A descriptive report of the rapid implementation of automated MRC-ICU calculations in the EMR of an academic medical center.

PURPOSE: Numerous clinical scoring tools exist for a variety of patient populations and disease states, but few tools provide information specifically designed for use by critical care pharmacists. The medication regimen complexity-intensive care unit (MRC-ICU) score was designed to provide high-level information about the complexity of critically ill patients' medication regimens for use by critical care pharmacists. To date, implementation of this score in the electronic medical record (EMR) has not been reported. SUMMARY: Using an agile project management framework, the MRC-ICU score was rapidly implemented into an academic medical center's EMR. The score is automatically calculated for all critically ill patients and is available for critical care pharmacists to triage patient review in their individual workflow. Reporting capabilities of the score also allow for granular complexity trending over time and between units, supplementing other objective measures of pharmacist workload. CONCLUSION: The MRC-ICU score can be quickly implemented into the EMR for pharmacist use in real time. Future investigations into how pharmacists utilize this information and how to harness reporting capabilities for pharmacist workload assessment are warranted.

Fluid Stewardship of Maintenance Intravenous Fluids.

Despite the frequent use of maintenance intravenous fluids (mIVF) in critically ill patients, limited guidance is available. Notably, fluid overload secondary to mIVF mismanagement is associated with significant adverse patient outcomes. The Four Rights (right drug, right dose, right duration, right patient) construct of fluid stewardship has been proposed for the safe evaluation and use of fluids. The purpose of this evidence-based review is to offer practical insights for the clinician regarding mIVF selection, dosing, and duration in line with the Four Rights of Fluid Stewardship.

Vasopressor Discontinuation Order in Septic Shock With Reduced Left Ventricular Function.

BACKGROUND: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order. OBJECTIVE: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation. METHODS: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality. RESULTS: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed. CONCLUSION: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.

Medication Regimen Complexity Score as an Indicator of Fluid Balance in Critically Ill Patients.

BACKGROUND: Critically ill patients are at increased risk for fluid overload, but objective prediction tools to guide clinical decision-making are lacking. The MRC-ICU scoring tool is an objective tool for measuring medication regimen complexity. OBJECTIVE: To evaluate the relationship between MRC-ICU score and fluid overload in critically ill patients. METHODS: In this multi-center, retrospective, observational study, the relationship between MRC-ICU and the risk of fluid overload was examined. Patient demographics, fluid balance at day 3 of ICU admission, MRC-ICU score at 24 hours, and clinical outcomes were collected from the medical record. The primary outcome was relationship between MRC-ICU and fluid overload. To analyze this, MRC-ICU scores were divided into tertiles (low, moderate, high), and binary logistic regression was performed. Linear regression was performed to determine variables associated with positive fluid balance. RESULTS: A total of 125 patients were included. The median MRC-ICU score at 24 hours of ICU admission for low, moderate, and high tertiles were 9, 15, and 21, respectively. For each point increase in MRC-ICU, a 13% increase in the likelihood of fluid overload was observed (OR 1.128, 95% CI 1.028-1.238, p = 0.011). The MRC-ICU score was positively associated with fluid balance at day 3 (ß-coefficient 218.455, 95% CI 94.693-342.217, p = 0.001) when controlling for age, gender, and SOFA score. CONCLUSIONS: Medication regimen complexity demonstrated a weakly positive correlation with fluid overload in critically ill patients. Future studies are necessary to establish the MRC-ICU as a predictor to identify patients at risk of fluid overload.

Time to blood, respiratory and urine culture positivity in the intensive care unit: Implications for de-escalation.

