Article

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

March 2021
Journal of Pharmacy Practice 35(6):089719002199979

DOI:10.1177/0897190021999792

Authors:

University of Georgia

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 (β-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.

Pharmacist Metrics in the Pediatric Intensive Care Unit: an Exploration of the Medication Regimen Complexity-Intensive Care Unit (MRC-ICU) Score

Article

Dec 2023

INTRODUCTION The medication regimen complexity-intensive care unit (MRC-ICU) score has been developed and validated as an objective predictive metric for patient outcomes and pharmacist workload in the adult critically ill population. The purpose of this study was to explore the MRC-ICU and other workload metrics in the pediatric ICU (PICU). METHODS This study was a retrospective cohort of pediatric ICU patients admitted to a single institution between February 2, 2022 – August 2, 2022. Two scores were calculated, including the MRC-ICU and the pediatric Daily Monitoring System (pDMS). Data were extracted from the electronic health record. The primary outcome was the correlation of the MRC-ICU to mortality, as measured by Pearson correlation coefficient. Additionally, the correlation of MRC-ICU to number of orders was evaluated. Secondary analyses explored the correlation of the MRC-ICU with pDMS and with hospital and ICU length of stay. RESULTS A total of 2,232 patients were included comprising 2,405 encounters. The average age was 6.9 years (standard deviation [SD] 6.3 years). The average MRC-ICU score was 3.0 (SD 3.8). For the primary outcome, MRC-ICU was significantly positively correlated to mortality (0.22 95% confidence interval [CI 0.18 – 0.26]), p<0.05. Additionally, MRC-ICU was significantly positively correlated to ICU length of stay (0.38 [CI 0.34 – 0.41]), p<0.05. The correlation between the MRC-ICU and pDMS was (0.72 [CI 0.70 – 0.73]), p<0.05. CONCLUSION In this pilot study, MRC-ICU demonstrated an association with existing prioritization metrics and with mortality and length of ICU stay in PICU population. Further, larger scale studies are required.

Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score

Article

Sep 2022
CRIT CARE MED

Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not opti- mized 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.

Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU)

Article

Jun 2022

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.

Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction

Preprint

Full-text available

Mar 2024

INTRODUCTION: Intravenous (IV) medications are a fundamental cause of fluid overload (FO) in the intensive care unit (ICU); however, the association between IV medication use (including volume), administration timing, and FO occurrence remains unclear. METHODS: This retrospective cohort study included consecutive adults admitted to an ICU ≥72 hours with available fluid balance data. FO was defined as a positive fluid balance ≥7% of admission body weight within 72 hours of ICU admission. After reviewing medication administration record (MAR) data in three-hour periods, IV medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess for temporal clusters associated with FO using the Wilcoxon rank sum test. Exploratory analyses of the medication cluster most associated with FO for medications frequently appearing and used in the first 24 hours was conducted. RESULTS: FO occurred in 127/927 (13.7%) of the patients enrolled. Patients received a median (IQR) of 31 (13-65) discrete IV medication administrations over the 72-hour period. Across all 47,803 IV medication administrations, ten unique IV medication clusters were identified with 121-130 medications in each cluster. Among the ten clusters, cluster 7 had the greatest association with FO; the mean number of cluster 7 medications received was significantly greater in patients in the FO cohort compared to patients who did not experience FO (25.6 vs.10.9. p<0.0001). 51 of the 127 medications in cluster 7 (40.2%) appeared in > 5 separate 3-hour periods during the 72-hour study window. The most common cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of cluster 7 medications to a prediction model with APACHE II score and receipt of diuretics improved the ability for the model to predict fluid overload (AUROC 5.65, p =0.0004). CONCLUSIONS: Using ML approaches, a unique IV medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict development of fluid overload in ICU patients compared with traditional prediction models. This method may be further developed into real-time clinical applications to improve early detection of adverse outcomes.

Medication regimen complexity (MRC-ICU) for in-hospital mortality prediction in COVID-19 patients

Article

Full-text available

Dec 2023
Hosp Pharm

Purpose The medication regimen complexity-intensive care unit (MRC-ICU) score was developed prior to the existence of COVID-19. The purpose of this study was to assess if MRC-ICU could predict in-hospital mortality in patients with COVID-19. Methods A single-center, observational study was conducted from August 2020 to January 2021. The primary outcome of this study was the area under the receiver operating characteristic (AUROC) for in-hospital mortality for the 48-hour MRC-ICU. Age, sequential organ failure assessment (SOFA), and World Health Organization (WHO) COVID-19 Severity Classification were assessed. Logistic regression was performed to predict in-hospital mortality as well as WHO Severity Classification at 7 days. Results A total of 149 patients were included. The median SOFA score was 8 (IQR 5-11) and median MRC-ICU score at 48 hours was 15 (IQR 7-21). The in-hospital mortality rate was 36% (n = 54). The AUROC for MRC-ICU was 0.71 (95% Confidence Interval (CI), 0.62-0.78) compared to 0.66 for age, 0.81 SOFA, and 0.72 for the WHO Severity Classification. In univariate analysis, age, SOFA, MRC-ICU, and WHO Severity Classification all demonstrated significant association with in-hospital mortality, while SOFA, MRC-ICU, and WHO Severity Classification demonstrated significant association with WHO Severity Classification at 7 days. In univariate analysis, all 4 characteristics showed significant association with mortality; however, only age and SOFA remained significant following multivariate analysis. Conclusion In the first analysis of medication-related variables as a predictor of severity and in-hospital mortality in COVID-19, MRC-ICU demonstrated acceptable predictive ability as represented by AUROC; however, SOFA was the strongest predictor in both AUROC and regression analysis.

