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Background: Albumin infusions may be renally protective or harmful in patients with septic shock who have kidney impairment. This can affect the need for renal replacement therapy (RRT) and in-hospital mortality., Research Question: Does the early use of albumin mitigate the need for RRT or in-hospital mortality in patients with septic shock and kidney impairment on hospital admission., Study Design and Methods: This was a retrospective, multicenter, inverse probability-of-treatment weighted cohort study conducted in 220 geographically diverse community and teaching hospitals across the U.S. Adult patients were included if they had septic shock and kidney impairment on hospital admission. Patients were categorized as those who received albumin (within 24h of admission) or no albumin during hospitalization. Proportion of patients with RRT or in-hospital mortality were compared between groups., Results: Of the 9988 patients included in the final cohort, 7929 did not receive albumin and 2059 received albumin. Patients had a mean (SD) age of 67.8 years (14.8), 46.3% were female, and mean (SD) eGFR was 32 (12) ml/min/1.73m 2 on the day of admission. In the weighted cohort, the composite outcome of RRT or in-hospital mortality occurred in 33.8% without albumin and 39.7% with albumin (OR 1.29, 95% CI 1.14 - 1.47, p<0.001). There was no significant difference with 5% albumin (OR 1.07, 95% CI 0.84 - 1.37), but there was a significantly increased risk with 25% albumin (OR 1.43, 95% CI 1.16 - 1.76)., Interpretation: In patients with septic shock and kidney impairment on hospital admission, early albumin use may be associated with an increased composite outcome of RRT or in-hospital mortality. This increased risk is most associated with hyperoncotic rather than iso-oncotic albumin., (Copyright © 2024. Published by Elsevier Inc.)

Background: Acute kidney injury (AKI) is associated with increased mortality and new or progressive chronic kidney disease (CKD). Inflammatory cells play an important role in acute organ injury. We previously demonstrated that serum IL-17A levels were significantly elevated in critically ill patients with AKI and independently associated with hospital mortality. We hypothesize that IL-17A levels are elevated in hospitalized patients with AKI at diagnosis, and sustained elevation after discharge is associated with subsequent CKD incidence or progression., Methods: Observational convenience sampling study of hospital survivors of Stage 2 or 3 AKI and controls without AKI from the ASSESS-AKI study. Patients were classified as progression or non-progression based on a composite of CKD incidence, progression, or end-stage kidney disease. IL-17A levels were evaluated with S-Plex assay (MSD) at 0- (during hospitalization), 3- and 12-month post-discharge, and analyzed along with clinical and biomarker data up to 84 months following discharge., Results: Among 171 AKI and 175 non-AKI participants, IL-17A levels were elevated in AKI vs. non-AKI patients at 0M, 3M and 12M timepoints (p<0.05 for all comparisons). Further, IL-17A levels were elevated in the progression vs. non-progression group at the 3- and 12-month timepoints for outcomes occurring at 3-6 months and 12-84 months, respectively (p<0.05 for both). In adjusted multivariable models, IL-17A levels were not independently associated with progression of kidney disease. IL-17A levels were positively correlated with kidney disease and immune activation biomarkers at all timepoints (p<0.001)., Conclusions: IL-17A was higher in patients with AKI vs. without AKI during hospitalization and up to 1-year post-discharge. IL-17A was higher in patients with progression of kidney disease after hospitalization but not independently associated with subsequent progression of kidney disease in fully adjusted models., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Purpose: Pharmacy residents often aspire to develop research skills through conducting a research project. Project publication rates among pharmacy residents are variable and at times low; however, previous studies have been limited to specific geographic regions and timeframes. This study sought to conduct a systematic review and meta-analysis to determine the proportion of pharmacy resident research projects published in the peer-reviewed literature., Methods: A systematic review of PubMed MEDLINE, Embase, and the Web of Science Core Collection was performed from database inception to May 25, 2023. Articles were included if they were full-text, peer-reviewed manuscripts of original research presenting observational data regarding pharmacy resident research project publication rates. Data extraction and assessment of risk of bias were conducted by 2 independent reviewers. A proportional meta-analysis using a random effects model of the included studies was conducted to generate a pooled, overall proportion., Results: The search yielded 5,225 records and 12 articles that met the inclusion criteria. All studies were retrospective and observational. Risk of selection and cohort identification biases was "high," whereas that of detection and timeframe biases was "low." The included studies represented 6,990 resident research projects, 777 of which were published in the peer-reviewed literature. Publication rates across individual studies ranged from 1.8% to 36.2%. The pooled proportion (scale of 0 to 1) of projects published was 0.13 (95% CI, 0.09-0.19)., Conclusion: Pharmacy resident research project publication rates are low at 13%. Furthermore, studies reporting project publication rates over time suggest a neutral or negative trend in publication rates despite an exponential increase in the number of pharmacy residents., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Describe continuous infusion (CI) ketamine practices in pediatric intensive care units (PICUs) and evaluate its effect on pain/sedation scores, exposure to analgesics/sedatives, and adverse effects (AEs)., Methods: Multicenter, retrospective, observational study in children <18 years who received CI ketamine between 2014 and 2017. Time spent in goal pain/sedation score range and daily cumulative doses of analgesics/sedatives were compared from the 24 hours (H) prior to CI ketamine to the first 24H and 25-48H of the CI. Adverse effects were collected over the first 7 days of CI ketamine., Results: Twenty-four patients from 4 PICUs were included; median (IQR) age 7 (1-13.25) years, 54% female ( n  = 13), 92% intubated ( n  = 22), 25% on CI vasopressors ( n  = 6), and 33% on CI paralytics ( n  = 8). Ketamine indications were analgesia/sedation ( n  = 21, 87.5%) and status epilepticus ( n  = 3, 12.5%). Median starting dose was 0.5 (0.48-0.70) mg/kg/hr and continued for a median of 2.4 (1.3-4.4) days. There was a significant difference in mean proportion of time spent within goal pain score range (24H prior: 74% ± 14%, 0-24H: 85% ± 10%, and 25-48H: 72% ± 20%; p =0.014). A significant reduction in median morphine milligram equivalents (MME) was seen (24H prior: 58 (8-195) mg vs. 0-24H: 4 (0-69) mg and p =0.01), but this was not sustained (25-48H: 24 (2-246) mg and p =0.29). Common AEs were tachycardia (63%), hypotension (54%), secretions/suctioning (29%), and emergence reactions (13%)., Conclusions: Ketamine CI improved time in goal pain score range and significantly reduced MME, but this was not sustained. Larger prospective studies are needed in the pediatric population., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2024 Christine M. Groth et al.)

