Effect of Granisetron on Morphine Induced Pruritus in Cesarean Section

Summary

Neuraxial anesthesia, which includes epidural anesthesia and intrathecal anesthesia, is a frequent anesthetic approach for caesarean delivery and other lower abdominal and lower limb anesthetic procedures. The addition of neuraxial morphine to local anesthetics provides an effective and prolonged postoperative analgesia. Neuraxial administration of morphine which is considered as a gold standard for analgesia has been associated with a frequent incidence of pruritus and postoperative nausea and vomiting. The incidence of neuraxial opioid induced pruritus varies widely from 30% - 60% after orthopedic surgery with intrathecal morphine injection and from 60% - 100% in pregnant women after neuraxial opioid administration. Parturients appear to be the most susceptible to neuraxial opioid-induced pruritus which probably might be due to the interaction of estrogens with opioid receptors. Although the exact mechanism of neuraxial opioid induced pruritus is unclear, the postulated mechanisms include the presence of an "itch center" in the central nervous system (CNS), medullary dorsal horn activation, antagonism of inhibitory transmitters, modulation of 5-hydroxytryptamine subtype 3 (5-HT3) or serotonergic pathways and the involvement of prostaglandins. There is dense concentration of opioid receptors and 5-HT3 receptors in the dorsal part of the spinal cord and the nucleus of the spinal tract of the trigeminal nerve in the medulla. Activation of these receptors by neuraxial opioid administration or by circulating estrogen in parturients results in neuraxial opioid induced pruritus which is usually localized to the face, neck, or upper thorax. Nalbuphine, propofol and ondansetron have been used effectively in the treatment of pruritus associated with neuraxial morphine in surgical patients. Granisetron is a potent and highly selective 5-HT3 receptor antagonist that has little or no affinity for other 5-HT receptors, or dopaminergic, adrenergic, benzodiazepine, histaminic, or opioid receptors. Its onset of action is 1-3 min, peak plasma level 30 min, plasma half-life is 4-6 h and duration of action up to 24 h. Its longer duration of action than that of ondansetron may coincide with the peak incidence of pruritus after intrathecal morphine (6-9 h). In contrast, other 5-HT3-receptor antagonists have affinities for various receptor-binding sites. For example, ondansetron has detectable binding to 5-HT1B, 5-HT1C, α1-adrenergic, and μ-opioid receptor sites. Although not proven, the binding of these agents to additional receptor subtypes other than their target receptor may underlie the inferior adverse event profile seen with ondansetron compared with granisetron.

Timeline

Start

2018-06-01

Primary completion

2020-10-01

Completion

2020-10-30

Publications

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• Results Koju RB, Gurung BS, Dongol Y. Prophylactic administration of ondansetron in prevention of intrathecal morphine-induced pruritus and post-operative nausea and vomiting in patients undergoing caesarean section. BMC Anesthesiol. 2015 Feb 17;15:18. doi: 10.1186/1471-2253-15-18.
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• Results Perez EA, Hesketh P, Sandbach J, Reeves J, Chawla S, Markman M, Hainsworth J, Bushnell W, Friedman C. Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. J Clin Oncol. 1998 Feb;16(2):754-60. doi: 10.1200/JCO.1998.16.2.754.
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Drugs

Indications

No indication recorded.