An Evaluation of the Relationship Between Medication Regimen Complexity as Measured by the MRC-ICU to Medication Errors in Critically Ill Patients

Article

Full-text available

Dec 2023
Hosp Pharm

Purpose: The purpose of this study was to determine the relationship between medication regimen complexity-intensive care unit (MRC-ICU) score at 24 hours and medication errors identified throughout the ICU. Methods: A single-center, observational study was conducted from August to October 2021. The primary outcome was the association between MRC-ICU at 24 hours and total medication errors identified. During the prospective component, ICU pharmacists recorded medication errors identified over an 8-week period. During the retrospective component, the electronic medical record was reviewed to collect patient demographics, outcomes, and MRC-ICU score at 24 hours. The primary outcome of the relationship of MRC-ICU at 24 hours to medication errors was assessed using Pearson correlation. Results: A total of 150 patients were included. There were 2 pharmacists who recorded 634 errors during the 8-week study period. No significant relationship between MRC-ICU and medication errors was observed (r² = .13, P = .11). Exploratory analyses of MRC-ICU relationship to major interventions and harm scores showed that MRC-ICU scores >10 had more major interventions (27 vs 14, P = .27) and higher harm scores (15 vs 7, P = .33), although these values were not statistically significant. Conclusion: Medication errors appear to occur independently of medication regimen complexity. Critical care pharmacists were responsible for mitigating a large number of medication errors.

Optimization of critical care pharmacy clinical services: A gap analysis approach

Article

Jun 2021

What gets measured, gets improved. —Robert Sharma Every critically ill patient requires care by a critical care pharmacist (CCP) for best possible outcomes. Indeed, these highly trained professionals generate benefit through direct patient care (eg, pharmacist-driven protocols, medication monitoring, etc), participation on the intensive care unit (ICU) interprofessional team (eg, pharmacotherapy recommendations, team education, etc), and leadership in the development and implementation of quality improvement initiatives.¹ However, clinical CCP services are not provided for all ICU patients, and CCP staffing models often vary substantially across ICUs in a given hospital and among ICUs in the United States.²⁻⁴ In this narrative review, we use a gap analysis approach to define current levels of clinical CCP services, identify barriers to reaching an optimal level of these services, and propose strategies focused on expanding clinical CCP services and justifying those that currently exist. Current critical care pharmacy clinical services The broad scope of beneficial activities performed by the CCP has been extensively reviewed and supported by a position statement from the American Society of Health-System Pharmacists (ASHP), the American College of Clinical Pharmacy (ACCP), and the Society of Critical Care Medicine (SCCM): the CCP is an essential member of the healthcare team for delivery of patient-centered care in the ICU.

Machine learning based prediction of prolonged duration of mechanical ventilation incorporating medication data

Article

Full-text available

Sep 2023

Rationale Duration of mechanical ventilation is associated with adverse outcomes in critically ill patients and increased use of resources. The increasing complexity of medication regimens has been associated with increased mortality, length of stay, and fluid overload but has never been studied specifically in the setting of mechanical ventilation. Objective The purpose of this analysis was to develop prediction models for mechanical ventilation duration to test the hypothesis that incorporating medication data may improve model performance. Methods This was a retrospective cohort study of adults admitted to the ICU and undergoing mechanical ventilation for longer than 24 hours from October 2015 to October 2020. Patients were excluded if it was not their index ICU admission or if the patient was placed on comfort care in the first 24 hours of admission. Relevant patient characteristics including age, sex, body mass index, admission diagnosis, morbidities, vital signs measurements, severity of illness, medication regimen complexity as measured by the MRC-ICU, and medical treatments before intubation were collected. The primary outcome was area under the receiver operating characteristic (AUROC) of prediction models for prolonged mechanical ventilation (defined as greater than 5 days). Both logistic regression and supervised learning techniques including XGBoost, Random Forest, and Support Vector Machine were used to develop prediction models. Results The 318 patients [age 59.9 (SD 16.9), female 39.3%, medical 28.6%] had mean 24-hour MRC-ICU score of 21.3 (10.5), mean APACHE II score of 21.0 (5.4), mean SOFA score of 9.9 (3.3), and ICU mortality rate of 22.6% (n=72). The strongest performing logistic model was the base model with MRC-ICU added, with AUROC of 0.72, positive predictive value (PPV) of 0.83, and negative prediction value (NPV) of 0.92. The strongest overall model was Random Forest with an AUROC of 0.78, a PPV of 0.53, and NPV of 0.90. Feature importance analysis using support vector machine and Random Forest revealed severity of illness scores and medication related data were the most important predictors. Conclusions Medication regimen complexity is significantly associated with prolonged duration of mechanical ventilation in critically ill patients, and prediction models incorporating medication information showed modest improvement in this prediction.

Cluster analysis driven by unsupervised latent feature learning of medications to identify novel pharmacophenotypes of critically ill patients

Article

Full-text available

Sep 2023

Unsupervised clustering of intensive care unit (ICU) medications may identify unique medication clusters (i.e., pharmacophenotypes) in critically ill adults. We performed an unsupervised analysis with Restricted Boltzmann Machine of 991 medications profiles of patients managed in the ICU to explore pharmacophenotypes that correlated with ICU complications (e.g., mechanical ventilation) and patient-centered outcomes (e.g., length of stay, mortality). Six unique pharmacophenotypes were observed, with unique medication profiles and clinically relevant differences in ICU complications and patient-centered outcomes. While pharmacophenotypes 2 and 4 had no statistically significant difference in ICU length of stay, duration of mechanical ventilation, or duration of vasopressor use, their mortality differed significantly (9.0% vs. 21.9%, p < 0.0001). Pharmacophenotype 4 had a mortality rate of 21.9%, compared with the rest of the pharmacophenotypes ranging from 2.5 to 9%. Phenotyping approaches have shown promise in classifying the heterogenous syndromes of critical illness to predict treatment response and guide clinical decision support systems but have never included comprehensive medication information. This first-ever machine learning approach revealed differences among empirically-derived subgroups of ICU patients that are not typically revealed by traditional classifiers. Identification of pharmacophenotypes may enable enhanced decision making to optimize treatment decisions.

