Robert MacLaren

Background: Glomerular filtration rate (GFR) is commonly estimated with equations using creatinine, cystatin C, or a combination of both. Drug dosages may differ depending on the which equation. Objectives: This study determined estimated GFRs from 4 common equations, their correlations, and the subsequent variations of predicted vancomycin half-life (t _1/2 ). Methods: Retrospective cohort study of critically ill adults with GFR estimations based on Cockcroft-Gault (CrCl _CG ), 2021 CKD-EPI Creatinine (eGFR _cr ), 2012 CKD-EPI Cystatin C (eGFR _cys ), and 2021 CKD-EPI Creatinine-Cystatin (eGFR _cr-cys ). Patients were excluded if pregnant, dialysis dependent prior to admission, or sampling occurred within 24 hours of renal replacement therapy. Statistical analyses used MANOVA and Pearson correlation coefficient ( r ² ). Bayesian modeling population estimates predicted vancomycin t _1/2 . Results: Sixty-three patients with 104 GFR estimates were assessed. Mean age was 58.5 ± 15.2 years. Mean creatinine and cystatin C were 1.78 ± 2.1 mg/dL and 2.28 ± 1.2 mg/L, respectively. Mean estimated GFRs were 76.6 ± 59.2 mL/min, 72 ± 41.4 mL/min, 38 ± 27.5 mL/min, and 47.3 ± 32.7 mL/min for CrCl _CG , eGFR _cr , eGFR _cys , and eGFR _cr-cys , respectively ( P < 0.0001). r ² (all P < 0.0001) were 0.82 for CrCl _CG versus eGFR _cr , 0.54 for CrCl _CG versus eGFR _cys , 0.72 for CrCl _CG versus eGFR _cr-cys , 0.57 for eGFR _cr versus eGFR _cys , 0.77 for eGFR _cr versus eGFR _cr-cys , and 0.92 for eGFR _cys versus eGFR _cr-cys . Mean creatinine and cystatin C for vancomycin half-life estimations were 2.72 ± 3.48 mg/dL and 2.76 ± 1.1 mg/L, respectively. Mean predicted t _1/2 values from 17 patients with vancomycin monitoring were 33.3 ± 22.7 hours, 35.7 ± 27.5 hours, 43.2 ± 40.9 hours, and 38.7 ± 37.3 hours, respectively ( P = 0.85). Conclusions and Relevance: GFR estimations varied substantially with creatinine-based equations resulting in higher values. Correlation analyses revealed moderate to strong associations between equations. Discrepancies between GFR estimations were more apparent at higher GFRs. The variable GFR estimations led to substantial differences in predicted vancomycin t _1/2 . Clinicians must be aware that dosing disparities may occur based on the GFR estimation used.

Background: Critical care pharmacists are well‐established, valuable members of the intensive care unit interprofessional team with unique skills to perform comprehensive medication management in complex critically ill patients. However, standardized and consequential productivity metrics for critical care pharmacists have not been established.Objective: To characterize the utilization and perception of contemporary critical care pharmacy productivity metrics utilized among individual institutions.Design, Setting, and Participants: An electronic survey was distributed to critical care pharmacist members of the Society of Critical Care Medicine Clinical Pharmacy and Pharmacology Section and the American College of Clinical Pharmacy Critical Care Practice and Research Network.Main Outcomes and Measures: The survey included 23 questions to assess institution demographics, individual respondent demographics, institution practices, and individual respondent perceptions about the value of critical care pharmacist productivity metrics.Results: A total of 204 critical care pharmacists, largely from the United States, responded to the survey between July and November 2022. Institutional metrics captured by more than 50% of the respondents' institutions included order verification rate/number of orders verified (60%), number of clinical interventions (57%), and intravenous to enteral product interchanges (52%). Of these metrics, critical care pharmacists only agreed with the value of the number of clinical interventions, were indifferent to the value of intravenous to oral product interchanges, and disagreed with the value of order verification rate/number of orders verified.Conclusions: Significant discrepancies exist between institutional productivity metric practices and their perceived value and utility among critical care pharmacists.

