least one endpoint pending statistical proof of non-inferiority for both endpoints in a first step.. Two hundred sixty-six trauma patients were randomized to receive either tapentadol (n = 133) or oxycodone/naloxone (n = 133). Analgesic efficacy: Mean (±SD) daily pain levels in the first five post-operative days were 2.8 ± 1.3 in both groups. Mean maximum pain intensity during exercise in the first 24 h after surgery was 3.8 ± 1.9 (tapentadol) and 3.8 ± 2.1 (oxycodone/naloxone). Statistically tapentadol was non-inferior but not superior to oxycodone/naloxone.. Vomiting on day 1 occurred in 11%, constipation in 35% of the tapentadol patients and in 16% and 30% of the oxycodone/naloxone patients (p = 0.60 and 0.33), respectively. The incidence of sedation/ vertigo was <10%, that of somnolence <2% in both groups (p > 0.3, respectively). The sum score of side effect events was 51% in the tapentadol vs. 49% in the oxycodone/naloxone group; risk difference 3% [95% CI, -8 to 14%]; p = 0.6). Non-inferiority of tapentadol could not be concluded as the pre-defined non-inferiority margin was exceeded.. With both concepts, mean maximum pain intensity during exercise within the first 24 h after orthopedic/trauma surgery was reduced to a score of <4. This analgesic efficacy came at the cost of mainly gastro-intestinal side effects. Thus, we now use a prophylaxis against nausea and vomiting and pre-emptive laxatives as part of these concepts.. https://eudract.ema.europa.eu (EudraCT- Nr. 2011-003238-15 ); October 24th, 2012.

Topics: Analgesics, Opioid; Constipation; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Naloxone; Orthopedic Procedures; Oxycodone; Pain Measurement; Pain, Postoperative; Phenols; Postoperative Nausea and Vomiting; Prospective Studies; Single-Blind Method; Tapentadol

Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone.. Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml-1 remifentanil with 0.05 μg kg-1 h-1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml-1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery.. The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22-3.84) vs 3.84 (3.76-4.00) vs 3.80 (3.69-4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups.. The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain.. NCT02856087.

Topics: Adult; Aged; Analgesics, Opioid; Double-Blind Method; Female; Humans; Hyperalgesia; Intraoperative Care; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Prospective Studies; Remifentanil; Young Adult

Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection.. In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance. Secondary endpoints included a composite endpoint of gut function (tolerance of solid food, low nausea/vomiting score, passage of flatus or faeces).. Eighty-two patients were screened and 62 randomized (76 per cent); the attrition rate was 19 per cent (12 of 62), leaving 50 patients who received the allocated intervention with 100 per cent follow-up and retention (modified intention-to-treat cohort). Protocol compliance was more than 90 per cent. Return of gut function by day 3 was similar in the two groups: 13 (48 per cent) of 27 in the oxycodone-naloxone group and 15 (65 per cent) of 23 in the control group (95 per cent c.i. for difference -10·0 to 40·7 per cent; P = 0·264). However, patients in the oxycodone-naloxone group had a shorter time to first bowel movement (mean(s.d.) 87(38) h versus 111(37) h in the control group; 95 per cent c.i. for difference 2·3 to 45·4 h, P = 0·031) and reduced total (oral plus parenteral) opioid consumption (mean(s.d.) 78(36) versus 94(56) mg respectively; 95 per cent c.i. for difference -10·2 to 42·8 mg, P = 0·222).. High participation, retention and protocol compliance confirmed feasibility. Potential benefits of oxycodone-naloxone in reducing time to bowel movement and total opioid consumption could be tested in a randomized trial. Registration number: NCT02109640 (https://www.clinicaltrials.gov/).

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Colectomy; Defecation; Delayed-Action Preparations; Drug Combinations; Drug Utilization; Eating; Feasibility Studies; Female; Flatulence; Humans; Laparoscopy; Male; Middle Aged; Naloxone; Oxycodone; Pain, Postoperative; Patient Compliance; Pilot Projects; Preanesthetic Medication; Time Factors

Opioids are needed for postoperative pain in spine surgery patients, but opioid-induced constipation is a harmful adverse event. The aim of this clinical trial was to compare the use of a controlled-release oxycodone-naloxone combination product with oxycodone controlled-release tablets in these patients. The main outcome measure was the prevalence of constipation at 7 days postoperatively assessed with a Bowel Function Index questionnaire. A follow-up assessment at 21 days after surgery was also included.. A total of 180 patients undergoing spine surgery, 91 having preoperative opioids in use and 89 opioid-naïve, were randomized to receive twice-daily oxycodone 10 mg or oxycodone-naloxone 10/5 mg controlled-release tablets for the first 7 postoperative days. Patients were followed-up for 21 days after surgery.. At baseline, prevalence of constipation was common both in the opioid-naïve-25/87 (29%) and on-opioid groups 43/90 (48%) (P = 0.009). This increased at 7 days postoperatively with no difference between the groups, 54/89 with oxycodone and 54/88 with oxycodone-naloxone had constipation. At 21 days, constipation was less than in the baseline in both groups, in the opioid-naïve group the prevalence of constipation was 3/43 (7%) in patients with oxycodone-naloxone compared to 9/44 (21%) with oxycodone (effect size 0.68; P = 0.068). Both study compounds provided similar pain relief and were well tolerated.. In patients presented for back surgery, the prevalence of constipation was significantly higher than that in the community. In opioid-naïve subjects, oxycodone-naloxone was beneficial concerning constipation; but this was not distinguishable in subjects with chronic opioid use. The analgesic efficacy of oxycodone and oxycodone-naloxone was similar.. European Clinical Trials Database (EudraCT no. 2012-001816-42) and ClinicalTrials.gov database (Identifier: NCT02573922).

Topics: Adult; Aged; Analgesics, Opioid; Constipation; Delayed-Action Preparations; Drug Combinations; Female; Humans; Male; Middle Aged; Naloxone; Neurosurgical Procedures; Outcome Assessment, Health Care; Oxycodone; Pain, Postoperative; Prospective Studies; Single-Blind Method; Surveys and Questionnaires

The purpose of this study was to examine the effect of postoperative prolonged release oxycodone/naloxone (OXN) in comparison to other opioids (control group) on the early postoperative rehabilitation outcome after total knee replacement.. In a prospective, noninterventional, nonrandomized clinical trial, 80 patients were assigned to either the OXN group or a control group. Postoperative outcome and pain level at days 3, 6, 21, 35, and 6months were evaluated using the Bowel Function Index, Brief Pain Inventory Short Form questionnaire, the Hospital for Special Surgery score, modified Larson score, and the ability to attend physiotherapy. Medications were recorded and safety analysis was done. Both groups were compared using an analysis of covariance.. There were no significant differences between both groups regarding pain levels. OXN group patients reported better bowel function (median values of 0.0 for the OXN group and 20.0 for the control group). No effect of treatment group (P=.19) and no treatment-by-visit interaction on Hospital for Special Surgery final score (P=.67) could be detected, but Larson function score in the early postoperative phase was significantly better in the OXN group (P=.018). The proportion of OXN group patients who were able to attend without any restriction was 58.1%. The proportions of patients in the OXN group and control group who experienced mild or moderate adverse drug reactions were 23.3% and 37.8%, respectively. There were no serious adverse drug reactions.. In conclusion, OXN provides an effective analgesia and offers several benefits such as higher ability to participate in physiotherapy and better functional results. Incidence and severity of constipation can be reduced by using prolonged-released OXN as compared with other opioids.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Constipation; Delayed-Action Preparations; Female; Humans; Intestines; Male; Middle Aged; Naloxone; Narcotic Antagonists; Oxycodone; Pain Measurement; Pain, Postoperative; Physical Therapy Modalities; Postoperative Complications; Prospective Studies

This study aims to evaluate the effect of naloxone on intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia.A total of 90 patients, who underwent intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia, were included into this study. All patients were randomly divided into 3 groups (each group, n=30): naloxone group (naloxone+fentanyl), tropisetron group (tropisetron+fentanyl), and fentanyl group (fentanyl). Patients in each group were given a corresponding dose of naloxone. Postoperative analgesia effect and the incidence of side effects such as nausea and vomiting were observed.Small doses of naloxone or tropisetron combined with fentanyl used for intravenous patient-controlled analgesia can significantly reduce the incidence of nausea and vomiting. Six hours after surgery, visual analogue scale (VAS) scores were significantly lower in patients that underwent intravenous patient-controlled analgesia using low-dose naloxone combined with fentanyl compared with patients who received fentanyl alone; however, the postoperative analgesic effect of tropisetron was not observed. Compared with the combination of tropisetron and fentanyl, low-dose naloxone combined with fentanyl can obviously reduce the incidence of nausea and vomiting in patients who underwent intravenous patient-controlled analgesia after laparoscopic cholecystectomy, and enhance the analgesic effect of fentanyl 6 hours after surgery.Low-dose naloxone can reduce the incidence of nausea and vomiting in patients who underwent laparoscopic cholecystectomy under total intravenous anesthesia, and exhibits a certain synergic analgesic effect.

Topics: Aged; Analgesia, Patient-Controlled; Analgesics, Opioid; Anesthetics, Intravenous; Antiemetics; Cholecystectomy, Laparoscopic; Drug Therapy, Combination; Female; Fentanyl; Humans; Indoles; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Tropisetron

Previous studies have shown that preincisional epidural morphine, bupivacaine, and ketamine combined with epidural anesthesia (EA) and general anesthesia (GA) provided pre-emptive analgesia for upper abdominal surgery. Recent studies reported that ultralow-dose naloxone enhanced the antinociceptive effect of morphine in rats. This study investigated the benefits of preincisional and postoperative epidural morphine + ropivacaine + ketamine + naloxone (M + R + K + N) treatment for achieving postoperative pain relief in upper abdominal surgery.. Eighty American Society of Anesthesiology I-II patients scheduled for major upper abdominal surgery were allocated to four groups in a randomized, single-blinded study. All patients received combined GA and EA with a continuous epidural infusion of 2% lidocaine (6-8 mL/h) 30 minutes after pain regimen. After GA induction, in Group I, an epidural pain control regimen (total 10 mL) was administered using 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg; M + R); in Group II, 1% lidocaine 8 (mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg; M + R + K); in Group III, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + naloxone (2 μg; M + R + N); and in Group IV, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg) + naloxone (2 μg; M + R + K + N), respectively. All patients received patient-controlled epidural analgesia (PCEA) with different pain regimens to control subsequent postoperative pain for 3 days following surgery. During the 3-day period following surgery, PCEA consumption (mL), numerical rating scale (NRS) score while cough/moving, and analgesic-related adverse effects were recorded.. Total PCEA consumption for the 3-day observation period was 161.5±17.8 mL, 103.2±21.7 mL, 152.4±25.6 mL, and 74.1±16.9 mL for Groups I, II, III, and IV, respectively. (p < 0.05). The cough/moving NRS scores were significantly lower in Group IV patients than Groups I and III patients at 4 hours, 12 hours, and on Days 1 and 2 following surgery except for Group II (p < 0.05).. Preincisional and postoperative epidural M + R + K + N treatment provides an ideal postoperative pain management than preincisional and postoperative epidural M + R, M + R + K, and M + R + N treatments in upper abdominal surgery.

Topics: Abdomen; Adult; Aged; Amides; Analgesia, Epidural; Analgesia, Patient-Controlled; Female; Humans; Ketamine; Male; Middle Aged; Morphine; Naloxone; Pain, Postoperative; Ropivacaine; Single-Blind Method

Morphine administered by continuous opioid infusion (COI) or by patient-controlled analgesia (PCA) is associated with opioid-induced pruritus (OIP). Intravenous naloxone administered separately to the morphine infusion at a dose of 0.25-1.65 μg·kg(-1)·hr(-1) can provide effective prevention from OIP. Nevertheless, this strategy requires a dedicated intravenous line and an additional infusion pump. The purpose of this study was to determine whether an admixture of naloxone with morphine in normal saline administered via COI or PCA would also prevent OIP in children without attenuation of analgesia or increased opioid utilization.. In this randomized controlled trial, children meeting the inclusion criteria (aged 8-18 yr, American Society of Anesthesiologists physical status I-III, normal developmental profile and prescribed COI/PCA morphine for postoperative analgesia) were randomized to receive an infusion containing a naloxone, opioid, and saline admixture (NOSA) of 12 μg naloxone per 1 mg morphine per 1 mL normal saline or morphine only (control). The severity of opioid-induced pruritus was assessed by self-report using a modified colour analogue scale (mCAS; score 0-10). The groups were also compared for opioid utilization, pain scores, and administration of antipruritic medications, which were recorded for up to 48 hr or until the COI/PCA was discontinued.. Ninety-two participants were enrolled in the study. The median [interquartile range] dose of naloxone administered to the NOSA participants was 0.37 [0.30-0.48] μg·kg(-1)·hr(-1). The incidence of OIP, determined by self-report and treatment, was not different between groups: 22% in the NOSA group vs 36% in the control group (mean difference, -15%; 95% confidence interval [CI], -33 to 4; P = 0.164). The severity of opioid-induced pruritus was similar in the two groups, with a median difference in the participants' mean mCAS score of -0.29 (95% CI, -0.75 to 0.26; P = 0.509). Opioid utilization did not differ between groups, with a median difference of -1.35 μg·kg(-1)·hr(-1) (95% CI, -5.85 to 7.55; P = 0.518), and pain scores did not differ, with a median difference of 0.0 (95% CI, -1.0 to 1.5; P = 0.659).. This admixture of naloxone and morphine in normal saline did not decrease the incidence or severity of OIP in this sample. Separate administration of naloxone may be the more effective strategy for prevention of OIP. This trial was registered at ClinicalTrials.gov (NCT01071057).

Topics: Adolescent; Analgesia, Patient-Controlled; Analgesics, Opioid; Child; Double-Blind Method; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Postoperative Nausea and Vomiting; Pruritus; Survival Analysis

In this study, the effect of naloxone on duration of supraclavicular brachial plexus block was evaluated. It was hypothesized that naloxone can increase the duration of neural blockade.. Sixty-eight patients scheduled for surgery under supraclavicular brachial plexus block were randomly assigned to receive 30 ml bupivacaine (Group C); 30 ml bupivacaine with 100 μg of fentanyl (Group F); 30 ml bupivacaine with 100 ng naloxone (Group N); or 30 ml bupivacaine with 100 μg of fentanyl and 100 ng naloxone (Group N + F). Sensory and motor blockade were recorded at 5, 15, and 30 min following the block, and every 10 min following the end of surgery. Duration of sensory and motor block was considered to be the time interval between the complete block and the first postoperative pain and complete recovery of motor functions.. Sensory and motor onset times were the same in all groups. The duration of sensory and motor block in Group C (11.3 ± 1.7 h and 4.56 ± 1.0 h) and Group F (12.8 ± 3.3 h and 5.1 ± 2.0 h) were less than in the other groups (18.1 ± 2.2 h and 6.18 ± 1.0 h in Group N, and 15.8 ± 2.9 h and 6.53 ± 1.1 h in Group N + F, P < 0.0001).. Addition of naloxone to bupivacaine in supraclavicular brachial plexus block prolonged the duration of the neural blockade.

Topics: Adjuvants, Anesthesia; Adult; Anesthetics, Local; Brachial Plexus; Brachial Plexus Block; Bupivacaine; Drug Synergism; Drug Therapy, Combination; Female; Fentanyl; Humans; Male; Motor Activity; Naloxone; Narcotic Antagonists; Pain, Postoperative; Time Factors

Tolerance to remifentanil during sevoflurane anesthesia may increase postoperative analgesic requirements. Low-dose naloxone not only has been shown to block the development of acute opioid tolerance but also to ameliorate undesired opioid-induced side effects. We hypothesized that naloxone prevents the acute opioid tolerance produced by a large dose of remifentanil, and reduces the incidence of opioid-induced side effects.. Seventy-two patients undergoing open colorectal surgery were randomly assigned to receive intraoperative remifentanil (1) small dose at 0.1 μg/kg/min; (2) large dose at 0.30 μg/kg/min; or (3) large dose at 0.30 μg/kg/min combined with low-dose naloxone at 0.25 μg/kg/h just after the induction. Cumulative morphine consumption, postoperative pain scores, incidence of opioid-related side effects, time to recovery of bowel function, and length of hospital stay were recorded.. Cumulative morphine consumption at 24 h after surgery was higher in the large-dose remifentanil group (28 ± 12 mg) compared with the small-dose remifentanil group (17 ± 12 mg), and large-dose remifentanil-naloxone group (18 ± 9 mg), (P < 0.001). The median time to return of bowel function was shorter in the large-dose remifentanil-naloxone group than the other two groups (P < 0.05). The median length of hospital stay was lower in the large-dose remifentanil-naloxone group (8 [interquartile range: 8-12] days) compared with the small-dose remifentanil group (12 [interquartile range: 9-15] days) and large-dose remifentanil group (12 [interquartile range: 10-13] days), (P < 0.001).. Naloxone infusion prevented the acute opioid tolerance, provided a quicker recovery of bowel function, and reduced the length of hospital stay after open colorectal surgery.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Double-Blind Method; Humans; Infusions, Intravenous; Middle Aged; Naloxone; Narcotic Antagonists; Pain, Postoperative; Prospective Studies; Young Adult

Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans.. Patients submitted to unilateral, primary, open groin hernia repair will be included in this randomized, placebo-controlled, double-blind, crossover study. The experimental days take place 6-8 weeks after surgery, time-points at which patients are expected to be almost pain- free. Prior to administration of naloxone or placebo, the primary outcome (a summated measure of pain: at rest, during transition from supine to standing position, and evoked by pressure algometry) and the secondary outcomes (secondary hyperalgesia/allodynia, pressure pain thresholds, assessed at the surgical site and at the mirror-site in the contralateral groin, and, opioid withdrawal symptoms) will be assessed. These assessments will be repeated at each step of the target-controlled infusion of placebo or naloxone at estimated median (95 % CI) plasma concentrations of 344 ng/ml (130;567), 1059 ng/ml (400;1752) and 3196 ng/ml (1205;5276).. We aim to demonstrate opioid-mediated latent sensitization in a post-surgical setting, using pain as a clinical relevant variable. Impairment of the protective endogenous opioid system may play an important role in the transition from acute to chronic pain. In order to sufficiently block the endogenous opioid system, a high-dose target-controlled naloxone-infusion is used, in accordance with recent findings in animal studies.. 2015-000793-36 (Registration date: 16 February 2015) Clinicaltrials.gov: NCT01992146 (Registration date: 12 December 2014).

Topics: Analgesics, Opioid; Central Nervous System Sensitization; Clinical Protocols; Cross-Over Studies; Denmark; Double-Blind Method; Drug Monitoring; Hernia, Inguinal; Herniorrhaphy; Humans; Hyperalgesia; Infusions, Parenteral; Naloxone; Narcotic Antagonists; Pain Measurement; Pain Threshold; Pain, Postoperative; Research Design; Treatment Outcome

Cardiac surgery and sternotomy are procedures accompanied by substantial postoperative pain which is challenging to treat. In general, intravenous (IV) opioids are used in the immediate postoperative phase, followed by oral opioids. Oral opioids are easier to use and generally less expensive. Our goal was thus to determine whether a new opioid preparation provides adequate analgesia after sternotomy. In particular, we tested the primary hypothesis that total opioid use (in morphine equivalents) is not greater with oral opioid compared with patient-controlled IV morphine. Our secondary hypothesis was that analgesic efficacy is similar with oral and IV opioids.. A total of 51 patients having elective cardiac surgery were enrolled in this study. After rapid postoperative respiratory weaning, the patients were randomised into one of two groups receiving different types of analgesia: oral Targin (a combination of oxycodone-hydrochloride and the opioid antagonist naloxone hydrochloride-dihydrate) or patient-controlled IV morphine. Pain score (visual analogue scale), sedation (Ramsey score), respiratory rate and side effects were assessed at 3, 5, 7, 9 and 11 h after surgery, and every 6 h throughout the third postoperative evening.. The total opioid dose in morphine equivalent doses was significantly lower with oral opioid than with IV morphine (adjusted geometric means [95 % confidence interval]: 34 [29; 38] vs. 69 [61; 78] mg, respectively). Pain scores were similar in each group.. Analgesic quality was comparable with oral and IV opioids, suggesting that postoperative pain even after very painful procedures can be sufficiently managed with oral opioids.

Topics: Administration, Intravenous; Administration, Oral; Aged; Analgesia, Patient-Controlled; Analgesics, Opioid; Cardiac Surgical Procedures; Drug Combinations; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Oxycodone; Pain, Postoperative

Targiniq®, an oxycodone prolonged-release (PR) formulation combined with the opioid antagonist naloxone PR, aims to prevent opioid-induced constipation without impairing the analgesic efficacy. This has been confirmed during prolonged use in chronic pain or cancer patients. The purpose of our study was to compare clinical effects of oxycodone PR with oxycodone PR + naloxone PR for short-term post-operative pain management.. This randomised, double-blind, prospective study included 85 women undergoing laparoscopic hysterectomy. The two groups received either oxycodone PR 10 mg or oxycodone PR 10 mg + naloxone PR 5 mg as pre-medication and twice daily for 3 days. As rescue analgesic, the patients received oxycodone intravenous during the first 24 h post-operatively and oxycodone tablets in the 24-72-h period. Constipation, other side effects, pain and satisfaction were registered during the first 7 post-operative days.. Demographic, pre- and perioperative variables and the use of rescue analgesics were similar in the groups. There were no significant differences in variables related to constipation. In the oxycodone PR + naloxone PR group, 25% had no defecation during the first 72 h post-operatively, compared with 20% in the oxycodone PR group (mean 1.2 ± 1.1 vs. 2.1 ± 2.4 defecations). Other opioid-induced effects and side effects showed no significant differences. Only 7% were dissatisfied with their oral pain treatment.. Addition of naloxone to oxycodone PR tablets in a pain regimen administered twice daily the first three post-operative days had no significant clinical effects on constipation or other variables during the first week after hysterectomy.

