No abstract

PUI = persons under investigation; RANZCOG = xxx; RCOA-OAA = xxx; RCOG = xxx; RNA = ribonucleic acid; RT-PCR = real-time reverse transcriptasepolymerase chain reaction; SMFM-SOAP = xxx; SOAP = xxx; SOGC = xxx; Spo 2 = pulse oximetry; SARS = severe acute respiratory syndrome; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SPG = sphenopalatine ganglion With increasing numbers of Coronavirus Disease 2019 (COVID 19) cases due to efficient human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States, preparation for the unpredictable setting of labor and delivery is paramount. The priorities are 2-fold in the management of obstetric patients with COVID-19 infection or persons under investigation (PUI): (1) caring for the range of asymptomatic to critically ill pregnant and postpartum women; (2) protecting health care workers and beyond from exposure during the delivery hospitalization (health care providers, personnel, family members). The goal of this review is to provide evidence-based recommendations or, when evidence is limited, expert opinion for anesthesiologists caring for pregnant women during the COVID 19 pandemic with a focus on preparedness and best clinical obstetric anesthesia practice.

Background Perioperative bronchospasm refractory to β-agonists continues to challenge anesthesiologists and intensivists. The TMEM16A calcium-activated chloride channel modulates airway smooth muscle (ASM) contraction. We hypothesized that TMEM16A antagonists would relax ASM contraction by modulating membrane potential and calcium flux. Methods Human ASM, guinea pig tracheal rings or mouse peripheral airways were contracted with acetylcholine (Ach) or leukotriene D4 (LTD4) and then treated with the TMEM16A antagonists: benzbromarone, T16Ainh-A01, MONNA or B25. In separate studies, guinea pig tracheal rings were contracted with Ach and then exposed to increasing concentrations of isoproterenol (0.01nM-10μM) ± benzbromarone. Plasma membrane potential and intracellular calcium concentrations were measured in human ASM cells. Results Benzbromarone was the most potent TMEM16A antagonist tested for relaxing an Ach-induced contraction in guinea pig tracheal rings (n=6). Further studies were done to investigate benzbromarone’s clinical utility. In human ASM, benzbromarone relaxed either an acetylcholine- or LTD4-induced contraction (n=8). Benzbromarone was also effective in relaxing peripheral airways (n=9) and potentiating relaxation by β-agonists (n=5–10). In cellular mechanistic studies, benzbromarone hyperpolarized human ASM cells (n=9–12) and attenuated intracellular calcium flux from both the plasma membrane and sarcoplasmic reticulum (n=6–12). Conclusions TMEM16A antagonists work synergistically with β-agonists and through a novel pathway of interrupting ion flux both at the plasma membrane and sarcoplasmic reticulum to acutely relax human airway smooth muscle.