Purpose: Each year, roughly 5,000 residents conduct research on clinical and practice-based topics to meet the requirements of the ASHP residency standards related to research and project management. Several investigators have evaluated residency research project publication rates, but redundancy among projects has not been evaluated. The primary objective of this study was to determine the rate of redundancy among pharmacy residency research projects., Methods: This was a retrospective cohort analysis of abstracts accepted to various regional pharmacy residency conferences from 2017 through 2020. Each abstract was placed in a pharmacy domain by therapeutic area. The categorized data for each year were then further evaluated to identify clinical categories for the year. Topics were labeled as redundant if at least 10 projects fell into the same focus area within a clinical category. Descriptive statistics were used to quantify the incidence of redundancy each year., Results: A total of 4,027 abstracts were included. The most common pharmacy domains were infectious disease, internal medicine, and benefit of pharmacy services. Overall, 8.2% projects (332 of 4,027) were categorized as redundant. The most common focus areas were rapid diagnostics, opioid reduction protocols, and vancomycin area-under-the-curve vs trough monitoring., Conclusion: Pharmacy residency research projects encompassed topics across a wide range of pharmacotherapy areas. Approximately 1 in 12 projects was redundant. This is likely because the project addressed a "hot topic" in practice and may represent an opportunity for institutions to collaborate to optimize project efficiency and impact., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: The American College of Clinical Pharmacy (ACCP) Pharmacotherapy Didactic Curriculum Toolkit has been used by colleges and schools of pharmacy as a guide for curricular development and revisions since its inaugural publication in 2009. The toolkit was last revised and updated by the 2019 Publications Committee., Objectives: The 2023 ACCP Publications Committee was charged with reviewing the 2019 Update to the ACCP Pharmacotherapy Didactic Curriculum Toolkit to determine any necessary revisions/updates., Methods: The committee revised tier classifications, shifting the focus of the 2023 toolkit to content within the Pharm.D. curriculum. Multiple literature sources were reviewed to assess conditions for inclusion in the 2023 toolkit, and external feedback was solicited from various practice disciplines. All topics were voted on by a simple majority rule during virtual meetings or by electronic votes., Results: There are a total of 231 topics in the 2023 toolkit, a decrease of 77 (23.2%) from the 2019 edition. Topics in each tier are as follows: 68 as tier 1 (29%), 111 as tier 2 (48%), and 52 as tier 3 (23%). Although some topics were removed completely, others were combined with other line items or revised, which may further minimize curricular overload. Similar to the 2016 and 2019 toolkits, many tier 2 topics remain in the 2023 toolkit, emphasizing the continued need for additional training through postgraduate residencies or fellowships (or "on-the-job" equivalent experiences), board certifications, and various certificate training programs., Conclusion: The 2023 ACCP Pharmacotherapy Didactic Curriculum Toolkit is designed to assist individual faculty and colleges and schools of pharmacy with curricular development and revisions. It will continue to be reviewed every 3 years to identify needed revisions on the basis of the pharmacist's evolving role, advances in therapeutics and pharmacy practice, and changes to accreditation standards and recognized professional competencies., Competing Interests: Conflicts of Interest: All other authors declare no conflicts of interest.

Background & Aims: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis., Methods: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other)., Results: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all)., Conclusion: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed., Impact and Implications: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: The job of a critical care pharmacy specialist has evolved to include quality improvement and administrative tasks. As such, the American Society of Health-System Pharmacists (ASHP) highlights specific goals and objectives to ensure post-graduate year two (PGY2) critical care residents are sufficiently trained to perform these tasks. The PGY2 critical care pharmacy residency leadership at the University of Kentucky sought to develop a four-week learning experience entitled, "Critical Care Administration / Medication Use Quality & Outcomes," as a unique rotation to capture these requirements and activities., Objectives: The focus of this commentary is to serve as a guide for other residency programs to develop such a rotation, highlight resulting resident contributions to the department, describe perceived benefits of this rotation for residents, and highlight how this rotation impacted graduated residents' early years as practitioners., Conclusions: This learning experience is pivotal to providing a more balanced view of the entire medication use process and the healthcare ecosystem during a specialty residency. PGY2 critical care residents can gain valuable experiences away from the bedside that better prepare them for future tasks in addition to patient care that will be expected of them as clinical pharmacists., Competing Interests: Conflict of interest statement: The authors declare no conflicts of interest.

Dexmedetomidine is a selective alpha-2 adrenergic agonist utilized for sedation in critically ill patients. 1 We present the case of a morbidly obese critically ill patient who experienced profound hyperthermia, with a maximum temperature of 41.4°C, hours after starting a dexmedetomidine infusion that was otherwise not explained by her clinical diagnoses. The hyperthermia resolved hours following cessation of the infusion. Dexmedetomidine was assessed as probable in terms of causing this adverse effect. Dexmedetomidine may be associated not only with low-grade fever, but as demonstrated in our case, it may be associated with significant temperature elevations requiring cessation of therapy to restore normothermia.

Abstract: AKI occurs frequently in critically ill patients. Patients with AKI, including those who require KRT, experience multiple pharmacokinetic and pharmacodynamic perturbations that dynamically influence medication effectiveness and safety. Patients with AKI may experience both subtherapeutic drug concentrations, which lead to ineffective therapy, and supratherapeutic drug concentrations, which increase the risk for toxicity. In critically ill patients with AKI not requiring KRT, conventional GFR estimation equations, especially those based on serum creatinine, have several limitations that can limit the accuracy when used for medication dosing. Alternative methods to estimate kidney function may be informative, including use of measured urinary creatinine clearance, kinetic eGFR, and equations that integrate novel kidney biomarkers. For critically ill patients with AKI requiring KRT, physicochemical properties of the drug, the KRT prescription and circuit configuration, and patient-specific factors each contribute to medication clearance. Evidence-based guidance for medication dosing during AKI requiring KRT is often limited. A working knowledge of the basic tenets of drug elimination during KRT can provide a framework for how to approach decision making when the literature is lacking. Iterative re-evaluation of a patient's progress toward therapeutic goals with a medication must occur over the arc of critical illness, including and especially in the setting of dynamic kidney function., (Copyright © 2023 by the American Society of Nephrology.)