Topics: Adult; Analgesics, Opioid; Constipation; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hysterectomy; Laparoscopy; Middle Aged; Naloxone; Narcotic Antagonists; Oxycodone; Pain, Postoperative; Prospective Studies

The evidence that an infusion of a low dose of naloxone reduces post-operative pain and opioid analgesic consumption is somewhat conflicting. Thus, the aim of the present study was to investigate the effect of an ultra-low dose of naloxone on patient-controlled morphine analgesia.. Ninety patients, 35-55 years old, scheduled for total abdominal hysterectomy, were enrolled in this prospective, randomized, double-blind and placebo-controlled study. Post-operatively, they received either saline (n = 45) or naloxone (n = 45) for 24 h. A standard general anesthesia was administered in both groups. In the recovery room, patients received morphine by a patient-controlled analgesia device. An ultra-low dose of naloxone was infused intravenously at 0.25 μg/kg/h for 24 h in the intervention group. Saline was infused in the control group. Following the surgery, morphine consumption, numeric rating score for pain intensity, nausea and vomiting, pruritus, and requests for antiemetic were recorded at baseline, 30 min, 1, 4, 8,16, 20, and 24 h following their discharge from recovery.. Naloxone reduced morphine consumption over the first 24 post-operative hours significantly compared with the controls (saline) {19.5 [standard deviation (SD) 3.4] mg vs. 27.5 [SD 5.9] mg; P < 0.001}. The incidence and severity of nausea and vomiting was significantly reduced in the naloxone group. The incidence of pruritus and the pain scores at rest and activity were not significantly different.. Following hysterectomy, an ultra-low dose of naloxone infusion proved to reduce morphine consumption as well as the incidence and severity of opioid-induced nausea and vomiting.

Topics: Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Cough; Double-Blind Method; Female; Humans; Hysterectomy; Infusions, Intravenous; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Postoperative Nausea and Vomiting; Pruritus; Treatment Outcome

These studies evaluated the feasibility of using oral prolonged-release oxycodone/naloxone (OXN PR) for the management of acute postoperative pain.. Three studies were undertaken: (i) the analgesic efficacy of OXN PR was compared with prolonged-release oxycodone (OXY PR) in patients with knee arthroplasty in an immediate postoperative period (IPOP) study; (ii) OXN PR treatment was compared with other opioids during rehabilitation after knee arthroplasty in a noninterventional study (NIS); and (iii) surgical patients on other opioids were switched to OXN PR postoperatively during a quality improvement programme (QIP).. In the IPOP study, the pain intensity at rest score decreased by a similar amount in the OXN PR and OXY PR groups, indicating similar analgesic efficacies. In the NIS, patient assessments indicated enhanced efficacy and tolerability for OXN PR compared with other opioids. The QIP indicated significant improvements in bowel function and less difficulty passing urine at the end of OXN PR treatment compared with baseline. No safety concerns were raised.. The analgesic efficacies of OXN PR and OXY PR were similar in postoperative pain settings. OXN PR reduced the degree of restriction in relation to patients carrying out physiotherapy compared with other opioids, and improved bowel and bladder function.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Constipation; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Naloxone; Oxycodone; Pain Management; Pain, Postoperative; Spine; Treatment Outcome; Young Adult

Opioid-induced side effects, such as pruritus, nausea, and vomiting are common and may be more debilitating than pain itself. A continuous low-dose naloxone infusion (0.25 μg/kg/h) ameliorates some of these side effects in many but not all patients without adversely affecting analgesia. We sought to determine the optimal dose of naloxone required to minimize opioid-induced side effects and to measure plasma morphine and naloxone levels in a dose escalation study.. Fifty-nine pediatric patients (24 male/35 female; average age 14.2 ± 2.2 years) experiencing moderate to severe postoperative pain were started on IV patient-controlled analgesia morphine (basal infusion 20 μg/kg/h, demand dose 20 μg/kg, 5 doses/h) and a low-dose naloxone infusion (initial cohort: 0.05 μg/kg/h; subsequent cohorts: 0.10, 0.15, 0.25, 0.40, 0.65, 1, and 1.65 μg/kg/h). If 2 patients developed intolerable nausea, vomiting, or pruritus, the naloxone infusion was increased for subsequent patients. Dose/treatment success occurred when 10 patients had minimal side effects at a naloxone dose. Blood samples were obtained for measurement of plasma morphine and naloxone levels after initiation of the naloxone infusion, processed, stored, and measured by tandem mass spectrometry with electrospray positive ionization.. The minimum naloxone dose at which patients were successfully treated with a <10% side effect/failure rate was 1 μg/kg/h; cohort size varied between 4 and 11 patients. Naloxone was more effective in preventing pruritus than nausea and vomiting. Concomitant use of supplemental medicines to treat opioid-induced side effects was required at all naloxone infusion rates. Plasma naloxone levels were below the level of assay quantification (0.1 ng/mL) for infusion rates ≤0.15 μg/kg/h. At rates >0.25 μg/kg/h, plasma levels increased linearly with increasing infusion rate. In each dose cohort, patients who failed therapy had comparable or higher plasma naloxone levels than those levels measured in patients who did not fail treatment. Plasma morphine levels ranged between 3.52 and 172 ng/mL, and >90% of levels ranged between 10.2 and 61.6 ng/mL. Plasma morphine levels were comparable between patients who failed therapy and those patients who achieved symptom control.. Naloxone infusion rates ≥1 μg/kg/h significantly reduced, but did not eliminate, the incidence of opioid-induced side effects in postoperative pediatric patients receiving IV patient-controlled analgesia morphine. Patients who failed therapy generally had plasma naloxone and morphine levels that were comparable to those who had good symptom relief suggesting that success or failure to ameliorate opioid-induced side effects was unrelated to plasma levels.

Topics: Adolescent; Analgesia, Patient-Controlled; Analgesics, Opioid; Antiemetics; Antipruritics; Baltimore; Child; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Morphine; Naloxone; Narcotic Antagonists; Nausea; Odds Ratio; Pain Measurement; Pain, Postoperative; Prospective Studies; Pruritus; Regression Analysis; Severity of Illness Index; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Vomiting

Subarachnoid (SA) morphine, highly effective for the management of pain after a cesarean delivery, is associated with a significant incidence of pruritus in up to 80% of patients. No previous study has compared the effectiveness of ondansetron (5-HT(3) antagonist) vs. diphenhydramine (H(1) receptor blocker) for the treatment of this side effect.. In this randomized, double-blind study, 113 patients with a pruritus score 3 or 4 (1=absent; 2=mild, no treatment required; 3=moderate pruritus, treatment required; and 4=severe pruritus) after SA morphine 0.2 mg were assigned to group ondansetron, which received 4 mg intravenously (i.v.) ondansetron, and group diphenhydramine, which received 25 mg i.v. diphenhydramine. Patients who continued to have pruritus > or =3, 30 min after the study drug were considered treatment failures and were treated with naloxone 0.04 mg i.v. repeatedly, as well as patients who relapsed. Pain scores, nausea, vomiting, and sedation were determined before and 30 min after the study drugs were administered. Patients were followed up for 24 h.. The success rate was comparable between the two groups [40/57 (70%) and 38/56 (70%), P=0.79, in group ondansetron and group diphenhydramine, respectively]. Among the successfully treated patients, the recurrence rates of moderate to severe pruritus were 11/40 (28%) in group ondansetron and 13/38 (35%) in group diphenhydramine, P=0.52. The side effect profile was similar between the two groups.. Ondansetron is as effective as diphenhydramine in relieving pruritus caused by SA morphine in patients undergoing a cesarean delivery. However, up to 50% of patients required naloxone either for primary failure or for recurrence.

Topics: Adult; Cesarean Section; Diphenhydramine; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Ondansetron; Pain, Postoperative; Patient Satisfaction; Postoperative Nausea and Vomiting; Pregnancy; Pruritus; Recurrence; Serotonin Antagonists; Severity of Illness Index

In this prospective, randomized, double-blind study, we evaluated the effect of an ultra-low dose of naloxone added to lidocaine and fentanyl mixture on the onset and duration of axillary brachial plexus block.. One hundred twelve patients scheduled for elective forearm surgery under axillary brachial plexus block were randomly allocated to receive 34 mL lidocaine 1.5% with 3 mL of isotonic saline chloride (control group, n = 28), 34 mL lidocaine 1.5% with 2 mL (100 microg) of fentanyl and 1 mL of isotonic saline chloride (fentanyl group, n = 28), 34 mL lidocaine 1.5% with 2 mL saline chloride and 100 ng (1 mL) naloxone (naloxone group, n = 28), or 34 mL lidocaine 1.5% with 2 mL (100 microg) of fentanyl and 100 ng (1 mL) naloxone (naloxone + fentanyl group, n = 28). A multiple stimulation technique was used in all patients. After performing the block, sensory and motor blockades of radial, median, musculocutaneous, and ulnar nerves were recorded at 5, 15, and 30 min. The onset time of the sensory and motor blockades was defined as the time between the last injection and the total abolition of the pinprick response and complete paralysis, respectively. The duration of sensory and motor blocks was considered as the time interval between the complete block and the first postoperative pain and complete recovery of motor functions.. Sensory and motor onset times were longer in the naloxone (sensory onset time: 15 +/- 3, and motor onset time: 21 +/- 4) and naloxone + fentanyl group than control or fentanyl groups (sensory onset time: 10 +/- 3 min in control group, 10 +/- 4 min in fentanyl group, and 17 +/- 3 min in naloxone + fentanyl group, motor onset time: 15 +/- 5 min in control group, 14 +/- 7 min in fentanyl group, and 17.3 +/- 3.4 min in naloxone + fentanyl group) (P < 0.001). The duration of time to first postoperative pain and motor blockade was significantly longer in the naloxone (92 +/- 10 and 115 +/- 10 min) and naloxone + fentanyl groups (98 +/- 12 and 122 +/- 16 min) than control (68 +/- 7 and 89 +/- 11 min) and fentanyl groups (68 +/- 11 and 90 +/- 12 min) (P < 0.001). The time to first postoperative pain was significantly longer in the naloxone and naloxone + fentanyl groups than in the control or fentanyl groups (P < 0.001).. The addition of an ultra-low dose of naloxone to lidocaine 1.5% solution with or without fentanyl solution in axillary brachial plexus block prolongs the time to first postoperative pain and motor blockade but also lengthens the onset time.

Topics: Adult; Analgesics, Opioid; Anesthetics, Local; Axilla; Brachial Plexus; Double-Blind Method; Drug Combinations; Elective Surgical Procedures; Female; Fentanyl; Forearm; Humans; Lidocaine; Male; Middle Aged; Naloxone; Narcotic Antagonists; Nerve Block; Pain Measurement; Pain Threshold; Pain, Postoperative; Postoperative Nausea and Vomiting; Prospective Studies; Pruritus; Recovery of Function; Time Factors; Treatment Outcome; Young Adult

We develop a mechanistic model for post-operative pain and apply it to describe the pharmacodynamic effects of the kappa-opioids nalbuphine and naloxone administered either alone or in combination in patients after surgical removal of one or more madibular third molar teeth. Data were obtained from 6 clinical studies in which a total of 304 patients were intravenously administered single doses of 2.5, 5, 10 or 20 mg of nalbuphine. Some groups also received 0.2 or 0.4 mg of naloxone. A total of 3,040 Visual analog scale (VAS) pain ratings were recorded at 20 min intervals for 3 h after drug administration. We used a two-site indirect action model to describe early and late pain and to incorporate the effect of nalbuphine and naloxone on pain over time. A mixed effects statistical model was used to account for inter- and intra-individual variability. Our model estimated the population average baseline pain score in men to be lower than that in women (68 vs. 76 mm on the 100 mm VAS scale). The model confirmed a late increase in pain (anti-analgesia) and estimated the lag time for the start of anti-analgesia to be 73 min after study drug administration. The maximum early phase pain score is 81.6 mm while the maximum anti-analgesia is 16.1 mm. The nalbuphine dose required to reduce early pain by 50% (ED(50)) was estimated to be 5.85 mg and the naloxone dose required to reduce late phase pain by 50% was estimated to be 0.5 mg. The model confirmed the results from conventional statistical analyses performed previously on individual studies.

Topics: Double-Blind Method; Female; Humans; Male; Models, Chemical; Models, Statistical; Nalbuphine; Naloxone; Pain, Postoperative; Sex Characteristics

The purpose of this prospective clinical trial was to investigate the analgesic efficacy of three oral medication groups on postoperative endodontic pain in male and female dental patients, with an emphasis on analgesic differences between the sexes. Forty-three patients were administered ibuprofen 600 mg, placebo, or pentazocine 50 mg/0.5 mg naloxone in a randomized, double-blinded manner. Beginning immediately after endodontic treatment, patients took the assigned medication every 6 hours for 24 hours and recorded their degree of discomfort on a 100-mm visual analog scale. Statistical analysis of the data showed that ibuprofen 600 mg provided statistically significantly greater analgesia than placebo at 6 and 12 hours (P = 0.0014 and 0.0024), and pentazocine/naloxone provided statistically significantly greater analgesia than placebo at 12 hours (P = 0.0084). Sex-dependent differences were noted within the pentazocine/naloxone group, which showed significantly greater analgesia in females compared with males (P = 0.007).

Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Double-Blind Method; Drug Combinations; Female; Humans; Ibuprofen; Likelihood Functions; Linear Models; Male; Naloxone; Pain Measurement; Pain, Postoperative; Pentazocine; Periapical Periodontitis; Prospective Studies; Pulpitis; Root Canal Therapy; Sex Factors; Surveys and Questionnaires; Toothache

Opioid receptors are expressed on peripheral nerve endings and opioid peptides (beta-endorphin, END) are produced in various immune cells of synovial tissue after knee trauma. Because corticotropin-releasing hormone (CRH) acts through its receptors on END-containing immune cells, this randomized controlled trial investigated whether the intra-articular (IA) injection of CRH reduces postoperative pain intensity and supplemental analgesic consumption in patients undergoing arthroscopic knee surgery.. Patients were randomly assigned to one of the following IA and IV treatments: group saline (SAL) (n=17) received isotonic SAL IA and 10 microg CRH IV; group CRH (n=16) received 10 microg CRH IA and SAL IV; group CNL (n=18) received 10 microg CRH plus 0.12 mg naloxone IA and SAL IV. Patients pain intensity at rest and during exercise, cortisol plasma concentrations as well as supplemental analgesics were documented. Immunohistochemistry analyzed colocalization of CRH receptors and END.. IA but not IV CRH resulted in a significant but short lasting reduction of postoperative pain under both resting and exercise conditions without changes in cortisol plasma concentrations. Coadministration of naloxone reversed this pain reduction under resting but not exercise conditions. The majority of CRH receptor expressing cells contained END within synovial tissue.. In conclusion, this first clinical trial provides preliminary evidence for a short but not robust analgesic effect of a single dose of IA CRH in patients undergoing arthroscopic knee surgery. Further clinical studies will have to examine different doses of IA CRH-induced analgesia and to support the involvement of opioid peptides.

Topics: Adult; Aged; Arthroscopy; beta-Endorphin; Corticotropin-Releasing Hormone; Dose-Response Relationship, Drug; Drug Combinations; Exercise; Hormones; Humans; Immunohistochemistry; Injections, Intra-Articular; Injections, Intravenous; Knee Injuries; Knee Joint; Middle Aged; Naloxone; Pain, Postoperative; Receptors, Corticotropin-Releasing Hormone; Rest; Severity of Illness Index; Synovial Membrane

Epidural opioids have excellent analgesic properties, but their side-effects limit their use in patient-controlled epidural analgesia. This study was designed to evaluate the effect of epidural naloxone on the side-effects of sufentanil, focusing on postoperative nausea and vomiting (PONV) in patients undergoing total knee replacement (TKR).. After obtaining Institutional Review Board approval and informed consent, 50 patients undergoing unilateral TKR were randomly assigned to receive either sufentanil in ropivacaine alone (Group C, n = 25) or the same solution with naloxone (Group N, n = 25) for their postoperative epidural analgesia. Episodes of PONV and five-point-scaled nausea scores were evaluated at 6, 12, and 24 h after epidural analgesia was started. Visual analogue scale (VAS) score for pain and the incidence of sedation, pruritus, hypotension, and respiratory depression were also evaluated at each of three time points.. The nausea score in Group N was significantly lower than that in Group C. The VAS pain score at rest and on movement were significantly lower in Group N than in Group C at 24 h. Other opioid-induced side-effects were not significantly different.. Epidural naloxone was effective in reducing PONV induced by epidural sufentanil and additionally enhanced the analgesic effect. Therefore, concomitant infusion of a small dose of epidural naloxone should be considered to reduce PONV, especially in patients at greater risk for PONV.

Topics: Aged; Analgesia, Epidural; Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Pruritus; Sufentanil

The purpose of this series was to explore a 12.5:1 fixed-dose ratio of an intravenous nalbuphine and naloxone mixture (NNM) for use in patients following gynecologic surgery.. Open-label, nonrandomized case series. The first series was a dose-ranging investigation for 12 patients following elective total abdominal hysterectomy or myomectomy. In this series, fentanyl was used for intraoperative analgesia, and patients were assigned to a lower NNM (2.5 mg/0.2 mg) or to a higher NNM (5 mg/0.4 mg) dose group. The second series evaluated the fixed dose of 5 mg nalbuphine/0.4 mg naloxone for four patients undergoing ambulatory gynecologic procedures. In the second series, no opioid agents were administered intraoperatively to eliminate the possibility of mu-opioid reversal by naloxone postoperatively.. Pain control was assessed using a Verbal Pain Scale (0-10). Vital signs, side effects, and adverse events were recorded to determine drug safety.. In the first series, there were no adverse events; however, each patient required rescue medication (either morphine or fentanyl). In the second series, two of the four patients reported a reduction in pain following drug administration and did not require any further analgesic agents in the 3-hour postoperative period. One patient had an asymptomatic lowering of heart rate after receiving the drug.. Additional research of the unique combination therapy of nalbuphine and naloxone is warranted to further determine its potential clinical efficacy and safety.

Topics: Adult; Analgesics; Dose-Response Relationship, Drug; Drug Combinations; Female; Gynecologic Surgical Procedures; Humans; Infusions, Intravenous; Middle Aged; Nalbuphine; Naloxone; Pain, Postoperative

The aim of this study was to compare safety and efficacy of catheter-mediated femoral nerve block analgesia with systemic pain therapy in patients with proximal femoral fractures in the pre-operative and post-operative setting using a protocol for coordinating pain management.. In a prospective randomised trial of patients attending the emergency department, 100 individuals were selected with a clinically diagnosed proximal femoral fracture. Patients were divided into two equal groups A and B. Group A (n=50) received a catheter-mediated femoral nerve block with 1% prilocaine (40 ml) and post-operatively 0.2% ropivacaine (30 ml) 6 hourly. Group B (n=50) initially received intravenous metamizol (1 g) and a fixed combination of oral tilidine (100 mg) + naloxone (8 mg). Patients aged 90 years or more received a reduced dose (tilidine 75 mg + naloxone 6 mg). In the post-operative period regular oral ibuprofen (400 mg, 8 hourly) in addition to oral tilidine (50 mg) + naloxone (4 mg) was given as required for break through pain. Pain intensity was measured using a verbal rating scale (VRS) from 1 to 5: pain free (=1), mild pain (=2), moderate pain (=3), severe pain (=4), excruciating pain (=5). Pain scores were recorded at rest (R), during passive anteflection (30 degrees) of the hip (PA) on arrival and at 15 and 30 min after initial administration of analgesia. Thereafter, recordings were made 4 times a day up to the third post-operative day.. Pain scores were comparable for both groups on admission (VRS in R 2.50 vs. 2.46; VRS during PA 4.30 vs. 4.34). Significant pain relief was achieved in both groups following initial administration of analgesia, but the total pain scores in group A were significantly lower than in group B (VRS in R 1.22 vs. 1.58, p<0.01 and VRS during PA 2.66 vs. 3.26; p<0.001). No difference was noted between the two groups during the first 3 post-operative days. No severe complications occurred as a result of analgesia, however, the catheter was dislodged in 20% of patients in group A resulting in the need for systemically administered analgesia.. All patients presenting with proximal femoral fractures should receive adequate analgesia within the emergency department even prior to radiographic imaging. Femoral nerve block should be considered as the method of choice. The insertion of a femoral nerve block catheter has the dual advantage of early analgesia permitting repeated clinical examination in addition to continued post-operative pain management. The cumbersome logistics inherent in this technique within the clinical setting limits its practical application. An initial single-shot regional nerve block followed by a systemic post-operative analgesia protocol was considered an appropriate alternative. The execution of safe, consistent and appropriate regional nerve block anaesthesia is reliant on formal guidelines and protocols as agreed by the multidisciplinary teams involved with patient-directed pain management and good clinical practice.

