Calcium Chloride for Prevention of Uterine Atony During Cesarean

The primary outcome of interest is the presence of clinical uterine atony, as defined the by any of the following: 1. Administration of \> 1 bolus of oxytocin 2. Increase in the oxytocin infusion rate above the standard 7.5units/hour 3. Administration of a second line uterotonic including methylergonovine, carboprost, or misoprostol 4. Mechanical surgical interventions for uterine atony including placement of an intrauterine balloon, B-lynch sutures, or O'Leary sutures 5. Requirement for embolization of the uterine arteries by interventional radiology 6. Estimated blood loss\> 1000 milliliters 7. Transfusion of blood products during or within 4 hours of Cesarean

Time frame: From time of fetal delivery until 4 hours after fetal delivery

Ionized calcium levels measured by phlebotomy. Analyzed prior to any study drug administration.

Time frame: Prior to study drug (up to 5 minutes for blood draw)

Population: Because this outcome was assessed at baseline prior to study drug administration, participants in the active and placebo groups who consented to phlebotomy were combined for this analysis.

Changes from preoperative to standard postoperative day 1 hematocrit in patients. The hematocrit represents the percentage by volume of red blood cells in a blood sample and decreases after losing blood. The change in hematocrit was calculated by subtracting the number obtained the morning after surgery from the number obtained prior to surgery.

Time frame: Drawn on postoperative day 1 as standard care

Pharmacokinetic parameters were analyzed based upon ionized calcium concentrations over time. Blood calcium concentration was measured at the following time points: baseline (pre-drug delivery), 0-20 minutes after drug administration, and 20-90 minutes after delivery. The reported values for concentration over time were obtained using NONMEM (Non Linear Mixed Effects Modeling).

Time frame: Samples drawn at baseline, at random time points after study drug administration while in the operating room, and upon arrival to the recovery room (up to 90 minutes)

Population: Patients who received calcium chloride and consented to blood sampling for PK analysis. Patients who received placebo were not included since they did not receive calcium chloride and had no data collected for the outcome.

In milliliters. By blinded obstetrician, taking into account drape, sponge, and suction canister contents

Time frame: Immediately upon surgery completion, as patient exits operating theater

Population: Quantitative blood loss was not able to be performed, so estimated blood loss was used for all participants

Subjective assessment of uterine tone by the obstetrician, from 0-100%. Obstetricians were blinded to study assignment arm, and were instructed that 0% indicates a completely atonic (un-contracted) uterus, and 100% indicates a perfectly, firmly contracted uterus. They were asked to provide this score by palpating the fundus (top) of the uterus as soon as the study drug infusion was complete.

Time frame: A one-time value collected 10 minutes after Cesarean fetal delivery

Heart rate monitored for 45 minutes after study drug infusion (well past peak)

Time frame: 45 minutes after study drug infusion is complete

Baseline mean arterial pressure was established upon entry into the operating room after at least 3 minutes had passed since positioning onto the operating room bed and prior to commencement of the cesarean delivery or to block placement. Mean arterial blood pressure was recorded every 5 minutes from this baseline timepoint until completion of the cesarean. Maximal decrease was calculated as the difference between the baseline and the lowest recorded mean arterial blood pressure.

Time frame: While in the operating room, generally about 2 hours

Population: All participants

Baseline mean arterial pressure was established upon entry into the operating room after at least 3 minutes had passed since positioning onto the operating room bed and prior to commencement of the cesarean delivery or to block placement. Mean arterial blood pressure was recorded every 5 minutes from this baseline timepoint until completion of the cesarean. Maximal increase was calculated as the difference between the baseline and the highest recorded mean arterial blood pressure.

Time frame: While in the operating room, generally about 2 hours

Population: All participants

Heart rate is recorded every minute throughout delivery. Heart rate values over the first 45 minutes after study drug completion will be compared to baseline calcium chloride to placebo group

Time frame: first 45 minutes after study drug completion

Amount of saline administered during cesarean

Time frame: During entire Cesarean delivery record (generally about 2 hours)

Pharmacokinetic parameters were analyzed based upon ionized calcium concentrations over time. Blood calcium concentration was measured at the following time points: baseline (pre-drug delivery), 0-20 minutes after drug administration, and 20-90 minutes after delivery. The resulting values for concentration over time were evaluated with NONMEM

Time frame: Samples drawn at baseline, at random time points after study drug administration while in the operating room, and upon arrival to the recovery room (up to 90 minutes)

Population: Patients who received calcium chloride and consented to blood sampling for PK analysis. Patients who received placebo were not included since they did not receive calcium chloride and had no data collected for the outcome.