Introduction: Sepsis is a life-threatening medical emergency and a leading cause of morbidity and mortality worldwide. Reductions in time to antibiotics in patients presenting with sepsis or septic shock are associated with reduced mortality, and Surviving Sepsis Campaign guidelines recommend antibiotics within one hour of recognition. Pharmacists are well-equipped to help navigate the therapeutic and operational challenges associated with achieving this goal., Objectives: To assess the association of pharmacist involvement in sepsis response with time to antibiotics in hospitalized patients with sepsis and septic shock., Methods: A systematic review of the following databases was conducted: PubMed/MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Studies must have included a designated role of an individual pharmacist in the management of sepsis or septic shock and not be considered an operational change. The primary outcome of interest was time to antibiotic administration, with secondary outcomes including intensive care unit (ICU) and hospital length of stay as well as in-hospital mortality., Results: We identified 10 studies including 1772 patients with sepsis or septic shock that evaluated a sepsis response in which a pharmacist was included. Studies included patients in the ICU, emergency department, and hospital ward setting. Seven studies demonstrated a significant reduction in time to antibiotics, with two other studies supporting this conclusion in extrapolation or sensitivity analysis. There was not a consistent reduction in ICU or hospital length of stay nor in-hospital mortality between those interventions involving a pharmacist compared with their defined control groups., Conclusion: Pharmacist involvement in sepsis response, often as part of a multi-professional team-based approach to sepsis care, is associated with a reduced time to antibiotic administration for hospitalized patients with sepsis or septic shock., Competing Interests: Conflict of Interest Statement: The authors declare no conflicts of interest.

Background: During continuous renal replacement therapy (CRRT), anticoagulants are recommended for patients at low risk of bleeding and not already receiving systemic anticoagulants. Current anticoagulants used in CRRT in the US are systemic heparins or regional citrate. To better understand use of anticoagulants for CRRT in the US, we surveyed nephrologists and critical care medicine (CCM) specialists., Methods: The survey contained 30 questions. Respondents were board certified and worked in intensive care units of academic medical centers or community hospitals., Results: 150 physicians (70 nephrologists and 80 CCM) completed the survey. Mean number of CRRT machines in use increased ∼30% from the pre-pandemic era to 2022. Unfractionated heparin was the most used anticoagulant (43% of estimated patients) followed by citrate (28%). Respondents reported 29% of patients received no anticoagulant. Risk of hypocalcemia (52%) and citrate safety (42%) were the predominant reasons given for using no anticoagulant instead of citrate in heparin-intolerant patients. 84% said filter clogging was a problem when no anticoagulant was used, and almost 25% said increased transfusions were necessary. Respondents using heparin ( n  = 131) considered it inexpensive and easily obtainable, although of moderate safety, citing concerns of heparin-induced thrombocytopenia and bleeding. Anticoagulant citrate dextrose solution was the most used citrate. Respondents estimated that 37% of patients receiving citrate develop hypocalcemia and 17% citrate lock., Conclusions: Given the increased use of CRRT and the lack of approved, safe, and effective anticoagulant choices for CRRT in the US, effective use of current and other anticoagulant options needs to be evaluated.

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., Competing Interests: Dr. Newsome has received research funding through the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR002378 and KL2TR002381. Dr. Rech’s institution received funding from Spero Pharmaceuticals; she received funding from Harm Reduction Therapeutics. Dr. DePriest received funding from Baxter. Dr. Flannery’s institution received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the American Society of Nephrology, and La Jolla Pharmaceutical Company. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: To evaluate the effect of renin-angiotensin system (RAS) inhibiting medications prior to admission on the severity of kidney injury in patients presenting with sepsis-associated acute kidney injury (SA-AKI)., Materials and Methods: A single center, retrospective cohort study of critically ill adult patients admitted with diagnoses of both sepsis and AKI. RAS inhibition was defined as angiotensin converting enzyme inhibitors or angiotensin receptor blockers. The primary outcome was Kidney Disease: Improving Global Outcomes stage AKI upon hospital admission., Results: Of 707 individuals studied, patients receiving RAS inhibition prior to admission (vs. those not) had more stage 3 AKI (40.1% vs. 28.7%; p = 0.008) and more frequently reached stage 3 AKI during the first week (49.8% vs. 41.1%; p = 0.047). In an adjusted multinomial regression model, patients receiving RAS inhibition (vs. those not) had an increased relative risk of presenting with stage 3 AKI on admission (vs. stage 1 AKI reference): RRR 2.32 (95% CI 1.50-3.59). Similar findings were observed in a propensity score matched analysis., Conclusion: Patients receiving RAS inhibition (vs. those not) prior to an admission with SA-AKI presented with more severe AKI on admission and during the first week. Hospital mortality and kidney function at discharge were similar between groups., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Interleukin-17 (IL-17) antagonism in rats reduces the severity and progression of AKI. IL-17-producing circulating T helper-17 (TH17) cells is increased in critically ill patients with AKI indicating that this pathway is also activated in humans. We aim to compare serum IL-17A levels in critically ill patients with versus without AKI and to examine their relationship with mortality and major adverse kidney events (MAKE)., Methods: Multicenter, prospective study of ICU patients with AKI stage 2 or 3 and without AKI. Samples were collected at 24-48 h after AKI diagnosis or ICU admission (in those without AKI) [timepoint 1, T1] and 5-7 days later [timepoint 2, T2]. MAKE was defined as the composite of death, dependence on kidney replacement therapy or a reduction in eGFR of ≥ 30% from baseline up to 90 days following hospital discharge., Results: A total of 299 patients were evaluated. Patients in the highest IL-17A tertile (versus lower tertiles) at T1 had higher acuity of illness and comorbidity scores. Patients with AKI had higher levels of IL-17A than those without AKI: T1 1918.6 fg/ml (692.0-5860.9) versus 623.1 fg/ml (331.7-1503.4), p < 0.001; T2 2167.7 fg/ml (839.9-4618.9) versus 1193.5 fg/ml (523.8-2198.7), p = 0.006. Every onefold higher serum IL-17A at T1 was independently associated with increased risk of hospital mortality (aOR 1.35, 95% CI: 1.06-1.73) and MAKE (aOR 1.26, 95% CI: 1.02-1.55). The highest tertile of IL-17A (vs. the lowest tertile) was also independently associated with higher risk of MAKE (aOR 3.03, 95% CI: 1.34-6.87). There was no effect modification of these associations by AKI status. IL-17A levels remained significantly elevated at T2 in patients that died or developed MAKE., Conclusions: Serum IL-17A levels measured by the time of AKI diagnosis or ICU admission were differentially elevated in critically ill patients with AKI when compared to those without AKI and were independently associated with hospital mortality and MAKE., (© 2022. The Author(s).)