Topics: Acute Disease; Aged; Aged, 80 and over; Amides; Analgesics, Opioid; Anesthetics, Local; Catheterization; Female; Femoral Neck Fractures; Femoral Nerve; Humans; Male; Methimazole; Middle Aged; Models, Organizational; Naloxone; Narcotic Antagonists; Nerve Block; Pain; Pain Measurement; Pain, Postoperative; Prilocaine; Prospective Studies; Ropivacaine; Tilidine

Opioids are frequently associated with side effects such as nausea, vomiting, and pruritus. We hypothesized that a prophylactic, continuous small-dose naloxone infusion would reduce the incidence of opioid-induced side effects without affecting analgesia or opioid consumption. In this prospective, double-blind, randomized, controlled clinical trial, we studied 46 postoperative patients (M:F, 21:25), averaging 14 +/- 2.5 yr and 53 +/- 17 kg, at the start of morphine IV patient-controlled analgesia. Patients were randomized to either saline (control, n = 26) or naloxone 0.25 microg . kg(-1) . h(-1) (n = 20). We found that the incidence and severity of pruritus (77% versus 20%; P < 0.05) and nausea (70% versus 35%; P < 0.05) was significantly more frequent in the placebo group compared with the naloxone group. Morphine consumption (1.02 +/- 0.41 mg . kg(-1) . d(-1) versus 1.28 +/- 0.61 mg . kg(-1) . d(-1)), pain scores at rest (4 +/- 2 versus 3 +/- 2), and pain scores with coughing (6 +/- 2 versus 6 +/- 2) were not different. We conclude that, in children and adolescents, a small-dose naloxone infusion (0.25 microg . kg(-1) . h(-1)) can significantly reduce the incidence and severity of opioid-induced side effects without affecting opioid-induced analgesia. When initiating morphine IV patient-controlled analgesia for the treatment of moderate to severe pain, clinicians should strongly consider starting a concomitant small-dose naloxone infusion.

Topics: Adolescent; Adult; Analgesia; Analgesia, Patient-Controlled; Analgesics, Opioid; Child; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Prospective Studies; Pruritus

To compare the analgesic effect and side effects of morphine for intravenous patient-controlled analgesia (PCA) with or without low-dose naloxone after abdominal surgery.. Fifty-nine ASA I - II patients undergoing elective abdominal surgery were randomly divided into two groups: group morphine received postoperative PCA with 0.4 mg/ml morphine (a 1 mg bolus with a 5 min lockout), group naloxone received morphine 0.4 mg/ml with 6 microg/kg naloxone. Blood pressure, heart rate, respiratory rate, and pulse oxygen saturation were monitored. Visual analogue scale (VAS), nausea/vomiting, pruritus, sedation and consumption of morphine were recorded for 24 hours.. VAS had no difference between group morphine and group naloxone, but group naloxone had significantly lower VAS for pain at rest or movement (beyond 4-8 h), and the incidence of nausea/vomiting significantly decreased in group naloxone (P < 0.05). No differences existed in pruritus, sedation, respiratory rate, and hemodynamic parameters between these two groups. The 24 hours postoperative morphine consumption was (36.6 +/- 13.5) mg in group naloxone and (43.7 +/- 14.6) mg in group morphine (P < 0.05).. For morphine PCA, morphine with 6 microg/kg naloxone is effective in preventing some PCA morphinerelated side effects. Naloxone not only reduces postoperative morphine requirements but also improves the analgesic effect.

Topics: Abdomen; Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Hysterectomy; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative

Ultralow doses of naloxone (0.001-0.1 microg/kg) produce analgesia in animal models. However, no clinical study has evaluated the combination of ultralow dose naloxone and morphine using patient-controlled analgesia (PCA). This randomized, double blind controlled study sought to determine if the combination of ultralow dose naloxone and morphine in PCA solutions affects opioid requirements, analgesia, and side effects. Two-hundred and sixty-five patients (18-65 years old) undergoing operations were randomized to receive PCA morphine 1 mg/ml (n=129) or PCA morphine 1 mg/ml plus naloxone 0.6 microg/ml (n=136). We evaluated the numbers of supplemental rescue doses, the cumulative dose of each PCA solution, pain intensity, pain relief, and opioid side effects during the first 24 h after surgery. We found that opioid requirements did not differ significantly between groups. The morphine+naloxone group on average required 0.07 mg more morphine (95% CI -1.1 to 1.3) during the 24 h than the morphine group. Pain intensity levels were also similar in both groups. The morphine+naloxone group had 0.06 units lower (95% CI -0.5 to 0.4) pain intensity levels than the morphine group. The morphine+naloxone group had a lower incidence of nausea and pruritus than the morphine group (P=0.01 for both symptoms). However, the incidence of vomiting, time to tolerate fluids, sedation, and urinary retention were similar between groups (all P values >0.1). The combination of ultralow dose naloxone and morphine in PCA does not affect analgesia or opioid requirements, but it decreases the incidence of nausea and pruritus.

Topics: Adolescent; Adult; Aged; Analgesia, Patient-Controlled; Dose-Response Relationship, Drug; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Pain Measurement; Pain, Postoperative; Prospective Studies; Time Factors

In recent studies we demonstrated that the analgesic effect of the kappa-like opioids is significantly greater in women, that low dose nalbuphine (5 mg) produces profound anti-analgesia (i.e. enhances pain) in men, and that addition of a low dose of the non-selective opioid receptor antagonist naloxone (0.4 mg) to nalbuphine (5 mg) abolishes the sex difference and results in significantly enhanced analgesia in both sexes. To further delineate the dose-dependent analgesic and anti-analgesic effects of nalbuphine, the present study evaluated the effect of a lower dose of nalbuphine (2.5 mg), with and without naloxone, on dental postoperative pain. In women, nalbuphine alone induced modest, short duration analgesia, which was antagonized rather than enhanced by the addition of naloxone (0.4 mg). In men, this dose of nalbuphine alone did not produce analgesia or anti-analgesia, and naloxone (0.4 mg) did not alter the response to nalbuphine. Thus, the anti-analgesic effect of nalbuphine, present in both sexes at the 5 mg dose disappears at the lower dose of nalbuphine. In addition, the mild analgesia in women produced by this lower dose of nalbuphine is antagonized by naloxone.

Topics: Adult; Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Nalbuphine; Naloxone; Pain, Postoperative; Receptors, Opioid, kappa; Sex Factors; Tooth Extraction

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 sexes at the 2.5 mg dose and that the dose ratio of nalbuphine to naloxone is an important determinant of the analgesic efficacy of this combination.

Topics: Adult; Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Nalbuphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Sex Factors; Tooth Extraction

The efficacy of intrathecal (spinal) morphine in the treatment of pain after posterior spinal fusions was assessed.. To investigate improved posterior pain control with fewer side effects in patients with posterior spinal fusions.. After multilevel spinal fusion with instrumentation, patients experience considerable pain that is difficult to treat.. For this study, 65 patients undergoing elective multilevel posterior spinal instrumentation were randomized to receive spinal morphine as follows: 10 microgram/kg, 20 microgram/kg, or none. These patients were assessed after surgery for pain control and narcotic-associated complications.. The patients who received 20 microgram/kg of spinal morphine were more comfortable immediately after surgery, remained pain free for a longer period, and required significantly less additional narcotic. These patients also had fewer respiratory complications.. Relatively high-dose spinal morphine administration provides simple, reliable postoperative pain control after posterior spinal fusions. This may contribute to reduced postoperative respiratory morbidity and an improved outcome.

Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Injections, Spinal; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Pruritus; Respiratory Insufficiency; Self Administration; Spinal Fusion; Treatment Outcome

The continuous infusion of low doses of naloxone has been reported to decrease postoperative opioid requirements and opioid side effects. However, there is no study that evaluates the effectiveness of the combination of a low dose of naloxone and morphine using patient-controlled analgesia (PCA). This prospective, randomized double-blind controlled study sought to determine if the combination of a low dose of naloxone and morphine in a PCA solution decreases postoperative opioid requirements and pain intensity. One hundred sixty-six patients (18-65 years old) undergoing operations of less than 3 h duration with an American Society of Anesthesiologist physical status I or II were randomized to receive PCA morphine 1 mg/cc plus normal saline or PCA morphine 1 mg/cc plus naloxone 6 microg/cc. Initial PCA settings were 0.5 cc per demand with a lockout time of 10 min. The numbers of 2.5 cc supplemental rescue doses and the cumulative dose of each solution were recorded in the first 24 h after the surgical procedure. Pain intensity and opioid side effects were evaluated every 10 min in the post-anesthesia care unit and every 4 h afterwards. Patient satisfaction was assessed at the end of the 24 h of observation. The morphine+naloxone group had more treatment failures (P=0.0001), higher opioid requirements (P=0.0097), greater pain intensity (P=0.04), less pain relief (P=0.004), and less satisfaction (P=0.01) than the morphine group. The incidence of side effects was similar in both groups (P=0.3). Contrary to previous reports, adding low doses of naloxone to a morphine PCA solution increases opioid requirements and pain.

Topics: Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Prospective Studies; Sex Factors

Epidural morphine is associated with decreased bowel motility and increased transit time. Low doses of intravenous naloxone reduce morphine-induced pruritus without reversing analgesia, but the effect of epidural naloxone on bowel motility has not been studied. Therefore we evaluated bowel motility and analgesia when naloxone was co-administered with morphine into the epidural space.. Forty-three patients having combined thoracic epidural and general anesthesia for subtotal gastrectomy were randomly assigned to one of two study groups. All received a bolus dose of 3 mg epidural morphine at the beginning of surgery, followed by a continuous epidural infusion containing 3 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (control group, n = 18) or a calculated dose of 0.208 microg x kg(-1) x hr(-1) of naloxone (experimental group, n = 25) for 48 hr. We measured the time to the first postoperative passage of flatus and feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain during rest and movement. Scores were assessed at 2, 4, 8, 16, 24, 36 and 48 hr postoperatively.. The experimental group had a shorter time to the first postoperative passage of flatus (5 1.9 +/- 1 6.6 hr vs 87.0 +/- 19.5 hr, P < 0.001 ) and feces (95.3 +/- 25.0 hr vs 132.9 +/- 29.4 hr, P < 0.001). No differences were found in either resting or active VAS between the two groups.. Epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing its analgesic effects.

Topics: Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Female; Gastrectomy; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Injections, Epidural; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative

A series of double-blind, placebo-controlled clinical trials demonstrated that low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intraligamentary space of a chronically inflamed hyperalgesic tooth produced a dose-related naloxone-reversible analgesia. This analgesic effect is mediated by a local mechanism in the inflamed tissue, because subcutaneous administration of a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast, submucosal administration of 1.2 mg morphine or 50 microg fentanyl to the site of extraction of an impacted third molar after the onset of acute pain failed to elicit an analgesic response despite demonstration of a sensitive bioassay. These data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans.

Topics: Acute Disease; Adult; Analgesics, Opioid; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fentanyl; Humans; Injections; Male; Mepivacaine; Morphine; Naloxone; Pain Measurement; Pain, Postoperative; Periodontitis; Time Factors; Tooth Extraction; Toothache; Treatment Outcome

Over the past 5 yr, we have treated nonsurgical and postoperative pain in children <6 yr of age by using a patient-controlled analgesia pump to deliver small-dose continuous IV opioid infusions supplemented by parent- and nurse-controlled opioid bolus dosing. We call this technique parent-/nurse-controlled analgesia (PNCA). Because the safety and efficacy of PNCA have not been previously evaluated, we have undertaken a prospective, 1-yr observational study to determine patient demographics, effectiveness of analgesia, and the incidence of complications (pruritus, vomiting, and respiratory depression) in patients receiving PNCA. Data were collected on 212 children (98 female) who were treated on 240 occasions with PNCA for episodes of pain. Patients averaged 2.3 +/- 1.7 yr of age and 11 +/- 5 kg, and received a median of 4 (range 2-54) days of PNCA therapy. Maximum daily pain scores were < or =3/10 (objective pain scale) or < or =2/5 (objective or self-report pain scale) in more than 80% of all occasions of PNCA use. PNCA usage was associated with an 8% incidence of pruritus and a 15% incidence of vomiting on the first day of treatment. Nine children studied received naloxone, four (1.7%) for treatment of PNCA-related apnea or desaturation. All had improvement in their symptoms after naloxone administration.. Parent-/nurse-controlled analgesia provided effective pain relief in most children <6 yr of age experiencing nonsurgical or postoperative pain. The observed incidence of vomiting and pruritus was similar to that seen in older patients treated with patient-controlled analgesia. However, significant respiratory depression, although uncommon, did occur, thus reinforcing the need for close patient monitoring.

Topics: Analgesics, Opioid; Child, Preschool; Female; Humans; Infant; Male; Naloxone; Narcotic Antagonists; Nurses; Pain Measurement; Pain, Postoperative; Parents; Postoperative Complications; Postoperative Nausea and Vomiting; Prospective Studies; Pruritus

This study was designed to determine whether low doses of intrathecal morphine still result in itching and it evaluates the outcome of a standardized treatment using promethazine and - for intractable itch - naloxone. Patients (n = 143) scheduled for total hip surgery were allocated to four groups (in a double blind manner) with bupivacaine 20 mg in 4 mL but different doses of intrathecal morphine: Group I, 0.025 mg, Group II, 0.05 mg, Group III, 0.1 mg and Group IV, 0.2 mg. The presence or absence of itching was noted every three hours for a 24-h period. When required, standardized treatment was provided. The incidence of itching was: Group I: 14. 3%; Group II: 21.6%; Group III: 48.6%; and, Group IV: 61.7%. Itch was treated by administering promethazine intramuscularly in 2.9% (Group I); 8.1% (Group II); 10.8% (Group III), and 8.9% (Group IV), respectively. Only in group IV there was a single patient who needed naloxone to treat itching. The incidence and severity of itching is a dose-related side-effect in the dose range of 0.025-0.2 mg of intrathecal morphine. Itching still occurs after the low doses of intrathecal morphine, but symptoms vanish after promethazine 25 mg intramuscularly.

Topics: Aged; Analgesics, Opioid; Antipruritics; Arthroplasty, Replacement, Hip; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Injections, Spinal; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Promethazine; Pruritus

Recent studies have suggested that giving opioids locally into inflamed tissue may cause analgesia. This antinociceptive effect has been attributed to the interaction of the drug with opioid receptors upregulated by inflammation in the peripheral tissues. We have compared the analgesic effect of intra-articular morphine with that of normal saline and a combination of morphine and its antagonist naloxone after arthroscopy of the temporomandibular joint (TMJ). Twenty-one patients took part in a randomized controlled double-blind trial and received one of these three solutions at the end of operation. The pain scores, time to the first request for analgesia, and the analgesic consumption of the patients in the three groups did not differ significantly at any time during the study period.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Arthroscopy; Female; Humans; Injections, Intra-Articular; Male; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Postoperative Care; Statistics, Nonparametric; Temporomandibular Joint; Time Factors

The purpose of the study was to compare the analgesic and side effects of two epidurally administered mixtures of bupivacaine and fentanyl with the same drug ratios.. One hundred patients scheduled for colorectal surgery were randomized to receive a thoracic epidural infusion of either bupivacaine 0.12% with fentanyl 2 micrograms/ml or bupivacaine 0.24% with fentanyl 4 micrograms/ml during 48 h postoperatively. The pumps were adjusted to keep the visual analogue scale (VAS) pain score at 3 or less (on a scale of 0-10) with a minimum of adverse effects.. There were no statistically significantly differences between the two groups in VAS pain scores. The average VAS pain score resting varied between 0.5 and 1, and coughing between 1.9 and 3.4. One case of respiratory depression with breathing frequency 7 occurred in each group, but none of the patients required naloxone. One patient in the low concentration group developed partial motor weakness in both legs 36 h postoperatively. Equal drug amounts--bupivacaine 10.8-11 mg/h and fentanyl 18-18.4 micrograms/h--were given in both groups throughout the study.. Both groups had low pain scores with few and comparable adverse effects. It thus seems that the volume is not important when mixtures of bupivacaine and fentanyl in the studies concentrations are infused epidurally at a low thoracic level. Practical reasons favour the higher concentration mixture.

Topics: Aged; Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Buprenorphine; Colon; Cough; Fentanyl; Follow-Up Studies; Humans; Infusion Pumps; Injections, Intravenous; Leg; Middle Aged; Muscle Weakness; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Rectum; Respiration

Almost all patients treated with opioids suffer from constipation. Numerous laxatives are used to overcome the problem, but none has yet been found to yield favourable results in all patients. Several studies have attempted to reverse opioid-induced constipation by the use of oral naloxone. Experiments carried out in rats showed that morphine-induced constipation is reduced by oral naloxone without impairment of antinociception [4]. However, evaluation of clinical studies reveals that there is uncertainty about the dosage regimen (the daily dose of naloxone ranged from 0.5% to about 60% that of morphine) and a lack of larger numbers of patients studied.. Fifteen patients suffering from opioid-induced constipation participated in the present study. Constipation had been present for 5 to 14 days despite the use of laxatives. According to the results obtained in the animal experiments [4], it was originally planned to administer oral naloxone at a dose ratio of 1:1 with respect to morphine on day 1 and 2; reducing it on day 3 and 4 to one-half and then to one-fourth of the initial dose on day 5 and 6.. Twelve patients experienced a strong laxative effect with spontaneous bowel evacuation 1 to 4 h after the first intake of oral naloxone. Three patients had no laxative effects even after repeated doses. Eleven of the 15 patients reported an average loss of 10%-15% of analgesia after oral naloxone as measured by visual analogue scales. Increasing the morphine dose by about 15% restored the previous level of analgesia without reappearance of constipation. Eight of the 12 patients having a laxative effect experienced abdominal cramps, and therefore, the total dose of naloxone was reduced on day 2 to 2%-15% of that originally planned; this dose still produced a laxative effect. Four of the 15 patients had a withdrawal syndrome. A single dose of morphine equivalent to their daily morphine intake abolished the symptoms.. The medical history of the 3 patients in whom naloxone failed to abolish constipation revealed neurological disturbances. Treatment of these patients included the use of neuroleptics, antiemetics, and other drugs. In this context, it should be noted that oral naloxone can be expected to abolish only opioid-induced constipation. In conclusion, it was found that the treatment of opioid-induced constipation by administration of oral naloxone produced positive results. A controlled study will show, whether the side effects can be minimized by reducing the naloxone dose.

Topics: Aged; Analgesics, Opioid; Cathartics; Constipation; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative

In patients who reported mild postoperative pain, we evoked a nocebo response, a phenomenon equal but opposite to placebo. Patients who gave informed consent to increase their pain for 30 min received a substance known to be non-hyperalgesic (saline solution) and were told that it produced a pain increase. A nocebo effect was observed when saline was administered. However, if a dose of 0.5 or 5 mg of the cholecystokinin antagonist proglumide was added to the saline solution, the nocebo effect was abolished. A dose of 0.05 mg of proglumide was ineffective. The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone. These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids. Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety, we suggest that nocebo hyperalgesia may be due to a cholecystokinin-dependent increase of anxiety.

Topics: Analgesics, Non-Narcotic; Cholecystokinin; Double-Blind Method; Female; Humans; Hyperalgesia; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pain, Postoperative; Placebo Effect; Proglumide

A naloxone infusion is effective in reducing epidural and intrathecal opioid-related side effects. The use of naloxone infusion concomitant with intravenous morphine patient-controlled analgesia (PCA) has not been evaluated, probably because of an expected direct antagonism of the systemic opioid effect. The authors compared the incidence of morphine-related side effects and the quality of analgesia from two small doses of naloxone infusion.. Sixty patients classified as American Society of Anesthesiologists physical status 1, 2, or 3 who were scheduled for total abdominal hysterectomies were enrolled in the study. Patients received a standardized general anesthetic. In the postanesthetic care unit, patients received morphine as a PCA. They were randomized to receive either 0.25 microg x kg(-1) x h(-1) naloxone (low dose), 1 microg x kg(-1) x h(-1) (high dose), or saline (placebo) as a continuous infusion. Verbal rating scores for pain, nausea, vomiting, and pruritus; sedation scores; requests for antiemetic; and morphine use were recorded for 24 h. Blood pressure, respiratory rate, and oxyhemoglobin saturation were also monitored.. Sixty patients completed the study. Both naloxone doses were equally effective in reducing the incidence of nausea, vomiting, and pruritus compared with placebo (P < 0.05 by the chi-squared test). There was no difference in the verbal rating scores for pain between the groups. The cumulative morphine use was the lowest in the low-dose group (42.3 +/- 24.1 mg; means +/- SD) compared with the placebo (59.1 +/- 27.4 mg) and high-dose groups (64.7 +/- 33.0 mg) at 24 h (P < 0.05 by analysis of variance). There was no incidence of respiratory depression (<8 breaths/min) and no difference in sedation scores, antiemetic use, respiratory rate, and hemodynamic parameters among the groups.. Naloxone is effective in preventing PCA opioid-related side effects. Naloxone infusion at 0.25 microg x kg(-1) x h(-1) not only attenuates these side effects but appears to reduce postoperative (beyond 4-8 h) opioid requirements. This dosing regimen can be prepared with 400 microg naloxone in 1,000 ml crystalloid given in 24 h to a patient weighing 70 kg.

