Magnesium sulfate is one of the most commonly used medications in obstetrics, most notably for the prevention of eclamptic seizures and fetal neuroprotection of the extremely preterm neonate. ...Pharmacokinetic and pharmacodynamic studies have demonstrated a variety of IV and IM regimens are effective for these indications. Existing models and data can be used to tailor treatment regimens to increase coverage in poor resource areas, maximize efficacy and minimize toxicity for patients of different weights and renal function.
To examine the relationship between the maternal serum bisphenol A (BPA) concentration at the time of the missed menstrual cycle and miscarriage risk.
Retrospective cohort of prospectively collected ...serum samples.
Academic fertility center.
Women presenting for early pregnancy monitoring with singleton pregnancies.
Stored serum samples from 4 to 5 weeks' gestation analyzed for conjugated serum BPA concentrations.
Live birth, miscarriage, and chromosome content of miscarriage.
With the 115 women included in the study, there were 47 live births and 68 clinical miscarriages (46 aneuploid and 22 euploid). Median conjugated BPA concentrations were higher in the women who had miscarriages than in those who had live births (0.101 vs. 0.075 ng/mL). Women with the highest quartile of conjugated BPA had an increased relative risk of miscarriage (1.83; 95% CI, 1.14-2.96) compared with the women in the lowest quartile. We found a similar increase risk for both euploid and aneuploid miscarriages.
Maternal conjugated BPA was associated with a higher risk of aneuploid and euploid miscarriage in this cohort. The impact of reducing individual exposure on future pregnancy outcomes deserves further study.
The aim of this review is to describe the proposed mechanisms of action of magnesium sulfate for fetal neuroprotection, different dosing regimens of the drug that have shown benefit, and to review ...recent pharmacokinetic studies of the drug to better inform clinicians regarding expected benefits and remaining research questions.
Retrospective secondary analysis of the beneficial effects of antenatal magnesium sulfate trial database and prospective pharmacokinetic/pharmacodynamic modeling indicate magnesium sulfate administration for duration longer than 18 h, given within 12 h of delivery, and maintaining a maternal serum level of 4.1 mg/dl may maximize the neuroprotective benefits of the drug.
Magnesium sulfate in some dosage given before very preterm pregnancy delivery is beneficial for fetal neuroprotection. The exact dose, duration, and timing of administration to maximize this benefit may be more precisely studied using pharmacokinetic/pharmacodynamic modeling techniques before conducting larger randomized trials.
To evaluate whether obese women need greater doses of magnesium sulfate to obtain therapeutic serum concentrations for eclamptic seizure prevention.
Women with preeclampsia and a body mass index ...(BMI) of 35 or higher were randomly allocated to either the Zuspan regimen of magnesium sulfate (4-g intravenous IV loading dose, then a 1-g/h infusion) or to alternate dosing (6-g IV loading dose, then a 2-g/h infusion). Women had serum magnesium concentrations obtained at baseline, as well as after administration of magnesium sulfate at 1 hour, 4 hours, and delivery. The primary outcome was the proportion of women who had subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration. A sample size of 18 women per group was planned to compare the proportion of women with subtherapeutic serum magnesium concentrations in each group.
From July 12, 2016, to March 14, 2019, 89 women with preeclampsia were screened and 37 were enrolled: 18 to the Zuspan regimen and 19 to the alternate regimen. A significantly greater proportion of women administered the Zuspan regimen had subtherapeutic serum magnesium concentrations at 4 hours (100% 95% CI 59-100 vs 63% 95% CI 41-81; P=.01) compared with women administered the alternate higher dose regimen. At 4 hours, mean concentrations were significantly higher in the alternate regimen group (3.53 mg/dL±0.3 Zuspan regimen vs 4.41±0.5 alternate regimen; P<.01).
The alternate dosing regimen of a 6-g IV loading dose followed by a 2-g/h IV maintenance dose more reliably achieves therapeutic serum magnesium concentrations (as defined by a concentration of at least 4.8 mg/dL) in obese women with preeclampsia.
ClinicalTrials.gov, NCT02835339.
Racial and ethnic disparities have been identified in the provision of neuraxial labor analgesia. These disparities may exist in other key aspects of obstetric anesthesia care. We sought to determine ...whether racial/ethnic disparities exist in mode of anesthesia for cesarean delivery (CD).