Background: Sepsis-associated acute kidney injury (SA-AKI) is associated with significant morbidity and mortality. Immune dysregulation is a hallmark of sepsis, with important contributions to organ dysfunction including injury and repair mechanisms in AKI. Macrolide antibiotics, such as azithromycin, have previously demonstrated in preclinical models a myriad of immunomodulatory effects that may benefit critically ill patients with SA-AKI. The aim of this study was to determine if early receipt of azithromycin in SA-AKI is associated with a reduction in major adverse kidney events (MAKE) at hospital discharge., Methods: This was a single center, retrospective cohort study of critically ill adult patients with SA-AKI. Early exposure to azithromycin was defined as receipt of one or more doses within 48 h of a hospital admission with SA-AKI. The primary outcome of MAKE assessed at hospital discharge was the composite of death, requirement for kidney replacement therapy, or a decline in estimated glomerular filtration rate of 25% or more. Multivariable logistic regression was used to account for potential confounders in the assessment., Results: Of 737 included patients with SA-AKI, 152 (20.6%) received azithromycin. Patients that received early azithromycin were less likely to experience MAKE at hospital discharge when compared to those patients not receiving azithromycin: 38.8% versus 48.4% (P = 0.035). In multivariable logistic regression, receipt of azithromycin was independently associated with a decreased odds of MAKE at hospital discharge (aOR 0.62, 95% CI 0.41-0.93)., Conclusions: Early exposure to azithromycin in SA-AKI is independently associated with lower odds of MAKE at hospital discharge., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Introduction: Consensus guidelines recommend targeting a vancomycin area under the curve to minimum inhibitory concentration (AUC 24 :MIC) ratio of 400-600 to improve therapeutic success and reduce nephrotoxicity. Although guidelines specify either Bayesian software or first-order equations may be used to estimate AUC 24 , there are currently no large studies directly comparing these methods., Objective: To compare calculated vancomycin AUC 24 using first-order equations with two-drug concentrations at steady state to Bayesian two- and one-concentration estimations., Methods: This was a single-center, retrospective cohort study of 978 adult hospitalized patients receiving intravenous vancomycin between 2017 and 2019. Patients were included if they received at least 72 h of vancomycin and had two-serum drug concentrations obtained. AUC 24 was calculated using first-order analytic (linear), Bayesian two-concentration, and Bayesian one-concentration methods for each patient. The InsightRx™ software platform was used to calculate Bayesian AUC 24 . Pearson's correlation and clinical agreement (based on AUC 24  classified as subtherapeutic, therapeutic, or supratherapeutic) were used to assess agreement between methods. Bland-Altman plots were used to assess mean difference (MD) and 95% limits of agreement (LOA)., Results: Excellent agreement was observed between linear and Bayesian two-concentration methods (r = 0.963, clinical agreement = 87.4%) and Bayesian two-concentration and one-concentration methods (r = 0.931, clinical agreement = 88.5%); however, a degree of variability was noted with 95% LOA -99 to 76 (MD = -11.5 mg*h/L) and -92 to 113 (MD = -10.4 mg*h/L), for the respective comparisons. The agreement between linear and Bayesian one-concentration approaches was less than prior comparisons (r = 0.823, clinical agreement = 76.8%) and demonstrated the greatest amount of variability with 95% LOA -197 to 153 (MD = -21.9 mg*h/L)., Conclusions: Linear and Bayesian two-concentration methods demonstrated high-level agreement with acceptable variability and may be considered comparable to estimate vancomycin AUC 24 . As linear and Bayesian one-concentration methods demonstrated significant variability and suboptimal agreement, concerns exist surrounding the interchangeability of these methods in clinical practice, particularly at higher extremes of AUC 24 ., (© 2022 Pharmacotherapy Publications, Inc.)

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: 68.9% [66.7-72.6%], 0-24 hr: 78.6% [74.3-82.5%], 25-48 hr: 80.3% [74.6-84.3%]; p < 0.001) and time spent within goal sedation score (24 hr prior: 57.1% [52.5-60.0%], 0-24 hr: 64.1% [60.7-67.2%], 25-48 hr: 68.9% [65.5-79.5%]; p < 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 [25-400], 0-24 hr: 118 [10-363], 25-48 hr: 80 [5-328]; p < 0.005), midazolam (mg) equivalents (24 hr prior: 11 [4-67], 0-24 hr: 6 [0-68], 25-48 hr: 3 [0-57]; p < 0.001), propofol (mg) (24 hr prior: 942 [223-4,018], 0-24 hr: 160 [0-2,776], 25-48 hr: 0 [0-1,859]; p < 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 [276-1,925], 0-24 hr: 285 [0-1,283], 25-48 hr: 0 [0-826]; p < 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% [17.0-47.0%], 0-24 hr: 39.5% [27.0-43.8%], 25-48 hr: 0% [0-43.7%]; p = 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study., Conclusions and Relevance: There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: Early recognition and treatment are critical to improving sepsis outcomes. We sought to identify the frequency and types of encounters that patients have with the healthcare system in the week prior to a sepsis hospitalization., Data Sources: PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and the Cochrane Library., Study Selection: Observational cohort studies of patients hospitalized with sepsis or septic shock that were assessed for an outpatient or emergency department encounter with the healthcare system in the week prior to hospital admission., Data Extraction: The primary outcome was the proportion of patients with a healthcare encounter in the time period assessed (up to 1 week) prior to a hospitalization with sepsis., Data Synthesis: Six retrospective observational studies encompassing 6,785,728 sepsis admissions were included for evaluation, ranging from a 263-patient single-center cohort to a large database evaluating 6,731,827 sepsis admissions. The average (unweighted) proportion of patients having an encounter with the healthcare system in the week prior to a sepsis hospitalization was 32.7% and ranged from 10.3% to 52.9%. These encounters commonly involved presentation or potential symptoms of infectious diseases, antibiotic prescriptions, and appeared to increase in frequency closer to a sepsis hospitalization admission. No consistent factors were identified that distinguished a healthcare encounter as more or less likely to precede a sepsis hospitalization in the subsequent week., Conclusions: Patients that present to the hospital with sepsis are frequently evaluated in the healthcare system in the week prior to admission. Further research is necessary to understand if these encounters offer earlier opportunities for intervention to prevent the transition from infection to sepsis, whether they merely reflect the comorbidities of sepsis patients with a high baseline rate of healthcare encounters, or the declining trajectory of a patient's overall health in response to infection., Competing Interests: Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccejournal). The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: The combination of vancomycin/piperacillin-tazobactam is associated with increases in serum creatinine compared to other antibiotic combinations in the treatment of infections for hospitalized patients. However, the available literature is limited to the study of incident acute kidney injury (AKI). The combination has not been evaluated in patients with AKI already present and the degree to which the trajectory of AKI is influenced by this combination is unknown., Methods: This was a single center, retrospective cohort study of adult patients with sepsis and AKI present on admission prescribed a combination of vancomycin with either piperacillin-tazobactam or cefepime within the first 3 days of admission. The primary outcome was maximum serum creatinine observed within days 2-7 of the hospital stay. Subsequent kidney outcomes were evaluated at one week and hospital discharge., Results: Of 480 patients with sepsis and AKI who met inclusion criteria, 288 (60%) received vancomycin/piperacillin-tazobactam, and 192 (40%) received vancomycin/cefepime. Patients were well-matched on clinical factors, including severity of illness, stage of AKI, exposure to other nephrotoxins, and durations of antimicrobial therapy. There were no differences in AKI trajectory during the first week as assessed by maximum serum creatinine (2.1 (1.4-3.5) mg/dl vs. 2.1 (1.4-3.0) mg/dl; p=0.459) and AKI progression (24.0% vs. 23.4%; p=0.895). No differences were observed with other kidney related outcomes, including the need for dialysis (14.6% vs. 13.0%; p=0.628) or major adverse kidney events at hospital discharge (48.3% vs. 47.9%; p=0.941)., Conclusions: In patients with sepsis and AKI, the combination of vancomycin/piperacillin-tazobactam compared to vancomycin/cefepime was not associated with higher serum creatinine values or AKI progression in the week following ICU admission., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions., Design: A multicenter, prospective, observational study was performed between August 2018 and January 2019., Setting: Community hospitals and academic medical centers in the United States., Participants: ICU clinical pharmacists., Interventions: Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance., Measurements and Main Results: Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated $23,404,089 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established sections was adverse drug event prevention (5,777 interventions; $5,822,539 CA), resource utilization (12,630 interventions; $4,491,318), individualization of patient care (29,284 interventions; $9,680,036 cost avoidance), prophylaxis (1,639 interventions; $1,414,465 cost avoidance), hands-on care (1,828 interventions; $1,339,621 cost avoidance), and administrative/supportive tasks (4,768 interventions; $656,110 cost avoidance). Mean cost avoidance was $418 per intervention, $845 per patient day, and $7,435 per ICU pharmacist shift. The annualized cost avoidance from an ICU pharmacist is $1,784,302. The potential monetary cost avoidance to pharmacist salary ratio was between $3.3:1 and $9.6:1., Conclusions: Pharmacist involvement in the care of critically ill patients results in significant avoidance of healthcare costs, particularly in the areas of individualization of patient care, adverse drug event prevention, and resource utilization. The potential monetary cost avoidance to pharmacist salary ratio employing an ICU clinical pharmacist is between $3.3:1 and $9.6:1., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: To compare the ventilatory and clinical outcomes associated with a fixed-dose cisatracurium infusion versus a titrated infusion strategy in patients with Acute Respiratory Distress Syndrome (ARDS)., Materials and Methods: Single-center, retrospective, cohort study in a medical ICU of a tertiary care academic medical center. Adult patients ≥18 years old with a continuous infusion of cisatracurium for ≥12 h for treatment of ARDS were included. The primary outcome was the PaO2 /FiO2 ratio assessed at 24 and 48 h following cisatracurium initiation. Secondary outcomes included amount of average dose of drug administered, 28-day ventilator-free days, LOS, and hospital mortality., Results: 167 patients were included; median baseline PaO2/FiO2 was 97 (76-146), median SOFA score of 9 (7-11), and ICU mortality was 71/167 (43%). In a mixed-effects model, fixed dose and titrated cisatracurium associated with similar changes in PaO2/FiO2 assessed at 24 and 48 h (p = 0.316). Fixed-dose was associated with a >3-fold increase in drug exposure (average dose 6.4 (5.4-8.0) vs. 2.0 (1.5-2.8) mcg/kg/min; p < 0.001, respectively). No differences were observed in secondary clinical endpoints., Conclusion: Fixed-dose cisatracurium was associated with similar ventilatory and clinical outcomes compared to titrated strategy, yet it was associated with a 3-fold increase in dose administered., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients., Methods: Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5-7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline., Results: Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without., Conclusions: In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality., (© 2021. The Author(s).)

