Morphine-induced Pruritus Research Articles

Prevention Versus Treatment of Intrathecal Morphine-induced Pruritus With Ondansetron

Prevention Versus Treatment of Intrathecal Morphine-induced Pruritus With Ondansetron

Comparación de los efectos profilácticos del droperidol y del ondansetrón sobre el prurito provocado por la morfina subaracnoidea

Background and objectivesThe prophylactic effect of ondansetron on subarachnoid morphine-induced pruritus is controversial, while evidence suggests that droperidol prevents pruritus. The aim of this study is to compare the effects of droperidol and ondansetron on subarachnoid morphine-induced pruritus. MethodsOne hundred eighty patients ASA I or II patients scheduled to undergo cesarean sections under subarachnoid anesthesia combined with morphine 0.2mg were randomized to receive, after the child's birth, metoclopramide 10mg (Group I-control), droperidol 2.5mg (Group II) or ondansetron 8mg (Group III). Postoperatively, the patients were assessed for pruritus (absent, mild, moderate or severe) or other side effects by blinded investigators. Patients were also blinded to their group allocation. The tendency to present more severe forms of pruritus was compared between groups. NNT was also determined. ResultsPatients assigned to receive droperidol (proportional odds ratio: 0.45 [95% confidence interval 0.23-0.88]) reported less pruritus than those who received metoclopramide. Ondansetron effect was similar to metoclopramide (proportional odds ratio: 0.95 [95% confidence interval 0.49-1.83]). The NNT for droperidol and ondansetron was 4.0 and 14.7, respectively. ConclusionsOndansetron does not inhibit subarachnoid morphine-induced pruritus.

Comparison of droperidol and ondansetron prophylactic effect on subarachnoid morphine-induced pruritus

Background and objectivesThe prophylactic effect of ondansetron on subarachnoid morphine-induced pruritus is controversial, while evidence suggests that droperidol prevents pruritus. The aim of this study is to compare the effects of droperidol and ondansetron on subarachnoid morphine-induced pruritus. Methods180 ASA I or II patients scheduled to undergo cesarean sections under subarachnoid anesthesia combined with morphine 0.2mg were randomized to receive, after the child's birth, metoclopramide 10mg (Group I – control), droperidol 2.5mg (Group II) or ondansetron 8mg (Group III). Postoperatively, the patients were assessed for pruritus (absent, mild, moderate or severe) or other side effects by blinded investigators. Patients were also blinded to their group allocation. The tendency to present more severe forms of pruritus was compared between groups. NNT was also determined. ResultsPatients assigned to receive droperidol [Proportional odds ratio: 0.45 (95% confidence interval 0.23–0.88)] reported less pruritus than those who received metoclopramide. Ondansetron effect was similar to metoclopramide [Proportional odds ratio: 0.95 (95% confidence interval 0.49–1.83)]. The NNT for droperidol and ondansetron was 4.0 and 14.7, respectively. ConclusionsOndansetron does not inhibit subarachnoid morphine-induced pruritus.

Methylnaltrexone to prevent intrathecal morphine-induced pruritus after Caesarean delivery: a multicentre, randomized clinical trial

Intrathecal morphine-induced pruritus is a very common side-effect that is difficult to prevent or treat. Central and peripheral mechanisms are believed to be involved. The aim of this study was to determine if a peripherally acting, μ-opioid antagonist would reduce morphine-induced pruritus. We conducted a multicentre, randomized, blinded, placebo-controlled trial of women having elective Caesarean section under spinal anaesthesia with intrathecal morphine 100 μg. After delivery, participants received either subcutaneous methylnatrexone bromide 12 mg (MNTX group, n=69) or saline (placebo group, n=68). Pruritus, nausea, pain, analgesic use, and side-effects were assessed at 2, 4, 8, and 24 h. The primary outcome was the severity of pruritus (0-10 score). One hundred and thirty-seven women completed the study, with five major protocol violations. There was no statistically significant difference between the MNTX and placebo groups for the median (IQR) pruritus AUC scores [24 (9-47) vs 36 (11-68), median difference 8.5, 95% confidence interval (CI) 0-20, P=0.09] or the worst pruritus score [3 (2-7) vs 5 (2-6), median difference 1, 95% CI 0-2, P=0.24]. The incidence of pruritus was 84% in the MNTX group and 88% in the placebo group (P=0.48). Analgesic and gastrointestinal outcomes did not significantly differ between the groups. A single dose of subcutaneous methylnaltrexone bromide 12 mg did not reduce the overall severity or incidence of pruritus. In this study, treatment with a peripherally acting μ-opioid antagonist was generally ineffective against intrathecal morphine-induced pruritus, but a small clinical effect cannot be excluded. Australian New Zealand Clinical Trials Registry (ACTRN12611000345987).