Topics: Adult; Aged; Analgesia, Patient-Controlled; Analgesics, Opioid; Dose-Response Relationship, Drug; Humans; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative

This randomized, double-blind study compared the efficacy of two mu-receptor antagonists, naloxone and nalbuphine, in the prophylactic management of pruritus in postcesarean section patients receiving epidural morphine. Dosages of study drugs were individualized by the use of a patient self-administration (PSA) device. All 51 patients were healthy women who received a uniform epidural anesthetic and epidural morphine (5 mg). Coded solutions were infused for 24 h, with 5-min PSA lockout times: Group A (n = 17), nalbuphine 2.5 mg/h, PSA nalbuphine 1 mg; Group B (n = 16), naloxone 50 micrograms/hr, PSA saline; Group C (n = 18), naloxone 50 micrograms/h, PSA naloxone 40 micrograms. Patients were assessed for pruritus and pain every 8 h for 24 h. Both naloxone and nalbuphine provided good relief for pruritus; median pain and pruritus scores were in the none-to-mild range (0-3) for all groups at all assessment intervals. The pruritus scores of the PSA saline group were higher during the 16- to 24-h period (P < 0.05) than the scores of either group receiving A-receptor antagonist by PSA. There was evidence of shortening of the duration of analgesia in patients receiving naloxone who required treatment for pruritus after 16 h. Patients who self-administered large doses of nalbuphine over the first 8 h also reported pain scores consistent with reversal of analgesia. The potency ratio for naloxone:nalbuphine for antagonism of the pruritic effects of epidural morphine was approximately 40:1. Intervention to treat either unrelieved pruritus or pain, respectively, was necessary in the following numbers of patients: Group A, 0/1; Group B, 1/1; Group C, 2/2. Prophylactic infusions offer the potential for labor cost savings by minimizing the need for episodic therapeutic interventions to treat pruritus.

Topics: Analgesia, Epidural; Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Opioid; Cesarean Section; Cost Savings; Double-Blind Method; Female; Humans; Linear Models; Morphine; Nalbuphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Pregnancy; Pruritus; Receptors, Opioid, mu

To investigate the effect on the use of intravenous patient-controlled analgesia (PCA) of varying the dose (D) and lockout interval (LI) while keeping the hourly maximum dose constant.. Randomized, prospective study.. Teaching hospital.. 75 patients scheduled to receive PCA morphine following abdominal surgery.. Postoperatively, patients were randomly assigned to receive PCA morphine with the following parameters: D = 1 mg, LI = 6 min (Group 1-6), D = 1.5 mg, LI = 9 min (Group 1.5-9), or D = 2 mg, LI = 12 min (Group 2-12), so that each group could receive a maximum hourly dose or 10 mg. Inadequate analgesia was managed by increasing the dose and lockout interval, while excessive sedation or respiratory rate less than 10 breaths/min resulted in decreasing the dose and lockout interval.. Patients were assessed for pain [visual analog scale (VAS), verbal rating scale (VRS)] and side effects at 1, 2, 4, and 24 hours. The number of doses administered, missed attempts, and morphine used for the first 24 hours was recorded by automatic printout from the PCA machine. There was no difference in the total 24-hour morphine consumption, analgesia, or incidence of side effects among the three groups at any of the measurement times. Two patients, one each in the 1.5-9 and 2-12 groups, required naloxone for respiratory depression. The number of PCA injections, attempts, missed attempts, and the incidence of dosage adjustment were all significantly higher for the 1-6 group (p < 0.05).. The use of 1.0 mg with a 6-minute lockout may represent appropriate dose titration because this group obtained equivalent analgesia, morphine use, and side effects as the two larger dose and lockout groups. However, the increased number of PCA attempts and missed attempts may reflect lower satisfaction with PCA therapy.

Topics: Abdomen; Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Analysis of Variance; Consciousness; Female; Humans; Incidence; Injections, Intravenous; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Patient Satisfaction; Prospective Studies; Respiration; Time Factors

To determine whether transdermal fentanyl can provide a significant component of postoperative analgesia.. Randomized, double-blind study.. Inpatient surgery in a university hospital.. 40 adult patients scheduled for orthopedic surgery with general anesthesia.. 20 patients in each group had general anesthesia with propofol, isoflurane in nitrous oxide and oxygen (O2), and small boli of alfentanil or sufentanil. Preoperatively, the first group (F) received a transdermal therapeutic system fentanyl patch (75 micrograms/hr) for 72 hours, and the second group (P) received a placebo patch. Morphine was given postoperatively according to clinical necessity.. Morphine consumption, pain visual analog scale, and eventual sedation were assessed, as well as respiratory rate and blood pressure. Plasma fentanyl concentrations were determined. Only 11 Group F patients needed morphine compared with 19 Group P patients, and mean morphine dose was significantly lower in Group F. One Group F patient had decreased O2 saturation and intense sedation, necessitating administration of naloxone. The mean maximum plasma fentanyl concentration in Group F was 1.63 ng/ml.. Efficacy of transdermal fentanyl for postoperative pain relief is shown, but intense respiratory depression is sometimes seen.

Topics: Administration, Cutaneous; Adult; Analgesia; Anesthesia, Inhalation; Anesthesia, Intravenous; Blood Pressure; Bone and Bones; Double-Blind Method; Female; Fentanyl; Humans; Male; Middle Aged; Morphine; Naloxone; Oxygen; Pain Measurement; Pain, Postoperative; Placebos; Respiration

In a prospective, randomized, double-blind clinical trial, we compared the efficacy of propofol and naloxone for the treatment of spinal-morphine-induced pruritus. Forty patients presenting with severe pruritus within 24 h of epidural morphine administration were allocated to receive either propofol 10 mg intravenously (i.v.) or naloxone 2 micrograms/kg. In the absence of a positive response, a second dose of the same treatment was given 5 min later. Pruritus and the level of post-operative pain were assessed every 5 min up to the end of the study period (45 min) using a verbal rating scale. The overall success rate in treating pruritus was similar in the two groups (80%). The rate of success after the first injection of the treatment drug was also similar (55%). The level of postoperative pain decreased after drug treatment in six patients (30%) in the propofol group versus none in the naloxone group (P < 0.05). Forty-five percent of the patients in the naloxone group had an increase in the level of postoperative pain versus none in the propofol group (P < 0.05). In conclusion, these results suggest that propofol and naloxone are equally effective in treating spinal-morphine-induced pruritus. However, the level of postoperative pain is significantly less in the propofol group.

Topics: Adult; Aged; Analgesia, Epidural; Double-Blind Method; Elective Surgical Procedures; Humans; Middle Aged; Morphine; Naloxone; Pain, Postoperative; Propofol; Prospective Studies; Pruritus

Opioids produce analgesia by interacting with local opioid receptors in peripheral inflamed tissue. This study investigated whether endogenous ligands of these receptors are present in synovia and whether such opioid peptides can inhibit pain by activation of intra-articular opioid receptors. Samples of synovium from 8 patients undergoing arthroscopic knee surgery were examined by immunohistochemistry for the presence of beta-endorphin, met-enkephalin, and dynorphin. All tissue samples showed synovitis. Inflammatory cells stained strongly for beta-endorphin and met-enkephalin but not for dynorphin. To find out whether blockade of intra-articular opioid receptors affected pain, we randomly assigned 22 patients undergoing arthroscopic knee surgery to receive naloxone (0.04 mg) intra-articularly (n = 10) or intravenously (n = 12); each patient received a placebo injection into the other site. Postoperative pain was assessed by visual analogue scale, a numerical rating scale, the McGill pain questionnaire, and supplementary analgesic consumption during the next 24 h. All pain scores were higher in the intra-articular naloxone group than in the intravenous naloxone group. The differences were significant (p < 0.05) during the first 4 h. Supplementary analgesic consumption was significantly higher in the intra-articular group (52.5 [14.0] vs 15.6 [8.0] mg diclofenac, p < 0.05). Opioid peptides are present in inflamed synovial tissue and can inhibit pain after knee surgery through an action specific to intra-articular opioid receptors. These findings expand the gate control theory of pain and suggest new approaches such as the development of peripherally acting opioid analgesics without central side-effects.

Topics: Adult; Aged; Arthroscopy; beta-Endorphin; Double-Blind Method; Dynorphins; Endorphins; Enkephalin, Methionine; Humans; Immunohistochemistry; Injections, Intra-Articular; Injections, Intravenous; Knee Joint; Middle Aged; Naloxone; Pain, Postoperative; Receptors, Opioid; Synovial Membrane; Synovitis

This study compared naloxone and nalbuphine when administered for treatment of side effects after epidural morphine, 5 mg, given for postcesarean analgesia. Patients requesting treatment for pruritus or nausea randomly received, in a double-blind fashion, up to three intravenous doses of either naloxone 0.2 mg (group 1; n = 20) or nalbuphine 5 mg (group 2; n = 20). The incidence of vomiting, the severity of nausea and pruritus, and the degree of sedation and pain were assessed before and 30 min after each dose. The first dose of nalbuphine decreased the incidence of vomiting (P < 0.005) and the severity of nausea and pruritus (P < 0.01), whereas naloxone caused no significant changes. Sedation scores increased after nalbuphine (P < 0.05) and remained unchanged after naloxone, whereas pain scores increased after naloxone (P < 0.01) and were unchanged after nalbuphine. Eighteen patients in group 1 and 12 in group 2 received a second dose, and 8 and 4 patients, respectively, a third dose. Other than decreased pruritus after the second dose with both drugs, no further changes occurred. We conclude that nalbuphine is superior to naloxone for the treatment of side effects after epidural morphine. However, persistent symptoms may require supplemental therapy, as repeated doses proved less effective than the initial dose.

Topics: Adult; Analgesia, Epidural; Cesarean Section; Female; Humans; Morphine; Nalbuphine; Naloxone; Pain, Postoperative; Pregnancy

The influence of an intravenous infusion of naloxone 1 microgram kg-1 h-1, in combination with intrathecal diamorphine, on analgesia and hormonal stress responses after laminectomy was assessed in a blinded, randomized, placebo-controlled study. Twenty-seven patients undergoing laminectomy with postoperative analgesia provided by intrathecal diamorphine were investigated. Analgesia was reduced by naloxone (P less than 0.05), and the duration of analgesia was shortened by 180 min. The postoperative concentrations of both blood glucose and serum cortisol were reduced in the naloxone group compared to the control group (P less than 0.05). These results may indicate an excitatory role for the hypothalamic mu receptor in hypothalamo-pituitary-adrenocortical axis regulation.

Topics: Adult; Aged; Blood Glucose; Female; Heroin; Humans; Hydrocortisone; Infusions, Intravenous; Injections, Spinal; Male; Middle Aged; Naloxone; Pain, Postoperative; Stress, Physiological; Surgical Procedures, Operative

Opioids can produce potent antinociceptive effects by interacting with local opioid receptors in inflamed peripheral tissue. In this study we examined the analgesic effects of the intraarticular, as compared with intravenous, administration of morphine after arthroscopic knee surgery.. In a double-blind, randomized trial, we studied 52 patients who had received one of four injections at the end of surgery. The patients in group 1 (n = 18) received 1 mg of morphine intraarticularly and saline intravenously; those in group 2 (n = 15), saline intraarticularly and 1 mg of morphine intravenously; those in group 3 (n = 10), 0.5 mg of morphine intraarticularly and saline intravenously; and those in group 4 (n = 9), 1 mg of morphine and 0.1 mg of naloxone intraarticularly and saline intravenously. The volume of the intraarticular injections was 40 ml, and that of the intravenous injections was 1 ml. After 1, 2, 3, 4, 6, and 24 hours, postoperative pain was assessed with a visual-analogue scale, a numerical-rating scale, and the McGill pain questionnaire. The need for supplemental analgesic agents, the patients' vital signs, and the occurrence of side effects were monitored.. All pain scores were lower in group 1 than in group 2 at all times. The differences were significant (P less than 0.05) at three, four, and six hours (mean [+/- SD] visual-analogue score at six hours, 9 +/- 13 mm vs. 37 +/- 31 mm). The mean (+/- SD) consumption of supplemental analgesic medication per 24 hours was significantly lower in group 1 (36 +/- 51 mg of diclofenac and 1.2 +/- 3.4 mg of meperidine) than in group 2 (75 +/- 42 mg of diclofenac and 14 +/- 18 mg of meperidine, P less than 0.05). The visual-analogue scores in group 3 were slightly but not significantly higher than those in group 1 at all times except 6 and 24 hours after injection. The visual-analogue scores were significantly higher in group 4 than in group 1 one to four hours after injection (P less than 0.05), indicating that the analgesic effect of intraarticular morphine was reversible by naloxone.. Low doses of intraarticular morphine can significantly reduce pain after knee surgery through an action specific to local opioid receptors that reaches its maximal effect three to six hours after injection.

Topics: Adult; Aged; Analgesia; Arthroscopy; Female; Humans; Injections, Intra-Articular; Injections, Intravenous; Knee; Male; Middle Aged; Morphine; Naloxone; Pain Measurement; Pain, Postoperative; Postoperative Care; Receptors, Opioid; Time Factors

The analgesic efficiency of ketamine and pethidine was compared in experimental ischemic pain and postoperative pain after oral surgery. Naloxone 1.6 mg or placebo was given 5 min before the analgesic drug. The subjects recorded their pain on a visual analogue scale. Both ketamine 0.3 mg/kg and pethidine 0.7 mg/kg were effective as analgesics against the two types of pain studied. Naloxone prevented the analgesic effect of pethidine, but had no effect on ketamine analgesia. The results are in accordance with the hypothesis that the analgesic effect of ketamine is mediated by a non-opioid mechanism, possibly involving PCP-receptor-mediated blockade of the NMDA-receptor-operated ion channel.

Topics: Adult; Female; Humans; Ischemia; Ketamine; Meperidine; Naloxone; Pain; Pain, Postoperative; Visual Pathways

Eighty patients recovering from major operations were investigated to evaluate the influence of naloxone on the analgesic and respiratory depressant properties of buprenorphine. They were randomly assigned to two groups to self-administer either buprenorphine (Group B) or a mixture of buprenorphine and naloxone (fraction 60%; Group BN) in the early postoperative period by means of the On-Demand Analgesia Computer (ODAC). The duration of patient-controlled analgesia (PCA) was 21.0 h (B) or 23.5 h (BN), during which 12.2 (B) and 18.2 (BN) demands per patient were recorded, representing significantly different consumption of buprenorphine 0.80 (B) and 1.07 (BN) microgram.kg-1.h-1. Retrospective pain scores were significantly better in Group B, and respiratory rate was significantly higher in Group BN. The analgesia was judged superior by 81% (B) and 88% (BN) of the patients compared to conventional postoperative pain treatment. The minimum effective buprenorphine concentration (MEC) varied greatly in both groups with no significant differences between them (median 0.4 ng.ml-1, range 0.1-8.6 ng.ml-1); intra-individual variability was lower (67.9% B, and 58.2% BN) than inter-individual variability (107.3% B and 84.0% BN). Accumulation in plasma and acute tolerance did not occur. Thus, admixture of 60% naloxone decreased both the analgesic and respiratory depressant effects of buprenorphine which were generally independent of plasma concentrations. The analgesia achieved with the buprenorphine/naloxone mixture under patient-controlled conditions was comparable to that of other narcotic analgesics. Accordingly, this drug combination may be expected to give clinically adequate analgesia without notable impairement of spontaneous respiration, whilst withdrawal symptoms would probably arise in drug addicts abusing other opiates.

Topics: Blood Pressure; Buprenorphine; Drug Interactions; Heart Rate; Humans; Male; Naloxone; Pain, Postoperative; Respiration

It has been suggested in various studies that the opiate agonist/antagonist nalbuphine (Nubain) provides for effective reversal of the respiratory depression after fentanyl while maintaining postoperative analgesia. We tested this hypothesis in a relatively large number of patients. The study consisted of two parts: one randomized open, the other randomized double-blind, each with 150 ASA I or II patients aged 18 to 65 years. After premedication with atropine 0.5 mg and flunitrazepam 0.5 mg, anaesthesia was induced with flunitrazepam 0.5 mg, fentanyl 0.1 mg, and etomidate 10 mg and maintained with N2O/O2, 2/1, and additional increments of 0.1 mg fentanyl as required. Relaxation for intubation and surgery was obtained with vecuronium, atracurium, or pancuronium depending on the expected duration of anesthesia. After the operation the patients were extubated and the residual effects of fentanyl antagonized with naloxone 0.05 mg or nalbuphine 10 mg or 20 mg i.v. (randomized open or double-blind). The patient data and fentanyl dosages are given in Table 1. Postoperative pain was assessed by the time interval between administration of the opiate antagonist and the requirement for the first analgesic medication. Figures 1a and b and Table 2 indicate that after nalbuphine 20 mg the first analgesic was required significantly later than after naloxone 0.05 mg (median 115 or 123 min after nalbuphine 20 mg vs 56 or 52 min after naloxone 0.05 mg; P less than 0.02). There was no significant difference between nalbuphine 10 mg and naloxone 0.05 mg. The open and double-blind studies gave virtually identical results. Sixty minutes after administration of 20 mg nalbuphine, vigilance was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adolescent; Adult; Aged; Anesthesia, Inhalation; Arousal; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Fentanyl; Humans; Middle Aged; Morphinans; Nalbuphine; Naloxone; Pain, Postoperative

Twenty-eight patients suffering acute pain following operative removal of impacted third molars took part in the present study. In 20 patients who reported pain reduction exceeding 25% of the initial pain intensity during vibratory stimulation (100 Hz) or TENS (2 or 100 Hz), only 1 patient (given 2 Hz TENS) reported pain increase after injection of 0.8 mg naloxone (i.v.). In 8 patients, not treated with afferent stimulation, 2 experienced increase in pain intensity after naloxone injection. The results show that pain relief using TENS or vibration is not influenced by naloxone.

Topics: Acute Disease; Adolescent; Adult; Clinical Trials as Topic; Electric Stimulation Therapy; Facial Pain; Female; Humans; Male; Mouth Diseases; Naloxone; Pain, Postoperative; Tooth, Impacted; Transcutaneous Electric Nerve Stimulation; Vibration

Forty-five patients undergoing Caesarean section under epidural anesthesia with bupivacaine were randomly allocated to three groups. Group 1 received 4 mg of epidural morphine immediately postoperatively and 2 mg naloxone by intravenous infusion for 12 hours postoperatively; group 2 was treated as group 1 but without naloxone infusion; group 3 received 10 mg morphine intramuscularly and 20 ml epidural saline after delivery of the baby. Epidural morphine 4 mg produced better postoperative analgesia than 10 mg of morphine intramuscularly (p less than 0.001) and the intravenous infusion of naloxone did not ablate the analgesic effects of epidural morphine. The incidence of itching and vomiting was higher in the epidural opioid groups (p less than 0.05) and intravenous naloxone, although it reduced the severity of the itching, did not reduce its overall incidence. Respiratory depression was not detected in any of the three groups.

Topics: Adolescent; Adult; Anesthesia, Epidural; Cesarean Section; Epidural Space; Female; Humans; Injections; Injections, Intramuscular; Morphine; Naloxone; Pain, Postoperative; Pregnancy

1 In a controlled crossover study identical oral surgical procedures were performed on two separate occasions in six patients. 2 Two h after surgery, either 40 mg methylprednisolone (Solu-Medrol) or placebo (saline) was administered intravenously in a double-blind randomized fashion. 3 Five h after surgery, three patients received 4 mg naloxone (Nalonee) while 3. Five h after surgery, three patients received 4 mg naloxone (Nalonee) while three patients received placebo (saline) intravenously, followed by a crossover to alternative injections 1 h thereafter. 4 Several measurements/assessments were recorded for a paired comparison of the post-operative courses. 5 The mean pain assessment (VAS) was reduced by about 50% 45 min after the steroid injection (P = 0.03). 6 Neither increasement of the post-operative pain nor reversal of the steroid-induced analgesia could be demonstrated by injection of 4 mg naloxone. 7 Swelling was reduced by 46% on day 3 after the operation when the steroid was injected as compared to placebo (P = 0.06); on day 6 the reduction averaged 60% (P = 0.04). 8 According to overall assessments after the second operation all patients expressed clear preference for the post-operative course when the steroid was injected. 9 Present and previous results in this model with bilateral oral surgery suggest that short term corticosteroid administration deserves attention as an efficient means which may be of value in reducing pain and excessive inflammation in surgery and traumatology.

Topics: Adrenal Cortex Hormones; Adult; Double-Blind Method; Endorphins; Female; Humans; Male; Methylprednisolone; Naloxone; Pain, Postoperative; Random Allocation; Surgery, Oral

This double blind study showed the effect of four drugs, levallorphan, naloxone, doxapram and amiphenazole, an opiate-induced analgesia and respiratory depression. Satisfactory analgesia was induced by administration of morphine intravenously in a dose of up to 0.33 mg/kg; such a dose, however, produced significant depression of respiration. Administration of levallorphan, naloxone, and amiphenazole produced reversal of respiratory depression and analgesia. Doxapram reversed the respiratory depression but did not alter analgesia.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Doxapram; Humans; Levallorphan; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Random Allocation; Respiratory Insufficiency; Thiazoles; Time Factors

Naloxone was used in 20 patients divided into two series: series A consisted of 10 adults with an average age of 50.6 years (+/- 12.03) and series B 10 children with an average age of 8.5 years (+/- 5.16). Naloxone was given in the treatment of postoperative respiratory depression related to persistence of morphine impregnation, the patients having received either fentanyl (mean dose 0.04 mg/kg/h) or dextromoramide (mean dose 1.15 mg/kg/h). The mean dose of naloxone was 0.26 mg +/- 0.10, i.e. 3.9 microgram/kg in series A, and 0.13 mg +/- 0.11, i.e. 5.3 microgram/kg in series B. In both series, study of ventilatory function showed correction and stabilisation of the various parameters (F/min, Vt and V) up to 180 minutes after the injection. Recovery was rapid in both groups (7 to 10 min) and of good quality. Whilst it was accompanied in a number of cases by the recurrence of pain, the latter never required specific relief. The administration of naloxone was associated with an increase in heart rate (non-significant) at 10 min in series A and 30 min in series B. Apart an episode of nausea in one case of series A, no disagreeable side effects were observed.