Ascorbic acid (AA) is an essential nutrient with many physiologic roles not limited to the prevention of scurvy. Beyond its role as a supplement, it has gained popularity in the acute care setting as an inexpensive medication for a variety of conditions. Because of limitations with absorption of oral formulations and reduced serum concentrations observed in acute illness, intravenous (IV) administration, and higher doses, may be needed to produce the desired serum concentrations for a particular indication. Following a PubMed search, we reviewed published studies relevant to AA in the acute care setting and summarized the results in a narrative review. In the acute care setting, AA may be used for improved wound healing, improved organ function in sepsis and acute respiratory distress syndrome, faster resolution of vasoplegic shock after cardiac surgery, reduction of resuscitative fluids in severe burn injury, and as an adjunctive analgesic, among other uses. Each indication differs in its level of evidence supporting exogenous administration of AA, but overall, AA was not commonly associated with adverse effects in the identified studies. Use of AA remains an active area of clinical investigation for various indications in the acute care patient population., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background: While albumin has not been shown to reduce mortality in sepsis and septic shock, a tertiary analysis of a large trial suggested that it may reduce the duration of vasopressor use in septic shock., Objective: We sought to test if 25% albumin administration was associated with reduced cumulative vasopressor use in septic shock in a real-world setting., Methods: This was a retrospective, propensity score-matched cohort study of septic shock in which patients receiving albumin were compared with a matched cohort of those not receiving albumin. The primary outcome was days alive and free of vasopressors., Results: The matched cohort included 335 patients who received albumin and 335 who did not. The days alive and free of vasopressors were similar between the albumin and no albumin groups: 17.4 (0-24.8) versus 19.4 (0-25.3); P = 0.160. Similarly, in-hospital mortality was no different between groups (46.9% vs 44.8%; P = 0.587). Receipt of albumin was associated with fewer ventilator-free and intensive care unit (ICU)-free days: 0 (0-19) versus 11 (0-23), P = 0.007, and 0 (0-18) versus 10.6 (0-22.1), P = 0.002, respectively., Conclusion and Relevance: Albumin use in septic shock was not associated with additional days alive and free of vasopressors or in-hospital mortality. The finding of fewer ventilator- and ICU-free days may reflect selection of patients who were critically ill for longer periods of time before or after albumin administration. Additional study is needed to clarify the impact that timing may have on the effectiveness of albumin in septic shock.