Prophylactic administration of ondansetron in prevention of intrathecal morphine-induced pruritus and post-operative nausea and vomiting in patients undergoing caesarean section.

BackgroundIntrathecal morphine is commonly used for post caesarean analgesia. However, their use is frequently associated with the incidence of troublesome side effects such as nausea, vomiting and pruritus. Various mechanisms have been postulated for the opioid-induced pruritus, with a variety of medications with different mechanisms of actions formulated for the prevention and treatment. But, the results are inconsistent and hence the prevention and treatment of opioid-induced pruritus still remains a challenge. Ondansetron which is antiemetic, non-sedative and has no antianalgesic effect is an antagonist to 5-HT3 receptor, the receptor with which opioids interacts and imparts its effects. Ondansetron, thus, would be an attractive treatment strategy for both opioid-induced pruritus and post-operative nausea and vomiting.MethodsAfter the approval from institutional review committee and written consent received from the patient, 50 healthy parturients of ASA I and II physical status undergoing caesarean section under spinal anaesthesia were enrolled for the study. They were randomly categorized into placebo group (2 ml normal saline) and treatment group (2 ml of 4 mg ondansetron), each group containing 25 patients. Pruritus and post-operative nausea and vomiting scores were recorded up to 24 hours after the administration of intrathecal morphine. Statistical analysis was performed using chi-square test.ResultsThe incidence, severity and necessity of treatment for pruritus in the treatment group was significantly reduced compared to the placebo group (16% vs 88%). Similarly, the risk of post-operative nausea and vomiting in the treatment group was less compared to the placebo group (8% vs 56%).ConclusionProphylactic administration of ondansetron to parturients receiving intrathecal morphine for post-operative analgesia provides a significant reduction of intrathecal morphine-induced pruritus and nausea and vomiting.Trial registrationCTRI/2015/01/005362 registered on 07/01/2015 in Clinical Trials Registry – India (ctri.nic.in).

The Effect of Propofol on Intrathecal Morphine-Induced Pruritus and Its Mechanism

Liu, Xiulan; Zhang, Jing; Zhao, Hongyan; Mei, Hongxia; Lian, Qingquan; Shangguan, Wangning Author Information

Butorphanol Prevents Morphine-induced Pruritus Without Increasing Pain and Other Side Effects

Purpose Pruritus is a frequent adverse event after administration of morphine. Butorphanol has been used to prevent morphine-induced pruritus, but its efficacy is still controversial. The aim of this systematic review was to evaluate the efficacy of using butorphanol to prevent morphine-induced pruritus.

Prevention versus treatment of intrathecal morphine-induced pruritus with ondansetron

BackgroundIntrathecal morphine is used for post-cesarean analgesia, but pruritus is a common side effect. Ondansetron would be an attractive treatment because it prevents nausea, is non-sedative or has no anti-analgesic effect. We undertook a study to assess the efficacy of ondansetron for treatment or prophylaxis of intrathecal morphine-induced pruritus. MethodsHealthy paturients undergoing cesarean delivery with intrathecal morphine 250μg and fentanyl 25μg were randomized to receive: prophylaxis (ondansetron 8mg at cord clamping, normal saline 4mL for treatment of pruritus in the post-anaesthesia care unit); treatment (normal saline 4mL at cord clamping, ondansetron 8mg as required in the post-anesthesia care unit) or control (normal saline 4mL in both). Visual analogue scale scores for pruritus, nausea and pain were recorded preoperatively, on arrival to, at 30, 60, and 120min and on discharge from the post-anesthesia care unit. The primary outcome was the peak pruritus score. ANOVA with Bonferroni correction or Fisher’s exact test were used to analyze data; P<0.05 was considered significant. ResultsThe study was terminated early when interim analysis indicated no effect. Eighty-two of the intended 180 paturients completed the protocol (26 in control group, 32 in treatment group and 24 in prophylaxis). There were no differences in the rate or severity of pruritus at any assessment point, or the request for treatment. Pruritus was reduced after administration of treatment syringe. ConclusionProphylactic ondansetron did not reduce pruritus when compared with placebo. The use of ondansetron as a treatment did not decrease the severity of pruritus when compared with placebo.