Topics: Adolescent; Adult; Aged; Cardiovascular System; Child; Child, Preschool; Clinical Trials as Topic; Consciousness; Female; Humans; Hypoventilation; Male; Middle Aged; Naloxone; Neuroleptanalgesia; Pain, Postoperative; Postoperative Complications; Respiratory Function Tests

The object of this study was the use of naloxone to correct hypoventilation related to the use of morphinomimetics without suppressing the analgesic effect of these agents. The study involved ten patients undergoing gynaecological surgery under neuroleptanalgesia and who at the end of surgery had hypoventilation due to the use of fentanyl (average dose : 4.87 microgram/kg/h) or phenoperidine (average dose : 48.7 microgram/kg/h). Naloxone was administered intravenously in an average dose of 1.37 microgram/kg (in one or two injections) followed by an intramuscular injection of an average of 0.73 microgram/kg. Under these conditions, respiratory depression was completely corrected in all cases, the effect being durable. Good analgesia was retained and there was a normal return to consciousness without undesirable effects.

Topics: Adult; Clinical Trials as Topic; Consciousness; Drug Evaluation; Female; Fentanyl; Genital Diseases, Female; Humans; Hypoventilation; Middle Aged; Naloxone; Neuroleptanalgesia; Pain, Postoperative; Phenoperidine; Respiration

The effect of naloxone on dental postoperative pain was studied to examine the hypothesis that endorphins mediate placebo analgesia. All patients had extraction of impacted mandibular third molars with diazepam, N2O, and local block with mepivacaine. 3 h and 4 h after surgery naloxone or a placebo was given under randomised, double-blind conditions. Pain was evaluated on a visual analogue scale. Patients given naloxone reported significantly greater pain than those given placebo. Patients given placebo as their first drug was either placebo responders, whose pain was reduced or unchanged, or nonresponders whose pain increased. Naloxone given as a second drug produced no additional increase in pain levels in nonresponders but did increase pain levels of placebo responders. Nonresponders had a final mean pain rating identical to that of responders who received naloxone as their second drug. Thus the enhancement of reported pain produced by naloxone can be entirely accounted for by its effect on placebo responders. These data are consistent with the hypothesis that endorphin release mediates placebo analgesia for dental postoperative pain.

Topics: Adolescent; Adult; Analgesia; Anesthesia, Dental; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Endorphins; Female; Humans; Male; Molar; Morphine; Naloxone; Pain, Postoperative; Placebos; Research Design; Time Factors; Tooth Extraction; Tooth, Impacted

Topics: Analgesia; Clinical Trials as Topic; Drug Antagonism; Humans; Hyperalgesia; Naloxone; Pain, Postoperative; Placebos; Research Design

To investigate the antagonistic effect of naloxone on fentanyl-induced respiratory depression, 55 patients (randomly divided into various study and control groups were studied during nitrous-oxide-oxygen-halothane anaesthesia. Respiratory depression after 0.1 mg of fentanyl was totally reversed by 10 microgram/kg of naloxone, measured as 100% restoration of spontaneous respiration, normal minute volume and end-tidal CO2, while 15 microgram/kg of naloxone was needed to antagonize 0.2 mg of fentanyl. The respective control groups remained apnoeic. If no fentanyl had previously been administered, there was no difference in the respiratory behaviour of naloxone-treated and control patients, which indicates that no unspecific analeptic effect of naloxone could be demonstrated. The circulatory changes after fentanyl were nearly reversed by naloxone, as has been found earlier with other narcotics. Recovery from anaesthesia was scored from 0 to 10 (using a modification of Apgar scores for newborns), and somewhat higher mean scores were obtained with the naloxone-treated patients than with their controls. However, higher postoperative pain scores were recorded in these patients as well as a higher incidence of nausea and vomiting. The study demonstrates the dose-relationships of fetanyl and naloxone for estimation of total antagonism; however, the use of naloxone for partial antagonism at the termination of anaesthesia cannot be based on these findings.

Topics: Adult; Aged; Anesthesia, Inhalation; Blood Pressure; Carbon Dioxide; Female; Fentanyl; Halothane; Humans; Male; Middle Aged; Naloxone; Nitrous Oxide; Pain, Postoperative; Pulse; Respiration; Tidal Volume

Different modes of naloxone administration were studied in 100 patients following N2O-O2-relaxant anaesthesia, where fentanyl was administered for analgesia according to a standardized dose schedule (mean 4.3 microgram/kg/h). After reversal of muscular relaxation, the patients were randomly given naloxone--either 1.0 or 2.5 microgram/kg i.v. or 2.5 or 5.0 microgram/kg i.m., or none (control). Each group consisted of 20 patients. Awakening was fastest after 2.5 microgram/kg i.v. of naloxone (1.8 +/- 0.1 min), the time being significantly shorter (P less than 0.025) than in the control group (2.7 +/- 0.4 min). After 15 min, the minute volume and frequency of respiration were significantly higher (P less than 0.05) in all naloxone groups than in the control group. However, the arterialized venous PCO2 did not show significant differences during the recovery. It is therefore suggested that naloxone reversal may cause an increase in CO2 production. The immediate postoperative pain (score 0-3) was mildest in the control group (1.0 mean) and severest after 2.5 microgram/kg i.v. of naloxone (1.8 mean); the difference was statistically significant (P less than 0.05). The groups receiving 1.0 microgram/kg i.v. and 2.5 microgram/kg i.m. did not differ from each other (1.2 mean). Nausea and vomiting were reported more often after 5.0 microgram/kg im. of naloxone than in other groups. After moderate doses of fentanyl during balanced anaesthesia, routine use of naloxone does not seem to be necessary, but if rapid recovery is essential, 1.0 microgram/kg i.v. or 2.5 microgram/kg i.m. of naloxone may be recommended and these doses do not cause a higher incidence of side effects.

Topics: Adjuvants, Anesthesia; Adolescent; Adult; Aged; Anesthesia; Female; Fentanyl; Humans; Male; Middle Aged; Naloxone; Pain, Postoperative; Partial Pressure; Respiration

Topics: Analgesics, Opioid; Anesthesia, Epidural; Humans; Morphine; Naloxone; Pain, Postoperative

Opioid drugs have analgesic properties used to treat chronic and post-surgical pain due to descending pain modulation. The use of opioids is often associated with adverse effects or clinical issues. This study aimed to evaluate the toxicity of opioids by exposing the neuroblastoma cell line (SH-SY5Y) to 0, 1, 10, and 100 µM oxycodone and naloxone for 24 h. Analyses were carried out to evaluate cell cytotoxicity, identification of cell death, DNA damage, superoxide dismutase (SOD), glutathione S-transferase (GST), and acetylcholinesterase (AChE) activities, in addition to molecular docking. Oxycodone and naloxone exposure did not alter the SH-SY5Y cell viability. The exposure to 100 µM oxycodone and naloxone significantly increased the cells' DNA damage score compared to the control group. Naloxone exposure significantly inhibited AChE, GST, and SOD activities, while oxycodone did not alter these enzymes' activities. Molecular docking showed that naloxone and oxycodone interact with different amino acids in the studied enzymes, which may explain the differences in enzymatic inhibition. Naloxone altered the antioxidant defenses of SH-SY5Y cells, which may have caused DNA damage 24 h after the exposure. On the other hand, more studies are necessary to explain how oxycodone causes DNA damage.

Topics: Acetylcholinesterase; Analgesics, Opioid; Cell Line; Constipation; Delayed-Action Preparations; Drug Combinations; Humans; Molecular Docking Simulation; Naloxone; Neuroblastoma; Oxycodone; Pain, Postoperative; Superoxide Dismutase

Topics: Analgesics; Animals; Dexmedetomidine; Hyperalgesia; Interleukin-6; Male; Naloxone; Pain, Postoperative; Plant Extracts; Rats; Rats, Sprague-Dawley; Rubus; Yohimbine

Shortages of opioid analgesics critically disrupt clinical practice and are detrimental to patient safety. There is a dearth of studies assessing the safety implications of drug shortages.. We aimed to assess perioperative opioid analgesic use and related postoperative hypoxemia (oxygen saturation less than 90%) in surgical patients exposed to prescription opioid shortages compared to propensity score-matched patients non-exposed to opioid shortages.. We conducted a retrospective study including adult patients who underwent elective surgery at The University of California San Francisco in the period August 2018-December 2019. We conducted a Gamma log-link generalized linear model to assess the effect of shortages on perioperative use of opioids and a weighted logistic regression to assess the likelihood of experiencing postoperative hypoxemia.. There were 1119 patients exposed to opioid shortages and 2787 matched non-exposed patients. After full matching, patients exposed to shortages used a greater mean of morphine milligram equivalents/day (146.94; 95% confidence interval 123.96-174.16) than non-exposed patients (117.92; 95% confidence interval 100.48-138.38; p = 0.0001). The estimated effect was a 1.25 (95% confidence interval 1.12-1.40; p = 0.0001) times greater use of opioids in patients exposed to opioid shortages than non-exposed patients. After full matching, a greater proportion of patients exposed to shortages (19.06%) experienced hypoxemia compared with non-exposed patients (16.91%). In addition, a greater proportion of patients exposed to opioid shortages (1.20%) experienced hypoxemia reversed by intravenous naloxone administration compared with non-exposed patients (0.44%).. Given the shortage prevalence, reliance on opioid medications, and related risk of respiratory depression, harm prevention measures remain critical to prevent postoperative complications that may compromise patients' safety.

Topics: Adult; Analgesics, Opioid; Humans; Hypoxia; Naloxone; Pain, Postoperative; Retrospective Studies

Topics: Adult; Analgesics, Opioid; Humans; Naloxone; Pain, Postoperative; Retrospective Studies

To determine the incidence of and predictors for serious opioid-related adverse drug events (ORADEs) in postoperative inpatients.. A retrospective cohort study design of serious ORADEs in surgical inpatients between 2015 and 2017, who were abstracted from the electronic health record, in an 800-bed academic medical health center.. A total of 27,942 surgery patients met the inclusion criteria. Of those, 25,208 patients (90%) were exposed to opioids after surgery. A total of 25,133 (99.7%) patients exposed to opioids did not experience a serious ORADE while 75 (0.3%) patients did experience a serious ORADE and required naloxone. The predictors for ORADEs include age (OR = 1.040, P-value < .0001); gender (OR = 0.394, P-value = .0006); psychiatric disorder (OR = 4.440, CI: 2.435, 8.095); morphine level with respect to hydrocodone-acetaminophen (OR = 5.841, P-value = .0384); and were almost six times more likely to experience a serious ORADE when morphine is prescribed and 4.44 times more likely in patients with a psychiatric disorder (P-value < .0001).. Once a baseline incidence is known, predictors for serious ORADEs in surgical inpatients are useful in guiding medical-surgical nurses' opioid safety practices, with more frequent focused respiratory assessments before opioid dosing and closer monitoring when opioids are prescribed postoperatively, especially in higher-risk surgical inpatients.

Topics: Acetaminophen; Analgesics, Opioid; Drug-Related Side Effects and Adverse Reactions; Humans; Hydrocodone; Incidence; Length of Stay; Naloxone; Pain, Postoperative; Retrospective Studies

Neuraxial administration of long-acting opioid is the "gold standard" for the management of postoperative pain following cesarean delivery. Respiratory depression, however, remains a concerning complication.. This retrospective single-center study of 4963 patients evaluated the frequency of respiratory depression after neuraxial morphine administration in a post-cesarean delivery population. The spinal dose of morphine varied from 100 to 450 µg intrathecally, and from 3 to 5 mg epidurally. The primary outcome was the initiation of a Rapid Response Team (RRT) event for respiratory failure due to neuraxial opioid in the 24 h following morphine administration. Secondary outcomes studied included oxygen desaturation events (SpO. There were no respiratory RRT events within the study period (95% confidence interval [CI] 0 to 7 per 10 000). There were no desaturation events recorded and no patients received supplemental oxygen therapy or naloxone (95% CI 0 to 7 per 10 000).. Clinically significant respiratory depression is rare among patients receiving neuraxial morphine for post-cesarean delivery analgesia.

Topics: Analgesia, Epidural; Analgesics, Opioid; Female; Humans; Morphine; Naloxone; Oxygen; Pain, Postoperative; Pregnancy; Respiratory Insufficiency; Retrospective Studies

Tissue injury induces a long-lasting latent sensitization (LS) of spinal nociceptive signaling that is kept in remission by an opposing µ-opioid receptor (MOR) constitutive activity. To test the hypothesis that supraspinal sites become engaged, we induced hindpaw inflammation, waited 3 weeks for mechanical hypersensitivity to resolve, and then injected the opioid receptor inhibitors naltrexone, CTOP or β-funaltrexamine subcutaneously, and/or into the cerebral ventricles. Intracerebroventricular injection of each inhibitor reinstated hypersensitivity and produced somatic signs of withdrawal, indicative of LS and endogenous opioid dependence, respectively. In naïve or sham controls, systemic naloxone (3 mg/kg) produced conditioned place aversion, and systemic naltrexone (3 mg/kg) increased Fos expression in the central nucleus of the amygdala (CeA). In LS animals tested 3 weeks after plantar incision, systemic naltrexone reinstated mechanical hypersensitivity and produced an even greater increase in Fos than in sham controls, particularly in the capsular subdivision of the right CeA. One third of Fos+ profiles co-expressed protein kinase C delta (PKCδ), and 35% of PKCδ neurons co-expressed tdTomato+ in Oprm1

Topics: Animals; Central Amygdaloid Nucleus; Female; Hyperalgesia; Male; Mice; Naloxone; Narcotic Antagonists; Pain, Postoperative; Receptors, Opioid; Receptors, Opioid, mu

Intrathecal drug delivery systems (IDDS) have been utilized for over 3 decades for management of chronic pain and spasticity. Patients with IDDS may present for surgical procedures unrelated to the IDDS device, although data are limited regarding perioperative outcomes.. This is a historical matched cohort study conducted between January 1, 2007 and December 31, 2016 of patients with an opioid-based IDDS versus matched control patients undergoing surgery excluding interventional pain procedures. Patients in the IDDS group were matched with up to 2 patients without an IDDS. Multivariable regression analyses were utilized to assess differences in the primary outcome of cumulative perioperative opioid consumption (ie, intraoperative and postanesthesia care unit [PACU] opioid consumption), and opioid consumption during the first 24 and 72 postoperative hours. Postoperative clinical outcomes were also assessed including escalating oxygen requirements, naloxone administration, pain-sedation mismatch, and perioperative pain service consultation.. A total of 321 surgeries were included, 112 with IDDS and 209 controls, with median (interquartile range [IQR]) age of 57 (49-64) years. Compared to matched controls, patients with an IDDS had greater perioperative opioid consumption (median [IQR] oral morphine milligram equivalents [OME] of 110 [60-163] vs 93 [IQR, 53-142]; adjusted multiplicative increase 1.28 [95% confidence interval {CI}, 1.03-1.59]; P = .026). IDDS patients also had greater opioid consumption in the first 24 and 72 postoperative hours (multiplicative increases of 2.23 [95% CI, 1.36-3.63], P = .001, and 2.46 [95% CI, 1.41-4.32], P = .002, respectively). There were no significant differences in postoperative oxygen requirements, naloxone administration, or pain-sedation mismatch. Inpatient pain medicine consultation was more frequent in IDDS patients compared to controls (51.8% vs 6.2%; P < .001).. Patients with opioid-based IDDS received more perioperative opioids and were more likely to receive postoperative pain service consultation compared to matched controls. There were no significant differences in clinical safety outcomes, suggesting tolerance for higher opioid doses. Further research is warranted to optimize perioperative outcomes in those with IDDS.

Topics: Adult; Aged; Analgesics, Opioid; Chronic Pain; Drug Delivery Systems; Drug Tolerance; Female; Humans; Injections, Spinal; Male; Middle Aged; Multivariate Analysis; Naloxone; Pain Management; Pain, Postoperative; Perioperative Period; Postoperative Period; Regression Analysis; Retrospective Studies; Treatment Outcome

Compare total perioperative opioid use in patients receiving naloxone continuousinfusion (NCI) for spinal cord ischemia prophylaxis, versus patients not receiving NCI, in endovascular aortic repair.. Single-center, retrospective cohort review.. Academic medical center.. Patients undergoing elective thoracic, thoracoabdominal, or abdominal aortic endovascular repair.. Patients were separated based on the use of naloxone continuous infusion as part of a spinal protection protocol. Primary endpoint was opioid requirements, in milligram morphine equivalents (MME), during the first 48 hours or during NCI. Secondary endpoints included: postoperative pain scores during the same interval; opioid requirements during hours 48 to 72; and pain scores during hours 48 to 72.. Ninety-five procedures were included; 43 received naloxone continuous infusion and 52 patients were in the non-naloxone group. Opioid use from a linear mixed model was elevated across the entire continuum in the naloxone group (18 MMEs, 95% CI 13-24), with the greatest difference seen at the 24-to-48-hour interval (51 MMEs, 95% CI 26-75) after adjustment for age, incisions, and prehospital opioid use. In the naloxone group, pain score estimates were elevated at each postoperative interval of evaluation, with similar adjustment. Across the continuum this was 0.7 higher (95% CI 0.2-1.3); the zero-six-hour and six-to-12-hour intervals were 0.9 (95% CI 0.4-1.4) and 1.2 higher (95% CI 0.7-1.7).. Patients receiving anloxone continuous infusion to prevent spinal cord ischemia required greater quantities of opioids and had higher postoperative pain, compared with patients not requiring naloxone.

Topics: Analgesics, Opioid; Humans; Naloxone; Pain, Postoperative; Retrospective Studies; Spinal Cord

To identify spine patients' barriers to appropriate postoperative opioid use, comfort with naloxone, knowledge of safe opioid disposal practices, and associated factors.. We preoperatively surveyed 174 spine patients about psychobehavioral barriers to appropriate opioid use, comfort with naloxone, and knowledge about opioid disposal. Multivariable logistic regression identified factors associated with barriers and knowledge (α = 0.05).. Common barriers were fear of addiction (71%) and concern about disease progression (43%). Most patients (78%) had neutral/low confidence in the ability of nonopioid medications to control pain; most (57%) felt neutral or uncomfortable with using naloxone; and most (86%) were familiar with safe disposal. Anxiety was associated with fear of distracting the physician (adjusted odds ratio [aOR], 3.8; 95% confidence interval [CI], 1.1-14) and with lower odds of knowing safe disposal methods (aOR, 0.18; 95% CI, 0.04-0.72). Opioid use during the preceding month was associated with comfort with naloxone (aOR, 4.9; 95% CI, 2.1-12). Patients with a higher educational level had lower odds of reporting fear of distracting the physician (aOR, 0.30; 95% CI, 0.09-0.97), and those with previous postoperative opioid use had lower odds of concern about disease progression (aOR, 0.25; 95% CI, 0.09-0.63) and with a belief in tolerating pain (aOR, 0.34; 95% CI, 0.12-0.95).. Many spine patients report barriers to appropriate postoperative opioid use and are neutral or uncomfortable with naloxone. Some are unfamiliar with safe disposal. Associated factors include anxiety, lack of recent opioid use, and no previous postoperative use.

Topics: Adult; Aged; Analgesics, Opioid; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pain, Postoperative; Spinal Diseases

Buprenorphine is a partial-agonist opioid that is prescribed as a medication-assisted treatment (MAT) for opioid use disorder (OUD). Buprenorphine is also a potent analgesic with high opioid-receptor affinity and binding coefficient; when buprenorphine is administered simultaneously with a μ-opioid receptor full agonist ("full agonist opioid" [FAO]), the combination can yield unexpected outcomes depending on dosing and timing. Buprenorphine is sometimes perceived as a powerful competitive opioid blocker that will hamper pharmacologic management that necessitates the use of FAO. When patients receiving buprenorphine-MAT (BUP-MAT) formulations have presented for operative procedures, there has been clinical variance in approach to their BUP-MAT management. Recognizing the risk management challenge from both analgesia and BUP-MAT perspectives, we convened a multidisciplinary group of clinicians who treat BUP-MAT patients and completed a literature review with the goal of generating a guideline for appropriate management of these patients presenting for a broad spectrum of surgical procedures. Our conclusion is that continuous simultaneous administration of buprenorphine products with FAO is safe when accounting for dose and timing, including surgeries that historically produce moderate to severe pain, and may further provide an analgesic advantage, lessen FAO burden, and reduce relapse risk to this group.