To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions., Design: A multicenter, prospective, observational study was performed between August 2018 and January 2019., Setting: Community and academic hospitals in the United States., Participants: Emergency medicine clinical pharmacists., Interventions: Recommendations classified into one of 38 intervention categories associated with cost avoidance., Measurements and Main Results: Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions; $2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122; $1,787,170), prophylaxis (24; $22,804), hands-on care (3,533; $2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was $538.61 per intervention, $875.60 per patient, and $8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between $1.4:1 and $10.6:1., Conclusions: Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between $1.4:1 and $10.6:1., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Rationale & Objective: Sepsis-associated acute kidney injury often leads to acute kidney disease (AKD), predisposing patients to long-term complications such as chronic kidney disease (CKD), kidney failure with replacement therapy (KFRT), or mortality. Risk stratification of patients with AKD represents an opportunity to assist with prognostication of long-term kidney complications., Study Design: Single-center retrospective cohort., Setting & Participants: 6,290 critically ill patients admitted to the intensive care unit with severe sepsis or septic shock. Patients were separated into cohorts based on incident acute kidney injury or not, and survivors identified who were alive and free of KFRT up to 90 days., Predictors: AKD stage (0A, 0C, or ≥1) using the last serum creatinine concentration available by discharge or up to 90 days postdischarge., Outcome: Time to development of incident CKD, progression of CKD, KFRT, or death., Analytical Approach: Multivariable Cox proportional hazards models., Results: Patients surviving kidney injury associated with sepsis often fail to return to baseline kidney function by discharge: 577/1,231 (46.9%) with stage 0C or 1 or greater AKD. AKD stage was significantly associated with the composite primary outcome. Stages 0C AKD and 1 or greater AKD were significantly and progressively associated with the primary outcome when compared with stage 0A AKD (adjusted HR [aHR], 1.74; 95% CI, 1.32-2.29, and aHR, 3.25; 95% CI, 2.52-4.20, respectively). Additionally, stage 1 or greater AKD conferred higher risk above stage 0C AKD (aHR, 1.87; 95% CI, 1.44-2.43). CKD incidence or progression and KFRT, more so than mortality, occurred with greater frequency in higher stages of AKD., Limitations: Retrospective design, single center, exclusion of patients with KFRT within 90 days of discharge, potential ascertainment bias, and inability to subclassify above AKD stage 1., Conclusions: Risk stratification using recommended AKD stages at hospital discharge or shortly thereafter associates with the development of long-term kidney outcomes following sepsis-associated acute kidney injury., (© 2021 The Authors.)

Background: Evidence suggests the standard vancomycin trough goal of 15 to 20 mg/L for serious Staphylococcus aureus infections is associated with acute kidney injury, whereas appropriate monitoring of 24-hour area under the curve (AUC) may decrease nephrotoxicity. As a result, institutions have transitioned to AUC monitoring, the predictive pharmacokinetic/pharmacodynamic parameter of vancomycin to improve safety outcomes. However, this method may require increased pharmacist time and effort. Pharmacist perception of the practice change is largely unknown and warrants investigation., Methods: An electronic survey was disseminated via e-mail to pharmacists 5 months post-AUC implementation. Items of interest were focused on pharmacist perception, including quantity of patients monitored using AUC, justification of the practice change, differences in efficacy and safety, and changes in monitoring time requirements., Results: The pharmacist survey was distributed to 196 pharmacists and 84 responded (43% response rate). Eighty-one pharmacists had monitored patients using AUC methods. Sixty-nine percent of these respondents perceived the change to result in increased or slightly increased patient safety, 27% described no difference, and 4% stated safety was decreased or slightly decreased. Forty-two percent perceived the transition to result in increased or slightly increased efficacy, while 48% noted no difference and 10% responded that efficacy was decreased or slightly decreased. Pharmacists stated the creation of an institutional calculator decreased the time required to calculate AUC., Conclusion: After the change to AUC monitoring, pharmacists perceived improvements in safety outcomes while efficacy was at least similar if not increased.

Background: While vancomycin loading doses may facilitate earlier pharmacokinetic-pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults., Methods: Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent., Results: There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% versus 72.8%; p  = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences., Conclusion: Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Acute care pharmacists play an integral role in identifying drug-drug interactions that may predispose patients to QT prolongation. Although most pharmacists are equipped with a baseline understanding of drug interactions and the risks of QTc prolongation, few understand the limitations of QTc calculation and interpretation. In this commentary, we put forth the notion that at times health care providers, including pharmacists, place an overemphasis on the QTc interval. In the context of using the QTc to guide pharmacotherapy decisions, unintended consequences may include a cascade of effects leading to delays in treatment, suboptimal medication selection, alert fatigue, and overutilization of resources.

Background: Early attainment of target area under the curve (AUC) to minimum inhibitory concentration (MIC) ratios have been associated with clinical success, as well as lower incidence of acute kidney injury (AKI), in patients receiving vancomycin for methicillin-resistant Staphylococcus aureus (MRSA). Critically ill patients are particularly vulnerable to poor outcomes from infection and face multiple risk factors for AKI, thus early precision dosing of vancomycin is vital in this population. We hypothesized that a personalized dosing approach, using vancomycin levels obtained after the first dose to guide further dosing, would be superior to empiric dosing in terms of AUC target attainment assessed at steady state (SS)., Methods: A retrospective cohort study of 66 critically ill adult patients admitted to the medical intensive care unit without AKI and receiving vancomycin with at least two SS concentrations obtained for AUC calculation was performed. Patients were separated into cohorts based on whether they had two concentrations assessed after the first dose of vancomycin and were subsequently dosed based on personalized pharmacokinetic calculations (first-dose kinetics) or whether they were empirically dosed using population estimates. The primary outcome was AUC target attainment (400-600 mg hour/L) at SS., Results: Compared with patients receiving empiric dosing by population estimates, using first-dose kinetics to guide subsequent dosing resulted in significantly greater AUC target attainment at SS (58.6% first-dose vs 32.4% empiric; p=0.033). Patients dosed empirically yielded more variable AUC values across a wide range compared with the first-dose kinetics group (coefficient of variation 40.7% empiric vs 26.1% first-dose). There was no difference in AKI up to 48 hours after SS concentrations between the two dosing schemes., Conclusions: A dosing strategy using two vancomycin serum concentrations after the first dose and calculating personalized pharmacokinetic parameters to guide subsequent dosing is associated with greater AUC target attainment at SS compared with empiric dosing of vancomycin in critically ill adults with relatively stable renal function., (© 2020 Pharmacotherapy Publications, Inc.)

Due to the inconsistent correlation of vancomycin trough concentrations with 24-hour area under the curve (AUC) and a desire to reduce rates of vancomycin-associated acute kidney injury, an institutional guideline was implemented by the Antimicrobial Stewardship Team in September 2017 to monitor vancomycin using AUC. Three stages were utilized to organize the process: preparation, implementation, and evaluation. The preparation stage was used to present literature to key stakeholders, and pharmacy meetings focused on the development of a dosing and monitoring guideline. Along with institution-wide education, the implementation stage included information technology development and support. The evaluation stage was comprised of quality improvement and clinical research. Future plans include dissemination of the results and analyses. Numerous lessons were learned due to barriers experienced during the process, but the transition was successful.

