A Narrative Review of the Impact of Extracorporeal Membrane Oxygenation on the Pharmacokinetics and Pharmacodynamics of Critical Care Therapies.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) utilization is increasing on a global scale, and despite technological advances, minimal standardized approaches to pharmacotherapeutic management exist. This objective was to create a comprehensive review for medication dosing in ECMO based on the most current evidence. DATA SOURCES: A literature search of PubMed was performed for all pertinent articles prior to 2022. The following search terms were utilized: ECMO, pharmacokinetics, pharmacodynamics, sedation, analgesia, antiepileptic, anticoagulation, antimicrobial, antifungal, nutrition. Retrospective cohort studies, case-control studies, case series, case reports, and ex vivo investigations were reviewed. STUDY SELECTION AND DATA EXTRACTION: PubMed (1975 through July 2022) was the database used in the literature search. Non-English studies were excluded. Search terms included both drug class categories, specific drug names, ECMO, and pharmacokinetics. DATA SYNTHESIS: Medications with high protein binding (>70%) and high lipophilicity (logP > 2) are associated with circuit sequestration and the potential need for dose adjustment. Volume of distribution changes with ECMO may also impact dosing requirements of common critical care medications. Lighter sedation targets and analgosedation may help reduce sedative and analgesia requirements, whereas higher antiepileptic dosing is recommended. Vancomycin is minimally affected by the ECMO circuit and recommendations for dosing in critically ill adults are reasonable. Anticoagulation remains challenging as optimal aPTT goals have not been established. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review describes the anticipated impacts of ECMO circuitry on sedatives, analgesics, anticoagulation, antiepileptics, antimicrobials, antifungals, and nutrition support and provides recommendations for drug therapy management. CONCLUSIONS: Medication pharmacokinetic/pharmacodynamic parameters should be considered when determining the potential impact of the ECMO circuit on attainment of therapeutic effect and target serum drug concentrations, and should guide therapy choices and/or dose adjustments when data are not available.

Impact of Early Reinitiation of Neuropsychiatric Medications on Agitation and Delirium in the Intensive Care Unit: A Retrospective Study.

BACKGROUND: Approximately 17% of intensive care unit (ICU) patients are prescribed at least 1 home neuropsychiatric medication (NPM). When abruptly discontinued, withdrawal symptoms may occur manifesting as agitation or delirium in the ICU setting. OBJECTIVE: To evaluate the impact of early reinitiation of NPMs. METHODS: This was a retrospective, observational cohort of adult ICU patients in a tertiary care hospital. Patients were included if admitted to the ICU and prescribed a NPM prior to arrival. Study groups were based on the timing of reinitiation of at least 50% of NPMs: ≤72 hours (early group) versus >72 hours (late group). RESULTS: The primary outcome was the proportion of patients with at least 1 agitation or delirium episode in the first 72 hours. Agitation and delirium were defined as at least 1 RASS assessment between +2 to +4 and a positive CAM-ICU assessment, respectively. A total of 300 patients were included, with 187 (62%) and 113 (38%) in the early and late groups, respectively. There was no difference in agitation or delirium (late 54 [48%] vs early 62 [33%]; adjusted odds ratio [aOR] = 1.5; 95% CI = 0.8-2.8; P = 0.193). Independent risk factors found to be associated with the primary outcome were restraints (aOR = 12.9; 95% CI = 6.9-24.0; P < 0.001) and benzodiazepines (BZDs; aOR = 2.0; 95% CI = 1.0-3.7; P = 0.038). CONCLUSIONS: After adjustment for baseline differences, there was no difference in agitation or delirium. Independent risk factors were restraint use and newly initiated BZDs.

Antihypertensive Medications Prior to Shock Onset Do Not Impact Initial Vasopressor Requirements in Patients With Shock.

Purpose: The effect of the use of antihypertensive agents in patients prior to the development of shock is unclear. The purpose of this study was to determine the impact of antihypertensive agents on vasopressor dose and duration in shock. Materials and Methods: This retrospective, single-center study included patients with shock who received at least one vasopressor for at least 24 hours after shock onset from January 1 to June 30, 2017. Patients taking an antihypertensive agent(s) were compared to those who were not. The primary outcome was the number of vasopressor-free hours at 72 hours. Secondary outcomes included maximum and cumulative vasopressor doses, intensive care unit length of stay, and 30-day mortality. Results: One hundred and sixty-eight patients were included and 99 (59%) were on antihypertensives. Distributive shock was the most common type of shock (75.5%) and more patients taking antihypertensives had hypertension, coronary artery disease, and dyslipidemia at baseline. There was no difference in the number of vasopressor-free hours at 72 hours between patients taking an antihypertensive medication(s) and the control group (2 hours vs 1 hour; P = .11). No difference was found between any of the secondary outcomes. Conclusion: Patients taking antihypertensive agents prior to shock onset did not require increased vasopressor doses or duration.

Major Publications in the Critical Care Pharmacotherapy Literature: 2021.

To summarize the most impactful articles relevant to the pharmacotherapy of critically ill adult patients published in 2021. DATA SOURCE: PubMed/MEDLINE. STUDY SELECTION: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critical care patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2021, and December 31, 2021. DATA EXTRACTION: Candidate articles were organized by clinical domain based on the emerging themes from all studies. A modified Delphi process was applied to obtain consensus on the most impactful publication within each clinical domain based on overall contribution to scientific knowledge and novelty to the literature. DATA SYNTHESIS: The search revealed 830 articles, of which 766 were excluded leaving 64 candidate articles for the Delphi process. These 64 articles were organized by clinical domain including: emergency/neurology, cardiopulmonary, nephrology/fluids, infectious diseases, metabolic, immunomodulation, and nutrition/gastroenterology. Each domain required the a priori defined three Delphi rounds. The resultant most impactful articles from each domain included five randomized controlled trials and two systematic review/meta-analyses. Topics studied included sedation during mechanical ventilation, anticoagulation in COVID-19, extended infusion beta-lactams, interleukin-6 antagonists in COVID-19, balanced crystalloid resuscitation, vitamin C/thiamine/hydrocortisone in sepsis, and promotility agents during enteral feeding. CONCLUSIONS: This synoptic review provides a summary and perspective of the most impactful articles relevant to the pharmacotherapy of critically ill adults published in 2021.