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OBSTETRIC ANESTHESIA

Does Ondansetron or Granisetron Prevent Subarachnoid Morphine-Induced Pruritus After Cesarean Delivery?

From the Department of Anesthesiology, American University of Beirut Medical center, Beirut, Lebanon.

Address correspondence and reprint requests to Sahar Siddik-Sayyid, MD, FRCA, American University of Beirut, Department of Anesthesiology, P.O.Box 11-0236, Beirut, Lebanon. Address e-mail to ss01{at}aub.edu.lb.

	Abstract

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BACKGROUND: We compared the efficacy of granisetron and ondansetron for the prevention of subarachnoid morphine-induced pruritus after cesarean delivery.

METHODS: The incidence of pruritus was assessed in parturients who were randomly allocated into Group G (granisetron 3 mg IV, n = 45), Group O (ondansetron 8 mg IV, n = 42), and Group S (saline IV, n = 42).

RESULTS: The incidence of pruritus was not significantly different among the 3 groups (86.6% in Group S, 83.3% in Group O, and 88% in the Group G).

CONCLUSION: Neither prophylactic ondansetron nor granisetron reduced the incidence of subarachnoid morphine-induced pruritus when compared with the saline group.

	Introduction

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Subarachnoid (SA) morphine, which is highly effective for the management of pain after cesarean delivery (1–3), is associated with a significant incidence of pruritus, nausea, and vomiting (4–8). There are conflicting results when ondansetron, a 5-hydroxytryptamine type 3 (5-HT₃) receptor antagonist, is administered prophylactically in an attempt to reduce the frequency of SA morphine-induced pruritus in patients undergoing cesarean delivery under spinal anesthesia (4–7). Granisetron is a potent and highly selective 5-HT₃ receptor antagonist (9). Its longer duration of action than that of ondansetron may coincide with the peak incidence of pruritus after SA morphine (6–9 h) (10). Granisetron has been used successfully at a dose of 3 mg to treat severe pruritus in a cancer patient (11). However, its prophylactic effect on SA morphine-induced pruritus has never been studied.

We compared the efficacy of IV granisetron 3 mg and ondansetron 8 mg with that of saline for the prevention of SA morphine-induced pruritus in patients undergoing cesarean delivery under spinal anesthesia.

	METHODS

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After IRB approval, written informed consent was obtained from 135 parturients ASA I–II, undergoing cesarean delivery under spinal anesthesia. Exclusion criteria included preeclampsia, eclampsia, major systemic disease, current pruritus, current nausea, or known allergy to any of the medications used in the study.

Patients were assigned using a computer-generated table of random numbers to one of three groups: Group G (granisetron 3 mg IV), Group O (ondansetron 8 mg IV), and Group S (saline IV). The study drug was administered immediately after the umbilical cord was clamped. Patients and anesthesiologists performing the spinal anesthesia and collecting the data were blinded to the study drugs. Monitoring included electrocardiogram, pulse oximetry, and noninvasive arterial blood pressure. Spinal anesthesia was performed, with patients in the sitting position, at the L2–3 or L3–4 interspace with a 25-gauge pencil point needle using 12.75 mg of 0.75% hyperbaric bupivacaine plus 0.2 mg of preservative-free morphine.

The occurrence of pruritus, nausea and vomiting, pain, and adverse reactions from granisetron and ondansetron, including headache, cardiac dysrhythmia, and extrapyramidal signs, was evaluated at 0.5, 2, 4, 6, 8, 12, and 24 h after placement of the spinal anesthetic. The location and degree of pruritus was classified as 1 = no pruritus, 2 = mild pruritus, 3 = moderate pruritus, 4 = severe pruritus. Nausea severity was graded according to a 4-point rating score with 1 = no nausea or vomiting, 2 = queasy, 3 = severe nausea, 4 = vomiting. Pain was assessed using visual analog scale with 0 = no pain, and 10 = worst pain imaginable. Cardiac dysrhythmia was evaluated with cardiac auscultation after any patient reported palpitations, and verified by electrocardiogram. Extrapyramidal signs were assessed by the anesthesiologist as the presence of twitching, dystonia, akathisia, or rigor.

The possible side effects were explained to the patients who were told that they could have treatment upon request. Pruritus was treated with diphenhydramine 12.5 mg IV every 4 h and, if the pruritus was not relieved, incremental doses of naloxone 0.04 mg IV were given. Nausea and/or vomiting were treated with metoclopramide 10 mg every 8 h. Diclofenac 100 mg suppository and/or paracetamol 1 g IV were used, if needed, for pain relief.

Continuous data are reported as means ± standard deviation and were analyzed using ANOVA. Categorical data are reported as numbers and percentages and were analyzed using ² or Fisher’s exact test as appropriate. Nonparametric data such as scores are reported as medians and ranges and were analyzed using Mann–Whitney U test. The sample size was determined to be 44 patients per group to detect a decrease of pruritus from 80% to 55% at the 0.05 significance level with 80% power.

	RESULTS

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Six patients were excluded because of protocol violation (three from Group O and three from group G), and 129 were analyzed.

Patients’ and operative characteristics were comparable among the three groups (Table 1). The sites of pruritus were mainly at the face, neck, trunk, and back. The overall incidence and highest score of pruritus, the number of patients requesting treatment for pruritus (Table 2), as well as the severity and incidence of pruritus at different time intervals (Fig. 1) were similar among the three groups.

View larger version (18K): [in this window] [in a new window]   Figure 1. Pruritus. (A) Severity of pruritus. (B) Incidence of pruritus at different time intervals.

There was no difference in the overall incidence and highest score of nausea and/or vomiting (Table 2), or in the severity and incidence of nausea and vomiting at different time intervals among the three groups (Fig. 2). However, the number of patients requesting treatment for nausea and/or vomiting was significantly less in Group O and group G when compared with Group S (Table 2).

View larger version (19K): [in this window] [in a new window]   Figure 2. Nausea and vomiting. (A) Severity of nausea. (B) Incidence of nausea and/or vomiting at different time intervals.

Pain scores were not different among the three groups. The incidence of patients requiring supplemental analgesics postoperatively was 76% in Group S, 73% in Group O, and 80% in Group G (P > 0.05). The mean time for the first analgesic requirement in those patients was 11 ± 7 h, 11 ± 6.4 h, and 8.4 ± 6.7 h (P > 0.05). Mild headache was observed in two patients in Group O and two patients in group G. Cardiac dysrhythmia and extrapyramidal symptoms were not noted in any patient.

	DISCUSSION

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In the obstetric population, pruritus is very common after neuraxial opioids, possibly related to the interaction of estrogen with opioid receptors in the spinal cord and the increased cephalad spread of spinally administered drugs (12). In our parturients, the incidence of pruritus after SA morphine was more than 83% in all three groups, and peaked at 4–6 h after spinal injection. The incidence of pruritus in other obstetrical studies ranged between 70%–93% (4–7,13).

One of the mechanisms of SA morphine-induced pruritus seems to be related to direct stimulation of 5-HT₃ receptors by morphine in the dorsal horn of the spinal cord and medulla; thus, 5-HT₃ receptor antagonist may prevent this pruritus (14). However, our report showed that neither prophylactic ondansetron nor granisetron reduced the incidence or severity of pruritus when compared with the saline group. Similarly, two previous studies reported the failure of ondansetron and tropisetron to prevent pruritus after cesarean delivery (6,7). It seems that even with the use of higher doses of these 5-HT₃ receptor antagonists than are commonly used in the management of postoperative nausea and vomiting (15), neither ondansetron nor granisetron provided any benefit in the prevention of pruritus produced by SA morphine. However, Yeh et al. (4) and Charuluxananan et al. (5) demonstrated that prophylactic ondansetron reduced the frequency of SA morphine-related pruritus in patients undergoing cesarean delivery. These conflicting results may be attributed to the different doses of SA morphine administered, different scales and definitions used, as well as different time periods for assessment.

SA morphine induces not only pruritus, but also nausea and vomiting, by acting on 5-HT₃ receptors in the chemoreceptor trigger zone (16). Serotonin receptor antagonists might be effective in the prevention of SA morphine-induced nausea and vomiting. Although our report showed that the incidence of nausea and vomiting was not significantly different among the three groups, fewer patients requested rescue antiemetics in the ondansetron group and granisetron group when compared with those in the saline group. This lack of significant difference in the incidence of nausea and vomiting among the three groups may have been related to the possibility that other mechanisms, independent of serotonin receptors, are involved in the pathogenesis of SA morphine-induced nausea and vomiting, or to insufficient statistical power of the study to investigate this secondary outcome.

In conclusion, the prophylactic administration of ondansetron or granisetron did not reduce the incidence of pruritus. However, both drugs resulted in a significant decrease in the number of patients requesting rescue antiemetics.

	Footnotes

 
Accepted for publication October 25, 2006.

	REFERENCES

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Siddik-Sayyid, S. M. Articles by Baraka, A. S. Search for Related Content PubMed PubMed Citation Articles by Siddik-Sayyid, S. M. Articles by Baraka, A. S. Related Collections Obstetrics Pharmacology