Background: Several biomarkers of AKI have been examined for their ability to predict AKI before serum creatinine. Few studies have focused on using kidney biomarkers to better predict major adverse kidney events (MAKE), an increasingly used composite outcome in critical care nephrology research., Methods: Single-center prospective study collecting blood and urine samples from critically ill patients with AKI Kidney Disease Improving Global Outcomes stage 2 or above, and matched controls from a single, tertiary care intensive care unit (ICU). Samples were collected at 24-48 hours after AKI diagnosis (patients) or ICU admission (controls), 5-7 days later, and 4-6 weeks after discharge for patients with AKI. The primary outcome of interest was MAKE at hospital discharge (MAKE-DC), consisting of the composite end point of death, RRT dependence, or a decrease in estimated glomerular filtration to <75% of baseline., Results: Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary cystatin C, and urinary kidney injury molecule-1 early in the AKI or ICU course were all significantly higher in patients with MAKE-DC compared with those not experiencing MAKE-DC. Additionally, serum/urinary NGAL and serum cystatin C measurements at the first time point remained significantly associated with MAKE events at 3, 6, and 12 months. Serum cystatin C, and to a lesser extent serum NGAL, significantly improved upon a logistic regression clinical prediction model of MAKE-DC (AUROC 0.94 and 0.87 versus 0.83; P =0.001 and P =0.02, respectively). Patients without MAKE-DC experienced a greater decline in serum NGAL from first to second measurement than those patients experiencing MAKE-DC., Conclusions: Early measures of kidney biomarkers in patients who are critically ill are associated with MAKE-DC. This relationship appears to be greatest with serum NGAL and cystatin C, which display additive utility to a clinical prediction model. Trending serum NGAL may also have utility in predicting MAKE-DC., Competing Interests: J. Lambert reports honoraria from SAS Institute, outside the submitted work. A.H. Flannery is supported by KidneyCure/American Society of Nephrology and the La Jolla Pharmaceutical company, outside the submitted work. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Introduction: Critically ill patients and their pharmacokinetics present complexities often not considered by consensus guidelines from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Prior surveys have suggested discordance between certain guideline recommendations and reported infectious disease pharmacist practice. Vancomycin dosing practices, including institutional considerations, have not previously been well described in the critically ill patient population., Objectives: To evaluate critical care pharmacists' self-reported vancomycin practices in comparison to the 2009 guideline recommendations and other best practices identified by the study investigators., Methods: An online survey developed by the Research and Scholarship Committee of the Clinical Pharmacy and Pharmacology (CPP) Section of the Society of Critical Care Medicine (SCCM) was sent to pharmacist members of the SCCM CPP Section practicing in adult intensive care units in the spring of 2017. This survey queried pharmacists' self-reported practices regarding vancomycin dosing and monitoring in critically ill adults., Results: Three-hundred and sixty-four responses were received for an estimated response rate of 26%. Critical care pharmacists self-reported largely following the 2009 vancomycin dosing and monitoring guidelines. The largest deviations in guideline recommendation compliance involve consistent use of a loading dose, dosing weight in obese patients, and quality improvement efforts related to systematically monitoring vancomycin-associated nephrotoxicity. Variation exists regarding pharmacist protocols and other practices of vancomycin use in critically ill patients., Conclusion: Among critical care pharmacists, reported vancomycin practices are largely consistent with the 2009 guideline recommendations. Variations in vancomycin dosing and monitoring protocols are identified, and rationale for guideline non-adherence with loading doses elucidated., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Prealbumin (PAB) has been shown to be a useful index of nutrition status in clinically stable patients. In the setting of critical illness, however, PAB is a negative acute phase reactant and may also reflect severity of illness. The purpose of this study was to evaluate the relationship between PAB and clinical outcomes in critically ill patients., Methods: This was a single-center, retrospective, nonrandomized cohort study of adult intensive care unit (ICU) patients. Baseline PAB and change in PAB were analyzed. The primary outcome was in-hospital mortality, and the secondary outcome was hospital length of stay (LOS). Data collected included PAB levels, Charlson Comorbidity Index, LOS, in-hospital mortality, and nutrition intake. Linear and logistic regressions were used to characterize the association between PAB levels and clinical outcomes., Results: Our study included 926 patients. Patients expiring in hospital experienced a greater decrease in PAB over time, -1.3 vs -0.7 mg/dL (odds ratio 0.94 [0.9-0.98] in multivariable regression, P = .002). Baseline PAB was not associated with in-hospital mortality or LOS. Exploratory analyses demonstrated a weak correlation between nutrition and change in PAB., Conclusion: Our data demonstrate that change in PAB is associated with hospital mortality. Nutrition intake weakly correlated with change in PAB. PAB does not appear to be a robust marker of nutrition therapy but may have value as a prognostic indicator in the ICU setting., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Objectives: Critically ill patients routinely receive vancomycin as empiric antibiotic therapy. A continuous infusion administration strategy may be superior to intermittent infusion by minimizing peak concentrations and variability thereby optimizing safety. We performed a systematic review and meta-analysis to investigate the impact of vancomycin infusion strategy on acute kidney injury in critically ill adults., Data Sources: A systematic search of MEDLINE, CINAHL, Web of Science, International Pharmaceutical Abstracts, and Google Scholar was undertaken., Study Selection: We included randomized controlled trials and observational studies evaluating acute kidney injury in critically ill adults comparing vancomycin administered by intermittent and continuous infusion. Secondary outcomes included mortality and pharmacokinetic target attainment., Data Extraction: Eleven studies were identified for analysis with baseline demographics, endpoints, protocol definitions, and outcomes extracted., Data Synthesis: When compared with intermittent infusion, continuous infusion was associated with a reduction in acute kidney injury in critically ill adults (odds ratio, 0.47; 95% CI, 0.34-0.65) and a 2.6 greater odds of pharmacokinetic target attainment (odds ratio, 2.63; 95% CI, 1.52-4.57). No difference in mortality was observed (odds ratio, 1.04; 95% CI, 0.80-1.35)., Conclusions: When administered via a continuous infusion, vancomycin is associated with a 53% reduction in the odds of acute kidney injury and a 2.6-fold higher odds of pharmacokinetic target attainment when compared with intermittent infusion without influencing overall mortality.