Evaluation of medication regimen complexity as a predictor for mortality

Article

Full-text available

Jul 2023

While medication regimen complexity, as measured by a novel medication regimen complexity-intensive care unit (MRC-ICU) score, correlates with baseline severity of illness and mortality, whether the MRC-ICU improves hospital mortality prediction is not known. After characterizing the association between MRC-ICU, severity of illness and hospital mortality we sought to evaluate the incremental benefit of adding MRC-ICU to illness severity-based hospital mortality prediction models. This was a single-center, observational cohort study of adult intensive care units (ICUs). A random sample of 991 adults admitted ≥ 24 h to the ICU from 10/2015 to 10/2020 were included. The logistic regression models for the primary outcome of mortality were assessed via area under the receiver operating characteristic (AUROC). Medication regimen complexity was evaluated daily using the MRC-ICU. This previously validated index is a weighted summation of medications prescribed in the first 24 h of ICU stay [e.g., a patient prescribed insulin (1 point) and vancomycin (3 points) has a MRC-ICU = 4 points]. Baseline demographic features (e.g., age, sex, ICU type) were collected and severity of illness (based on worst values within the first 24 h of ICU admission) was characterized using both the Acute Physiology and Chronic Health Evaluation (APACHE II) and the Sequential Organ Failure Assessment (SOFA) score. Univariate analysis of 991 patients revealed every one-point increase in the average 24-h MRC-ICU score was associated with a 5% increase in hospital mortality [Odds Ratio (OR) 1.05, 95% confidence interval 1.02–1.08, p = 0.002]. The model including MRC-ICU, APACHE II and SOFA had a AUROC for mortality of 0.81 whereas the model including only APACHE-II and SOFA had a AUROC for mortality of 0.76. Medication regimen complexity is associated with increased hospital mortality. A prediction model including medication regimen complexity only modestly improves hospital mortality prediction.

Improving irregular temporal modeling by integrating synthetic data to the electronic medical record using conditional GANs: a case study of fluid overload prediction in the intensive care unit

Preprint

Full-text available

Jun 2023

Objective: The challenge of irregular temporal data, which is particularly prominent for medication use in the critically ill, limits the performance of predictive models. The purpose of this evaluation was to pilot test integrating synthetic data within an existing dataset of complex medication data to improve machine learning model prediction of fluid overload. Materials and Methods: This retrospective cohort study evaluated patients admitted to an ICU ≥ 72 hours. Four machine learning algorithms to predict fluid overload after 48-72 hours of ICU admission were developed using the original dataset. Then, two distinct synthetic data generation methodologies (synthetic minority over-sampling technique (SMOTE) and conditional tabular generative adversarial network (CTGAN)) were used to create synthetic data. Finally, a stacking ensemble technique designed to train a meta-learner was established. Models underwent training in three scenarios of varying qualities and quantities of datasets. Results: Training machine learning algorithms on the combined synthetic and original dataset overall increased the performance of the predictive models compared to training on the original dataset. The highest performing model was the meta-model trained on the combined dataset with 0.83 AUROC while it managed to significantly enhance the sensitivity across different training scenarios. Discussion: The integration of synthetically generated data is the first time such methods have been applied to ICU medication data and offers a promising solution to enhance the performance of machine learning models for fluid overload, which may be translated to other ICU outcomes. A meta-learner was able to make a trade-off between different performance metrics and improve the ability to identify the minority class.

Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model

Article

Full-text available

May 2023

Background Identifying patterns within ICU medication regimens may help artificial intelligence algorithms to better predict patient outcomes; however, machine learning methods incorporating medications require further development, including standardized terminology. The Common Data Model for Intensive Care Unit (ICU) Medications (CDM-ICURx) may provide important infrastructure to clinicians and researchers to support artificial intelligence analysis of medication-related outcomes and healthcare costs. Using an unsupervised cluster analysis approach in combination with this common data model, the objective of this evaluation was to identify novel patterns of medication clusters (termed ‘pharmacophenotypes’) correlated with ICU adverse events (e.g., fluid overload) and patient-centered outcomes (e.g., mortality). Methods This was a retrospective, observational cohort study of 991 critically ill adults. To identify pharmacophenotypes, unsupervised machine learning analysis with automated feature learning using restricted Boltzmann machine and hierarchical clustering was performed on the medication administration records of each patient during the first 24 h of their ICU stay. Hierarchical agglomerative clustering was applied to identify unique patient clusters. Distributions of medications across pharmacophenotypes were described, and differences among patient clusters were compared using signed rank tests and Fisher's exact tests, as appropriate. Results A total of 30,550 medication orders for the 991 patients were analyzed; five unique patient clusters and six unique pharmacophenotypes were identified. For patient outcomes, compared to patients in Clusters 1 and 3, patients in Cluster 5 had a significantly shorter duration of mechanical ventilation and ICU length of stay ( p < 0.05); for medications, Cluster 5 had a higher distribution of Pharmacophenotype 1 and a smaller distribution of Pharmacophenotype 2, compared to Clusters 1 and 3. For outcomes, patients in Cluster 2, despite having the highest severity of illness and greatest medication regimen complexity, had the lowest overall mortality; for medications, Cluster 2 also had a comparably higher distribution of Pharmacophenotype 6. Conclusion The results of this evaluation suggest that patterns among patient clusters and medication regimens may be observed using empiric methods of unsupervised machine learning in combination with a common data model. These results have potential because while phenotyping approaches have been used to classify heterogenous syndromes in critical illness to better define treatment response, the entire medication administration record has not been incorporated in those analyses. Applying knowledge of these patterns at the bedside requires further algorithm development and clinical application but may have the future potential to be leveraged in guiding medication-related decision making to improve treatment outcomes.

Cluster analysis driven by unsupervised latent feature learning of intensive care unit medications to identify novel pharmaco-phenotypes of critically ill patients

Preprint

Full-text available

Jun 2022

Unsupervised clustering of intensive care unit (ICU) medications may identify unique medication clusters (i.e., pharmacophenotypes) in critically ill adults. We performed an unsupervised analysis with Restricted Boltzmann Machine of 991 medications profiles of patients managed in the ICU to explore pharmacophenotypes that correlated with ICU complications (e.g., mechanical ventilation) and patient-centered outcomes (e.g., length of stay, mortality). Six unique pharmacophenotypes were observed, with unique medication profiles and clinically relevant differences in ICU complications and patient-centered outcomes. While pharmacophenotypes 2 and 4 had no statistically significant difference in ICU length of stay, duration of mechanical ventilation, or duration of vasopressor use, their mortality differed significantly (9.0% vs. 21.9%, p < 0.0001). Pharmacophenotype 4 had a mortality rate of 21.9%, compared with the rest of the pharmacophenotypes ranging from 2.5-9%. Phenotyping approaches have shown promise in classifying the heterogenous syndromes of critical illness to predict treatment response and guide clinical decision support systems but have never included comprehensive medication information. This first-ever machine learning approach revealed differences among empirically-derived subgroups of ICU patients that are not typically revealed by traditional classifiers. Identification of pharmacophenotypes may enable enhanced decision making to optimize treatment decisions.