Topics: Buprenorphine; Drug Administration Schedule; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Perioperative Care; Practice Guidelines as Topic

Sustained-release buprenorphine is widely used in mice with the intention of providing long-lasting analgesia. Statements about duration of therapeutic efficacy are based on persistence of serum buprenorphine levels over a minimum threshold, but behavioral data demonstrating sustained efficacy is not established. Additionally, chronic opioid exposure can induce tolerance and/or hyperalgesia; mice receiving sustained-release buprenorphine have not been evaluated for these effects. This study assessed clinical efficacy and duration of sustained-release buprenorphine in inflammatory, post-operative, and cancer pain; and screened for centrally-mediated opioid-induced hyperalgesia as well as opioid tolerance. At 1-2 mg/kg sustained-release buprenorphine, statistically significant analgesic efficacy occurred only at time points up to 2 h. These animals showed no changes in von Frey thresholds on the contralateral side, i.e. no centrally-mediated opioid hyperalgesia. To establish whether acute onset opioid tolerance resulted from a single sustained-release buprenorphine administration, we used the tail flick assay, exposing mice to sustained-release buprenorphine or saline on Day 1 and buprenorphine on Day 2. We measured duration and efficacy of 1 mg/kg buprenorphine after 1 mg/kg sustained-release buprenorphine, and also quantified a dose-response curve of buprenorphine (0.1-3 mg/kg) after 2 mg/kg sustained-release buprenorphine. Compared to control animals, mice previously exposed to sustained-release buprenorphine showed diminished analgesic response to buprenorphine; the resultant dose-response curve showed decreased efficacy. Pretreatment with naloxone, an opioid receptor antagonist, blocked sustained-release buprenorphine analgesic action. The short duration of antinociception following administration of sustained-release buprenorphine in mice is caused by the rapid development of tolerance.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cancer Pain; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Tolerance; Hyperalgesia; Male; Mice; Mice, Inbred C3H; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative

Topics: Algorithms; Analgesics, Opioid; Anti-Bacterial Agents; Buprenorphine; Drug Combinations; Endocarditis; Female; Humans; Inpatients; Morphine; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pain, Postoperative; Sepsis; Young Adult

To determine time to opioid cessation post discharge from hospital in persons who had been admitted to hospital for a surgical procedure and were previously naïve to opioids.. Retrospective cohort study using administrative health claims database from the Australian Government Department of Veterans' Affairs (DVA). DVA gold card holders aged between 18 and 100 years who were admitted to hospital for a surgical admission between 1 January 2014 and 30 December 2015 and naïve to opioid therapy prior to admission were included in the study. Gold card holders are eligible for all health services that DVA funds.. The outcome of interest was time to cessation of opioids, with follow-up occurring over 12 months. Cessation was defined as a period without an opioid prescription that was equivalent to three times the estimated supply duration. The proportion who became chronic opioid users was defined as those who continued taking opioids for greater than 90 days post discharge. Cumulative incidence function with death as a competing event was used to determine time to cessation of opioids post discharge.. In 2014-2015, 24 854 persons were admitted for a surgical admission. In total 3907 (15.7%) were discharged on opioids. In total 3.9% of those discharged on opioids became chronic users of opioids. The opioid that the patients were most frequently discharged with was oxycodone; oxycodone alone accounted for 43%, while oxycodone with naloxone accounted for 8%.. Opioid initiation post-surgical hospital admission leads to chronic use of opioids in a small percentage of the population. However, given the frequency at which surgical procedures occur, this means that a large number of people in the population may be affected. Post-discharge assessment and follow-up of at-risk patients is important, particularly where psychosocial elements such as anxiety and catastrophising are identified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Australia; Databases, Factual; Drug Prescriptions; Elective Surgical Procedures; Female; Humans; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Oxycodone; Pain, Postoperative; Patient Discharge; Retrospective Studies; Risk Factors; Young Adult

Cesarean section, as a stressor, inevitably produces negative emotions such as anxiety and may cause intraoperative discomfort and postoperative pain. Butorphanol is a commonly used analgesic in cesarean section. Butorphanol's postoperative analgesia can reduce the incidence of postoperative respiratory depression and play a good sedative effect. In this study, we observed the effect of the combination of naloxone and butorphanol on postoperatively analgesia. The result proved that the effect of naloxone and butorphanol on postoperative intravenous analgesia was significant, and the adverse effects of narcolepsy, dizziness, nausea and vomiting after operation were less. Medium concentration of naloxone and high concentration of naloxone had better effect on labor pain, but the adverse reaction rate of high concentration naloxone was higher. Therefore, we suggest that the concentration of naloxone should be 0.20~0.30 μg⋅kg-1⋅h-1. At the same time, research shows that good psychological nursing can obviously relieve patients' anxiety, and also has a certain effect on reducing pain during and after operation.

Topics: Adult; Analgesics, Opioid; Butorphanol; Cesarean Section; Female; Humans; Morphine; Naloxone; Pain Measurement; Pain, Postoperative; Pregnancy; Young Adult

Previous clinical trials have demonstrated benefit with the addition of continuous infusion (CI) ketorolac to a multimodal pain regimen in surgical patients. Data following major orthopedic surgery are minimal and conflicting.. To evaluate CI ketorolac use following unilateral total knee arthroplasty (TKA) through assessment of patient-reported pain scores, opioid consumption, and safety outcomes.. This was a retrospective, open-label cohort study that included patients undergoing unilateral TKA at a single-center teaching hospital. Participants were categorized into 2 study groups based on postoperative management: CI ketorolac or opioid protocol (OP). The first group received a ketorolac 30-mg bolus followed by CI 3.6 mg/h plus as-needed (PRN) opioids. The OP group received PRN narcotics in a tiered protocol. The primary end point was comparison of median pain scores. Secondary end points included opioid consumption (morphine equivalent units [MEUs]) in the first 48 hours postoperatively, length of stay, and adverse effects.. Of 447 patients screened, 191 were analyzed (CI ketorolac, n = 116; OP, n = 75). Median pain scores were significantly lower in the CI ketorolac group at 48 hours postoperatively (3 [2-4] vs 3.5 [2.5-5], P = 0.033). Cumulative MEUs at 48 hours were significantly lower in the CI ketorolac group (33.9 ± 38.5 mg vs 301.6 ± 36.6 mg, P < 0.001). Patients in the CI ketorolac group experienced less respiratory depression (5.2% vs 25.3%, P < 0.001) and less naloxone administration (0% vs 8%, P = 0.002) compared with the OP group. Other adverse effects were similar among groups.. Postoperative CI ketorolac improved pain control while reducing opioid consumption and adverse effects.

Topics: Aged; Analgesia; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Female; Humans; Ketorolac; Male; Middle Aged; Naloxone; Pain Management; Pain Measurement; Pain, Postoperative; Retrospective Studies

Preoperative narcotic use has been associated with poor outcomes after total joint arthroplasty (TJA). The purpose of this study is to compare clinical outcomes of patients undergoing elective TJA while concurrently being treated with methadone or buprenorphine/naloxone for prior heroin addiction to a matched control group.. From an electronic medical record, we collected age, gender, body mass index, the presence of back pain, smoking status, history of alcohol abuse, preoperative use of a pain clinic, and use of antipsychotics, antidepressants, or systemic corticosteroids. Validated outcome measures including the 12-Item Short Form Survey, Knee Society Score (KSS), and Harris Hip Score were used to assess functional outcomes preoperatively and postoperatively. Perioperative data were retrospectively obtained from patient charts. Postoperative functional outcomes were prospectively collected at follow-up visits. Subjects were matched to 2:1 control group on the basis of procedure, sex, diagnosis, age (±5 years), and body mass index (±5 kg/m(2)). Average follow-up was 27.2 months.. Significant preoperative differences between the groups included mean morphine-equivalent requirements (997.1 mg for study group vs 24.8 mg for controls), 12-Item Short Form Survey Mental Component Scores (MCS-12; 37.8 for study group vs 49.0 for controls), smoking history, and antipsychotic medication use. Perioperative referral to inpatient Acute Pain Service and mean in-hospital morphine-equivalent narcotic usage (793 mg/24 h for study group vs 109 mg/24 h for controls) also significantly differed between groups. Knee range of motion differed significantly between the cohorts at 1 year (77.5 for study group vs 109.4); however, no significant difference in KSS pain (87.6 vs 84.4), KSS function (61 vs 80.9), Harris Hip Score (89.2 vs 85.3), MCS-12 (47.1 vs 52.9), or complications was observed.. Equivalent pain control and successful clinical outcome at 1 year can be achieved in patients who use methadone or buprenorphine/naloxone preoperatively.

Topics: Aged; Arthroplasty, Replacement; Buprenorphine; Cohort Studies; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Pain Management; Pain, Postoperative; Prospective Studies; Registries; Retrospective Studies; Treatment Outcome

To define likely targets (i.e. glia) and protocols (analgesic combinations) to improve postoperative pain outcomes and reduce chronic pain after surgery. Specifically, to assess the antihyperalgesic effects of the dexketoprofen : tramadol (DEX : TRM) combination, exploring the implication of glial activation.. In a mouse model of postincisional pain, we evaluated mechanical nociceptive thresholds (Von Frey) for 21 days postoperatively. We assessed DEX and TRM alone and combined (1 : 1 ratio) on postoperative hyperalgesia (POH, day 1) and delayed latent pain sensitisation (substantiated by a naloxone challenge; PS, day 21). The interactions were analysed using isobolograms, and concomitant changes in spinal glial cell activation were measured.. On day 1, DEX completely blocked POH, whereas TRM induced 32% inhibition. TRM, but not DEX, partially (47%) protected against PS, at 21 days. Co-administration of DEX : TRM (1 : 1 ratio) showed additivity for antihyperalgesia. Both drugs and their combination totally inhibited surgery-induced microglia activation on day 1, but had no effect on surgery-induced astrocyte activation (1 day) or re-activation after naloxone (21 days).. The DEX : TRM combination could have clinical advantages: a complete prevention of POH after surgery, together with a substantial (48%) inhibition of the development of PS by TRM. Microglia, but not astrocyte activation, could play a relevant role in the development of postoperative pain hypersensitivity.

Topics: Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Drug Combinations; Hyperalgesia; Ketoprofen; Male; Mice; Naloxone; Neuroglia; Pain Threshold; Pain, Postoperative; Tramadol

Centhaquin has been shown to produce antinociception in the mouse hot plate and tail flick assays through the opioid, the α2A and α2B adrenoceptors. Present study was conducted to determine the effects of centhaquin in a rat model of postoperative pain. Involvement of opioid, and adrenergic receptors was assessed by pretreating rats with antagonists at the opioid (naloxone), α2-(atipamezole) or α2B-(imiloxan) adrenergic receptors. Postoperative pain was induced by hind paw plantar incision in male Sprague Dawley rats. Antihyperalgesic effects were determined by measurement of paw withdrawal latencies and withdrawal force, using dynamic von Frey filaments; attenuation of non-evoked guarding was measured by assigning pain scores to spontaneous behaviors. Rotarod test was used to determine motor impairment. Animals received saline, centhaquin or antagonist plus centhaquin. Centhaquin produced dose-dependent antihyperalgesic effect and attenuation of non-evoked guarding behavior, versus saline treated rats (P<0.05). Naloxone partially blocked while atipamezole and imiloxan significantly reversed centhaquin's antihyperalgesic effects (P<0.05). Attenuation of non-evoked guarding behavior was also blocked, but was not statistically significant. Imiloxan produced a greater block compared to atipamezole while naloxone had no significant effect. Rotarod testing indicated that centhaquin did not cause motor impairment. This is the first report demonstrating centhaquin antinociception in the rat postoperative pain model. Opioid, α2 adrenergic, and particularly α2B adrenergic receptors are involved in mediating antihyperalgesia while attenuation of nonevoked guarding is mediated by α2B/α2 adrenergic receptors. Centhaquin could be an effective non-sedating alternative in treating postoperative pain in ambulatory surgeries.

Topics: Analgesics; Animals; Behavior, Animal; Dose-Response Relationship, Drug; Hyperalgesia; Imidazoles; Male; Motor Activity; Naloxone; Pain, Postoperative; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-2; Receptors, Opioid

Preemptive analgesia involves introducing an analgesic before noxious stimulation. Electroacupuncture (EA) activates descending mechanisms that modulate nociceptive inputs into the spinal dorsal horn. This study evaluated whether preoperative EA is more effective than postoperative EA in reducing incision pain in rats. The nociceptive threshold to mechanical stimulation was utilized to examine the effects of an intraperitoneal injection of saline (0.1 mL/kg) or naloxone (1 mg/kg) on antinociception induced by a 20-minute period of 2-Hz or 100-Hz EA applied to the Zusanli (ST36) and Sanyinjiao (SP6) acupoints before surgical incision, or 10 minutes after or 100 minutes after surgical incision of the hind paw. The extent of mechanical hyperalgesia after the incision was significantly attenuated by the application of 100-Hz EA preoperatively, but not by its application at 10 minutes or 100 minutes postoperatively. By contrast, 2-Hz EA was effective against postoperative hyperalgesia when applied 10 minutes or 100 minutes after surgery but not when it was applied preoperatively. Only the effect of 2-Hz EA applied 10 minutes after surgery was sensitive to naloxone. The present study showed for the first time that 100-Hz EA, but not 2-Hz EA, exerts a nonopioidergic preemptive effect against postincision pain in rats.

Topics: Acupuncture Points; Animals; Electroacupuncture; Humans; Male; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Rats; Rats, Wistar

Many patients undergoing hip replacement have inadequate postoperative pain control, leading to suboptimal recovery. Oxycodone is effective in controlling pain, but is associated with adverse events such as postoperative nausea and vomiting (PONV). In patients with chronic pain, oral oxycodone-naloxone combination (OXN) provides comparable analgesia with fewer side effects. This retrospective, single-centre study evaluated analgesic effectiveness and tolerability of single-shot epidural spinal anaesthesia followed by OXN after total hip replacement.. Consecutive patients received perioperative spinal-epidural anaesthesia, OXN 10/5 mg and oral ketoprofen 100 mg q 12h for 4 days. Efficacy and tolerability were assessed on the evening post surgery and days 1-3 after. Efficacy endpoints included pain intensity at rest and upon movement (Numerical Rating Scale [NRS] Score), rescue analgesia and patient satisfaction (0-3 point scale).. Two hundred eighty-two patients were included in the observation (57.2% women, mean age 62.9±12 years). After surgery, pain intensity remained well controlled, both at rest (mean NRS: 1.1, 1.1, 1.2 and 1.2 on days 0-3 respectively; P=ns) and upon movement (2.1, 2.4, 2.1 and 2.0; P=ns). No patient reported severe pain throughout the observation. Rescue paracetamol was required on days 0-3 in 17.0%, 18.4%, 12.4% and 12.1% of patients, respectively (P<0.009); no patient required additional intravenous rescue morphine. Seventy-two percent of patients were 'very satisfied' with postoperative pain therapy.. Single-shot epidural spinal anaesthesia followed by OXN-based analgesia after hip replacement provided effective pain management, with high patient satisfaction rates.

Topics: Aged; Analgesics, Opioid; Anesthesia, Epidural; Anesthesia, Spinal; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Hip; Female; Humans; Ketoprofen; Male; Middle Aged; Naloxone; Narcotic Antagonists; Oxycodone; Pain Measurement; Pain, Postoperative; Patient Satisfaction; Retrospective Studies

We present this case to review the metabolism of oxycodone and the effects of end-stage renal disease on the elimination of oxycodone and its metabolites. A 42-year-old female with end-stage renal disease who was dependent on hemodialysis presented for left hamstring posterior capsule release. She had been receiving methadone for 2 years for chronic leg pain. On postoperative day 1, the patient's medication was changed from IV hydromorphone to oral oxycodone to treat breakthrough pain. By the next day, the patient was unarousable with notable respiratory depression. She did not fully recover after urgent hemodialysis but did have full recovery after receiving an IV naloxone infusion for 22 hours. Further study of the safety of oxycodone in hemodialysis patients is warranted.

Topics: Administration, Oral; Adult; Analgesics; Biotransformation; Chronic Pain; Female; Humans; Infusions, Intravenous; Joint Capsule Release; Kidney Failure, Chronic; Leg; Naloxone; Narcotic Antagonists; Oxycodone; Pain, Postoperative; Renal Dialysis; Respiratory Insufficiency; Treatment Outcome

Cedrus atlantica essential oil (CaEO) presents analgesic and anti-inflammatory sedative properties. However, it remains unknown whether CaEO alleviates acute postoperative pain.. Here, we investigated the effect of CaEO on postoperative pain and its mechanisms related to the descending pain control in Swiss males mice induced by a plantar incision surgery (PIS) in the hindpaw.. Inhalation of CaEO (5', 30' or 60') markedly reduced mechanical hypersensitivity. This effect was prevented by pre-treatment with naloxone or p-chlorophenylalanine methyl ester (PCPA, 100mg/kg, i.p.)-induced depletion of serotonin. In addition, p-alpha-methyl-para-tyrosin (AMPT, 100mg/kg, i.p.)-induced depletion of norepinephrine, intraperitoneal injection of the α2-adrenergic receptor antagonist yohimbine (0.15 mg/kg, i.p.) or haloperidol (1mg/kg, i.p.) an antagonist of dopaminergic (D1 and D2) receptors prevented the effect of CaEO on hypersensitivity.. These findings suggest that CaEO alleviates postoperative pain by activating the descending pain modulation pathways on the opioidergic, serotonergic, noradrenergic (α2-adrenergic) and dopaminergic (dopamine D1 and D2 receptors) systems.

Topics: Administration, Inhalation; Adrenergic alpha-2 Receptor Antagonists; alpha-Methyltyrosine; Analgesics; Animals; Behavior, Animal; Cedrus; Disease Models, Animal; Dopamine Antagonists; Fenclonine; Foot; Haloperidol; Hyperalgesia; Male; Mice; Motor Activity; Naloxone; Narcotic Antagonists; Oils, Volatile; Pain, Postoperative; Phytotherapy; Serotonin Antagonists; Yohimbine

Light-emitting diode therapy (LEDT) has been clinically used as an alternative to low-level laser therapy; nevertheless, the molecular basis for LEDT effects remains unclear. The objective of this study was to evaluate the analgesic effect of LEDT in the mouse plantar incision (PI) model of postoperative pain, as well as to investigate some of the possible mechanisms involved in this effect, i.e., peripheral and central opioid receptors; migration of opioid-containing leukocytes to PI site and the L-arginine/nitric oxide (NO) pathway. To that end, mice were subjected to PI and treated with LEDT (950 nm, 80 mW/cm(2), 1 through 13 J/cm(2)). Mechanical hypersensitivity was assessed as withdrawal frequency percentage to 10 presentations of a 0.4-g von Frey filament. In addition, the animals were pretreated with systemic (i.p.), intra-plantar (i.pl.), or intrathecal injection (i.t) of naloxone (a nonselective opioid receptor antagonist; 1 mg/kg, i.p.; 5 μg/right paw or 5 μg/site, respectively) or a systemic injection of fucoidin (100 μg/mouse, i.p., an inhibitor of leukocyte rolling through binding to L- and P-selectins). Our results demonstrate, for the first time, that LEDT induced a dose-response analgesic effect in the model of PI in mice. At the dose of 9 J/cm(2) LEDT presented the most significant results through (1) activation of peripheral opioid receptors which involve, at least partially, the recruitment of opioid-containing leukocytes to the PI site and; (2) activation of the L-arginine/NO pathway. These results extend previous literature data and suggest that LEDT might be useful in the treatment of postoperative pain.

Topics: Animals; Arginine; Disease Models, Animal; Dose-Response Relationship, Radiation; Injections, Spinal; Leukocytes; Male; Mice; Naloxone; Narcotic Antagonists; Nitric Oxide; Pain, Postoperative; Phototherapy; Receptors, Opioid

The aim of this study was to assess whether intraperitoneal administration of ginseng total saponins (GTS) has antihyperalgesic effects in a rat model of incisional pain. The proinflammatory responses and reversal of the antihyperalgesic effect of GTS by N-methyl-d-aspartate (NMDA) or naloxone were also evaluated.. Rats were injected intraperitoneally with 0.9% saline vehicle or various doses of GTS before or after a plantar incision. Paw withdrawal in response to application of the von Frey filament with the lowest bending force marked the mechanical withdrawal threshold (MWT). Blood samples were collected for the assessment of serum interleukin (IL)-1β and IL-6 levels. The IL levels were measured using an enzyme-linked immunosorbent assay kit. Rats were injected intraperitoneally with NMDA or naloxone before the GTS injection to assess the reversal of the antihyperalgesic effect of GTS.. The MWT measured 2 h after the plantar incision increased significantly after the postincision administration of 50, 100, or 200 mg/kg of GTS compared with the MWT at 2 h after plantar incision. The MWT also increased significantly after the preincision injection of 100 or 200 mg/kg of GTS compared with the MWT of the vehicle control. Administration of GTS suppressed the postincision rise in serum IL-1β levels and NMDA inhibited the increase in the MWT compared with GTS alone.. Intraperitoneal administration of GTS before or after surgery induces antihyperalgesic effects in a rat model of incisional pain. The effects on mechanical hyperalgesia may be associated with anti-inflammatory cytokines and NMDA signaling.

