OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS:A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (β coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (β coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (β coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (β coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (β coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (β coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS:Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

New training mechanisms may be needed to optimize research training that will provide residents with greater emphasis on areas of perceived deficiency.

Higher levels of the inflammatory biomarker interleukin-6 (IL-6) correlate with poor clinical outcome in acute ischemic stroke (AIS). Minocycline (MC) is a known anti-inflammatory agent; thus, the effect of MC on IL-6 in the first 24 h of AIS was investigated to determine potential anti-inflammatory activity. The Minocycline to Improve Neurologic Outcome in Stroke (MINOS) study was a non-randomized dose-escalation (3.0–10.0 mg/kg) trial of IV MC for AIS within 6 h of onset. Plasma IL-6 samples were collected prior to MC treatment at 1, 24, and 72 h and compared to those collected in a separate observational study of blood biomarkers in AIS. IL-6 levels were measured by commercially available ELISA kits. The lower limit of detection for IL-6 was 1 pg/ml. Sixty MINOS subjects and 29 non-MINOS subjects were enrolled, and there was no difference in baseline stroke severity. There was no significant difference in IL-6 level pre-MC treatment at 1, 24, or 72 h. However, the odds of a non-detectable IL-6 at 24 h in MINOS were 8.94 (95% CI 2.62–30.46) compared with non-MINOS subjects. It is likely that even low doses of MC have a potent systemic anti-inflammatory effect in AIS. Whether this results in improved outcome will be tested in a randomized clinical trial.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established. OBJECTIVES:To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium. DESIGN, SETTING, AND PARTICIPANTS:Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017. MAIN OUTCOMES AND MEASURES:Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after. RESULTS:A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation (n = 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior:

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

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