Objective: Administration of diuretics has been shown to assist fluid management and improve clinical outcomes in the critically ill post-shock resolution. Current guidelines have not yet included standardization or guidance for diuretic-based de-resuscitation in critically ill patients. This study aimed to evaluate the impact of a multi-disciplinary protocol for diuresis-guided de-resuscitation in the critically ill., Methods: This was a pre-post single-center pilot study within the medical intensive care unit (ICU) of a large academic medical center. Adult patients admitted to the Medical ICU receiving mechanical ventilation with either (1) clinical signs of volume overload via chest radiography or physical exam or (2) any cumulative fluid balance ≥ 0 mL since hospital admission were eligible for inclusion. Patients received diuresis per clinician discretion for a 2-year period (historical control) followed by a diuresis protocol for 1 year (intervention). Patients within the intervention group were matched in a 1:3 ratio with those from the historical cohort who met the study inclusion and exclusion criteria., Results: A total of 364 patients were included, 91 in the protocol group and 273 receiving standard care. Protocolized diuresis was associated with a significant decrease in 72-h post-shock cumulative fluid balance [median, IQR - 2257 (- 5676-920) mL vs 265 (- 2283-3025) mL; p < 0.0001]. In-hospital mortality in the intervention group was lower compared to the historical group (5.5% vs 16.1%; p = 0.008) and higher ICU-free days (p = 0.03). However, no statistically significant difference was found in ventilator-free days, and increased rates of hypernatremia and hypokalemia were demonstrated., Conclusions: This study showed that a protocol for diuresis for de-resuscitation can significantly improve 72-h post-shock fluid balance with potential benefit on clinical outcomes.

Background: Evidence-based medicine often has many barriers to overcome prior to implementation in practice, hence the importance of continuous quality improvement. We report on a brief (≤10 minutes) multidisciplinary meeting prior to rounds to establish a dashboard for continuous quality improvement and studied the success of this meeting on a particular area of focus: continuous infusion benzodiazepine minimization., Methods: This was a prospective observational study of patients admitted to the medical intensive care unit (MICU) of a large academic medical center over a 4-month period. A morning multidisciplinary prerounding meeting was implemented to report on metrics required to establish a dashboard for MICU care for the previous 24 hours. Fellows and nurse practitioners on respective teams reported on key quality metrics and other important data related to patient census. Continuous benzodiazepines were tracked daily as the number of patients per team who had orders for a continuous benzodiazepine infusion. The aim of this report is to describe the development of the morning multidisciplinary prerounding meeting and its impact on continuous benzodiazepine use, along with associated clinical outcomes., Results: The median number of patients prescribed a continuous benzodiazepine daily decreased over this time period and demonstrated a sustained reduction at 1 year. Furthermore, sedation scores improved, corresponding to a reduction in median duration of mechanical ventilation. The effectiveness of this intervention was mapped post hoc to conceptual models used in implementation science., Conclusions: A brief multidisciplinary meeting to review select data points prior to morning rounds establishes mechanisms for continuous quality improvement and may serve as a mediating factor for successful implementation when initiating and monitoring practice change in the ICU.

Rationale: Vasopressors such as norepinephrine are first line for support of mean arterial pressure (MAP) in the management of septic shock. Their use, however, is commonly associated with many adverse events. These detriments frequently trigger the use of alternative, noncatecholamine therapies, including vasopressin. Vasopressin deficiency is a known physiologic consequence of septic shock, and while guidelines recommend vasopressin in addition to norepinephrine, no consensus exists on the duration of deficiency or ideal time of cessation. Studies have suggested that vasopressin discontinuation prior to other vasopressors may lead to hypotension; however, data are limited. This study evaluates the optimal sequence for the discontinuation of vasopressin therapy in septic shock., Methods: This was a 1-year retrospective study of 152 patients admitted to the medical intensive care unit (ICU) with septic shock who received concurrent norepinephrine and vasopressin for vasoactive support. Patients were excluded if death occurred on vasopressors, within 24 hours after discontinuation of vasopressors, or within 48 hours of ICU admission. The primary outcome of hemodynamic instability included incidence of hypotension after vasopressor discontinuation (2 consecutive MAPs < 60 mm Hg), fluid bolus administration, greater than 0.05 μg/kg/min increase in norepinephrine requirements, or addition of an alternative vasopressor. Secondary outcomes included time to hypotension, total vasopressor duration, arrhythmias, mortality, and length of stay., Results: Ninety-one patients met exclusion criteria, resulting in 61 patients for evaluation. Vasopressin was the first vasoactive therapy to be discontinued in 19 patients and last in 42 patients. Baseline characteristics and the use of potentially confounding treatments known to effect MAP were similar between groups. Discontinuation of vasopressin first was associated with a significant increase in hemodynamic instability (74% vs 16.7%, P < .01), with a shorter time to hemodynamic instability (5 vs 15 hours, P < .01). Secondary outcomes were similar., Conclusion: Vasopressin discontinuation prior to cessation of norepinephrine infusion was associated with an increased risk of hemodynamic instability.

Background: Preceptor development is a focus of pharmacy residency programs across the country. Graduation from residency into the role of preceptor can be a challenge, as it is one of many transitions junior practitioners make in their early careers. Literature in recent years has brought attention to the need to establish preceptor development programs that adequately allow newer preceptors to develop their skills in experiential education, for both pharmacy residents and students. Furthermore, many preceptor development programs as implemented are often didactic in nature, and include readings, webinars, and other passive learning regarding the art of precepting. Objective: Given the need to develop a preceptor development program in our service line that met the needs of preceptors-in-training and full preceptors, we offer a description of our preceptor development program in the intensive care unit. Methods: We focused on active development of preceptor skills for multiple layers of resident and student learners. In addition, this model incorporated instructing, modeling, coaching, and facilitating, as the relationship between full preceptor and preceptor-in-training evolved. It also offered the opportunity for real-time feedback and discussion on precepting performance. Conclusions: We describe our coprecepting model as an opportunity that succeeded for us in helping to transition our preceptors-in-training to full preceptors. It met the needs of our department, staff, and patients, and we believe it has the potential to be valuable as a tool extrapolated to the preceptor development programs of other institutions., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Delivery of patient education materials to promote health literacy is a vital component of patient-centered care, which improves patients' decision-making, reduces patients' anxiety, and improves clinical outcomes., Objectives: To evaluate perceptions of television-based patient education among patients, caregivers, nurses, and other care providers (attending physicians, advanced practice nurses, physician assistants, and resident fellows) in the intensive care unit., Methods: A Likert-scale survey of the perceptions of patients, caregivers, nurses, and other care providers in the medical and cardiovascular intensive care units of a large academic medical center. Perceptions of the effects of television-based education on anxiety, knowledge, and health-related decision-making were assessed., Results: A total of 188 participants completed the survey. Among them, 75% of nurses and 76% of other providers agreed or strongly agreed that television-based education improved patients' and caregivers' knowledge ( P = .95). More nurses (47%) than other providers (29%) agreed that television-based education would lead to more informed health decisions by patients ( P = .04). Patients and caregivers are 23 times more likely than providers to strongly agree that television-based education reduces anxiety, and they are more optimistic regarding the benefits of television-based education (relative risk ratio 23.47; 95% CI 9.75-56.45; P < .001)., Conclusion: Patients and caregivers strongly suggested that television is a useful tool for providing health literacy education in an intensive care unit., (© 2019 American Association of Critical-Care Nurses.)