Topics: Acute Pain; Animals; Disease Models, Animal; Excitatory Amino Acid Agonists; Hyperalgesia; Injections, Intraperitoneal; Male; N-Methylaspartate; Naloxone; Narcotic Antagonists; Pain, Postoperative; Panax; Rats; Rats, Sprague-Dawley; Saponins

To investigate the effects of intrathecal morphine and fentanyl combined with low-dose naloxone on the expression of motilin and its receptor in a rat model of postoperative pain.. An intrathecal catheter was implanted, and saline, opioids (morphine and fentanyl) and naloxone were intrathecally administered 7 days later. An incisional pain model was established to induce pain behaviors in rats by unilateral plantar incision. Thermal hyperalgesia and mechanical allodynia were measured by using a radiant heat and electronic Von Frey filament, respectively. The expression of motilin in the hippocampus, stomach, duodenum, and plasma was determined by ELISA; and the expression of motilin receptor in the hippocampus was detected by Western blot assay.. Motilin and its receptor were detected in the hippocampus. Acute incisional pain increased the motilin expression in the hippocampus and duodenum, while decreasing its expression in the gastric body and plasma. Postoperative analgesia with morphine+fentanyl upregulated the expression of motilin in the hippocampus; however, motilin was downregulated in peripheral sites. Naloxone at 1 ng/kg restored motilin to baseline levels. Acute pain, morphine+fentanyl, and naloxone all induced the expression of motilin receptor in the hippocampus.. Acute pain, postoperative analgesia with opioids, and naloxone significantly impacted the expression of hippocampal and peripheral motilin. Variation trends in all sites were not identical. Intrathecal injection of low-dose naloxone upregulated paw withdrawal thermal latency and enhanced the analgesic effects of opioids. The findings presented here provide a new basis for central and peripheral regulations in GI motility, clinical postoperative analgesia, and management of analgesic complications.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Drug Therapy, Combination; Hippocampus; Injections, Spinal; Motilin; Naloxone; Pain Measurement; Pain, Postoperative; Rats; Rats, Sprague-Dawley; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Treatment Outcome; Up-Regulation

CR4056 is a novel imidazoline-2 (I2 ) ligand exhibiting potent analgesic activity in animal models of pain. In this study, we investigated the effects of CR4056 in a well-established model of postoperative pain where rats develop hyperalgesia in the injured hind paw.. By measuring paw withdrawal threshold to mechanical pressure, we studied the pharmacology of CR4056, potential sex differences in pain perception and response to treatment, and the pharmacodynamic interaction of CR4056 with morphine.. Oral CR4056 and subcutaneous morphine dose-dependently reversed the hyperalgesic response. Analgesic effects of CR4056 were completely suppressed by the non-selective imidazoline I2 /α2 -adrenoceptor antagonist idazoxan, were partially reduced (~30%; P < 0.05) by the selective α2 -adrenoceptor antagonist yohimbine, but were not influenced by the non-selective I1 /α2 -adrenoceptor antagonist efaroxan or by the μ opioid receptor antagonist naloxone. We found no differences in responses to CR4056 or morphine between male and female rats. However, females had a lower pain threshold than males, and needed lower doses of drugs to reach a significant analgesia. When CR4056 and morphine were combined, their median effective doses were lower than expected for additive effects, both in males and in females. Isobolographic analysis confirmed a synergism between CR4056 and morphine.. CR4056 is a novel pharmacological agent under development for postoperative pain both as stand-alone treatment and in association with morphine. CR4056 has successfully completed Phase I studies for tolerability and pharmacokinetics in healthy volunteers, and is currently entering the first proof-of-concept study in patients.

Topics: Adrenergic alpha-2 Receptor Antagonists; Analgesics; Analgesics, Opioid; Animals; Benzofurans; Binding Sites; Drug Synergism; Female; Hyperalgesia; Idazoxan; Imidazoles; Imidazoline Receptors; Male; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Quinazolines; Rats, Sprague-Dawley; Yohimbine

In today's literature there are no defined guidelines for the treatment of postoperative pain in corrective surgery of hallux valgus. In this study we evaluated the use of a new treatment protocol designed to minimize the postoperative pain related to the surgical treatment of hallux valgus.. The study involved 20 female patients (20 feet) treated for moderate to severe hallux valgus between September 2011 and December of 2012 with a percutaneous technique (10 feet) and minimally invasive surgery (Endolog System) (10 feet). All patients received postoperative as analgesic therapy 1 cp etoricoxib 120 mg/ day for 5 days + oxycodone hydrochloride/naloxone 5mg 1cp × 2/day for 15 days. The evaluation forms of pain VAS/VRS have been used for the evaluation of pre and postoperative pain at 15 and 30 days.. In both groups we found a significant reduction of pain in the days following surgery. At 30 days the VAS score was similar in between the two groups. Few and mild side effects were reported (1 case).. The co-administration of an anti-cox2 and an opioid in the first postoperative hours is useful to reduce soft tissue swelling and to control pain without causing significant side effects. The therapeutic protocol adopted, along with an adequate anesthesiological approach, has proved to be very effective for pain management in peri-and post-operative treatment of hallux valgus.

Topics: Adult; Aged; Analgesics, Opioid; Cyclooxygenase 2 Inhibitors; Drug Therapy, Combination; Etoricoxib; Female; Hallux Valgus; Humans; Middle Aged; Minimally Invasive Surgical Procedures; Naloxone; Narcotic Antagonists; Orthopedic Procedures; Oxycodone; Pain Management; Pain, Postoperative; Prospective Studies; Pyridines; Sulfones

Buprenorphine is a semisynthetic opioid with both agonist and antagonist activity at the opioid receptor. Currently, buprenorphine is commonly available in sublingual preparations combined with naloxone (e.g., Suboxone®, Subutex®). There has been increased use of buprenorphine derivatives in the areas of substance addiction and chronic pain. Nevertheless, there is limited and conflicting information in the literature pertaining to the optimal management of buprenorphine-stabilized patients presenting for surgery. We present our experience with a chronic pain patient on buprenorphine presenting for thoracic surgery.. A 47-yr-old female with a history of a Clagett window procedure for pulmonary aspergillosis and subsequent chronic pain presented to our institute for a window closure procedure. Preoperatively, her pain regimen included Suboxone 16 mg bid, which was continued perioperatively. Postoperatively, her course was complicated by suboptimal pain at the surgical site requiring in excess of 70 mg/24 hr of intravenous hydromorphone. Liberal addition of long-acting oral opioids was ineffective in improving pain management. Eventually, concern was raised regarding opioid receptor blockade by her long-acting Suboxone, and the decision was made to taper her Suboxone. Following this, her pain control improved dramatically and her opioid requirements were markedly reduced. By discharge, her Suboxone was discontinued and she was managed on oral hydromorphone.. In a chronic pain patient continued on Suboxone perioperatively, significant improvement in control of postoperative pain was observed following tapered doses, and eventually her use of Suboxone was discontinued. This case highlights the potential for opioid receptor blockade by Suboxone, which can interfere with acute pain management.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Female; Humans; Middle Aged; Naloxone; Pain, Postoperative; Pulmonary Aspergillosis; Thoracic Surgical Procedures

The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9 years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16 mg/naloxone 4 mg in conjunction with social and psychological support.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; Disease Management; Female; Heroin; Heroin Dependence; Humans; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Substance Withdrawal Syndrome; Young Adult

Buprenorphine/naloxone is used for the treatment of opioid dependence. In the following case, a potential use for the medication combination is explored in the arena of transplant surgery. Psychiatry was consulted for a 29-year-old woman with iatrogenic opioid dependence after bilateral ventricular assist device placement for congenital cardiomyopathy. Her ejection fraction was less than 15% and she was considered a poor candidate for transplant due to drug-seeking behaviors. We transitioned her onto buprenorphine/naloxone to prevent abuse and control symptoms, qualifying her for cardiac transplant. After transplant, we coordinated care with cardiothoracic surgeons to restart buprenorphine/naloxone, and the patient has been stable for 8 months.

Topics: Adult; Buprenorphine; Cardiomyopathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Transplantation; Heart-Assist Devices; Humans; Iatrogenic Disease; Naloxone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Substance Withdrawal Syndrome

Patients with Myotonic Dystrophy show an unpredictable response to several anesthetic drugs including opioids, neuromuscular blocking agents and especially reversal agents like neostigmine. We describe the case of a 40 year old patient with myotonic dystrophy who underwent laparoscopic cholecystectomy and ovarian cyst removal under general anesthesia. The authors suggest the use of the new reversal agent suggamadex, for reversing neuromuscular blockade caused by rocuronium, in patients suffering from neuromuscular disease and especially from Myotonic Dystrophy, because it rapidly and completely reverses any residual neuromuscular blockade, but also underline the increased susceptibility of these patients to opioids.

Topics: Adult; Analgesics, Opioid; Androstanols; Anesthesia Recovery Period; Anesthesia, General; Cholecystectomy, Laparoscopic; Female; gamma-Cyclodextrins; Humans; Meperidine; Myotonic Dystrophy; Naloxone; Narcotic Antagonists; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Ovarian Cysts; Pain, Postoperative; Respiratory Insufficiency; Rocuronium; Sugammadex

Combined regional anesthesia is frequently used as a tool for management of postoperative pain. The profile of side effects of the opioids used via this route is similar to those occurring after systemic administration. The onset of vertigo with vertical nystagmus is an adverse effect rarely described after the use of intrathecal, epidural or intravenous morphine. We report the case of a patient who presented this complication in the postoperative period of a partial nephrectomy, after the administration of intrathecal morphine, with complete resolution by intravenous naloxone.

Topics: Aged; Analgesics, Opioid; Humans; Injections, Spinal; Male; Morphine; Naloxone; Narcotic Antagonists; Nystagmus, Pathologic; Pain, Postoperative; Vertigo

Opioids are common drugs for pain treatment in preterm newborn infants, in spite of several adverse effects. Constipation is a frequent problem when opioids are used in both adults and neonates. Although several studies indicate that the oral administration of naloxone hydrochloride (NH) improves intestinal motility during opioid therapy, there is still a lack of evidence in newborns.. The aim of this study was to assess the efficacy of NH against reduced intestinal motility during opioid treatment.. A retrospective cohort study was performed. We analysed the medical records of fifteen infants (Group 1) treated with continuous morphine (MO) infusion and fourteen infants (Group 2) treated with both oral NH (3 microg/kg 4 times daily) and MO.. There was no statistically significant difference in the total MO dose. Infants treated both with NH and MO had a tendency to improve their mean stool frequency/day. A statistically significant improvement was observed in the mean total food intake (mL/kg/day) of the infants treated with NH (p = 0.014). No difference in the mean food retention between the two groups was observed.. Orally administrated NH seems to improve intestinal motility resulting in increased food intake/day and improved stool frequency/day in premature newborn infants treated with MO. Further studies are needed to corroborate these findings.

Topics: Female; Gastrointestinal Transit; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Retrospective Studies

Topics: Adolescent; Age Factors; Analgesia, Patient-Controlled; Child; Child, Preschool; Dose-Response Relationship, Drug; Droperidol; Drug Administration Routes; Gastrointestinal Diseases; Humans; Infant; Infant, Newborn; Morphine; Naloxone; Narcotics; Pain, Postoperative; Practice Guidelines as Topic; Pruritus; Respiratory Insufficiency; Risk Assessment; Urinary Retention

Topics: Analgesics, Opioid; Delayed-Action Preparations; Drug Administration Schedule; Drug Combinations; Drug Labeling; Gastric Emptying; Humans; Naloxone; Oxycodone; Pain, Postoperative; Patient Education as Topic; Patient Participation; Risk Assessment

We describe a case-report of an 85-year-male patient with a patient-controlled analgesia (PCA) after a total hip arthroplasty. Four hours after surgery, acute respiratory distress secondary to a morphine overdose occurred, requiring an antagonisation with naloxone. Morphine overdose during a PCA was always caused by a wrong use of the pump. In this case-report, no mistake of programming or administration's use was found. Too important morphine's doses managed in comparison with the patient's age and his renal failure could explain this morphine's accumulation and the respiratory distress. This observation reminds us the obligation to determine the optimal posology in accordance with the rate of glomerular filtration estimated by Cockcroft and Gault formula for patients using a PCA.

Topics: Acute Kidney Injury; Adjuvants, Anesthesia; Aged, 80 and over; Analgesia, Patient-Controlled; Analgesics, Opioid; Arthroplasty, Replacement, Hip; Droperidol; Glomerular Filtration Rate; Humans; Male; Morphine; Naloxone; Narcotic Antagonists; Oxygen Inhalation Therapy; Pain, Postoperative; Respiratory Distress Syndrome

The aim of the present study was to evaluate the antinociceptive effect of the novel pyrazoline methyl ester: 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4).. The effect of MPF4 was assessed in two models of pain: arthritic pain caused by Complete Freund's Adjuvant (CFA) and postoperative pain caused by surgical incision in mice.. MPF4 given intraperitoneally (1.0 mmol/kg, i.p.) produced marked antinociception in inflammatory allodynia caused by CFA. The antinociceptive effect produced by MPF4 was reversed with the pre-treatment of animals with naloxone or naltrindole. Oral administration of MPF4 (1.0 mmol/kg, p.o), dipyrone (1.0 mmol/kg, p.o.) and morphine (0.026 mmol/kg, p.o.) also produced an anti-allodynic effect. However, none of the compounds evaluated reversed the paw edema produced by CFA. Moreover, MPF4, dipyrone and morphine also produced an anti-allodynic effect in the surgical incisional pain model. The maximal inhibitions obtained with preemptive drug treatment were 66+/-7%, 73+/-9% and 88+/-8% for MPF4 (1.0 mmol/kg, p.o.), dipyrone (1.0 mmol/kg, p.o.) and morphine (0.026 mmol/kg, p.o.), respectively. The maximal inhibitions obtained with curative drug treatment were 53+/-9%, 83+/-7% and 84+/-7%, for MPF4, dipyrone and morphine, respectively. Unlike indomethacin, MPF4 did not induce gastric lesions at the dose that caused the highest antinociception (1.0 mmol/kg, p.o). The anti-allodynic action of MPF4, dipyrone and morphine was not associated with impairment of motor activity.. The results of the present study suggest that MPF4 represents a potential target for the development of new drugs to treat persistent inflammatory pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Dipyrone; Freund's Adjuvant; Indomethacin; Inflammation; Male; Mice; Morphine; Motor Activity; Naloxone; Naltrexone; Narcotic Antagonists; Pain; Pain, Postoperative; Postural Balance; Pyrazoles; Stomach Ulcer

This article describes two patients with major ischemic stroke symptoms who had extremely small areas of acute brain infarction, suggestive of acute intrahemispheric diaschisis. Both patients were using narcotic analgesics during their stroke, and in both cases the clinical deficits improved dramatically with naloxone.. We postulate that the narcotics amplified the ischemic stroke symptoms and that this effect was antagonized by naloxone.. This suggests that the opiate system may be involved in the process of intrahemispheric diaschisis.

Topics: Acute Disease; Aged; Brain Ischemia; Female; Humans; Hydrocodone; Hydromorphone; Male; Naloxone; Narcotic Antagonists; Narcotics; Pain, Postoperative

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pain, Postoperative; Self Administration; Surgical Procedures, Operative

The Institute for Healthcare Improvement challenges clinicians and administrators to raise care quality through its 5 Million Lives Campaign, a sequel to the 100,000 Lives Campaign. Here, review a case study on the importance of postoperative monitoring of opioid-naive patients who are receiving narcotics.

Topics: Adult; Analgesics, Opioid; Benchmarking; Clinical Protocols; Communication; Drug Monitoring; Drug Utilization Review; Female; Harm Reduction; Humans; Medical Audit; Minnesota; Naloxone; Narcotic Antagonists; Nursing Assessment; Nursing Audit; Pain, Postoperative; Postoperative Care; Professional Staff Committees; Respiratory Insufficiency; Systems Analysis; Total Quality Management

Previous studies have demonstrated that Fos-like immunoreactivity is increased in spinal dorsal horn neurons in several pain models, and have suggested that Fos-like immunoreactivity could be used as a marker of neurons activated by painful stimulation. In the present study, we evaluated nociceptive behaviors and spinal Fos-like immunoreactivity in a rat skin incision model of post-operative pain. In this model, evoked and non-evoked pain behaviors were observed at least for 2 days after paw surgery, an increased number of Fos-like immunoreactive neurons was observed in the spinal dorsal horn at lumbar levels 4-5 two-hour post-surgery. The number of Fos-like immunoreactive neurons was significantly greater in animals with skin-muscle incision compared to animals with skin-alone incision. Interestingly, spinal Fos-like immunoreactivity was quickly normalized in rats with paw surgery at later time points (8 and 24 h post-surgery), whereas nociceptive behaviors were still observed. Furthermore, at 24 h post-surgery, spinal Fos-like immunoreactivity induced by thermal stimulation (42, 44, 46, 48, 52 degrees C for 15 s) was not significantly different between sham animals and animals with surgery. In both groups, an increase in spinal Fos-like immunoreactive neurons was observed with increasing temperatures, with similar laminar distribution. Finally, systemic morphine reduced post-operative pain and Fos-like immunoreactivity in a naloxone reversible manner, with greater potency and efficacy on behavioral endpoints than on Fos-like immunoreactivity. These results demonstrate a different profile of nociceptive behaviors and spinal Fos-like immunoreactivity in the rat skin incision model, suggesting a limited potential of spinal Fos-like immunoreactivity to study post-surgical pain and its pharmacology.

Topics: Analgesics, Opioid; Animals; Dermatologic Surgical Procedures; Dose-Response Relationship, Drug; Hindlimb; Immunohistochemistry; Male; Morphine; Muscles; Naloxone; Narcotic Antagonists; Pain, Postoperative; Posterior Horn Cells; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Spinal Cord; Temperature; Time Factors

The administration of naloxone may be an important monitor of the quality and safety of postoperative pain management. However, studies that support the use of naloxone as a quality measure are absent. The purposes of this study are to determine the incidence and factors associated with naloxone administration in the postoperative setting and to critically examine naloxone as a potential quality measure. Participants included all postoperative adult inpatients at an academic hospital who received naloxone and an equal number of matched control patients who did not receive naloxone during the calendar year 2003. Medical record audits were performed to examine patient demographics, relevant medical history, postoperatively administered analgesics and central nervous system depressants, documented sedation and respiratory assessments, reason provided for naloxone administration, and patient outcome. Naloxone was administered to .53% (56/10,511) of all adult inpatient postoperative patients. Patients who received naloxone were significantly older and received more central nervous system depressants than cohorts. No significant differences were found in comorbidities, route of opioid administration, or amount of opioids taken by the two groups. Reversal of excessive opioid-induced sedation was the primary reason provided for naloxone administration. However, 25% of the patients were later determined to have a new diagnosis that contributed to sedation. Examination of naloxone administration proved useful in uncovering deficits in structures and processes of care. However, caution is warranted when using naloxone as a quality measure to avoid the implication that higher use indicates opioid analgesic over-treatment or error.

Topics: Adult; Analgesics, Opioid; Case-Control Studies; Central Nervous System Depressants; Drug Utilization Review; Female; Humans; Incidence; Male; Middle Aged; Midwestern United States; Naloxone; Narcotic Antagonists; Nurse's Role; Nursing Assessment; Nursing Audit; Nursing Evaluation Research; Outcome and Process Assessment, Health Care; Pain, Postoperative; Patient Selection; Postoperative Care; Quality Indicators, Health Care; Time Factors; Trauma Centers

Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Drug Therapy, Combination; Humans; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative

Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Drug Combinations; Humans; Naloxone; Narcotics; Pain Measurement; Pain, Postoperative; Tilidine; Tramadol; Wounds and Injuries

Orexin A and B (hypocretin 1 and 2) are the endogenous ligands of orexin receptors, a G-protein-coupled orphan receptor family containing orexin 1 (OX1) and orexin 2 (OX2) types. Orexin A induces analgesia in acute and inflammatory pain models. We further elucidated the possible antiallodynic effect of intrathecal orexins in a rat model of postoperative pain. Mechanical allodynia was induced by incising the rat hind paw and evaluated with the withdrawal threshold to von Frey filament stimulation. Intrathecal orexin A (0.03-1 nmol) and orexin B (0.1-3 nmol) dose dependently attenuated the incision-induced allodynia. Orexin A (ED50 = 0.06 nmol) is more potent than orexin B. The effects of orexin A and B were abolished by their respective antibodies, but not by naloxone, and were attenuated by suramin and strychnine, the P2X purinergic and glycine receptor antagonists, respectively. SB-334867, an OX1 receptor antagonist, at 30 nmol completely blocked the effect of orexin A but, even at 100 nmol, only partially antagonized the effect of orexin B. Orexin A antibody, SB-334867, suramin, strychnine, or naloxone enhanced the incision-induced allodynic response. It is concluded that intrathecal orexins reduce incision-induced allodynia through OX1 receptors. Glycine and P2X purinergic receptors, but not opioid receptors, might be involved in the antiallodynic effects of orexins. Endogenous orexin might be released after incision injury to activate the spinal OX1 receptors as an endogenous analgesic protector.

Topics: Animals; Antibodies, Blocking; Benzoxazoles; Carrier Proteins; Exophthalmos; gamma-Aminobutyric Acid; Glycine Agents; Injections, Spinal; Intracellular Signaling Peptides and Proteins; Male; Naloxone; Naphthyridines; Narcotic Antagonists; Neuropeptides; Orexin Receptors; Orexins; Pain Threshold; Pain, Postoperative; Physical Stimulation; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Glycine; Receptors, Neuropeptide; Receptors, Purinergic P2; Strychnine; Suramin; Synaptic Transmission; Urea

Topics: Analgesia, Epidural; Analgesics; Analgesics, Opioid; Humans; Injections, Intravenous; Ketamine; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative

Topics: Endorphins; History, 20th Century; Humans; Naloxone; Narcotic Antagonists; Pain, Postoperative; Placebo Effect; Tooth Extraction

We describe a case of neurological symptoms after the intrathecal use of an opioid. These symptoms were not reversible by the use of an opioid-antagonist.