Early Diuretics for De-resuscitation in Septic Patients With Left Ventricular Dysfunction

Article

Full-text available

May 2022

Introduction De-resuscitation practices in septic patients with heart failure (HF) are not well characterized. This study aimed to determine if diuretic initiation within 48 hours of intensive care unit (ICU) admission was associated with a positive fluid balance and patient outcomes. Methods This single-center, retrospective cohort study included adult patients with an established diagnosis of HF admitted to the ICU with sepsis or septic shock. The primary outcome was the incidence of positive fluid balance in patients receiving early (<48 hours) versus late (>48 hours) initiation of diuresis. Secondary outcomes included hospital mortality, ventilator-free days, and hospital and ICU length of stay. Continuous variables were assessed using independent t-test or Mann-Whitney U, while categorical variables were evaluated using the Pearson Chi-squared test. Results A total of 101 patients were included. Positive fluid balance was significantly reduced at 72 hours (−139 mL vs 4370 mL, P < .001). The duration of mechanical ventilation (4 vs 5 days, P = .129), ventilator-free days (22 vs 18.5 days, P = .129), and in-hospital mortality (28 (38%) vs 12 (43%), P = .821) were similar between groups. In a subgroup analysis excluding patients not receiving renal replacement therap (RRT) (n = 76), early diuretics was associated with lower incidence of mechanical ventilation (41 [73.2%] vs 20 (100%), P = .01) and reduced duration of mechanical ventilation (4 vs 8 days, P = .018). Conclusions Diuretic use within 48 hours of ICU admission in septic patients with HF resulted in less incidence of positive fluid balance. Early diuresis in this unique patient population warrants further investigation.

Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction

Article

Jan 2025
PHARMACOTHERAPY

Background Fluid overload (FO) in the intensive care unit (ICU) is common, serious, and may be preventable. Intravenous medications (including administered volume) are a primary cause for FO but are challenging to evaluate as a FO predictor given the high frequency and time‐dependency of their use and other factors affecting FO. We sought to employ unsupervised machine learning methods to uncover medication administration patterns correlating with FO. Methods This retrospective cohort study included 927 adults admitted to an ICU for ≥72 h. FO was defined as a positive fluid balance ≥7% of admission body weight. After reviewing medication administration record data in 3‐h periods, medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess their temporal association with FO. Results FO occurred in 127 (13.7%) of 927 included patients. Patients received a median (interquartile range) of 31(13–65) discrete intravenous medication administrations over the 72‐h period. Across all 47,803 intravenous medication administrations, 10 unique medication clusters, containing 121 to 130 medications per cluster, were identified. The mean number of Cluster 7 medications administered was significantly greater in the FO cohort compared with patients without FO (25.6 vs.10.9, p < 0.0001). A total of 51 (40.2%) of 127 unique Cluster 7 medications were administered in more than five different 3‐h periods during the 72‐h study window. The most common Cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of Cluster 7 medications to an FO prediction model including the Acute Physiologic and Chronic Health Evaluation (APACHE) II score and receipt of diuretics improved model predictiveness from an Area Under the Receiver Operation Characteristic (AUROC) curve of 0.719 to 0.741 ( p = 0.027). Conclusions Using machine learning approaches, a unique medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict FO compared to traditional prediction models. Integration of this approach into real‐time clinical applications may improve early detection of FO to facilitate timely intervention.

Relationship between medication regimen complexity and pharmacist engagement in fluid stewardship

Article

Dec 2024
AM J HEALTH-SYST PH

Purpose The medication regimen complexity intensive care unit (MRC-ICU) score has previously been associated with pharmacist workload and fluid overload. The purpose of this study was to determine the relationship of MRC-ICU score with pharmacist-driven fluid stewardship recommendations as a means of establishing its role in risk stratifying critically ill patients for pharmacist intervention. Methods Adult patients admitted to the medical ICU and followed by the academic pharmacy team were included in this retrospective, single-center cohort study. Patient and pharmacist data were collected via electronic medical record and surveillance tool, respectively. MRC-ICU and sequential organ failure assessment (SOFA) scores were captured at ICU admission. The primary outcome was correlation between MRC-ICU score and number of pharmacist-driven fluid stewardship recommendations. Secondary outcomes included the relationships between MRC-ICU score, accepted recommendations, and patient outcomes (fluid overload and length of stay [LOS]). Descriptive statistics were calculated for each variable. Spearman’s rank-order correlation was used. Results Of 168 patients, 22 (13%) experienced fluid overload. Median MRC-ICU and SOFA scores were 13 and 7, respectively, and were higher for patients experiencing fluid overload than for those without fluid overload. MRC-ICU had a weakly positive correlation with the number of pharmacist-driven fluid stewardship recommendations (ρ = 0.200; P = 0.010), fluid overload (ρ = 0.167; P = 0.030), and ICU LOS (ρ = 0.354; P < 0.001). These relationships remained true when looking at only the fluid stewardship recommendations that were accepted by the team. Conclusion MRC-ICU displayed a weakly positive correlation with pharmacist workload, suggesting its potential use in identifying patients likely to benefit from pharmacist intervention.