Background: Midazolam (MZ) is commonly used in critically ill neurosurgical patients. Neuro-penetration of MZ and its metabolite, 1-hydroxy-midazolam (1-OH-MZ), is not well characterized. Objective: This study evaluated correlations between serum and cerebrospinal fluid (CSF) concentrations of MZ and 1-OH-MZ and assessed implications on patient sedation. Methods: Adults in the neurosurgical intensive care unit (ICU) with external ventricular drains receiving MZ via continuous infusion were prospectively studied. Serum and CSF samples were obtained 12-24 h and 72-96 h after initiation, and concentrations were determined in duplicate by high-performance liquid chromatography with tandem mass spectrometry. Bivariate correlation analyses used Pearson coefficient. Results: A total of 31 serum and CSF samples were obtained from 18 subjects. At sampling, mean MZ infusion rate was 3.9 ± 4.4 mg/h, and previous 12-h cumulative dose was 51.4 ± 78.2 mg. Mean concentrations of MZ and 1-OH-MZ in serum and CSF were similar between timepoints. Similarly, ratios of 1-OH-MZ to MZ in serum and CSF remained stable over time. Serum MZ (126.2 ± 89.3 ng/mL) showed moderate correlation (r ² = 0.68, P < 0.001) with serum 1-OH-MZ (17.7 ± 17.6 ng/mL) but not CSF MZ (3.9 ± 2.5 ng/mL; r ² = 0.24, P = 0.005) or CSF 1-OH-MZ (2.5 ± 0.6 ng/mL; r ² = 0.47, P = 0.30). CSF MZ did not correlate with CSF 1-OH-MZ (r ² = 0.003, P < 0.001). Mean serum ratio of 1-OH-MZ to MZ (0.14 ± 0.2 ng/mL) did not correlate with CSF ratio (1.06 ± 0.83 ng/mL; r ² = 0.06, P = 0.19). Concentrations and ratios were unrelated to MZ infusion rate or 12-h cumulative dose. Sedation was weakly correlated with CSF 1-OH-MZ, but not with serum MZ, serum 1-OH-MZ, or CSF MZ. Conclusion and Relevance: Continuous infusions of MZ result in measurable concentrations of MZ and 1-OH-MZ in CSF; however, CSF concentrations of MZ and 1-OH-MZ poorly represent serum concentrations or dosages. Accumulation of MZ and 1-OH-MZ in serum or CSF over time was not evident. Concentrations of MZ and 1-OH-MZ do not predict sedation levels, reinforcing that pharmacodynamic assessments are warranted.

RATIONALE: Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB). OBJECTIVES: The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU. DESIGN: A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting. METHODS: The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance. RESULTS: The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing. CONCLUSIONS: The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient’s existing clinical status.

Study Objective: Severe coronavirus disease 2019 (COVID‐19) increases the risk of thrombotic complications with unfractionated heparin (UFH) as a commonly used agent in managing venous thromboembolism (VTE). The optimal anticoagulation intensity and monitoring parameters in intensive care unit (ICU) COVID‐19 patients remains controversial. The primary study aim was to evaluate the relationship between anti‐Xa and thromboelastography (TEG) reaction (R) time in patients with severe COVID‐19 receiving therapeutic UFH infusions.Design: Single‐center, retrospective study conducted over a 15‐month period (2020–2021).Setting: Academic medical center (Banner University Medical Center Phoenix).Patients: Adult patients with severe COVID‐19 administered therapeutic UFH infusions with one or more corresponding TEG, and anti‐Xa assessments drawn within ≤2 hours of each other were included. The primary end point was the correlation between anti‐Xa and TEG R time. Secondary aims were to describe the correlation between activated partial thromboplastin time (aPTT) and TEG R time, as well as clinical outcomes. Pearson's coefficient was used to evaluate the correlation using a kappa measure of agreement.