Topics: Aged; Analgesics, Opioid; Antiemetics; Depression, Chemical; Drug Interactions; Drug Resistance; Eye Diseases; Female; Humans; Injections, Spinal; Metoclopramide; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Respiration

Electroacupuncture has been proposed to be a low cost and practical method that allows effective pain management with minimal collateral effects. In this study we have examined the effect of electroacupuncture against the hyperalgesia developed in a model of post-incisional pain in rats. A 1-cm longitudinal incision was made through the skin and fascia of the plantar region of the animal hind paw. Mechanical hyperalgesia in the incision was evaluated 135 min after the surgery with von Frey filaments. The tension threshold was reduced from 75 g (upper limit of the test) to 1.36 +/- 0.36 g (mean +/- SEM) in control rats. It is shown that a 15-min period of electroacupuncture applied 120 min after surgery to the Zusanli (ST36) and Sanyinjiao (SP6) points, but not to non-acupoints, produces a significant and long-lasting reduction of the mechanical hyperalgesia induced by the surgical incision of the plantar surface of the ipsilateral hind paw. The tension threshold was reduced from 75 to 27.6 +/- 4.2 g in animals soon after the end of electroacupuncture. The mechanical threshold in this group was about 64% less than in control. Electroacupuncture was ineffective in rats treated 10 min earlier with naloxone (1 mg/kg, ip), thus confirming the involvement of opioid mechanisms in the antinociceptive effects of such procedure. The results indicate that post-incisional pain is a useful model for studying the anti-hyperalgesic properties of electroacupuncture in laboratory animals.

Topics: Animals; Case-Control Studies; Disease Models, Animal; Electroacupuncture; Hyperalgesia; Male; Naloxone; Narcotic Antagonists; Pain, Postoperative; Rats; Rats, Wistar; Time Factors

Long-term opioid therapy results in physical dependency. Therefore abrupt cessation of opioid treatment may cause acute abstinence symptoms. The doses of opioids should always be reduced gradually, even when other treatment options give good pain relief. Patients receiving long-term treatment with opioids become more sensitive to the opioid antagonist naloxone. Inappropriate use of naloxone in these patients can also result in acute abstinence symptoms. Opioid treatment is limited by toxic side effects, and the problem can be solved by changing the opioid. The author describes three cases to illustrate these problems.

Topics: Aged; Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Palliative Care; Substance Withdrawal Syndrome

We describe the experience of the acute pain service of the University Hospital of Galicia, Spain since its inception. We have treated 1214 patients using either patient-controlled analgesia (PCA) with morphine (72%), or patient-controlled epidural analgesia with fentanyl + bupivacaine (22%). Three hundred and five patients had minor complications, mainly pruritus (35%) in patients with patient-controlled epidural analgesia. Three (0.33%) patients using PCA had respiratory depression treated with naloxone; no patient with patient-controlled epidural analgesia had respiratory depression. In our experience the creation of an acute pain service and the associated development of pain-treatment protocols and the training of hospital personnel produced excellent results.

Topics: Academic Medical Centers; Analgesia, Epidural; Analgesia, Patient-Controlled; Bupivacaine; Fentanyl; Hospitals, University; Humans; Infusion Pumps; Monitoring, Physiologic; Morphine; Naloxone; Pain Clinics; Pain Measurement; Pain, Postoperative; Pruritus; Respiration; Respiration Disorders; Spain

The benefits of epidural narcotic analgesia (ENA) have been documented in mixed surgical populations. To assess the safety and utility of ENA after thoracic surgery and to assess potential interactions with intraoperative intravenous narcotics (IIN), we retrospectively examined the records of 130 consecutive patients having thoracotomy. The 116 patients who received ENA required a mean of 0.19 mg/kg of intravenous morphine sulfate (MS) within the first 48 postoperative hours, as opposed to 0.44 mg/kg for patients who did not receive ENA. The place in which nonepidural patients were extubated most frequently was the operating room (71%), followed by the intensive care unit (21%) and the recovery room (7%). Percentages were similar for epidural patients: 71% were extubated in the operating room, 20% in the intensive care unit, and 9% in the recovery room. Nonepidural patients had an immediate mean postoperative PCO2 of 39.2 mm Hg, epidural patients a mean of 40.1 mm Hg. There were no technical complications due to epidural catheter placement, and no reintubation was required within the first 72 postoperative hours. The concomitant administration of IIN did not produce a significant difference in postextubation PCO2 in either group of patients, although increasing doses resulted in a lower percentage of patients extubated in the operating room or recovery room. We conclude that ENA may be safely administered to patients having thoracotomy, and it diminishes the need for postoperative intravenous narcotics.

Topics: Adult; Aged; Aged, 80 and over; Analgesia, Epidural; Blood Gas Analysis; Carbon Dioxide; Drug Costs; Drug Interactions; Female; Fentanyl; Humans; Intraoperative Care; Intubation, Intratracheal; Lung Volume Measurements; Male; Middle Aged; Morphine; Naloxone; Pain, Postoperative; Pruritus; Respiratory Insufficiency; Retrospective Studies; Thoracotomy; Time Factors

The subcutaneous injection of formalin in the rat paw results in several minutes of flinching (phase 1) followed by cessation of activity then resumption of flinching (phase 2), which depends on facilitation of spinal transmission evoked by C-fiber activity generated immediately after the noxious stimulus. It was hypothesized that suppression of dorsal horn activity during and immediately after formalin injection by inhalation anesthetics or intrathecal opiates would block spinal facilitation and inhibit phase 2 flinching, even if the anesthetic or opiate were eliminated before phase 2.. Flinches/min were observed 1 and 5 min after formalin injection (phase 1) and at 5-min intervals thereafter for 60 min (phase 2) for five groups of rats: control (group 1); 1% isoflurane before and for 6 min after formalin (group 2); 2.5% isoflurane before and for 6 min after formalin (group 3); 1% isoflurane and 70% N2O before and for 6 min after the formalin (group 4); and 30 micrograms intrathecal morphine given 20 min before formalin and 30 micrograms intrathecal naloxone given 6 min after formalin, combined with 1% isoflurane as in group 2 (group 5).. All groups, except control, exhibited essentially complete suppression of phase 1 flinching. The changes in phase 2 flinching, expressed as a percent of total phase 2 flinches for the control animals, were: control (100%) = group 4 (109 +/- 17%) > group 2 (66 +/- 13%) = group 3 (66 +/- 14%) > group 5 (19 +/- 12%).. Isoflurane, even at high concentrations, administered during and shortly after a noxious stimulus produces only a modest reduction in facilitation of afferent processing. The addition of intrathecal morphine during the period of nociceptor activity results in marked attenuation of the facilitated state.

Topics: Anesthesia, Inhalation; Animals; Injections, Spinal; Isoflurane; Male; Morphine; Naloxone; Neurons, Afferent; Nitrous Oxide; Pain Measurement; Pain, Postoperative; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Synaptic Transmission

Topics: Analgesia; Anesthesia, Intravenous; Critical Illness; Drug Synergism; Humans; Naloxone; Pain, Postoperative; Pentazocine

The effect of the presence of either chronic or acute clinical pain on pain threshold and on the nociceptive flexion reflex (RIII) threshold was studied. The experimental pain sensation and the flexion reflex were evoked by trains of short electrical pulses. It was hypothesized that both kinds of clinical pain would be able to induce 'diffuse noxious inhibitory controls' (DNIC) and thereby raise the 2 experimental thresholds. Patients with chronic low back pain, patients with postoperative pain from oral surgery, and pain-free subjects were tested in 3 conditions: during baseline, after i.v. administration of a placebo, and after i.v. administration of naloxone. In comparison with 2 pain-free control groups, the 2 pain groups had a significantly higher pain threshold in all conditions. However, the RIII threshold was not significantly elevated in chronic or acute pain patients compared to controls. Naloxone had no effect on the RIII or pain threshold in any of the groups. It is concluded that the increased pain threshold which is frequently found in chronic pain patients, and which could be confirmed in the present study, does not result from a DNIC effect. The adaptation level theory offers an alternative explanation. Also, the acute postoperative pain in this study did not seem to induce DNIC. Because other forms of acute pain have been found to be effective in activating DNIC, future research should establish which pains are and which pains are not effective.

Topics: Adult; Aged; Aging; Blood Pressure; Chronic Disease; Electric Stimulation; Electromyography; Heart Rate; Humans; Low Back Pain; Male; Middle Aged; Mouth; Naloxone; Pain Threshold; Pain, Postoperative

We report the use of extradural diamorphine for postoperative analgesia as a nurse-based service on selected surgical wards in a district general hospital. Eight hundred patients received lumbar or thoracic extradural diamorphine analgesia for postoperative or traumatic pain. Diamorphine was administered in bolus form by suitably trained nursing staff. Satisfactory analgesia, recorded on a verbal rating scale at the conclusion of the service, was achieved in 94.6% of patients. The technique was considered by medical and nursing staff to be a safe and acceptable method of analgesia. Respiratory depression, defined as a ventilatory frequency of less than 10 b.p.m., occurred in seven patients (incidence of 0.9%). All occurred in the theatre recovery area or in the intensive care unit. Retrospectively, each was predictable and all responded to naloxone 0.4 mg.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesia, Epidural; England; Female; Heroin; Hospitals, District; Hospitals, General; Humans; Male; Middle Aged; Naloxone; Nursing Audit; Nursing Service, Hospital; Pain, Postoperative; Respiratory Insufficiency

Topics: Adult; Analgesia, Epidural; Female; Humans; Medication Errors; Morphine; Naloxone; Pain, Postoperative; Respiratory Insufficiency

Topics: Anesthesia, Dental; Fentanyl; Humans; Meperidine; Naloxone; Pain, Postoperative; Sufentanil

Topics: Adult; Analgesia, Epidural; Female; Humans; Hysterectomy; Meniere Disease; Morphine; Naloxone; Pain, Postoperative

1. Activity of the mimetic muscles of the upper face were recorded from awake and anesthetized patients by surface electromyography (SEMG). 2. High amplitude SEMG accompanied ketamine anesthesia and/or the presentation of pain-provoking stimuli. 3. During periods of elevated facial muscle activity, fentanyl or butorphanol decreased SEMG amplitude. 4. The opioid-induced SEMG depression was not consistently associated with either lowered vigilance or analgesia but did provide an objective measure of drug effect.

Topics: Adult; Aged; Butorphanol; Electromyography; Evoked Potentials; Facial Muscles; Fentanyl; Humans; Middle Aged; Morphinans; Naloxone; Pain; Pain, Postoperative; Succinylcholine

A patient not known in advance to have the sleep apnoea syndrome (SAS) was administered a combined epidural-general anaesthetic for a proposed radical prostatectomy. After surgery which had to be discontinued due to extensive tumoural spread, morphine 5 mg was administered through the epidural catheter for analgesia. Severe respiratory depression occurred eight hours later and was successfully reversed by repeated injections of naloxone. The potential danger of epidural morphine administration to SAS patients is discussed.

Topics: Aged; Anesthesia, Epidural; Anesthesia, General; Blood Gas Analysis; Humans; Male; Morphine; Naloxone; Oxygen Inhalation Therapy; Pain, Postoperative; Prostatectomy; Respiratory Insufficiency; Sleep Apnea Syndromes

The analgesic efficacy and tolerance of a single intramuscular injection of either buprenorphine (0.3 mg) or a buprenorphine (0.3 mg)/naloxone (0.2 mg) combination was compared in 70 patients suffering from moderate to severe pain after abdominal surgery. Patients in both treatment groups experienced good analgesia which was apparent within 10 minutes of administration and lasted for approximately 12 hours. The most frequently reported unwanted effects were drowsiness and/or sleepiness and nausea and/or vomiting which were of mild or moderate severity in most cases. No significant differences were seen between the two treatment groups with regard to the overall assessments of efficacy and tolerance.

Topics: Adult; Aged; Buprenorphine; Drug Combinations; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Naloxone; Pain, Postoperative

The opiate antagonist, naloxone, produces dose-dependent biphasic changes in clinical pain. The mechanism of the analgesia produced by low dose naloxone is unknown. To study the analgesic effect of naloxone, we have used a programmable infusion pump, which eliminates placebo-induced endorphin-mediated analgesia, to administer different doses of naloxone. We report that use of machine infusion of naloxone exclusively produces analgesia. The implications of this finding to the mechanism of naloxone-induced analgesia are discussed.

Topics: Analgesics; Double-Blind Method; Humans; Injections, Intravenous; Naloxone; Pain, Postoperative; Tooth Extraction; Tooth, Impacted

The epidural injection of a bolus of 250 micrograms somatostatin followed by continuous epidural infusion provided complete postoperative relief of pain in eight patients who had undergone abdominal surgery; no other analgesics were required. In two patients, intravenous and intramuscular naloxone had no effect on the analgesia provided by epidural somatostatin. In two patients, epidural somatostatin also produced adequate intraoperative analgesia. Epidural somatostatin was associated with no side effects.

Topics: Aged; Blood Chemical Analysis; Catheterization; Epidural Space; Female; Hemodynamics; Humans; Infusions, Parenteral; Injections; Male; Middle Aged; Naloxone; Pain, Postoperative; Respiration; Somatostatin

A prospective study of the effect and side-effects of epidural morphine for pain relief in 1085 patients after thoracic, abdominal, urologic, or orthopaedic surgery was performed. Morphine chloride was diluted in saline or bupivacaine and administered through an epidural catheter placed at a segmental level appropriate for the type of surgery. The initial dose was 4 or 6 mg morphine and supplementary doses were given when needed to obtain complete freedom from pain during deep breathing or nursing care. The total dose of epidural morphine from end of surgery until the next morning varied from 4 to 18 mg. 97% of hip arthroplasty patients, 91% of prostatectomy patients and thoracotomy patients, 90% of patients after major lower extremity surgery and 88% of patients after laparotomy were completely satisfied with the postoperative course. For hip arthroplasty and major extremity surgery, an initial dose of 4 mg of epidural morphine was as effective as 6 mg. After prostatectomy, laparotomy, and thoracotomy, an initial dose of 6 mg gave significantly better effect than 4 mg. Pruritus occurred in 11%, nausea or vomiting in 34%, and respiratory depression in 0.9% of the total patient population. Urinary retention occurred in 42% of patients not having urinary catheters in place. Postoperative nausea or vomiting was more frequent in women than in men (P less than 0.001). There was a higher incidence of nausea or vomiting in men experiencing pain than in men who were completely pain-free after abdominal surgery (P less than 0.001). Respiratory depression was rare and occurred as a gradually decreasing respiratory rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anesthesia, Epidural; Catheterization; Depression, Chemical; Epidural Space; Humans; Morphine; Naloxone; Nausea; Pain, Postoperative; Prospective Studies; Pruritus; Respiration; Time Factors; Vomiting

Buprenorphine 30 and 40 micrograms/kg was given as the sole intravenous analgesic in balanced anaesthesia to 12 patients undergoing cholecystectomy. Significant and severe respiratory depression was found 15 minutes after preoperative loading with buprenorphine. In the immediate postoperative period six patients were in pain. They were treated with naloxone 0.08-0.4 mg leading to a long lasting period of pain relief (median 22 hours).

Topics: Adult; Anesthesia, Intravenous; Buprenorphine; Depression, Chemical; Humans; Middle Aged; Morphinans; Naloxone; Pain, Postoperative; Prospective Studies; Respiration

Topics: Adult; Buprenorphine; Drug Interactions; Female; Humans; Morphinans; Naloxone; Pain, Postoperative

Topics: Adjuvants, Anesthesia; Alfentanil; Analgesics, Opioid; Anesthesia, General; Fentanyl; Humans; Naloxone; Narcotic Antagonists; Pain, Postoperative; Preanesthetic Medication; Sufentanil

Narcotics have been shown to act selectively upon nociceptive synaptic junctions in laminae 1 and 2 of the dorsal horn of the spinal cord. Subarachnoid or epidural injection of narcotics can produce selective segmental analgesia of great intensity and prolonged duration that is free of motor or sympathetic blockade. However, poorly lipid-soluble drugs, such as morphine, that tend to linger in the water phase of the CSF may spread rostrally to involve opiate receptors in brain stem nuclei. Delayed respiratory depression and lifethreatening apnoea is therefore the greatest danger. Other undesirable side effects include itching, nausea and vomiting and urinary retention. All side-effects are antagonized by naloxone. Intraspinal narcotic analgesia has many useful applications for the relief of acute or chronic pain. Obstetrical pain is less amenable to this approach. Effective and safe management of acute pain requires that the patients be under adequate surveillance to avoid the danger of insidious respiratory depression. Chronic malignant pain is well controlled by relatively small doses of narcotic, and these patients can be managed at home on a long-term basis.

Topics: Adjuvants, Anesthesia; Analgesia; Analgesics, Opioid; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthesia, Spinal; Chronic Disease; Epinephrine; Female; Humans; Male; Naloxone; Pain Management; Pain, Postoperative; Pregnancy; Respiration

Morphine 0.3 mg kg-1 was i.m. given to 25 patients after upper abdominal operations, for analgesia purpose. One hour later, naloxone 0.01 mg was injected i.v. for every 1 mg morphine given. Ten minutes later, pentazocine 0.5 mg kg-1 was also injected i.v. in order to appreciate how it could counteract the reduction in analgesia level caused by naloxone. Complete analgesia could be found in all patients after the mentioned dose of morphine. The minute-ventilation and respiratory frequency were reduced from 7.74 +/- 0.66 to 6.88 +/- 0.77 l (decrease not significant J and from 22.76 +/- 0.98 to 17.44 +/- 0.88 (p less than 0.001). Naloxone partially restored their values, to 7.70 +/- 0.55 l and 18.96 +/- 0.88, but 17 patients out of 25 immediately complained of wound pain. Pentazocine improved analgesia again, in all patients, but also depressed the minute-ventilation to 6.43 +/- 0.48 l, without evident changes in respiratory frequency. If the respiratory changes after morphine and naloxone-pentazocine are compared, it is to emphasize that the distribution of the values was much less after the drug combination, 0.56 in comparison with 1.44, P (Fischer Snédécor test) less than 0.001, showing a more homogeneous improving of the minute-ventilation. In conclusion, if pentazocine is added to naloxone, while a respiratory depression caused by morphine has to be reversed, the analgesia level is maintained and the respiration is insignificantly reduced.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Pain, Postoperative; Pentazocine; Respiration

This study was comprised of an experimental part (20 volunteers) and a clinical part (10 surgical patients). In the experimental part, the effects of either 2-, 4-, or 10-mg doses of epidural morphine on ventilatory responses to a standardized CO2 challenge were studied in healthy volunteers. In the clinical part, ventilatory responses to CO2 were evaluated in patients receiving 4 mg of epidural morphine for pain relief after gall bladder surgery. Naloxone infusion was given to five volunteers to determine whether ventilatory changes due to epidural morphine could be prevented. Using a nonrebreathing method, end-tidal PCO2 (PETCO2) and minute ventilation (tidal volume X frequency) were measured before and 1, 5, 8, 13, and 22 hr after epidural morphine injection. Ventilation was stimulated by 4% CO2 in 21% O2 and 75% N2. In the experimental study, a dose-related depression of ventilatory drive was seen after epidural morphine. After 2- and 4-mg doses, increases in PETCO2 were present up to 5 hr after injection with a corresponding reduction in minute ventilation. Ten mg of epidural morphine was followed by a significant reduction in minute ventilation and an increase in PETCO2 that started 1 hr after injection, peaked at 5 hr, and then remained almost unchanged for the next 17 hr. PETCO2 was higher and remained elevated longer in surgical patients than in volunteers given the same amount of epidural morphine (4 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anesthesia, Epidural; Depression, Chemical; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Pain, Postoperative; Respiration

Topics: Adolescent; Adult; Aged; Arousal; Consciousness; Droperidol; Drug Synergism; Female; Humans; Male; Middle Aged; Naloxone; Neuroleptanalgesia; Pain, Postoperative; Pentazocine

Topics: Anesthesia; Drug Interactions; Humans; Naloxone; Narcotic Antagonists; Narcotics; Pain, Postoperative

Topics: Adolescent; Adult; Endorphins; Humans; Naloxone; Nitrous Oxide; Pain, Postoperative; Tooth, Impacted

Topics: Adult; Anesthesia; Anesthesia, General; Anesthesia, Inhalation; Endorphins; Female; Fentanyl; Genital Diseases, Female; Hemorrhage; Humans; Menstruation; Naloxone; Narcotics; Nociceptors; Pain, Postoperative; Pituitary Hormones, Anterior; Prospective Studies; Receptors, Opioid

Topics: Adolescent; Analgesics; Child; Child, Preschool; Cyclohexanecarboxylic Acids; Drug Combinations; Female; Humans; Male; Naloxone; Pain; Pain, Postoperative; Tilidine; Wounds and Injuries

Topics: Adolescent; Adult; Aged; Cyclohexanecarboxylic Acids; Drug Combinations; Extremities; Female; Humans; Male; Middle Aged; Naloxone; Pain, Postoperative; Pentazocine; Tilidine

Topics: Aged; Cardiovascular System; Drug Evaluation; Fentanyl; Humans; Middle Aged; Morphine; Naloxone; Pain, Postoperative

Topics: Adult; Analgesics; Analysis of Variance; Blood Pressure; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Methadone; Middle Aged; Naloxone; Pain, Postoperative; Sleep; Statistics as Topic; Time Factors