A common data model for the standardization of intensive care unit medication features

Article

May 2024

Objective Common data models provide a standard means of describing data for artificial intelligence (AI) applications, but this process has never been undertaken for medications used in the intensive care unit (ICU). We sought to develop a common data model (CDM) for ICU medications to standardize the medication features needed to support future ICU AI efforts. Materials and Methods A 9-member, multi-professional team of ICU clinicians and AI experts conducted a 5-round modified Delphi process employing conference calls, web-based communication, and electronic surveys to define the most important medication features for AI efforts. Candidate ICU medication features were generated through group discussion and then independently scored by each team member based on relevance to ICU clinical decision-making and feasibility for collection and coding. A key consideration was to ensure the final ontology both distinguished unique medications and met Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles. Results Using a list of 889 ICU medications, the team initially generated 106 different medication features, and 71 were ranked as being core features for the CDM. Through this process, 106 medication features were assigned to 2 key feature domains: drug product-related (n = 43) and clinical practice-related (n = 63). Each feature included a standardized definition and suggested response values housed in the electronic data library. This CDM for ICU medications is available online. Conclusion The CDM for ICU medications represents an important first step for the research community focused on exploring how AI can improve patient outcomes and will require ongoing engagement and refinement.

Improving mixed-integer temporal modeling by generating synthetic data using conditional generative adversarial networks: A case study of fluid overload prediction in the intensive care unit

Article

Nov 2023
COMPUT BIOL MED

Machine learning vs. traditional regression analysis for fluid overload prediction in the ICU

Article

Full-text available

Nov 2023

Fluid overload, while common in the ICU and associated with serious sequelae, is hard to predict and may be influenced by ICU medication use. Machine learning (ML) approaches may offer advantages over traditional regression techniques to predict it. We compared the ability of traditional regression techniques and different ML-based modeling approaches to identify clinically meaningful fluid overload predictors. This was a retrospective, observational cohort study of adult patients admitted to an ICU ≥ 72 h between 10/1/2015 and 10/31/2020 with available fluid balance data. Models to predict fluid overload (a positive fluid balance ≥ 10% of the admission body weight) in the 48–72 h after ICU admission were created. Potential patient and medication fluid overload predictor variables (n = 28) were collected at either baseline or 24 h after ICU admission. The optimal traditional logistic regression model was created using backward selection. Supervised, classification-based ML models were trained and optimized, including a meta-modeling approach. Area under the receiver operating characteristic (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were compared between the traditional and ML fluid prediction models. A total of 49 of the 391 (12.5%) patients developed fluid overload. Among the ML models, the XGBoost model had the highest performance (AUROC 0.78, PPV 0.27, NPV 0.94) for fluid overload prediction. The XGBoost model performed similarly to the final traditional logistic regression model (AUROC 0.70; PPV 0.20, NPV 0.94). Feature importance analysis revealed severity of illness scores and medication-related data were the most important predictors of fluid overload. In the context of our study, ML and traditional models appear to perform similarly to predict fluid overload in the ICU. Baseline severity of illness and ICU medication regimen complexity are important predictors of fluid overload.

A Common Data Model for the standardization of intensive care unit (ICU) medication features in artificial intelligence (AI) applications

Preprint

Full-text available

Sep 2023

Objective: Common Data Models provide a standard means of describing data for artificial intelligence (AI) applications, but this process has never been undertaken for medications used in the intensive care unit (ICU). We sought to develop a Common Data Model (CDM) for ICU medications to standardize the medication features needed to support future ICU AI efforts. Materials and Methods: A 9-member, multi-professional team of ICU clinicians and AI experts conducted a 5-round modified Delphi process employing conference calls, web-based communication, and electronic surveys to define the most important medication features for AI efforts. Candidate ICU medication features were generated through group discussion and then independently scored by each team member based on relevance to ICU clinical decision-making and feasibility for collection and coding. A key consideration was to ensure the final ontology both distinguished unique medications and met Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles. Results: Using a list of 889 ICU medications, the team initially generated 106 different medication features, and 71 were ranked as being core features for the CDM. Through this process, 106 medication features were assigned to two key feature domains: drug product-related (n=43) and clinical practice-related (n=63). Each feature included a standardized definition and suggested response values housed in the electronic data library. This CDM for ICU medications is available online. Discussion: The CDM for ICU medications represents an important first step for the research community focused on exploring how AI can improve patient outcomes and will require ongoing engagement and refinement.

Critical Care Pharmacists: A Focus on Horizons

Article

Jul 2023

Andrea Sikora

Critical care pharmacy has evolved rapidly over the last 50 years to keep pace with the rapid technological and knowledge advances that have characterized critical care medicine. The modern-day critical care pharmacist is a highly trained individual well suited for the interprofessional team-based care that critical illness necessitates. Critical care pharmacists improve patient-centered outcomes and reduce health care costs through three domains: direct patient care, indirect patient care, and professional service. Optimizing workload of critical care pharmacists, similar to the professions of medicine and nursing, is a key next step for using evidence-based medicine to improve patient-centered outcomes.

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

Article

Feb 2022

Medication regimen complexity vs patient acuity for predicting critical care pharmacist interventions

Article

Dec 2021

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 Quantifying and predicting critical care pharmacist (CCP) workload has significant ramifications for expanding CCP services that improve patient outcomes. Medication regimen complexity has been proposed as an objective, pharmacist-oriented metric that demonstrates relationships to patient outcomes and pharmacist interventions. The purpose of this evaluation was to compare the relationship of medication regimen complexity versus a traditional patient acuity metric for evaluating pharmacist interventions. Summary This was a post hoc analysis of a previously completed prospective, observational study. Pharmacist interventions were prospectively collected and tabulated at 24 hours, 48 hours, and intensive care unit (ICU) discharge, and the electronic medical record was reviewed to collect patient demographics, medication data, and outcomes. The primary outcome was the relationship between medication regimen complexity–intensive care unit (MRC-ICU) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and pharmacist interventions at 24 hours, 48 hours, and ICU discharge. These relationships were determined by Spearman rank-order correlation (rS) and confirmed by calculating the beta coefficient (β) via multiple linear regression adjusting for patient age, gender, and admission type. Data on 100 patients admitted to a mixed medical/surgical ICU were retrospectively evaluated. Both MRC-ICU and APACHE II scores were correlated with ICU interventions at all 3 time points (at 24 hours, rS = 0.370 [P < 0.001] for MRC-ICU score and rS = 0.283 [P = 0.004] for APACHE II score); however, this relationship was not sustained for APACHE II in the adjusted analysis (at 24 hours, β = 0.099 [P = 0.001] for MRC-ICU and β = 0.031 [P = 0.085] for APACHE II score). Conclusion A pharmacist-oriented score had a stronger relationship with pharmacist interventions as compared to patient acuity. As pharmacists have demonstrated value across the continuum of patient care, these findings support that pharmacist-oriented workload predictions require tailored metrics, beyond that of patient acuity.