Dose-dependent attenuation of intravenous nalbuphine on epidural morphine-induced pruritus and analgesia after cesarean delivery

Epidural morphine in patient-controlled analgesia regimens controls postoperative pain well but easily induces pruritus and other epidural morphine-related side effects. With 90 pregnant American Society of Anesthesiologists physical status II females scheduled for elective cesarean delivery, the present study was designed to evaluate the efficacy and safety profile of patient-controlled antipruritus (PCP) use of intravenous nalbuphine-based regimens for attenuation of postoperative pruritus and related side effects in combination with epidural morphine patient-controlled analgesia with regard to the quality of postoperative pain management. Patients were randomly assigned to two nalbuphine groups (5 μg/kg/hour, Group N5 or 10 μg/kg/hour, Group N10) and bolus dose of 1.6 μg/kg for PCP or the control (normal saline) group. Comparable visual analog scale scores for rest pain at each measured time interval among the three groups demonstrated that adequate pain relief was offered; however, the cumulative dose of nalbuphine administered to the patients in Group N10 attenuated the analgesic effect of epidural morphine in moving pain at POh24 only. Fewer episodes and milder severity of pruritus were observed in patients in Groups N5 and N10 at all postoperative time intervals. Epidural morphine provided good postoperative pain relief but with incommodious side effects. In addition, intravenous nalbuphine not only attenuated the incidence of pruritus but also decreased total morphine consumption. In conclusion, intravenous administration of low-dose nalbuphine (5 μg/kg/hour) for PCP maintained analgesia produced by epidural morphine and offered low pruritus incidence.

The Effect of Propofol on Intrathecal Morphine-Induced Pruritus and Its Mechanism

Previous studies have shown that a low dose of propofol IV bolus had a beneficial effect on intrathecal morphine-induced pruritus in humans. However, its exact mechanism has not been fully understood. In this study, we hypothesized that propofol relieved intrathecal morphine-induced pruritus in rats by upregulating the expression of cannabinoid-1 (CB[1]) receptors in anterior cingulate cortex (ACC). Twenty-four Sprague-Dawley rats were divided into a control group and 20, 40, 80 μg/kg morphine groups to create an intrathecal morphine-induced scratching model. The effects of propofol on intrathecal 40 μg/kg morphine-induced scratching responses were then evaluated. Sixty rats were randomly assigned to control, normal saline, intralipid, and propofol groups, with pruritus behavior observation or killed 8 minutes after venous injection of normal saline, intralipid, or propofol, and brain tissues were then collected for assay. Immunohistochemistry was then performed to identify the expression of CB (1) receptor in ACC, and the concentration of CB(1) receptor in ACC was determined by Western blot analysis. Compared with the control group, rats in the 20, 40, 80 μg/kg morphine groups had higher mean scratching response rates after intrathecal morphine injection (P =0.020, 0.005, and 0.002, respectively). There was a statistical difference between 20 and 40 μg/kg morphine groups at 10 to 15 and 15 to 20 timepoints after intrathecal morphine injection (P = 0.049 and 0.017, respectively). Propofol almost abolished the scratching response that was induced by 40 μg/kg intrathecal morphine injection (F[2, 15] = 46.87, P < 0.001; F[22, 165] = 2.37, P = 0.001). Compared with the intralipid and normal saline groups, the scratching behavior was significantly attenuated in the propofol group (P < 0.001). Compared with control, normal saline, and intralipid groups, the protein expression of CB(1) receptor in ACC (Western blot) in the propofol group increased (0.86 ± 0.21, 0.94 ± 0.18, 0.86 ± 0.13, and 1.34 ± 0.32, respectively, P < 0.001). There was no significant difference among control, normal saline, and intralipid groups. Compared with the control, normal saline, and intralipid groups, the average number of neurons of CB(1) receptor in the ACC area were higher in the propofol group (21.0 ± 1.4, 19.3 ± 1.8, 24.8 ± 7.7, and 37.2 ± 3.3, respectively, P < 0.001). Morphine elicits dose-independent scratching responses after intrathecal injection in rats. Morphine 40 μg/kg intrathecal injection-induced scratching responses can be prevented by propofol. Increased protein expression of CB(1) receptors in ACC may contribute to the reversal of intrathecal morphine-induced scratching.

