Postpartum Hemorrhage, Pregnancy Related, Hypocalcemia, Parturition Complication
Conditions
Brief summary
Calcium is a life saving medicine in the care of parturients. It has many important uses including treatment of hypocalcemia, treatment of magnesium toxicity, prevention of hypocalcemia during blood transfusion (of citrate containing blood products), treatment of hyperkalemia, and others. Recent clinical trials also suggest that calcium given after cord clamping may decrease blood loss in patients undergoing cesarean delivery. 2 FDA approved forms of calcium can be given intravenously: calcium chloride and calcium gluconate. Over the last decade there have been times with drug shortages of either calcium chloride or calcium gluconate. So there have been and likely will continue to be times when one formulation or the other may not be adequately available. Despite the importance of calcium and the frequency in which it is used in parturients, there are no published studies in parturients to determine dose equivalence between calcium gluconate and calcium chloride. In this study the investigators will determine the population pharmacokinetics of calcium gluconate and calcium chloride in parturients and calculate the dose equivalent ratio the two drugs. This will help clinicians select appropriate doses of calcium and provide resilience to the drug supply chain in our era of frequent drug shortages.
Interventions
Infused intravenously over 10 minutes upon umbilical cord clamping. First 10 assigned patients received 2 grams per protocol. Subsequent 13 patients received 1.5 grams, dose recalibrated per protocol.
DRUGCalcium chloride
0.5 grams of calcium chloride, infused intravenously over 10 minutes upon umbilical cord clamping
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Pregnant female subjects delivering at the study institution via scheduled cesarean delivery at term (\>=37 weeks gestation)
Exclusion criteria
1. severe range blood pressure (BP \>160/\>110) within the 48 hours prior to delivery 2. patient age \<18 years or \>45 years 3. renal dysfunction with serum Cr \> 1.0 mg/dL 4. known history of congenital or acquired cardiac disease or history of arrhythmia 5. patient taking digoxin 6. patient currently taking a calcium channel blocker 7. Weight \<55kg or \>100kg, or 8. receiving magnesium infusion within 24 hours prior to or during cesarean delivery 9. administration of intraoperative doses of calcium by the anesthesiology team for clinical indications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Volume of distribution of second compartment of pharmacokinetic model (L) | Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion | Determined using population pharmacokinetic analysis in NONMEM |
| Bioequivalent ratio of calcium gluconate (g) to calcium chloride (g) | Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion | Calculated via NONMEM |
| Clearance from first to second compartment (L/min) | Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion | Determined using population pharmacokinetic analysis in NONMEM |
| Volume of distribution of first compartment of pharmacokinetic model (L) | Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion | Determined using population pharmacokinetic analysis in NONMEM |
| Clearance from second compartment (L/min) | Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion | Determined using population pharmacokinetic analysis in NONMEM |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline serum ionized calcium concentration | Baseline prior to calcium infusion | Ionized calcium will be measured in each participant prior to administration of the 10-minute calcium infusion. The ionized blood calcium levels will be immediately analyzed using an Abbott iStat machine. |
| Peak change in serum ionized calcium concentration (mmol/L) | Measured immediately at completion of the 10-minute calcium infusion. | Measured via venous blood draw and an Abbott iStat CG8+ cartridge |
| Time to half of peak change in ionized calcium (minutes) | 10-60 minutes after infusion initiation | A two-compartment model does not lend itself to a meaningful half-life approximation. However, the time to serum values measuring 1/2 of the peak change in ionized calcium can be calculated from the pharmacokinetic model |
| Serum pH | Baseline prior to calcium infusion, 6 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion | Serum pH will be measured in each participant from a maximum of 6 venous blood draws of 0.5mL (1/10th of a teaspoon). These blood draws will be the same blood draws used to measure serum ionized calcium concentration, no additional blood draws will be necessary. These draws will occur at the following target times: prior to calcium administration, at 6 minutes, 10 minutes, 15 minutes, minutes, minutes after beginning calcium administration. The serum pH levels will be immediately analyzed using an Abbott iStat machine. |
Countries
United States
Outcome results
None listed