From theory to bedside: Implementation of fluid stewardship in a medical ICU pharmacy practice

Article

Nov 2021

Purpose Intravenous fluids are the most commonly prescribed medication in the intensive care unit (ICU) and can have a negative impact on patient outcomes if not utilized properly. Fluid stewardship aims to heighten awareness and improve practice in fluid therapy. This report describes a practical construct for implementation of fluid stewardship services and characterizes the pharmacist’s role in fluid stewardship practice. Summary Fluid stewardship services were integrated into an adult medical ICU at a large community hospital. Data characterizing these services over a 2-year span are reported and categorized based on the 4 rights (right patient, right drug, right route, right dose) and the ROSE (rescue, optimization, stabilization, evacuation) model of fluid administration. The review encompassed 305 patients totaling 905 patient days for whom 2,597 pharmacist recommendations were made, 19% of which were related to fluid stewardship. This corresponded to an average of 1.52 fluid stewardship recommendations per patient. Within the construct of the 4 rights, 39% of recommendations were related to the right patient, 33% were related to the right route, 17% were related to the right drug, and 11% were related to the right dose. By the ROSE model, 1% of recommendations were related to the rescue phase, 3% were related to optimization, 79% were related to stabilization, and 17% were related to evacuation. Conclusion Implementation of fluid stewardship pharmacy services in a community hospital medical ICU is feasible. Integration of this practice contributed to 19% of pharmacy recommendations. The most common recommendations involved evaluation of the patient for the appropriateness of fluid therapy during the stabilization phase. The impact of fluid stewardship on patient outcomes needs to be explored.

Impact of protocolized diuresis for de-resuscitation in the intensive care unit

Article

Full-text available

Dec 2020

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.

Use of diuretics in shock: Temporal trends and clinical impacts in a propensity-matched cohort study

Article

Full-text available

Feb 2020
PLOS ONE

Objective Fluid overload is common among critically ill patients and is associated with worse outcomes. We aimed to assess the effect of diuretics on urine output, vasopressor dose, acute kidney injury (AKI) incidence, and need for renal replacement therapies (RRT) among patients who receive vasopressors. Patients and methods This is a single-center retrospective study of all adult patients admitted to the intensive care unit between January 2006 and December 2016 and received >6 hours of vasopressor therapy and at least one concomitant dose of diuretic. We excluded patients from cardiac care units. Hourly urine output and vasopressor dose for 6 hours before and after the first dose of diuretic therapy was compared. Rates of AKI development and RRT initiation were assessed with a propensity-matched cohort of patients who received vasopressors but did not receive diuretics. Results There was an increasing trend of prescribing diuretics in patients receiving vasopressors over the course of the study. We included 939 patients with median (IQR) age of 68(57, 78) years old and 400 (43%) female. The average hourly urine output during the first six hours following time zero in comparison with average hourly urine output during the six hours prior to time zero was significantly higher in diuretic group in comparison with patients who did not receive diuretics [81 (95% CI 73–89) ml/h vs. 42 (95% CI 39–45) ml/h, respectively; p<0.001]. After propensity matching, the rate of AKI within 7 days of exposure and the need for RRT were similar between the study and matched control patients (66 (15.6%) vs. 83 (19.6%), p = 0.11, and 34 (8.0%) vs. 37 (8.7%), p = 0.69, respectively). Mortality, however, was higher in the group that received diuretics. Ninety-day mortality was 191 (45.2%) in the exposed group VS 156 (36.9%) p = .009. Conclusions While the use of diuretic therapy in critically ill patients receiving vasopressor infusions augmented urine output, it was not associated with higher vasopressor requirements, AKI incidence, and need for renal replacement therapy.

Fluid Stewardship During Critical Illness: A Call to Action

Article

Full-text available

Jun 2019

Intravenous fluids (IVFs) are the most common drugs administered in the intensive care unit. Despite the ubiquitous use, IVFs are not benign and carry significant risks associated with under- or overadministration. Hypovolemia is associated with decreased organ perfusion, ischemia, and multi-organ failure. Hypervolemia and volume overload are associated with organ dysfunction, delayed liberation from mechanical ventilation, and increased mortality. Despite appropriate provision of IVF, adverse drug effects such as electrolyte abnormalities and acid–base disturbances may occur. The management of volume status in critically ill patients is both dynamic and tenuous, a process that requires frequent monitoring and high clinical acumen. Because patient-specific considerations for fluid therapy evolve across the continuum of critical illness, a standard approach to the assessment of fluid needs and prescription of IVF therapy is necessary. We propose the principle of “fluid stewardship,” guided by 4 rights of medication safety: right patient, right drug, right route, and right dose. The successful implementation of fluid stewardship will aid pharmacists in making decisions regarding IVF therapy to optimize hemodynamic management and improve patient outcomes. Additionally, we highlight several areas of focus for future research, guided by the 4 rights construct of fluid stewardship.

Early diuretic use and mortality in critically ill patients with vasopressor support: a propensity score-matching analysis

Article

Full-text available

Dec 2019

Background The effect of loop diuretic use in critically ill patients on vasopressor support or in shock is unclear. This study aimed to explore the relationship between loop diuretic use and hospital mortality in critically ill patients with vasopressor support. Methods Data were extracted from the Medical Information Mart for Intensive Care III database. Adult patients with records of vasopressor use within 48 h after intensive care unit admission were screened. Multivariable logistic regression and propensity score matching was used to investigate any association. Results Data on 7828 patients were included. The crude hospital mortality was significantly lower in patients with diuretic use (166/1469 vs. 1171/6359, p < 0.001). In the extended multivariable logistic models, the odds ratio (OR) of diuretic use was consistently significant in all six models (OR range 0.56–0.75, p < 0.05 for all). In the subgroup analysis, an interaction effect was detected between diuretic use and fluid balance (FB). In the positive FB subgroup, diuretic use was significantly associated with decreased mortality (OR 0.64, 95% confidence interval (CI) 0.51–0.78) but was insignificant in the negative FB subgroup. In the other subgroups of mean arterial pressure, maximum sequential organ failure assessment score, and lactate level, the association between diuretic use and mortality remained significant and no interaction was detected. After propensity score matching, 1463 cases from each group were well matched. The mortality remained significantly lower in the diuretic use group (165/1463 vs. 231/1463, p < 0.001). Conclusions Although residual confounding cannot be excluded, loop diuretic use is associated with lower mortality. Electronic supplementary material The online version of this article (10.1186/s13054-019-2309-9) contains supplementary material, which is available to authorized users.

