Sacco, Alicia

OBJECTIVES: We aimed to summarize the most significant and impactful publications describing the pharmacotherapeutic care of critically ill patients in 2023. DATA SOURCES: PubMed/MEDLINE and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials and prospective studies of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2023, and December 31, 2023, were eligible for inclusion in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included. An a priori defined three-round modified Delphi process was employed to achieve consensus on the most impactful publications based on the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update returned a total of 1202 articles, of which 1164 were excluded. The remaining 38 articles underwent a three-round modified Delphi process. In each round, articles were independently scored based on overall contribution to scientific knowledge and novelty to the literature. Included articles are summarized and their impact discussed. Article topics included hydrocortisone for severe community-acquired pneumonia, inhaled amikacin for prevention of ventilator-associated pneumonia, methylene blue for septic shock, restrictive vs. liberal fluid management for sepsis-induced hypotension, andexanet alfa for major bleeding associated with factor Xa inhibitors, and early administration of four-factor prothrombin complex concentrate in patients with trauma at risk for massive transfusion. CONCLUSIONS: This review provides a summary and perspective on the potential impact of the most relevant articles in 2023 describing advances in the pharmacotherapeutic care of critically ill patients.

Abstract Background Inappropriate use of carbapenems is a major driver of antimicrobial resistance. The intensive care unit (ICU) at Mayo Clinic Arizona had a higher meropenem (MER) days of therapy (DOT) per 1000 patient days (PD) compared to other Mayo Clinic Enterprise sites, despite low rates of Pseudomonal resistance to narrower spectrum anti-pseudomonal beta-lactams. Methods A multidisciplinary team of infectious diseases (ID) and critical care medicine (CCM) physicians and pharmacists was created to reduce inappropriate use of MER in the ICU. The baseline rate of appropriateness was determined by evaluating all MER days in the ICU during Q4 2019 and Q4 2020. Each MER day was designated as appropriate or inappropriate based on pre-determined criteria after review by at least one ID and one CCM member. Discordant days were evaluated by the whole team to achieve consensus. The team provided education to the CCM department on the initiative, baseline data, and strategies to reduce inappropriate MER use. The active intervention included prospective audit and feedback of all patients on MER performed by the ID clinical pharmacists Mon-Fri 0700-1530 in Q4 2022. DOT/1000 PD was assessed for the pre-intervention and intervention periods. Results The baseline rate of inappropriate MER use in the ICU was 52% (442/846 days). The two most common reasons for inappropriate MER use in the baseline period were: susceptible organism for which a narrower agent could have been used (93/442, 21%), and infectious workup/cultures negative (89/442, 20%). During the intervention period, the inappropriate rate of MER use was reduced to 23%, below the pre-determined goal of 30%. The MER DOT/1000 PD in the baseline period were 103.9 (Q4 2019) and 151.5 (Q4 2020) versus 66.1 (Q4 2022) in the intervention period. There was no difference in ICU sepsis-related mortality in the pre-intervention vs intervention period (13.4 vs 0%, p=0.04). Conclusion A multidisciplinary team approach, including education and prospective audit and feedback, reduced inappropriate MER use in the ICU of an academic medical center from 52 to 23%. An associated decrease in MER DOT/1000 patient days was also observed. Disclosures All Authors: No reported disclosures

Objectives: Refractory septic shock is associated with high morbidity and mortality. Hydroxocobalamin is used to treat postoperative vasoplegia; however, data supporting its use in the setting of refractory septic shock is limited and restricted to case reports. This study evaluates the effect of hydroxocobalamin on mean arterial pressure and vasopressor requirements in a series of patients with refractory septic shock. Design: Single-center, retrospective analysis. Setting: Urban, tertiary-care ICU. Patients: Adult ICU patients with refractory septic shock treated with hydroxocobalamin between August 2018 and January 2020. Interventions: Hydroxocobalamin 5 g IV infusion. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients were included for the analysis. Administration of hydroxocobalamin was associated with an increase in mean arterial pressure at 1, 6, and 24 hours postdose (+16.3, +14.3, and +16.3 mm Hg, respectively; p < 0.001). Increase in mean arterial pressure from baseline remained statistically significant when controlling for sex, age, and comorbid conditions. There was no change in the norepinephrine equivalents patients required 1 hour following hydroxocobalamin administration, but a statistically significant decrease in norepinephrine equivalent was observed at 6 and 24 hours postdose (p < 0.001). Conclusions: Hydroxocobalamin provides sustained hemodynamic benefit at 24 hours in patients with refractory septic shock.