OBJECTIVES: Concern for late detection of bacterial pathogens is a barrier to early de-escalation efforts. The purpose of this study was to assess blood, respiratory and urine culture results at 72 h to test the hypothesis that early negative culture results have a clinically meaningful negative predictive value. METHODS: We retrospectively reviewed all patients admitted to the medical intensive care unit between March 2012 and July 2018 with blood cultures obtained. Blood, respiratory and urine culture results were assessed for time to positivity, defined as the time between culture collection and preliminary species identification. The primary outcome was the negative predictive value of negative blood culture results at 72 h. Secondary outcomes included sensitivity, specificity, positive predictive value and negative predictive value of blood, respiratory and urine culture results. RESULTS: The analysis included 1567 blood, 514 respiratory and 1059 urine cultures. Of the blood, respiratory and urine cultures ultimately positive, 90.3%, 76.2% and 90.4% were positive at 72 h. The negative predictive value of negative 72-h blood, respiratory and urine cultures were 0.99, 0.82 and 0.97, respectively. Antibiotic de-escalation had good specificity, positive predictive value and negative predictive value for finalized negative cultures. CONCLUSION: Negative blood and urine culture results at 72 h had a high negative predictive value. These findings have important ramifications for antimicrobial stewardship efforts and support protocolized re-evaluation of empiric antibiotic therapy at 72 h. Caution should be used in patients with clinically suspected pneumonia, since negative respiratory culture results at 72 h were weakly predictive of finalized negative cultures.

Therapeutic Anticoagulation With an Ultra-Low Concentration Argatroban-Based Purge Solution for Percutaneous Ventricular Assist Device in Patient With Heparin-Induced Thrombocytopenia.

Purpose/Background: Percutaneous left ventricular assist devices (pVADs) require a continuous purge solution containing heparin to prevent pump thrombosis and device failure. Data regarding alternative options in patients who have suspected heparin-induced thrombocytopenia (HIT) are limited. Methods: In this report, we describe a 68-year-old white man with cardiogenic shock with an Impella CP device managed with a low concentration argatroban-based purge solution secondary to a suspected diagnosis of HIT. Results: The purge solution was initiated as argatroban in dextrose 10% at a concentration of 0.12 mg/mL and was subsequently decreased twice to 0.06 and 0.015 mg/mL based on the patient's clinical course. Conclusions: This case report describes the safe and effective use of argatroban purge solution necessary for anticoagulation although further studies are needed to confirm these findings.

Assessment of Electrolyte Replacement in Critically Ill Patients During a Drug Shortage.

Purpose: The purpose of this study was to determine if national drug shortages of electrolyte replacement products negatively impact patient care. Methods: This study was a single-center, retrospective, observational cohort of adults admitted to the medical, surgical, or trauma intensive care unit (ICU) that were ordered or would have qualified for the general or continuous renal replacement therapy electrolyte replacement protocol (ERP) between April 2017 and August 2018. In October 2017, ERP use was suspended and enteral replacement was promoted due to inability to maintain consistent inventory of intravenous replacement products. The primary objective was to compare the percentage of patient days that at least 1 critically low value of potassium, magnesium, and/or phosphorus existed between protocolized and nonprotocolized electrolyte replacement. Secondary objectives included characterizing the ratio of enteral replacement to duration of critically low electrolyte values during protocolized and nonprotocolized electrolyte replacement. Results: A total of 288 patients were included. The mean percentage of ICU days with low electrolyte levels in the protocolized period was significantly higher than in the nonprotocolized period (21.4% vs 17.5%, P = .0238). There was a negative relationship between the total electrolyte replacement that was given enterally and the percentage of patient days with critically low values indicating that as enteral replacement increased, percentage of days with low values decreased. The association between percentage of enteral replacement and days with critically low electrolyte values was significantly lower in the protocolized period. Conclusion: Intravenous electrolyte replacement product shortages did not result in an increased incidence of critically low electrolyte values. Enteral replacement was associated with a decreased incidence of low electrolyte values.

Scholastic synergy: A team prototype for pharmacy faculty engagement in education, research, and service.