Principles of fluid management and stewardship in septic shock: it is time to consider the four D’s and the four phases of fluid therapy

Article

Full-text available

Dec 2018

In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.

Cumulative Fluid Balance and Mortality in Septic Patients With or Without Acute Kidney Injury and Chronic Kidney Disease

Article

Full-text available

Jun 2016

Objective: Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients. Design: Retrospective cohort study. Setting: Urban academic medical center ICU. Patients: ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15 mL/min/1.73 m or receiving chronic dialysis were excluded. Interventions: None. Measurements and main results: A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality in all patients (adjusted odds ratio, 1.06 [95% CI] 1.04-1.08; p < 0.001), and in each acute kidney injury/chronic kidney disease subgroup (adjusted odds ratio, 1.06 [1.03-1.09] for acute kidney injury+/chronic kidney disease+; 1.09 [1.05-1.13] for acute kidney injury-/chronic kidney disease+; 1.05 [1.03-1.08] for acute kidney injury+/chronic kidney disease-; and 1.07 [1.02-1.11] for acute kidney injury-/chronic kidney disease-). There was a significant interaction between acute kidney injury and chronic kidney disease on cumulative fluid balance (p =0.005) such that different cumulative fluid balance cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for acute kidney injury+/chronic kidney disease+; 3.8 L for acute kidney injury-/chronic kidney disease+; 4.3 L for acute kidney injury+/chronic kidney disease-; and 1.5 L for acute kidney injury-/chronic kidney disease-. The addition of cumulative fluid balance to the admission Sequential Organ Failure Assessment score had increased prognostic utility for hospital mortality when compared with Sequential Organ Failure Assessment alone, particularly in patients with acute kidney injury. Conclusions: Higher cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality regardless of acute kidney injury or chronic kidney disease presence. We characterized cumulative fluid balance cut-offs associated with hospital mortality based on acute kidney injury/chronic kidney disease status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.

Increased body mass index and adjusted mortality in ICU patients with sepsis or septic shock: A systematic review and meta-analysis

Article

Full-text available

Dec 2016

Background At least 25 % of adults admitted to intensive care units (ICU) in the United States have an overweight, obese or morbidly obese body mass index (BMI). The effect of BMI on adjusted mortality in adults requiring ICU treatment for sepsis is unclear. We performed a systematic review of adjusted all-cause mortality for underweight, overweight, obese and morbidly obese BMIs relative to normal BMI for adults admitted to the ICU with sepsis, severe sepsis, and septic shock. Method PubMed, the Cochrane Library, and EMBASE electronic databases were searched through November 18, 2015, without language restrictions. We included studies that reported multivariate regression analyses for all-cause mortality using standard BMI categories for adults admitted to the ICU for sepsis, severe sepsis, and septic shock. Articles were selected by consensus among multiple reviewers. Electronic database searches yielded 10,312 articles, of which six were eligible. Data were extracted by one reviewer and then reviewed by three independent reviewers. For the meta-analyses performed, the adjusted odds ratios (aOR) of mortality were combined using a random-effects model. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale for cohort studies. ResultsFour retrospective (n = 6609 patients) and two prospective (n = 556) studies met inclusion criteria. Compared to normal BMI, across five studies each, overweight or obese BMIs reduced the adjusted odds ratio (95 % CI) of mortality [aOR] [0.83 (0.75, 0.91) p < 0.001 and 0.82 (0.67, 0.99) p = 0.04, respectively] with low or moderate heterogeneity (I2 = 15.7 %, p = 0.31 and I2 = 53.0 %, p = 0.07, respectively). Across three studies each, morbidly obese BMI and underweight BMI did not alter aOR [0.90 (0.59, 1.39), p = 0.64; I2 = 43.3 %, p = 0.17; and 1.24 (0.79, 1.95), p = 0.35; I2 = 15.6 %, p = 0.31 respectively]. Only one study clearly defined how and when height and weight measurements were calculated. Site of underlying infection and illness severity may have favored overweight and obese BMIs. Conclusions This is the first meta-analysis to show that overweight or obese BMIs reduce adjusted mortality in adults admitted to the ICU with sepsis, severe sepsis, or septic shock. More rigorous studies that address these limitations are needed to clarify the impact of BMI on sepsis ICU outcomes. Trial registrationPROSPERO International prospective register of systematic reviews 10.15124/CRD42014010556. Registered on July 11, 2014.

Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: A systematic review with suggestions for clinical practice

