An Observational Study of the Pharmacokinetics of Surgeon-Performed Intercostal Nerve Blockade With Liposomal Bupivacaine for Posterior-Lateral Thoracotomy Analgesia
ANESTHESIA AND ANALGESIA
Authors: Manson, William C.; Blank, Randal S.; Martin, Linda W.; Alpert, Salome B.; Dobrzanski, Tomasz P.; Schneider, Eric B.; Ratcliffe, Sarah J.; Durieux, Marcel E.
BACKGROUND: Intercostal nerve blocks with liposomal bupivacaine are commonly used for thoracic surgery pain management. However, dose scheduling is difficult because the pharmacokinetics of a single-dose intercostal injection of liposomal bupivacaine has never been investigated. The primary aim of this study was to assess the median time to peak plasma concentration (T-max) following a surgeon-administered, single-dose infiltration of 266 mg of liposomal bupivacaine as a posterior multilevel intercostal nerve block in patients undergoing posterolateral thoracotomy. METHODS: We chose a sample size of 15 adults for this prospective observational study. Intercostal injection of liposomal bupivacaine was considered time 0. Serum samples were taken at the following times: 5, 15, and 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours. The presence of sensory blockade, rescue pain medication, and pain level were recorded after the patient was able to answer questions. RESULTS: Forty patients were screened, and 15 patients were enrolled in the study. Median (interquartile range [IQR]) T-max was 24 (12) hours (confidence interval [CI], 19.5-28.5 hours) with a range of 15 minutes to 48 hours. The median (IQR) peak plasma concentration (C-max) was 0.6 (0.3) mu g/mL (CI, 00.45-0.74 mu g/mL) in a range of 0.3-1.2. The serum bupivacaine concentration was undetectable (<0.2 mu g/mL) at 96 hours in all patients. There was significant variability in reported pain scores and rescue opioid medication across the 15 patients. More than 50% of patients had return of normal chest wall sensation at 48 hours. All patients had resolution of nerve blockade at 96 hours. No patients developed local anesthetic toxicity. CONCLUSIONS: This study of the pharmacokinetics of liposomal bupivacaine following multilevel intercostal nerve blockade demonstrates significant variability and delay in systemic absorption of the drug. Peak serum concentration occurred at 48 hours or sooner in all patients. The serum bupivacaine concentration always remained well below the described toxicity threshold (2 mu g/mL) during the 96-hour study period.
Polycyclic aromatic hydrocarbon exposure results in altered CRH, reproductive, and thyroid hormone concentrations during human pregnancy
SCIENCE OF THE TOTAL ENVIRONMENT
Authors: Cathey, Amber L.; Watkins, Deborah J.; Rosario, Zaira Y.; Vega, Carmen M. Velez; Loch-Caruso, Rita; Alshawabkeh, Akram N.; Cordero, Jose F.; Meeker, John D.
Polycyclic aromatic hydrocarbons (PAHs) are byproducts of incomplete combustion reactions and are ubiquitous in the environment, leading to widespread human exposure via inhalation and ingestion pathways. PAHs have been implicated as endocrine disrupting compounds in previous animal and in vitro studies, but human studies are currently lacking. Pregnant women and their developing fetuses are particularly susceptible populations to environmental contaminants, in part because alterations in hormone physiology during gestation can have adverse consequences on the health of the pregnancy. We utilized data on 659 pregnant women from the PROTECT longitudinal birth cohort in Puerto Rico to assess associations between repeated measures of 3 urinary hydroxylated PAH (OH-PAH) metabolites and 9 serum hormones during gestation. Urine samples were collected at 3 study visits (median gestational ages of 18, 22, and 26 weeks at each visit, respectively) and serum samples were collected at the first and third study visits. Linear mixed effects models were used to ascertain longitudinal associations between OH-PAHs and hormones, and sensitivity analyses were employed to assess potential nonlinearity and differences in associations on the basis of fetal sex and timing of biomarker measurement. Among the multiple positive associations we observed between OH-PAHs and CRH, estriol, progesterone, T3, and the ratio of T3 to T4, and inverse associations with testosterone, the most notable are a 24.3% increase (95% Cl: 13.0, 36.7) in CRH with an interquartile range (1QR) increase in 1-hydroxyphenanthrene and a 17.2% decrease (95% CI: 8.13, 25.4) in testosterone with an 1QR increase in 1-hydroxynapthalene. Many associations observed were dependent on fetal sex, and some relationships showed evidence of nonlinearity. These findings demonstrate the importance of studying PAH exposures during pregnancy and highlight the potential complexity of their impacts on the physiology of human pregnancy. (C) 2020 Elsevier B.V. All rights reserved.