Pharmacotherapy
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Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. ⋯ The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.
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Heart failure (HF) impacts more than 6 million Americans with an annual mortality rate approaching 22%. Along with optimizing guideline-directed management and therapy (GDMT), the development of treatment options to improve mortality and morbidity in patients with HF with reduced ejection fraction (HFrEF) is paramount. Cardiovascular outcome trials in patients with type 2 diabetes have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors improve both cardiovascular (CV) and renal outcomes and have consistently reduced hospitalizations for HF in patients with and without a previous history of HF. ⋯ Data from these publications demonstrate significant benefit of dapagliflozin and empagliflozin on a variety of CV and HF quality of life end points in patients with HFrEF independent of the presence of type 2 diabetes. Now, widespread application of the clinical findings from the DAPA-HF and EMPEROR-Reduced trials must follow with SGLT2 inhibitors incorporated into GDMT for HFrEF regardless of the presence or absence of diabetes. In this review, we examine key literature surrounding the CV outcome data for SGLT2 inhibitors with a specific focus on patients with HFrEF.
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Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. ⋯ No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).
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Lefamulin is a novel pleuromutilin recently approved by the FDA for the treatment of community-acquired bacterial pneumonia. Given that, lefamulin is primarily metabolized by CYP450 Phase-1 reactions, this study evaluated the pharmacokinetics of IV lefamulin in subjects with various degrees of hepatic impairment as compared with matched healthy subjects. ⋯ Lefamulin was generally well tolerated. Differences in lefamulin and BC-8041 pharmacokinetics were small, relative to the overall variability, and any changes appear to be compensated by increases in renal clearance and decreased protein binding.
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Lefamulin is a novel IV and oral pleuromutilin recently approved for the treatment of community-acquired bacterial pneumonia (CABP). Given that renal comorbidities are common in patients admitted for CABP, understanding the pharmacokinetics of lefamulin in the face of severe renal impairment, including those requiring hemodialysis, is needed. ⋯ No dosage adjustment is required for patients with renal impairment, and lefamulin can be administered without regard to hemodialysis timing.