Impact of a Pharmacist-Driven Medication Diluent Volume Optimization Protocol on Fluid Balance and Outcomes in Critically Ill Patients.

Background: Volume overload (VO) is common in the intensive care unit (ICU) and associated with negative outcomes. Approaches have been investigated to curtail VO; however, none specifically focused on medication diluent volume optimization. Objective: Investigate the impact of a pharmacist-driven medication diluent volume optimization protocol on fluid balance in critically ill patients. Methods: A prospective, pilot study was conducted in a medical ICU during October 2021 to December 2021 (pre) and February 2022 to April 2022 (post). A pharmacist-driven medication diluent volume optimization protocol focusing on vasopressor and antimicrobial diluent volumes was implemented. Demographics and clinical data were collected during ICU admission up to 7 days. The primary outcome was net fluid balance on day 3. Secondary outcomes were medication volumes administered, net fluid balance, ICU length of stay, and mortality. Results: Supply chain shortages caused the study to stop at the end of February 2022. Overall, 152 patients were included (123 pre group, 29 post group). The most common admission diagnosis was acute respiratory failure (35%). Vasopressors and antimicrobials were utilized in 47% and 66% of patients, respectively. Net fluid balance on day 3 was greater but not significant in the post group (227.1 mL [-1840.3 to 3483.7] vs 2012.3 mL [-2686.0 to 4846.0]; P = .584). Antimicrobial diluent volumes were significantly less in the post group. No differences were seen in other secondary outcomes. Protocol group assignment was not associated with net fluid balance on day 3. Conclusion: Despite decreasing antimicrobial volume contributions, optimizing diluent volumes alone did not significantly impact overall volume status. Future studies should focus on comprehensive approaches to medication diluent optimization and fluid stewardship.

Cefepime Induced Neurotoxicity Following A Regimen Dose-Adjusted for Renal Function: Case Report and Review of the Literature.

Introduction: Cefepime induced neurotoxicity (CIN) is commonly associated with renal dysfunction, however CIN can occur in patients with normal renal function or renally dose-adjusted regimens. Few reports of this kind have obtained cefepime concentrations to assist in diagnosis. Patient Case: A 42-year old female with a complex past medical history was transferred to our facility with chief complaint of worsening shock and respiratory failure, and the patient was also noted to be hypernatremic, experiencing diabetic ketoacidosis (DKA), and acute kidney injury (AKI). Her DKA resolved and hypernatremia and AKI began to improve. As a result, cefepime was dose-adjusted for renal function estimated by the Cockcroft-Gault (CG) equation. Her hospital course was complicated by persistent altered mental status (AMS), preventing extubation. Cefepime was discontinued due to concern for CIN, and a concentration was obtained 13-hours after the last dose which was elevated at 49 µg/mL. Two days following cefepime discontinuation, the patient's mental status improved allowing for successful extubation. The patient remained stable and was discharged to an acute care floor and then ultimately back to home. Conclusion: CIN should be part of a wider differential diagnosis for patients experiencing encephalopathy, and inaccurate renal function estimation may be a risk factor for developing CIN. Furthermore, therapeutic drug monitoring (TDM) may serve as an important clinical tool in diagnosing and managing CIN.

Impact of Pharmacist Education on Incoming Medical Residents.

Introduction: The graduating medical student transitioning to the role of a first-year medical resident is expected to know the proper medications and dosages for routine patient conditions. Pharmacists on an interdisciplinary health care team can be effective teachers of medical residents. Given the small amount of pharmacy-based education included in medical school curricula, it is important that medical residents have a basic foundation of pharmacotherapeutic knowledge. The purpose of this study was to assess the effectiveness of a pharmacist-led education session in improving medical resident pharmacotherapy knowledge. Methods: During orientation in 2016 to 2019, first-year medical residents completed an 8-item pre-test assessing their choices of medications and dosages on 8 patient conditions. A post-test assessing these same items was taken after a 50-minute lecture from a pharmacist experienced in resident education. First-year medical residents at a separate institution within the university system completed the pre-test only. Results: Overall, 243 medical residents received the lecture and took both tests and 170 medical residents at the other institution completed the pre-test only (100% response rate). Using descriptive statistics, the 2 groups of medical residents were comparable in age, gender, and scores on the pre-test. Medical residents receiving the lecture showed an average 32% point change improvement in performance on the post-test. The pharmacist-led lecture consistently received the highest ratings (4.7 ± 0.5 out of 5) from residents of all the orientation topics presented. Conclusions: A pharmacist-led education session increased the pharmacotherapy knowledge of first-year medical residents at their resident orientation. Medical residents value reinforcement of basic pharmacotherapy knowledge to start their training.

