Jessica J.F. Kram

Does current cefazolin dosing achieve adequate tissue and blood concentrations in obese women undergoing cesarean section

BACKGROUND Prophylactic administration of antibiotics preceding cesarean delivery is the most effective measure taken for preventing postpartum infection. While obese women are at greater risk for infection than non-obese women, evidence-based recommendations for modifying dosing in these women are limited. OBJECTIVES The purpose of this study was to determine whether obese women undergoing cesarean delivery similarly reach adequate cefazolin concentrations within tissue and blood when weighing <120kg and dosed 2g versus weighing ≥120kg and dosed 3g. STUDY DESIGN We prospectively studied women ≥18 years old with body mass index ≥30kg/m2 who underwent scheduled cesarean delivery with singleton pregnancy from August 2014 through March 2016. Women were dosed with 2g and 3g of cefazolin for body weights <120kg and ≥120kg, respectively. Samples of subcutaneous adipose tissue (following skin incision and before skin closure), myometrial tissue, fetal cord blood, and maternal blood were collected to assess whether cefazolin concentrations were adequate, i.e., at/above the minimum inhibitory concentration (MIC). Concentrations, based on inhibition zones for Streptococcus sanguinis, were calculated per gram of solid tissue and milliliter of blood. For all sample types, log-transformed concentrations were compared between dosage groups. Using a range of published MICs (1-8μg/mL or μg/g), odds ratios, describing differential odds of falling below the MIC between dosage groups, were also computed. RESULTS Women who received 2g (n=65) versus 3g (n=19) of cefazolin did not significantly differ by maternal or gestational age, race/ethnicity, pre-operative hemoglobin, estimated blood loss, fluid administration, duration of surgery, or timing of sample collections relative to cefazolin administration (Ps>0.05). Dosage groups also did not differ in cefazolin concentration (median [interquartile range]) within adipose tissue following skin incision (5.30μg/g [3.00-9.60] vs. 6.35μg/g [3.90-8.40]; P=0.551), adipose tissue before skin closure (4.45μg/g [2.78-7.25] vs. 6.90μg/g [2.60-10.6]; P=0.342), myometrial tissue (13.1μg/g [8.60-19.6] vs. 15.7μg/g [10.8-21.7]; P=0.116), or maternal blood (41.6μg/mL [26.3-57.0] vs. 45.3μg/mL [36.7-68.3]; P=0.143). However, cord blood concentrations differed significantly (19.5μg/mL [13.7-28.5] vs. 27.9μg/mL [15.8-39.4]; P=0.032), and, in 3 of 5 sample types, group concentrations differed at the dosing cut-point of 120kg (Ps<0.02). Within the range of MICs considered, differences in the odds of concentration inadequacy were not detected between dosage groups for any sample type. Across all patients, inadequate concentrations in one or more solid tissue types were observed in 1.19%, 17.9%, 59.5%, and 86.9% of patients, given the MICs of 1μg/g, 2μg/g, 4μg/g and 8μg/g, respectively. In adipose tissues, specifically, and both dosage groups, mean concentrations were significantly lower than the MIC of 8μg/g (Ps<0.03). Concentrations in one or both blood sample types were inadequate for only 8.33% of patients, given the 8-μg/mL MIC. CONCLUSIONS Adequate cefazolin concentrations were achieved in blood for the majority of our patients. However, concentration adequacy was not achieved in solid tissue for a nearly equally large proportion of patients. Larger scale studies for determining modified protocols for dosing and applying MICs are warranted.

