Calcium Chloride for Prevention of Blood Loss During Intrapartum Cesarean Delivery (CALBLOC)

Calcium Chloride for Prevention of Blood Loss From Uterine Atony During Intrapartum Cesarean Delivery (CALBLOC): a Double Blind, Randomized, Placebo Controlled Trial and Nested Population Pharmacokinetic and Pharmacodynamic Analysis

Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Up to 80% of PPH is caused by uterine atony, the failure of the uterine smooth muscle to contract and compress the uterine vasculature after delivery. Laboratory and epidemiological studies show that low extracellular and serum calcium levels, respectively, decrease uterine contractility. A pilot study performed by the investigators supports the hypothesis that intravenous calcium chloride is well tolerated and may have utility in preventing uterine atony. The proposed research will establish the relationship between uterine tone and calcium through a clinical trial with an incorporated pharmacokinetic and pharmacodynamic (PK/PD) study. In a randomized, placebo-controlled, double-blind trial, investigators will establish the effect of 1 gram of intravenous calcium chloride upon quantitative blood loss and uterine tone during cesarean delivery in parturients with high risk of uterine atony. Investigators will concurrently collect serial venous blood samples to measure calcium for PK/PD modeling in this pregnant study cohort. High-quality clinical research and development of novel therapeutics to manage uterine atony are critical to reduce the high maternal morbidity and mortality from PPH.

The patient, obstetrician, anesthesiologist, and clinical research staff will be blinded to the intervention. Drugs will be labeled only as "study drug"

1 gram of calcium chloride in total volume 60mL with sterile saline, delivered over 10 minute controlled infusion at a constant rate (360mL/hour) beginning 2 minutes after fetal delivery and 1 minute after delayed cord clamp. This intervention occurs IN ADDITION TO standard care with oxytocin 2 unit bolus and infusion at 7.5 units per hour which begins immediately after fetal delivery.

60mL sterile saline, delivered over 10 minute controlled infusion at a constant rate (360mL/hour) beginning 2 minutes after fetal delivery and 1 minute after delayed cord clamp. This intervention occurs IN ADDITION TO standard care with oxytocin 2 unit bolus and infusion at 7.5 units per hour which begins immediately after fetal delivery.

Standardized volumetric and gravimetric assessment of blood loss during cesarean. Note: will analyze all participants, but planned subgroup analysis will also occur excluding patients with non-atonic reasons for blood loss including hysterotomy extension, placental abruption, cervical or vaginal laceration, etc

2, 7, and 12 minutes after fetal delivery. The absolute 12 minute score as well as delta from 12-2 and 12-7 minute scores will be analyzed

Yes/no: did the patient require treatment with methylergonovine, carboprost, and/or misoprostol for uterine atony

Baseline heart rate recorded as average of first 6 heart rates recorded in operating room. Percent change calculated as measured heart rate minus baseline, divided by baseline.

Baseline mean arterial blood pressure recorded as average of first 6 mean arterial blood pressures recorded in operating room. Percent change calculated as measured mean arterial blood pressure minus baseline, divided by baseline.

Measured pre-delivery hematocrit minus measured post-operative day 1 hematocrit. Correction factor of 3 hematocrit points per unit packed red blood cells transfused

Inclusion Criteria: Patient had a trial of labor for vaginal delivery prior to cesarean Patient received an oxytocin infusion for labor augmentation or induction prior to cesarean Exclusion Criteria: renal dysfunction with serum Cr >1.0 mg/dL known underlying cardiac condition treatment with digoxin within the last 2 weeks for a maternal or fetal indication treatment with a calcium channel blocker medication within 24 hours hypertension necessitating intravenous antihypertensive medication within 24 hours emergent case in which study participation could in any way impede patient care by the judgement of the obstetrician, anesthesiologist, or bedside nurse