Women who underwent CD between 1999 and 2002 at 19 different obstetric centers in the United States were identified from the Maternal-Fetal Medicine Units Network Cesarean Registry. Race/ethnicity was categorized as: Caucasian, African American, Hispanic, and Non-Hispanic Others (NHOs). Mode of anesthesia was classified as neuraxial anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) or general anesthesia. To account for obstetric and non-obstetric covariates that may have influenced mode of anesthesia, multiple logistic regression analyses were performed by using sequential sets of covariates.
The study cohort comprised 50,974 women who underwent CD. Rates of general anesthesia among racial/ethnic groups were as follows: 5.2% for Caucasians, 11.3% for African Americans, 5.8% for Hispanics, and 6.6% for NHOs. After adjustment for obstetric and non-obstetric covariates, African Americans had the highest odds of receiving general anesthesia compared with Caucasians (adjusted odds ratio aOR = 1.7; 95% confidence interval CI, 1.5-1.8; P < 0.001). The odds of receiving general anesthesia were also higher among Hispanics (aOR = 1.1; 95% CI, 1.0-1.3; P = 0.02) and NHOs (aOR = 1.2; 95% CI, 1.0-1.4; P = 0.03) compared with Caucasians, respectively. In our sensitivity analysis, we reconstructed the models after excluding women who underwent neuraxial anesthesia before general anesthesia. The adjusted odds of receiving general anesthesia were similar to those in the main analysis: African Americans (aOR = 1.7; 95% CI, 1.5-1.9; P < 0.001); Hispanics (aOR = 1.2; 95% CI, 1.1-1.4; P = 0.006); and NHOs (aOR = 1.2; 95% CI, 1.0-1.5; P = 0.05).
Based on data from the Cesarean Registry, African American women had the highest odds of undergoing general anesthesia for CD compared with Caucasian women. It is uncertain whether this disparity exists in current obstetric practice.
Background
Women with placenta increta (PI) and placenta percreta (PP) are at high risk of obstetric hemorrhage; however, the severity of hemorrhage and perioperative morbidity may differ according ...to the degree of placental invasion. We sought to compare blood component usage and perioperative morbidity between women with PI versus PP undergoing cesarean hysterectomy (CH).
Study Design and Methods
We identified 77 women who underwent CH for PI or PP from the NICHD MFMU Network Cesarean Registry, which sourced data from 19 centers from 1999 to 2002. We examined demographic, obstetric, and surgical data and rates of transfusion and perioperative morbidity. We performed statistical tests for between‐group analyses; p values less than 0.05 were significant.
Results
Rates of intraoperative or postoperative red blood cell (RBC) transfusion were similar between groups (PI 84% vs. PP 88%; p = 0.7). We observed no between‐group differences in rates of fresh‐frozen plasma (FFP) transfusion (intraoperative FFP—PI 30% vs. PP 41%; p = 0.3; postoperative FFP—PI 28% vs. PP 18%; p = 0.4) or platelet (PLT) transfusion (intraoperative PLTs—PI 14% vs. PP 29%; p = 0.2; postoperative PLTs—PI 9% vs. PP 9%; p = 1.0). Among the morbidities, a higher proportion of PP women underwent cystotomy (PI 14% vs. PP 38%; p = 0.02) and postoperative mechanical ventilation (PI 14% vs. PP 35%; p = 0.03).
Conclusion
Rates of intraoperative RBC, FFP, and PLT transfusion are similar for PI and PP women, and perioperative outcomes are worse for PP women. We suggest the same mobilization transfusion medicine support for both groups, including blood ordering (type and cross‐match for CH) and availability of emergency blood protocols including fibrinogen‐containing preparations.
The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and maternal serum concentration to prevent cerebral palsy in the extremely preterm fetus. We applied a ...previously constructed pharmacokinetic model adjusted for indication to a large cohort of pregnant women receiving magnesium sulfate to prevent cerebral palsy in their preterm offspring at 20 different US academic centers between December 1997 and May 2004. We simulated the population‐based individual maternal serum magnesium concentration at the time of delivery and the total magnesium dose for each woman who received magnesium sulfate to determine the relationship between maternal serum magnesium level at the time of delivery and the development of cerebral palsy. Among 1905 women who met inclusion criteria, the incidence of cerebral palsy in the cohort was 3.6% for women who had received magnesium sulfate and 6.4% for controls. The simulated maternal serum concentration at delivery associated with the lowest probability of delivering an infant with cerebral palsy was 4.1 mg/dL (95%CI 3.7 to 4.4). Our population‐based estimates of magnesium disposition suggest that to optimize fetal neuroprotection and prevent cerebral palsy, magnesium sulfate administration should target a maternal serum magnesium level between 3.7 and 4.4 mg/dL at delivery.