Foley catheter placement for induction of labor with or without stylette: a randomized clinical trial

BACKGROUND Foley catheters are used for cervical ripening during induction of labor. Previous studies suggest that use of a stylette (a thin, rigid wire) to guide catheter insertion decreases insertion failure. However, stylette effects on insertion outcomes have been sparsely studied. OBJECTIVE The purpose of this study was to compare catheter insertion times, patient-assessed pain levels, and insertion failure rates between women who received a digitally placed Foley catheter for cervical ripening with the aid of a stylette and women who received the catheter without a stylette. STUDY DESIGN We conducted a randomized clinical trial of women aged ≥ 18 years who presented for induction of labor. Inclusion criteria were singletons with intact membranes and cephalic presentation. Women received a computer-generated random assignment of a Foley catheter insertion with a stylette (treatment group, n = 62) or without a stylette (control group, n = 61). For all women, a standard insertion technique protocol was used. Three primary outcomes were of interest, including the following: (1) insertion time (total minutes to successful catheter placement), (2) patient-assessed pain level (0-10), and (3) failure rate of the randomly assigned insertion method. Treatment control differences were first examined using the Pearsons test of independence and the Student t test. Per outcome, we also constructed 4 regression models, each including the random effect of physician and fixed effects of stylette use with patient nulliparity, a history of vaginal delivery, cervical dilation at presentation, or postgraduate year of the performing resident physician. RESULTS Women who received the Foley catheter with the stylette vs without the stylette did not differ by age, race/ethnicity, body mass index, or any of several other characteristics. Regression models revealed that insertion time, patient pain, and insertion failure were unrelated to stylette use, nulliparity, and history of vaginal delivery. However, overall insertion time and failure were significantly influenced by cervical dilation, with insertion time decreasing by 21% (95% confidence interval [CI], 5-34%) and odds of failure decreasing by 71% (odds ratio, 0.29; 95% CI, 0.10-0.86) per 1 cm dilation. Resident postgraduate year also significantly influenced insertion time, with greater time required of physicians with less experience. Mean insertion time was 51% (95% CI, 23-69%) shorter for fourth-year than second-year residents. Statistically nonsignificant but prominent patterns in outcomes were also observed, suggesting stylette use may lengthen the overall insertion procedure but minimize variability in pain levels and decrease insertion failure. CONCLUSIONS The randomized trial suggests that, even after accounting for nulliparity, history of vaginal delivery, cervical dilation, and physician experience, Foley catheter insertions with and without a stylette are equivalent in insertion times, patient pain levels, and failure of catheter placement.

Management of the third stage of labor in second-trimester deliveries: How long is too long?

BACKGROUND Retained placenta is the most common second-trimester delivery complication. As the optimal third stage of labor duration remains undefined, complications associated with retained placentas are difficult to study. OBJECTIVE(S) To determine the optimal third stage of labor duration in second-trimester deliveries based on estimates of time-specific probabilities of placental delivery, placental intervention, and postpartum complication. STUDY DESIGN We retrospectively studied adult women with singleton second-trimester vaginal deliveries. We identified third stage of labor duration, placental delivery method (spontaneous vs. manual/operative intervention), and indication for intervention. Postpartum complication was examined as a composite outcome. Differences among groups defined by delivery method and postpartum complication were tested using parametric and nonparametric tests. Probability curves describing the time-specific probabilities of placental delivery were derived using lifetable methods with group differences tested using the log-rank test. Probability of placental intervention and complication by time to placental delivery were examined using logistic regression with adjustment for confounders and other predictors. RESULTS We identified 215 second-trimester placental deliveries (77% spontaneous, 23% intervention). Overall, 27% experienced postpartum complication, primarily hemorrhage (91%). Complication rates differed significantly between spontaneous placental deliveries (16%) and interventions (61%, P < 0.01). Both placental intervention and postpartum complication were strongly associated with longer time to placental delivery. Spontaneous placental deliveries occurred earlier than deliveries requiring intervention (P < 0.01). At 2 h, placental delivery rates were 93% in spontaneous deliveries and 39% in those requiring intervention. The overall postpartum complication rate for spontaneous placental deliveries (16%) was used as the threshold of tolerable risk and the criterion for placental intervention. Adjusted probability curves for deliveries of average gestational age (21.6 weeks) suggested that most patients (63.9%) may not require intervention until approximately 2 h following fetal delivery. Patients with PPROM would require intervention by 34 min, and those with intrapartum fever or delivery EBL ≥500 mL would already exceed the risk threshold at fetal delivery. CONCLUSIONS Our study suggests that an optimal third stage of labor duration of approximately 2 h maximizes probability of spontaneous delivery and minimizes complication risk. Timing of intervention may be further individualized for patients based on maternal characteristics and intrapartum conditions.

