Uterine atony is responsible for 70% to 80% of cases of postpartum hemorrhage. Standard medical treatments for PPH (uterotonics and TXA) are often limited by poor efficacy, patient contraindications, and side effects. We need more options!
Enter: Calcium Chloride (IV)
IV Calcium is most often used in cardiac resuscitations, to treat arrhythmias and hypermagnesemia, and in patients receiving blood transfusions (in whom hypocalcemia is fairly common). Exogenous calcium has been shown to increase uterine smooth muscle contraction in vitro, and in animal studies.
This pilot study was conducted at Stanford between 2019-2021 [2]:
40 pregnant women undergoing cesarean delivery with >2 risk factors for uterine atony (and normal baseline calcium levels), were included. Patients with renal dysfunction, cardiac issues, and those on digoxin or a calcium channel blocker were excluded (link to full trial criteria).
- Design: Randomized Controlled Trial: 2 arms
- Patients were randomized to receive either the intervention (CaCl) or placebo (normal saline) in addition to standard of care oxytocin. Both were administered as 60mL intravenous infusions over 10-min, started after umbilical cord clamping.
- Intervention (n=20): 1 g of calcium chloride [16.7 mg/mL]
- Placebo (n=20): normal saline
- Patients were randomized to receive either the intervention (CaCl) or placebo (normal saline) in addition to standard of care oxytocin. Both were administered as 60mL intravenous infusions over 10-min, started after umbilical cord clamping.
- Outcomes:
- Primary: Uterine Atony from time of fetal delivery + 4 hours Defined as: use of a 2nd line uterotonic, surgical intervention for atony, or EBL > 1000mL
- Secondary: Grading of uterine tone 10 min after delivery by OB (blinded), EBL, change in hematocrit, total crystalloid volume, changes in MAP and heart rate, and CaCl volume of distribution & clearance
- Results:
- CaCl group: 20% developed uterine atony
- Placebo group: 50% developed uterine atony (P=0.09)
- There was a trend toward an improved uterine tone score as determined by the OB: a median of 89% for calcium versus 80% for placebo (P=0.14).
- Side-effects: The CaCl infusion was well tolerated. Between groups, there was no difference in any side effect such as nausea, change in blood pressure, or injection site discomfort. Both groups reported complication rates of 30%.
Final Thoughts:
Current medical therapies for preventing and treating PPH leave much room for improvement. These findings suggest that 1g IV CaCl could make a significant difference for women at risk for PPH, without any major side effects. However, this small pilot study should be viewed as a proof of concept that must be confirmed in larger studies before we begin using CaCl routinely in patients with known risk factors for uterine atony.
References
1. Illustration from American Regent TM, www.americanregent.com/our-products/10-calcium-chloride-injection-usp/.
2. Ansari JR, Kalariya N, Carvalho B, Flood P, Guo N, Riley E. Calcium chloride for the prevention of uterine atony during cesarean delivery: A pilot randomized controlled trial and pharmacokinetic study. J Clin Anesth. 2022 Sep;80:110796. doi: 10.1016/j.jclinane.2022.110796. Epub 2022 Apr 18. PMID: 35447502.