Patel, Gourang

Objectives: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. Design: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. Setting: Thirty-three hospital sites in the United States ( n = 32) and Jordan ( n = 1). Patients: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. Interventions: None. Measurements and Main Results: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851–5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 μg/min norepinephrine equivalents (3.4–18.1 μg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 μg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16–1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. Conclusions: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Background: Use of nonbenzodiazepine agents propofol and dexmedetomidine are first line for sedation in the intensive care unit (ICU). These agents have been implicated in the development of bradycardia and hypotension in critical illness. Objectives: To compare the development of clinically significant hypotension and/or bradycardia (ie, negative hemodynamic event) in adults with sepsis yet to require vasopressors receiving either propofol or dexmedetomidine for continuous sedation. Methods: This was a retrospective multicenter cohort study of adults with non–vasopressor-dependent sepsis admitted to an ICU at two academic medical centers between July 2013-September 2017. Results: Patients in the propofol (n = 64) and dexmedetomidine (n = 31) groups developed a clinically significant negative hemodynamic event at statistically similar frequencies (34.4% vs 16.1%, P = 0.065). Patients receiving propofol developed a larger degree of hypotension (47.3 vs 34.7 mm Hg reduction, P = 0.031). In multivariable logistic regression modeling, independent predictors of a negative hemodynamic event were a past medical history of chronic kidney disease (odds ratio [OR] = 3.8; 95% CI = 1.17-12.2; P = 0.027) and baseline heart rate (OR = 1.02; 95% CI = 1.00-1.10; P = 0.036). Conclusions and Relevance: A minority of patients with sepsis who received either propofol or dexmedetomidine experienced an event. Patients with sepsis without shock receiving continuous infusions of propofol and dexmedetomidine experienced a negative hemodynamic event at similar frequencies, though the degree of hypotension seen with propofol was greater. The clinical significance of these adverse effects requires cautious use in sepsis and further investigation.

AbstractCurrent published guidelines for perioperative pharmacy services have limited information on the development and implementation of a robust clinical pharmacy program across the surgical continuum of care. This publication defines the responsibilities and scope of practice of the Perioperative Clinical Pharmacist (PCPh), supporting the PCPh as a critical member of the interprofessional surgical patient care team. Opportunities for pharmacist role integration into perioperative medication management processes are described along with published examples of successful PCPh practice models, including those with interventions targeted toward Enhanced Recovery Pathways (ERP). Recommended training and competencies for future and practicing perioperative pharmacists, in addition to considerations for precepting and scholarly activities, are also outlined. Finally, future developments in perioperative pharmacy practice are discussed, including technological advancements, improved predictive models, and expansion of collaborative practice agreements.