Robustness of a Newly Proposed Risk Schema for Lymphatic Dissemination in Endometrioid Endometrial Cancer

High Any TD, grade 1 or 2, MI >66% Any TD, grade 3, MI >50% TD >50 mm, any grade, MI >66% TD >50 mm, grade 2 or 3, 33% < MI ≤ 66% Risk Schema & Level Model Development Cohort Model Validation Cohort No LD (N=669) LD (N=68) No LD (N=218) LD (N=29) Standard Schema: Low ** 159 (23.8%) ** 1 (1.47%) ** 56 (25.7%) ** 2 (6.90%) Low-Intermediate 271 (40.5%) 12 (17.6%) 76 (34.9%) 6 (20.7%) High-Intermediate 99 (14.8%) 14 (20.6%) 25 (11.5%) 3 (10.3%) High 140 (20.9%) 41 (60.3%) 61 (28.0%) 18 (62.1%) Proposed Schema: Low ** 286 (42.8%) ** 0 (0%) ** 99 (45.4%) ** 4 (13.8%) Low-Intermediate 215 (32.1%) 17 (25.0%) 67 (30.7%) 5 (17.2%) High-Intermediate 77 (11.5%) 14 (20.6%) 20 (9.17%) 9 (31.0%) High 91 (13.6%) 37 (54.4%) 32 (14.7%) 11 (37.9%)

Geographic Distribution of Maternal Group B Streptococcus Colonization and Infant Death During Birth Hospitalization: Eastern Wisconsin

Purpose Maternal group B Streptococcus (GBS) can be transmitted from a colonized mother to newborn during vaginal delivery and may or may not contribute to infant death. This study aimed to explore the geographic distribution and risk factors of maternal GBS colonization and infant death during birth hospitalization. Methods We retrospectively studied mothers with live birth(s) in a large eastern Wisconsin hospital system from 2007 through 2013. Associations between maternal and neonatal variables, GBS colonization and infant death were examined using chi-squared, Mann-Whitney U and t-tests. Multivariable logistic regression models also were developed. Results Study population (N=99,305) had a mean age of 28.1 years and prepregnancy body mass index (BMI) of 26.7 kg/m 2 ; 64.0% were white, 59.2% married, 39.3% nulliparous and 25.7% cesarean delivery. Mean gestational age was 39.0 weeks. Rate of maternal GBS colonization (22.3% overall) was greater in blacks (34.1% vs. 20.1% in whites, P<0.0001), unmarried women (25.5% vs. 20.0% married, P<0.0001), women with sexually transmitted or other genital infections (P<0.0001) and residents of ZIP code group 532XX (P<0.0001), and was associated with increasing BMI (P<0.0001). All predictors of colonization were significant on multivariable analysis. Rate of infant death was 5.7 deaths/1,000 live births (n=558 excluding lethal anomalies and stillbirths) and was negatively associated with maternal GBS colonization (P<0.0001). On multivariable analysis, 532XX ZIP code group, lower gestational age, preterm labor, hyaline membrane disease, normal spontaneous vaginal delivery, hydramnios, oligohydramnios and absence of maternal GBS were associated with infant death. Conclusions Geographic characteristics were associated with infant death and maternal GBS colonization. Further research is needed to determine if increased surveillance or treatment of mothers colonized with GBS decreases the risk of infant demise at birth. (J Patient Cent Res Rev. 2016;3:66-78.)