INTRODUCTION: Many clinical faculty members are challenged by competing factors of scholarly productivity, education, service obligations, and patient care. A team-based approach has the potential to synergistically increase productivity and mitigate factors associated with burnout. METHODS: The purpose of this report is to discuss a prototype for a small, team-based, practice-oriented collaborative approach to advancing critical care pharmacy practice through research and education. Productivity was evaluated in the areas of scholarship and teaching. RESULTS: This team was formed in 2017 and includes five critical care faculty across four campuses from a single academic institution. This collaborative has published peer-reviewed articles, secured grant funding, and developed novel teaching modalities. CONCLUSIONS: Challenges encountered include timeline adherence, development of uniform data collection processes, clarifying roles and expectations for different projects, and authorship. This team may act as a prototype for clinical faculty teams to enhance engagement and scholarship productivity in a practice-based setting.

Cisatracurium attenuates LPS-induced modulation of MMP3 and junctional protein expression in human microvascular endothelial cells.

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury (ALI) associated with hypoxemic lung damage and inflammation. Matrix metalloproteinase protein-3 (MMP3 or Stromelysin-1) is known to promote vascular injury in ALI/ARDS. Cisatracurium, a nicotinic neuromuscular blocker, is used in ARDS patients to decrease mechanical ventilator dyssynchrony, increase oxygenation, and improve mortality. However, the magnitude and the underlying mechanisms of these potential benefits of cisatracurium remains unclear. We investigated the effect of cisatracurium on lipopolysaccharide-induced MMP3 expression in human microvascular endothelial cells. In our results, cisatracurium treatment significantly decreased LPS-induced MMP3 expression and increased expression of cell junction proteins such as vascular endothelial cadherin (VE-cadherin) and claudin-5.

Major publications in the critical care pharmacotherapy literature: 2019.

PURPOSE: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2019. MATERIALS AND METHODS: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 36 journals monthly for impactful articles and reviewed 113 articles during 2019 according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. RESULTS: Articles with a 1A grade, including three clinical practice guidelines, six meta-analyses, and five original research trials are reviewed here from those included in the monthly CCPLU. Clinical practice guidelines on the use of polymyxins and antiarrhythmic drugs in cardiac arrest as well as meta-analyses on antipsychotic use in delirium, stress ulcer prophylaxis (SUP), and vasoactive medications in septic shock and cardiac arrest were summarized. Original research trials evaluated delirium, sedation, neuromuscular blockade, SUP, anticoagulation reversal, and hemostasis. CONCLUSION: This clinical review and expert opinion provides summary and perspectives of clinical practice impact on influential critical care pharmacotherapy publications in 2019.

Development of Machine Learning Models to Validate a Medication Regimen Complexity Scoring Tool for Critically Ill Patients.

INTRODUCTION: The Medication Regimen Complexity -Intensive Care Unit (MRC-ICU) is the first tool for measuring medication regimen complexity in critically ill patients. This study tested machine learning (ML) models to investigate the relationship between medication regimen complexity and patient outcomes. METHODS: This study was a single-center, retrospective observational evaluation of 130 adults admitted to the medical ICU. The MRC-ICU score was utilized to improve the inpatient model's prediction accuracy. Three models were proposed: model I, demographic data without medication data; model II, demographic data and medication regimen complexity variables; and model III: demographic data and the MRC-ICU score. A total of 6 ML classifiers was developed: k-nearest neighbor (KNN), naïve Bayes (NB), random forest, support vector machine, neural network, and logistic classifier (LC). They were developed and tested using electronic health record data to predict inpatient mortality. RESULTS: The results demonstrated that adding medication regimen complexity variables (model II) and the MRC-ICU score (model III) improved inpatient mortality prediction.. The LC outperformed the other classifiers (KNN and NB), with an overall accuracy of 83%, sensitivity (Se) of 87%, specificity of 67%, positive predictive value of 93%, and negative predictive value of 46%. The APACHE III score and the MRC-ICU score at the 24-hour interval were the 2 most important variables. CONCLUSION AND RELEVANCE: Inclusion of the MRC-ICU score improved the prediction of patient outcomes on the previously established APACHE III score. This novel, proof-of-concept methodology shows promise for future application of the MRC-ICU scoring tool for patient outcome predictions.