Butorphanol prevents morphine-induced pruritus without increasing pain and other side effects: a systematic review of randomized controlled trials

Pruritus is a frequent adverse event after administration of morphine. Butorphanol has been used to prevent morphine-induced pruritus, but its efficacy is still controversial. The aim of this systematic review was to evaluate the efficacy of using butorphanol to prevent morphine-induced pruritus. We searched PubMed, Cochrane Library, EMBASE, and China's BioMedical Disc for full reports of randomized controlled trials that compared the use of butorphanol with either placebo or no treatment for preventing morphine-induced pruritus. The number of patients experiencing pruritus or other side effects was analyzed using relative risk (RR) with 95% confidence intervals (CI). Sixteen trials (795 patients) were analyzed. Continuous intravenous and epidural butorphanol reduced pruritus with RR 0.22 (95% CI 0.10 to 0.45) and RR 0.24 (95% CI 0.16 to 0.36), respectively. Use of epidural butorphanol decreased the number of patients requesting rescue treatment for pruritus (RR 0.57; 95% CI 0.41 to 0.81). Butorphanol decreased postoperative pain intensity at four, eight, and 12 hr with standardized mean differences of -0.29 (95% CI -0.52 to -0.05), -0.30 (95% CI -0.56 to -0.04), and -0.23 (95% CI -0.46 to -0.01), respectively. Epidural but not intravenous butorphanol reduced postoperative nausea and vomiting (PONV) (RR 0.35; 95% CI 0.19 to 0.66). Butorphanol did not increase respiratory depression (RR 0.71; 95% CI 0.31 to 1.63), somnolence (RR 0.71; 95% CI 0.22 to 2.37), or dizziness (RR 2.45; 95% CI 0.35 to 17.14). Butorphanol administered with morphine may be an effective strategy for preventing morphine-induced pruritus as it decreases pain intensity and PONV without increasing other side effects. Thus, it can be recommended for preventing morphine-induced pruritus during the perioperative period.

Intravenous butorphanol administration reduces intrathecal morphine-induced pruritus after cesarean delivery: a randomized, double-blind, placebo-controlled study

Pruritus associated with intrathecal opioid administration is a common side effect. There is evidence that κ-opioid receptor agonists have antipruritic activity. Butorphanol has agonist actions at both κ-opioid and μ-opioid receptors. This study was designed to evaluate the antipruritic efficacy of butorphanol after intrathecal morphine administration in the setting of a randomized, double-blind study of parturients undergoing cesarean section. Ninety-one women who received combined spinal-epidural anesthesia with 1.2 ml 0.5 % isobaric bupivacaine and 0.1 mg preservative-free morphine were included in this study. After delivery of the baby, the parturients were randomly allocated to two groups: butorphanol group (n = 46) and physiological saline group (n = 45). In the butorphanol group, parturients received an intravenous loading dose of 1 mg butorphanol followed by infusion of 0.2 mg/h butorphanol. The physiological saline group received an infusion of the same volume of physiological saline. The presence of pruritus, visual analog scores for pain, sedation scores, and adverse effects were recorded 1, 2, 4, 6, 8, 10, 12, and 24 h after intrathecal morphine administration. The incidence of pruritus at 24 h was significantly more frequent in the physiological saline group than in the butorphanol group (48.9 vs. 13.0 %, P < 0.001). The severity of pruritus was significantly greater in the saline group than in the butorphanol group 2, 4, 6, 8 and 10 h after intrathecal morphine injection (P = 0.004, 0.001, 0.002, and 0.003, respectively). The visual analog scale scores at 24 h were significantly lower in the butorphanol group than in physiological saline group (P < 0.001). The Ramsay sedation score in the butorphanol group was significantly higher than that in the physiological saline group after 1, 2, 4, 6, 8, 10, 12, and 24 h (P < 0.05). There were no significant differences between the two groups in nausea/vomiting and other adverse effects. Administration of intravenous butorphanol after delivery of the baby can reduce pruritus that has been induced by intrathecal morphine administration in cesarean delivery with combined spinal-epidural anesthesia.

