Does peripartum intravenous calcium administration reduce the occurrence of uterine atony in caesarean sections? A systematic review and meta-analysis

Citation:

Wegner GRM, Wegner BFM, González GL, Miranda AM, Felippe VA, Spagnol LW, Spagnol VW, Nascimento TSd. Does peripartum intravenous calcium administration reduce the occurrence of uterine atony in caesarean sections? A systematic review and meta-analysis. Eur J Anaesthesiol. 2026;43:1–4.

This systematic review and random effects meta-analysis pooled six small randomised controlled trials of peripartum intravenous calcium in caesarean section. Intravenous calcium may reduce uterine atony and blood loss and probably reduces intraoperative fluid requirements, without a clear effect on transfusion or hypotension, but certainty is very low for most clinical outcomes. The authors suggest calcium only as a conditional adjunct in high‑risk patients pending larger, standardised trials.

Study at a glance

- Design and setting: Prospectively registered systematic review and random effects meta-analysis of six randomised controlled trials including 746 women undergoing caesarean section, comparing peripartum intravenous calcium (calcium chloride or calcium gluconate, various doses and timings) with placebo or standard care plus standard uterotonic prophylaxis; overall review-level confidence was critically low by AMSTAR 2 and overall risk of bias unclear by ROBIS due to incomplete search reporting and possible publication bias.

- Primary outcome: uterine atony: Three randomised controlled trials reported uterine atony, defined as need for second-line uterotonics; pooled ratio of risks was 0.56 with a ninety five percent confidence interval from 0.42 to 0.75, very low statistical heterogeneity, but prediction interval 0.27 to 1.18 and leave-one-out analysis indicated study-dependent results. Certainty of evidence was rated very low (GRADE) after downgrades for clinical heterogeneity, imprecision and suspected publication bias, despite trial sequential analysis reaching the required information size.

- Uterine tone and blood loss: For uterine tone, calcium modestly increased five-minute tone scores (mean difference 0.53 points on a zero to ten scale; ninety five percent confidence interval 0.01 to 1.06) with high heterogeneity and study-dependent results, while ten-minute scores showed essentially no difference (mean difference 0.03; ninety five percent confidence interval minus 0.16 to 0.22); both outcomes were very low certainty. Pooled blood loss was lower with calcium by a mean of 46 millilitres (ninety five percent confidence interval minus 67 to minus 26 millilitres), but this reduction was judged not clinically meaningful, measurement methods varied widely, trial sequential analysis did not confirm the result, and certainty was very low (multiple GRADE downgrades).

- Transfusion, fluids and haemodynamic safety: Blood transfusion (four randomised controlled trials; ratio of risks 0.55, ninety five percent confidence interval 0.23 to 1.33) and hypotension (three randomised controlled trials; ratio of risks 0.68, ninety five percent confidence interval 0.45 to 1.05) did not differ clearly between calcium and control groups; prediction intervals were wide and included both benefit and harm, and certainty was very low. Intravenous fluid volume was consistently lower with calcium (six trials; mean difference minus 52 millilitres, ninety five percent confidence interval minus 83 to minus 22 millilitres, negligible heterogeneity, beneficial prediction interval), and with confirmation by leave-one-out and trial sequential analysis this outcome reached moderate certainty (GRADE) despite indirectness and suspected publication bias.

- Risk of bias and certainty of evidence: Four of six trials were judged at overall low risk of bias and two at some concerns using a modern risk-of-bias tool, but all pooled outcomes were downgraded at least once for clinical heterogeneity (different calcium formulations, doses, timing and baseline bleeding risk) and once for suspected publication bias. Additional downgrades for imprecision, driven by wide confidence and prediction intervals and unconfirmed trial sequential analysis for several endpoints, meant that certainty was very low for uterine atony, uterine tone, blood loss, transfusion and hypotension, and only moderate for intravenous fluid volume.

- Clinical implications: The evidence base suggests that peripartum intravenous calcium may reduce uterine atony, may modestly reduce blood loss, and probably reduces intraoperative fluid requirements, but effect sizes are small, many outcomes are study-dependent, and almost all clinically important endpoints rest on very low-certainty evidence. The authors propose only a conditional, adjunctive role for intravenous calcium in women at high risk of uterine atony, emphasising that standard uterotonic prophylaxis and haemorrhage protocols remain primary and that larger, standardised randomised controlled trials in diverse and high-risk populations are needed before recommending routine use.