Hypotension | Prophylactic Use Of

Attenuation of Hypotension

Ondansetron’s efficacy in mitigating hypotension before SAB is a recurrent theme within the literature. We found 18 studies indicating some degree of statistical significance. While evidence exists within the literature demonstrating little to no statistical significance, the limitations of those studies should be considered in addition to the wide variations of studied dose ranges and concomitant therapeutic adjuncts.

General Popuation

Several studies within the literature found observed a statistically significant decrease in hypotension in patients receiving ondansetron 4 mg, 6 mg, or 8 mg with the greatest preponderance of supportive evidence surround dosages of 8 mg.

Tatikonda et al [23] found no significant difference in measured hemodynamic values of patients receiving ondansetron 4 mg compared with placebo; however, statistical significance was demonstrated in the incidence of hypotension requiring treatment. (p=0.029). By comparison, Abd-Allah et al [20] found a statistically significant decrease in the incidence of hypotension in patients receiving ondansetron 4 mg or 8 mg compared with placebo and reported increased efficacy in the 8 mg intervention group. This result was echoed by Mendonça et al [10] in an RCT comparing ondansetron 8mg to placebo. A non-prespecified subgroup developed within the study, which demonstrated a significant increase in efficacy within elderly patients as compared to younger patients; however, the small sample size of the elderly subgroup limits any conclusions that may be drawn. [10] Within a small group of non-obstetric patients randomized to receive ondansetron 10 mg or placebo (without concomitant crystalloid preloading), Mohamed et al [27] found no significant differences in the overall incidence of hypotension. In contrast, in an RCT with a significantly larger sample size, Marashi et al [9] describes a statistically significant decrease in the incidence of hypotension in patients receiving either ondansetron 6 mg or 12 mg compared to placebo (p = 0.04); both groups received concomitant crystalloid preloading. Similar results were corroborated by several other RCTs comparing ondansetron 4 mg, [12–16,18,20,32] 6 mg, [3,4] and 8mg [8,10–12,14,17,19,20] to placebo.

In a small sample size of parturients presenting for cesarean delivery, Terkawi et al [26] found no statistical significance in the incidence of hypotension in patients receiving ondansetron 8 mg compared with placebo. Oofuvonget al [28] noted similar results in an RCT comparing weight-based ondansetron dosing (0.05 mg/kg, 0.1 mg/kg, max 8mg) to placebo in parturients. Potdar et al [12] found doses of 4 mg or 8 mg reduced the incidence of hypotension in parturients only within the first 5- and 10-minute time intervals. In a large RCT of parturients presenting for cesarean section, Ortiz-Gómez et al [11] agrees that ondansetron 8mg does not reduce the incidence of hypotension when compared with placebo (p = 0.482) but indicates the severity of hypotensive events are diminished by 50% (p = 0.011). Several RCTs comparing ondansetron 4 mg to placebo in parturients demonstrated comparable results with statistically lower drops in MAP [12,13,15,16,18] and/or decreased incidences of study-defined hypotension. [12,13,15,18,32]

Owczuk et al [8] aimed to demonstrate the efficacy of ondansetron outside the obstetric patient population and studied the effects of ondansetron 8 mg in patients
> 70 years of age compared to placebo. Changes in mean arterial pressure (MAP) and diastolic pressure were effectively attenuated in the intervention group.[8] In a larger RCT of patients 50-70 years of age, Kumar et al [17] found a statistically significant difference in the incidence of hypotension in patients receiving ondansetron 8 mg compared with placebo (p = 0.0359). Mostafa et al[19] found similar results in a comparable study with a smaller sample of patients > 65 years of age (p = 0.011).

In a recent large meta-analysis examining 25 RCTs, Hou et al[6] found a significant decrease in the occurrence of hypotension in doses of ondansetron ranging between 2 – 12 mg compared to control (p < 0.01), noting a high heterogeneity. This is comparable to the results of two smaller meta-analyses by Tubog et al[7] and Gao et al[25]; however, both earlier meta-analyses reported Egger’s test p-values of < 0.05, indicating some risk of publication bias.[7,25] Hou et al[6] reported an Egger’s test p-value of 0.554, indicating no obvious risk of publication bias.

Elderly

Ondansetron 8 mg was found to be efficacious in reducing the incidence and severity of hypotension. However, the number of studies specifically examining the effects of ondansetron prior to SAB in the elderly is limited.

Larger Studies

Parturients

Several studies within the literature found statistically lower drops in MAP or study defined incidences in hypotension in parturients receiving ondansetron 4 mg.