Dexamethasone for the Prophylaxis of Postoperative Nausea and Vomiting Associated with Neuraxial Morphine Administration

We performed a systematic review to assess the efficacy of dexamethasone in reducing postoperative nausea, vomiting (PONV), pruritus, and enhancing postoperative analgesia in patients receiving neuraxial anesthesia with neuraxial morphine. We searched Medline (1966-2011), the Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science for all randomized controlled trials comparing dexamethasone with placebo for the prevention of PONV and/or pruritus in patients receiving neuraxial morphine as part of a neuraxial anesthetic technique. Data were extracted independently by the authors on the incidence of PONV, pruritus, pain scores at 4 and 24 hours, and use of rescue antiemetics, antipruritics, and analgesics. Eight randomized controlled trials (4 cesarean deliveries, 4 total abdominal hysterectomies) were included. From these trials, 768 patients were analyzed with 473 receiving dexamethasone and 295 receiving placebo. The doses of dexamethasone investigated ranged from 2.5 to 10 mg. Dexamethasone reduced the incidence of postoperative nausea (relative risk, RR [95% confidence interval, CI] = 0.57 [0.45, 0.72]), vomiting (RR [95% CI] = 0.56 [0.43, 0.72]), and the use of rescue antiemetic therapy (RR [95% CI] = 0.47 [0.36, 0.61]) compared with placebo. There was no evidence of dose responsiveness with respect to its antiemetic effect. Dexamethasone also reduced 24-hour visual analog pain scores (measured on an 11-point scale [0-10]) (mean difference [95% CI] = -0.30 [-0.46, -0.13]) and the use of rescue analgesics (RR [95% CI] = 0.72 [0.52, 0.98]). Dexamethasone did not reduce the incidence of pruritus (RR [95% CI] = 0.98 [0.84, 1.15]). Examination of the funnel plots and Egger's test revealed evidence of publication bias in the primary outcomes. Dexamethasone is an effective antiemetic for patients receiving neuraxial morphine for cesarean delivery and abdominal hysterectomy. In addition, the doses used for antiemetic prophylaxis enhanced postoperative analgesia compared with placebo. However, dexamethasone was not effective for the prophylaxis against neuraxial morphine-induced pruritus.

Ondansetron Is as Effective as Diphenhydramine for Treatment of Morphine-induced Pruritus After Cesarean Delivery

Siddik-Sayyid, S.M.; Yazbeck-Karam, V.G.; Zahreddine, B.W.; Adham, A.M.; Dagher, C.M.; Saasouh, W.A.; Aouad, M.T. Author Information

A Randomized Controlled Trial of Pentazocine Versus Ondansetron for the Treatment of Intrathecal Morphine-induced Pruritus in Patients Undergoing Cesarean Delivery

Tamdee, D.; Charuluxananan, S.; Punjasawadwong, Y.; Tawichasri, C.; Patumanond, J.; Sriprajittichai, P. Author Information

A Randomized Controlled Trial of Pentazocine Versus Ondansetron for the Treatment of Intrathecal Morphine-Induced Pruritus in Patients Undergoing Cesarean Delivery

Survey of Anesthesiology: June 2010 - Volume 54 - Issue 3 - p 120 doi: 10.1097/01.SA.0000370214.72804.ba

A Randomized Controlled Trial of Pentazocine Versus Ondansetron for the Treatment of Intrathecal Morphine-Induced Pruritus in Patients Undergoing Cesarean Delivery

Ondansetron is effective for the treatment of intrathecal morphine-induced pruritus. There is evidence that kappa-opioid receptor agonists have antipruritic activity. Pentazocine is an agonist of kappa-opioid receptors and partial agonist at mu-opioid receptors. We therefore performed a randomized, double-blind trial to compare the efficacy of pentazocine and ondansetron for the treatment of pruritus associated with intrathecal injection of morphine in patients undergoing cesarean delivery. Two hundred eight parturients who developed moderate to severe pruritus after the administration of intrathecal morphine were randomly allocated to 2 groups: IV pentazocine 15 mg (n = 104) and IV ondansetron 4 mg (n = 104). The successful treatment of pruritus (no or mild pruritus) and other adverse effects were determined 15 min after study drug administration, and patients were observed for recurrence of pruritus for 4 h. The treatment success rate at 15 min was higher in the pentazocine group (96.1%) than in the ondansetron group (80.8%) (95% confidence interval of difference: 7.0%, 23.8%; P = 0.001). The recurrence rate of moderate to severe pruritus within 4 h after treatment in the pentazocine group (12.0%) was lower than in the ondansetron group (32.1%) (P = 0.001). There were no significant differences between groups in nausea/vomiting, sedation, shivering, pain scores, and pain at injection site. No respiratory depression was observed. Pentazocine 15 mg is superior to ondansetron 4 mg for the treatment of intrathecal morphine-induced pruritus and has a lower recurrence rate. The side effects after treatment are mild.

Preoperative Gabapentin Prevents Intrathecal Morphine-Induced Pruritus After Orthopedic Surgery

Survey of Anesthesiology: February 2009 - Volume 53 - Issue 1 - p 36 doi: 10.1097/SA.0b013e3181925cd8

Prophylactic mirtazapine reduces intrathecal morphine-induced pruritus

BackgroundActivation of the serotonergic system is an important factor in the pathogenesis of intrathecal morphine-induced pruritus. Mirtazapine is a new antidepressant that selectively blocks 5-HT2 and 5-HT3 receptors. We therefore tested the hypothesis that preoperative mirtazapine would reduce the incidence of intrathecal morphine-induced pruritus. MethodsOne hundred and ten ASA I patients undergoing lower limb surgery under spinal anaesthesia were randomly allocated into two equal groups and received either mirtazapine 30 mg or an orally disintegrating placebo tablet 1 h before operation in a prospective, double-blinded trial. All patients received an intrathecal injection of 15 mg of 0.5% isobaric bupivacaine and 0.2 mg preservative-free morphine. The occurrence and the severity of pruritus were assessed at 3, 6, 9, 12, and 24 h after intrathecal morphine. ResultsPruritus was significantly more frequent in the placebo group compared with the mirtazapine group (75% vs 52%, respectively; P=0.0245). The time to onset of pruritus in the two groups was also significantly different. The patients who experienced pruritus in the placebo group had a faster onset time than that in the mirtazapine group [mean (sd): 3.2 (0.8) vs 7.2 (4.1) h, P<0.0001]. ConclusionsMirtazapine premedication prevents pruritus induced by intrathecal morphine in patients undergoing lower limb surgery with spinal anaesthesia.

Preoperative Gabapentin Prevents Intrathecal Morphine-Induced Pruritus After Orthopedic Surgery

Pruritus is the most common side effect of intrathecal morphine. Gabapentin is an anticonvulsant and had been reported to be effective in some chronic pruritus conditions. Its effect in intrathecal morphine-induced pruritus has not yet undergone an evaluation. We randomly allocated 86 patients scheduled for lower limb surgery under spinal anesthesia into two equal groups that received either gabapentin 1200 mg or placebo 2 h before operation in a prospective, double-blind manner. All patients received an intrathecal injection of 15 mg of 0.5% isobaric bupivacaine and 0.2 mg preservative-free morphine. Pruritus was evaluated at 3, 6, 9, 12, and 24 h after intrathecal morphine administration. The incidence of pruritus was significantly more frequent in the placebo group compared with the gabapentin group (77.5% vs 47.5%; P = 0.01). The onset time of pruritus in the gabapentin group (6.2 +/- 1.8 h) was significantly delayed compared with that in the placebo group (3.1 +/- 0.8 h) (P < 0.0001). The severity of pruritus was significantly more in the placebo group compared with the gabapentin group at 3 and 6 h after intrathecal morphine injection. Preoperative gabapentin prevents pruritus induced by intrathecal morphine in patients undergoing lower limb surgery with spinal anesthesia.