Increased unfractionated heparin requirements with decreasing body mass index in pregnancy.

BACKGROUND: Pregnant women receiving low-molecular-weight heparin for therapeutic anticoagulation are often converted to unfractionated heparin in anticipation of labor. We aim to characterize the impact of maternal body mass index on attainment of target anticoagulation during the conversion process. METHODS: We conducted a five-year retrospective study of a pregnancy cohort converted from low-molecular-weight heparin to unfractionated heparin in the third trimester. Patient demographics, anticoagulation regimens, and clinical outcomes were extracted from the medical record. Nonparametric statistical methods were used for analysis by body mass index (<30, 30-35, and >35). RESULTS: Thirty-one subjects were evenly distributed by body mass index (p = 0.97). Linear regression revealed an inverse correlation between patient body mass index and unfractionated heparin dose needed to achieve therapeutic anticoagulation (p = 0.04). Subjects with body mass index > 35 attained therapeutic activated partial thromboplastin time levels at 18 U (Units)/kg/h, while subjects with body mass index < 30 required 25 U/kg/h (p = 0.02). CONCLUSION: Higher doses of unfractionated heparin are needed to achieve anticoagulation in patients with body mass index < 30 during pregnancy. This paradoxical relationship may be explained by physiologic characteristics that increase unfractionated heparin elimination, including diminished adiposity and increased renal clearance.

Pharmacokinetic comparison of nomogram-based and individualized vancomycin regimens in neonates.

PURPOSE: This study compared steady-state concentrations achieved with a dosing strategy using first-dose kinetics to individualize vancomycin regimens with the steady-state concentrations achieved using standardized nomograms. METHODS: Neonatal intensive care unit patients receiving vancomycin according to published nomograms (phase 1) were compared with patients receiving vancomycin using first-dose pharmacokinetic information to individualize the dosing regimen (phase 2). Retrospective chart review was used to gather demographic and patient-specific pharmacokinetic data. Data collected included gestational and postnatal ages, birth and dosing weights, first-dose peak and trough concentrations, serum creatinine, and information related to infection. Data were analyzed to determine the percentage of therapeutic concentrations at a steady state in each group. RESULTS: Phase 1 included 108 patients given doses according to published nomograms, and phase 2 included 85 patients who received vancomycin with first-dose pharmacokinetics. Steady-state concentrations were collected in 108 patients in phase 1 and 39 patients in phase 2. Both peak and trough concentrations were therapeutic at steady state in 39% in phase 1 versus 63% in phase 2 (p < 0.02). Therapeutic steady-state peak concentrations were achieved in 70% versus 76% while therapeutic steady-state trough concentrations were achieved in 50% versus 82% (p < 0.02) in phase 1 and phase 2, respectively. CONCLUSION: Compared with the use of nomograms, individualization of vancomycin regimens after the first dose in neonatal patients significantly increased the percentage of patients with target steady-state trough concentrations and with both target peak and trough concentrations. The benefits of individualized dosing were attained without additional venous sampling.

Gentamicin and clindamycin therapy in postpartum endometritis: the efficacy of daily dosing versus dosing every 8 hours.

OBJECTIVE: The objective of the study was to evaluate the efficacy of gentamicin and clindamycin given once daily versus the more common 8-hour dosing regimen for the treatment of postpartum endometritis. STUDY DESIGN: In a prospective, placebo-controlled, double-blinded study, patients who had postpartum endometritis diagnosed were randomly selected to receive 1.5 mg/kg gentamicin and 900 mg clindamycin phosphate administered every 8 hours versus gentamicin 5 mg/kg and clindamycin phosphate 2700 mg administered as a single-daily dose. The single-dose group received an infusion of gentamicin and clindamycin, followed by an administration of intravenous placebo 8 and 16 hours later to maintain blinding. Treatment success was defined as absence of fever 72 hours after initiation of antibiotic therapy. RESULTS: One hundred ten patients were enrolled. The daily-dose group (n = 55) and the thrice-daily dose group (n = 55) were similar with respect to age, gravidity, parity, gestational age, and maternal weight. Clinical characteristics (including maximum temperature, presence of predelivery chorioamnionitis, white blood cell count, and mode of delivery) were also similar. There was no difference in the mean time from initiation of therapy until becoming afebrile in the daily-dose group (27.4 +/- 24.9 hours) compared with the thrice-daily dose group (32.9 +/- 26.3 hours). Forty-five of 56 (82%) patients in the daily-dose group and 38 of 55 (69%) patients in the thrice-daily dose group had treatment success (P =.12). CONCLUSION: Once-daily dosing with gentamicin and clindamycin in women with postpartum endometritis has a similar success rate as the standard every 8-hour dosing schedule.