Prevention versus treatment of intrathecal morphine-induced pruritus with ondansetron

Highlights

• We assessed the efficacy of ondansetron for either treatment or prophylaxis of intrathecal morphine-induced pruritus.

• We found no difference in postoperative pruritus between ondansetron for prophylaxis or treatment when compared to placebo.

• Our data do not support the use of ondansetron for prevention or treatment of morphine-induced pruritus.

Abstract

Background

Intrathecal 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.

Methods

Healthy paturients undergoing cesarean delivery with intrathecal morphine 250 μg and fentanyl 25 μg were randomized to receive: prophylaxis (ondansetron 8 mg at cord clamping, normal saline 4 mL for treatment of pruritus in the post-anaesthesia care unit); treatment (normal saline 4 mL at cord clamping, ondansetron 8 mg as required in the post-anesthesia care unit) or control (normal saline 4 mL in both). Visual analogue scale scores for pruritus, nausea and pain were recorded preoperatively, on arrival to, at 30, 60, and 120 min 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.

Results

The 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.

Conclusion

Prophylactic 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.

Introduction

Intrathecal morphine is a highly effective analgesic following cesarean delivery. A common side effect is pruritus which occurs in 60–93% of patients. Pruritus is most commonly mild and localized to the face and trunk, but it can be severe and cause significant maternal discomfort.¹ The mechanism remains uncertain. Animal studies suggest the presence of an itch center in the lower medulla, with the trigeminal nucleus involved in the itch reflex.² Activation of the mu-opioid receptor is believed to cause pruritus, while the kappa-opioid receptor attenuates this side effect. Thus, naloxone, a mu receptor antagonist, is effective in treating opioid-induced pruritus, but carries the risk of reversing analgesia. Several other medications with variable efficacy and side-effect profiles have been studied, including propofol, gabapentin, pentazocine, nalbuphine, diphenhydramine.³

Opioids interact closely in the central nervous system with the 5-HT receptor, which plays a role in both pain transmission and nausea and vomiting. A possible interaction between the opioid and serotonergic systems has been suggested in the pathogenesis of pruritus in cholestatic jaundice.⁴ 5-HT antagonists developed for the treatment of nausea and vomiting have also been described as prophylactic or rescue treatment of opioid-induced pruritus. Ondansetron has been reported to be effective when administered for treatment of opioid-induced pruritus, but has been less likely to prevent pruritus when administered as a prophylactic agent.⁴ Theoretically, if the effectiveness of ondansetron were related to its serum concentration, early prophylactic administration would result in lower serum concentrations due to redistribution and decreased effectiveness compared to symptomatic treatment. We hypothesized that ondansetron would be more effective as treatment than as prophylaxis for pruritus caused by intrathecal morphine used for cesarean delivery.