Effect of vasoactive drugs used for management of hypotension during pregnancy on uterine hemodynamic parameters: a systematic review and meta-analysis of preclinical and clinical studies.

BACKGROUND

Anesthesia-associated hypotension in pregnant women is frequently managed with vasoactive drugs to avoid uterine hypoperfusion. We systematically reviewed the effect direction of these drugs on uterine hemodynamic parameters (improved/unchanged/worsened). As the uterus lacks autoregulation, we hypothesized improved uterine hemodynamics after administration of vasoactive drugs.

METHODS

Databases were searched from inception until November 2023. Clinical studies and animal studies in species with hemochorial placentas were eligible. The primary outcome was uterine hemodynamics (uterine blood flow or uterine resistance). Meta-analyses were performed on standardized mean differences (SMDs). Risk of bias was assessed using ROBINS-I and SYRCLE tools.

RESULTS

Twelve clinical studies involving 368 patients and 21 preclinical studies involving 206 animals were included in the analysis, investigating thirteen different drugs. Apart from three randomized controlled preclinical trials, all other studies used a before-after (impact) design. Both clinical and preclinical data showed unchanged or worsened uterine hemodynamics with ephedrine, phenylephrine, and norepinephrine. The only drug with improved uterine hemodynamics was angiotensin II, but only in preclinical studies (standardized mean difference 0.66; 95% confidence interval, 0.02 to 1.30). There was considerable heterogeneity in both clinical and preclinical studies. Risk of bias was low to moderate in clinical studies. The before-after design of preclinical studies is inherently susceptible to bias.

CONCLUSION

These findings suggest that vasoactive drugs do not improve uterine hemodynamics. Further research is warranted to investigate the clinical relevance of worsened uterine hemodynamics, especially in prolonged maternal and fetal surgery under general anesthesia, during laparoscopy, and in pregnancies with compromised fetal perfusion.