Background Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetrics. Despite its widespread use, there are limited data about magnesium pharmacokinetics, and ...magnesium is prescribed empirically without dose adjustment for different indications. Objective The aim of this study was to characterize the pharmacokinetics and placental transfer of magnesium sulfate in pregnant women and to determine key covariates that impact the pharmacokinetics. Study Design This is a prospective pharmacokinetic cohort study of pregnant women who were prescribed magnesium sulfate for preeclampsia, preterm labor, or extreme prematurity. Women received a 4-g loading dose and 2 g/h maintenance dose as clinically indicated. Maternal blood samples were obtained before and at multiple time points during and after magnesium administration. Cord blood also was sampled at delivery. A population pharmacokinetic approach that used a nonlinear mixed–effects modeling was used to characterize magnesium disposition. Results Pharmacokinetic profiles of 111 pregnant women were analyzed. Magnesium clearance was 3.98 L/h in preeclamptic women and 5.88 L/h non-preeclamptic women. Steady-state concentration of magnesium was 7.2 mg/dL in preeclamptic women compared with 5.1 mg/dL in non-preeclamptic women. Maternal weight significantly impacted time to steady state. The ratio of the mean umbilical vein magnesium level to the mean maternal serum magnesium level at the time of delivery was 0.94 ± 0.15. Conclusions The study accurately characterizes the pharmacokinetics of magnesium administered to pregnant women. Preeclamptic status and maternal weight significantly impact serum magnesium levels. This pharmacokinetic model could be applied to larger cohorts to help tailor magnesium treatment and account for these covariates.
A prospective randomized study.
To study the risk of infection, hematoma, and neurologic deficits following extensive lumbar spine surgery in patients with or without prophylactic closed wound ...suction drain placement.
One randomized study assessing prophylactic drain placement in one-level lumbar spine surgery suggested that the use of a wound drain is not effective at preventing infection and may actually increase the rate of this complication. Our study was designed to determine the efficacy of closed wound suction drainage in preventing complications after extensive lumbar spine surgery.
Eighty-three consecutive patients undergoing extensive lumbar spine surgery were prospectively randomized to one of two groups. Forty-two patients had a closed wound suction drain placed before wound closure and 41 patients did not have a drain placed. The two groups were then assessed for differences in postoperative infection rate, incidence of hematoma and neurologic deficits, operating room time, estimated blood loss, hemoglobin and hematocrit values, temperature, dressing drainage, and length of hospital stay. RESULTS.: No infections, epidural hematomas, or new neurologic deficits were encountered in either group of patients. The only significant finding was a higher temperature in the "no drain" group the first day after surgery (P = 0.0437).
Based on the findings in this and other studies, the decision to use or not use a wound drain following lumbar spine surgery should be left to the surgeon's discretion.
In this study, the authors sought to understand the effects of patient race, ethnicity, and socioeconomic status (SES) on outcomes for cervical cancer.
The Florida Cancer Data System and the Agency ...for Health Care Administration data sets (1998-2003) were merged and queried. Survival outcomes for patients with invasive cervical cancer were compared between different races, ethnicities, and community poverty levels.
In total, 5367 patients with cervical cancers were identified. The overall median survival was 43 months. Significantly longer survival was observed for Caucasians (47.1 months vs 28.8 months for African Americans AA; P<.001), Hispanics (52.8 months vs 41.6 months for non-Hispanics; P<.001), the insured (63 months vs 41.2 months for uninsured; P<.001), and patients from more affluent communities (53.3 months where <5% lived in poverty vs 36.9 months where >15% lived in poverty; P<.001). Surgery was associated with dramatically improved survival. AA women who were diagnosed with cervical cancer were significantly less likely to undergo surgical treatment with curative intent compared with Caucasian women (P<.001). However, on multivariate analysis, independent predictors of poorer outcomes were insurance status, tumor stage, tumor grade, and treatment. Neither race, nor ethnicity, nor SES was an independent predictor of poorer outcome.
Race, ethnic, and SES disparities in cervical cancer survival were explained by late-stage presentation and under-treatment. Earlier diagnosis and greater access to surgery and other treatments would significantly improve the survival of women with cervical cancer.
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