The times are changing: A primer on novel clinical trial designs and endpoints in critical care research.

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.

Publication of pharmacy resident research projects: A systematic review and meta-analysis.

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. 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 (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.

Assessing Cognitive Apprenticeship Impact on Clinical Reasoning in Third-Year Student Pharmacists.

OBJECTIVE: The objective of this study was to evaluate the impact of implementing a cognitive apprenticeship theory (CAT) model into a Doctor of Pharmacy course in improving clinical reasoning skills of third-year student pharmacists over time and preparing them for Advanced Pharmacy Practice Experiences (APPEs). METHODS: This was a single center, nonrandomized, observational before-and-after study from January 2022 through May 2022. Third-year student pharmacists enrolled in the Critical Care Integrated Drugs and Disease pharmacotherapy course at the University of Kentucky College of Pharmacy were administered a well-established and nationally recognized clinical patient case assessment on weeks 1 and 15 of the course. Students were asked to prioritize patient problems and provide recommendations for therapy, goals, and monitoring. Responses were then scored using a predefined case key. In addition, student pharmacists were asked to self-evaluate their confidence in APPE readiness on a 5-point Likert scale. RESULTS: Of the 136 student pharmacists enrolled in the course, 92 (68%) student pharmacists completed both week 1 and week 15 clinical cases and self-assessment surveys, provided informed consent, and were included. Cumulative clinical case scores were significantly increased from week 1 to week 15 (34.8 vs 39.7). In addition, significant improvement was seen in overall problem prioritization, overall recommendations, and self-perceived preparedness for APPE rotations. CONCLUSION: The use of a CAT model into a 15-week pharmacotherapy course improved comprehensive scores of clinical reasoning assessment in third-year student pharmacists and was associated with increased self-perceived confidence and readiness for APPEs.

Medication Management in the Critically Ill Patient with Acute Kidney Injury.

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.

Patient-Specific Risk Factors Associated With the Development of Hyperchloremia in a Neurocritical Care Intensive Care Unit.

BACKGROUND: Hypertonic sodium chloride (HTS) is used in intensive care unit (ICU) settings to manage cerebral edema, intracranial hypertension, and for the treatment of severe hyponatremia. It has been associated with an increased incidence of hyperchloremia; however, there is limited literature focusing on hyperchloremic risk in neurologically injured patients. Objective: The primary objective of this study was to determine risk factors associated with development of hyperchloremia in a neurocritical care (NCC) ICU population. METHODS: This was a retrospective case-control study performed in an adult NCC ICU and included patients receiving HTS. The primary outcome was to evaluate patient characteristics and treatments associated with hyperchloremia. Secondary outcomes included acute kidney injury and mortality. RESULTS: Overall, 133 patients were identified; patients who were hyperchloremic were considered cases (n = 100) and patients without hyperchloremia were considered controls (n = 33). Characteristics and treatments were evaluated with univariate analysis and a logistic regression model. In the multivariate model, APACHE II Score, initial serum osmolality, total 3% saline volume, and total 23.4% saline volume were significant predictors for hyperchloremia. In addition, patients with a serum chloride greater than 113.5 mEq/L were found to have a higher risk of acute kidney injury (AKI) (adjusted OR 3.15; 95% CI 1.10-9.04). CONCLUSIONS: This study demonstrated APACHE II Score, initial serum osmolality, and total 3% and 23.4% saline volumes were associated with developing hyperchloremia in the NCC ICU. In addition, hyperchloremia is associated with an increased risk of AKI.

RAS inhibition and sepsis-associated acute kidney injury.

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.

Azithromycin and Major Adverse Kidney Events in Critically Ill Patients With Sepsis-Associated Acute Kidney Injury.

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.

Progression of Kidney Injury with the Combination of Vancomycin and Piperacillin-Tazobactam or Cefepime in Sepsis-Associated Acute Kidney Injury.

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.

Altering Routine Intensive Care Unit Practices to Support Commensalism.

The gastrointestinal (GI) tract consists of trillions of organisms that support multiple functions in the body, from immunity, digestion, and absorption to drug metabolism. These microbes form an overall collection of microorganisms that form the body's microbiome. In critical illness, many of these functions are aberrant, and the microbiome is altered, leading to untoward effects. Some of the most common medications received by patients include antibiotics and proton pump inhibitors, which affect particular changes in the microbiome. In addition, patients receiving prolonged enteral and parenteral nutrition experience changes in the microbiological composition and diversity of their GI tracts. Research is ongoing to characterize the crosstalk between the microbiome and immune function as targets for drug and nutrition therapy.