title: Prevention of Spinal Anesthesia-Induced Hypotension During Cesarean Delivery by 5-Hydroxytryptamine-3 Receptor Antagonists: A Systematic Review and Meta-analysis and Meta-regression.
abstract: Hypotension remains a frequent complication of spinal anesthesia, increasing the risk of nausea and vomiting, altered mental status, and aspiration. The aim of this systematic review and meta-analysis was to determine whether 5-hydroxytryptamine3 (5-HT3) receptor antagonists, administered before the initiation of spinal anesthesia, mitigate hypotension.
  
  
  
  After a systematic literature search in various databases, randomized placebo-controlled double-blind trials studying the preventive effect of 5-HT3 receptor antagonists were included. A random-effects model was applied, risk ratio (RR, binary variables) or weighted mean difference (continuous variables) with 95% confidence intervals (CIs) were calculated. The primary outcome was the incidence of hypotension.
  
  
  
  Seventeen trials (8 obstetric, 9 non-obstetric) reporting on 1604 patients were identified. Ondansetron in doses from 2 to 12 mg was studied in 12 trials. Prophylactic 5-HT3 administration significantly reduced the risk of hypotension in the combined analysis of 17 trials, RR 0.54 (95% CI 0.36-0.81, I = 79%). In obstetric trials, the RR was 0.52, 95% CI 0.30-0.88, I = 87% (number needed to treat 4). In non-obstetric studies, the 95% CIs were wide and included a clinically relevant reduction in the risk of hypotension (RR 0.50, 95% CI 0.22-1.16; I = 66%). Contour-enhanced funnel plots confirmed publication bias. Meta-regression showed a significant ondansetron dose response in non-obstetric patients (β = -0.355, P = .04). In the combined and in the obstetric-only analysis, the risk of bradycardia was significantly reduced as was the use of phenylephrine equivalents.
  
  
  
  5-HT3 antagonists are effective in reducing the incidence of hypotension and bradycardia; the effects are moderate and are only significant in the subgroup of patients undergoing cesarean delivery. The effects in the non-obstetric population are not significant.
authors.affiliation: From the *Department of Anesthesia, Kantonsspital Baden, Baden, Switzerland; †Department of Anesthesia, Erasmus University Medical Center, The Netherlands; and ‡Department of Anesthesia, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heesen
authors.forename: Markus
authors.initials: M
authors.lastname: Klimek
authors.forename: Sanne E
authors.initials: SE
authors.lastname: Hoeks
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
mesh_terms: D000775:Anesthesia, Spinal / Q000009:adverse effects* / Q000379:methods; D002585:Cesarean Section / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced* / Q000517:prevention & control*; D011247:Pregnancy; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D012044:Regression Analysis; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000627:therapeutic use*
chemical_list: D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists