A Prospective, Randomized, Double-Blinded Study of the Effect of Intravenous Ondansetron on the Effective Dose in 50% of Subjects of Prophylactic Phenylephrine Infusions for Preventing Spinal Anesthesia–Induced Hypotension During Cesarean Delivery

Abstract

BACKGROUND: Ondansetron has been shown to reduce the incidence of hypotension and vasopressor requirement during spinal anesthesia for obstetric and nonobstetric surgery. However, the magnitude of this effect has not been fully quantified. In this parallel-group, randomized, double-blinded study, we determined the effective dose in 50% of subjects (ED50) of a prophylactic phenylephrine infusion for preventing hypotension in patients who received a single dose of intravenous ondansetron 4 mg or saline control before combined spinal–epidural anesthesia for elective cesarean delivery. ED50 values obtained were compared to estimate the effect of ondansetron versus placebo on vasopressor requirement. METHODS: Sixty parturients were randomly assigned to receive ondansetron (group O) or saline control (group C) 10 minutes before positioning for induction of spinal anesthesia. A prophylactic phenylephrine infusion was used to prevent hypotension. The first patient in each group received a phenylephrine infusion at the rate of 0.5 µg/kg/min. The infusion rate for each subsequent patient was varied with increments or decrements of 0.05 µg/kg/min based on the response of the previous patient, and the effective dose of the phenylephrine infusion for preventing hypotension in 50% of patients (ED50) was calculated for each group and compared using up-down sequential analysis. Probit regression was applied as a backup and sensitivity analysis was used to compare ED50 values for phenylephrine between groups by comparing calculated relative mean potency. RESULTS: The ED50 (mean [95% confidence interval (CI)]) of the rate of phenylephrine infusion was lower in group O (0.24 µg/kg/min [0.10–0.38 µg/kg/min]) compared with group C (0.32 µg/kg/min [0.14–0.47 µg/kg/min]) (P < .001). The total consumption of phenylephrine (mean ± standard deviation [SD]) until delivery was lower in group O (316.5 ± 25.9 µg) than in group C (387.7 ± 14.7 µg, P = .02). The estimate of relative median potency for phenylephrine for group O versus group C was 0.74 (95% CI, 0.37–0.95). CONCLUSIONS: Under the conditions of this study, intravenous ondansetron 4 mg reduced the ED50 of a prophylactic phenylephrine infusion by approximately 26% in patients undergoing cesarean delivery under combined spinal–epidural anesthesia.

Intravenous Palonosetron for Attenuation of Hypotensive Response and Bradycardia during Spinal Anaesthesia

“…These findings may be attributable to the smaller dose of palonosetron used in their study which is having a sufficient effect on chemoreceptor trigger zone but being insufficient to affect the bupivacaine in the intervertebral space [19] . Effects similar to our study were concluded by Mowafi et al who studied the effects of IV granisetron on the sensory and motor blockade produced by intrathecal bupivacaine [20] and with Fassoulaki et al and Rashad MM et al who studied the effects of IV ondansetron on the spinal anesthesia [21,22] .…”

<p>Does an Earlier or Late Intravenous Injection of Ondansetron Affect the Dose of Phenylephrine Needed to Prevent Spinal-Anesthesia Induced Hypotension in Cesarean Sections?</p>

“…It should be noted that the ED50 for prophylactic phenylephrine in this study was nearly 0.1µg/kg/min higher than in our prior study, in which we found that the ED50s for prophylactic phenylephrine were 0.32 and 0.24 µg/kg/min for preventing spinal anesthesia-induced hypotension in the control group and experimental group, respectively. 19 The inconsistency of the ED50s between the two studies may be due to several protocol details, such as different intrathecal injection rates (10s vs over 15s) that subsequently resulted in different degrees of sympathetic blocks and a different incidence of hypotension and its severity. However, the significant differences between the experimental and control groups were similar in our two studies.…”

Adjuvant Sufentanil Decreased the EC50 of Epidural Ropivacaine for Labor Analgesia in Healthy Term Pregnancy

“…The concentration of ropivacaine for the following parturient was determined using the up-down allocation methodology. 10 , 11 Parturients were asked to report their pain on a standard VAS 30 min after administering the study solution. A VAS score ≤ 3 was defined as effective analgesia.…”

“…The EC50 of epidural ropivacaine was determined by calculating the mean values of the midpoints of pairs in parturients where an inadequate response was followed by an effective response (crossover), as previously described. 10 , 11 , 14 The Student’s t -test was used for comparing the EC50s. Overlapping CI methodology was used to test the differences in CIs for the EC50 values between the two groups.…”