Article

Full-text available

Nov 2014

Sepsis is associated with generalised endothelial injury and capillary leak and has traditionally been treated with large volume fluid resuscitation. Some patients with sepsis will accumulate bodily fluids. The aim of this study was to systematically review the association between a positive fluid balance/fluid overload and outcomes in critically ill adults, and to determine whether interventions aimed at reducing fluid balance may be linked with improved outcomes. We searched MEDLINE, PubMed, EMBASE, Web of Science, The Cochrane Database, clinical trials registries, and bibliographies of included articles. Two authors independently reviewed citations and selected studies examining the association between fluid balance and outcomes or where the intervention was any strategy or protocol that attempted to obtain a negative or neutral cumulative fluid balance after the third day of intensive care compared to usual care. The primary outcomes of interest were the incidence of IAH and mortality. Among all identified citations, one individual patient meta-analysis, 11 randomised controlled clinical trials, seven interventional studies, 24 observational studies, and four case series met the inclusion criteria. Altogether, 19,902 critically ill patients were studied. The cumulative fluid balance after one week of ICU stay was 4.4 L more positive in non-survivors compared to survivors. A restrictive fluid management strategy resulted in a less positive cumulative fluid balance of 5.6 L compared to controls after one week of ICU stay. A restrictive fluid management was associated with a lower mortality compared to patients treated with a more liberal fluid management strategy (24.7% vs 33.2%; OR, 0.42; 95% CI 0.32-0.55; P < 0.0001). Patients with intra-abdominal hypertension (IAH) had a more positive cumulative fluid balance of 3.4 L after one week of ICU stay. Interventions to decrease fluid balance resulted in a decrease in intra-abdominal pressure (IAP): an average total body fluid removal of 4.9 L resulted in a drop in IAP from 19.3 ± 9.1 mm Hg to 11.5 ± 3.9 mm Hg. A positive cumulative fluid balance is associated with IAH and worse outcomes. Interventions to limit the development of a positive cumulative fluid balance are associated with improved outcomes. In patients not transgressing spontaneously from the Ebb to Flow phases of shock, late conservative fluid management and late goal directed fluid removal (de-resuscitation) should be considered.

Four phases of intravenous fluid therapy: A conceptual model

Article

Full-text available

Sep 2014

I.V. fluid therapy plays a fundamental role in the management of hospitalized patients. While the correct use of i.v. fluids can be lifesaving, recent literature demonstrates that fluid therapy is not without risks. Indeed, the use of certain types and volumes of fluid can increase the risk of harm, and even death, in some patient groups. Data from a recent audit show us that the inappropriate use of fluids may occur in up to 20% of patients receiving fluid therapy. The delegates of the 12th Acute Dialysis Quality Initiative (ADQI) Conference sought to obtain consensus on the use of i.v. fluids with the aim of producing guidance for their use. In this article, we review a recently proposed model for fluid therapy in severe sepsis and propose a framework by which it could be adopted for use in most situations where fluid management is required. Considering the dose–effect relationship and side-effects of fluids, fluid therapy should be regarded similar to other drug therapy with specific indications and tailored recommendations for the type and dose of fluid. By emphasizing the necessity to individualize fluid therapy, we hope to reduce the risk to our patients and improve their outcome.

Fluid overload is associated with increases in length of stay and hospital costs: pooled analysis of data from more than 600 US hospitals

Article

Full-text available

Jun 2013

Fluid overload, including transfusion-associated circulatory overload (TACO), is a serious complication of fresh frozen plasma (FFP) transfusion. The incidence of fluid overload is underreported and its economic impact is unknown. An evaluation of fluid overload cases in US hospitals was performed to assess the impact of fluid overload on length and cost of hospital stay. Retrospective analysis was performed using a clinical and economic database covering >600 US hospitals. Data were collected for all inpatients discharged during 2010 who received ≥1 unit FFP during hospitalization. Incidence of fluid overload was determined through International Classification of Diagnosis (ICD-9) codes. Multivariate regression analysis was performed for primary outcome measures: hospital length of stay (LOS) and total hospital costs. Data were analyzed for 129,839 FFP-transfused patients, of whom 4,138 (3.2%) experienced fluid overload (including TACO). Multivariate analysis, adjusting for baseline characteristics, found that increased LOS and hospital costs were independently associated with fluid overload. Patients diagnosed with fluid overload had longer mean LOS (12.9 days versus 10.0 days; P < 0.001) and higher mean hospital cost per visit (

46,644 versus

32,582; P < 0.001) compared with patients without fluid overload. For a population of US inpatients who received FFP during hospitalization, fluid overload was associated with a 29% increase in LOS and a $14,062 increase in hospital costs per visit. These findings suggest that the incidence of fluid overload in the general population is greater than historically reported. A substantial economic burden may be associated with fluid overload in the US.

One size does not fit all in severe infection: obesity alters outcome, susceptibility, treatment, and inflammatory response

Article

Full-text available

Jun 2013

Obesity is an increasingly common comorbidity in critically ill patients. Whether obesity alters sepsis outcome, susceptibility, treatment, and response is not completely understood. We conducted a retrospective analysis comparing three group of septic shock patients based on the intervals of actual body mass index (BMI) in patients enrolled in the VASST (Vasopressin in Septic Shock Trial) cohort. Primary outcome measurement was 28-day mortality. We tested for differences in patterns of infection by comparing the primary site of infection and organism. We also compared the treatments (fluids and vasopressors) and inflammatory response, measuring adipose tissue-related cytokine concentrations (interleukin [IL]-6, monocyte chemotactic protein [MCP]-1, tumor necrosis factor [TNF]-alpha, and resistin) in plasma in a subset of 382 patients. Of the 778 patients in VASST, 730 patients who had body weight and height measurements were analyzed. Patients with BMI <25 kg/m2 (n=276) were grouped as a reference and compared to "overweight" (25< BMI <30 kg/m2, n=209) and "obese" (BMI >30 kg/m2, n=245) patients. Obese patients had the lowest 28-day mortality followed by overweight patients while patients with BMI <25 kg/m2 had the highest mortality (p=0.02). Compared to the patients with BMI <25 kg/m2, obese and overweight patients also had a different pattern of infection with less lung (obese 35%, overweight 45%, BMI<25 kg/m2 50%, p=0.003) and fungal infection (obese 8.2%, overweight 11%, and BMI<25 kg/m2 15.6%, p=0.03). Per kilogram, obese and overweight patients received less fluid during the first four days (p<0.05) and received less norepinephrine (obese 0.14, overweight 0.21, BMI <25 kg/m2 0.26 ug/kg/min, p<0.0001) and vasopressin (obese 0.28, overweight 0.36, BMI <25 kg/m2 0.43 uU/kg/min, p<0.0001) on day 1 compared to patients with BMI <25 kg/m2. Obese and overweight patients also had a lower plasma IL-6 concentration at baseline (obese 106 [IQR 34-686], overweight 190 [IQR 44-2339], BMI <25 kg/m2 235 [IQR 44-1793] pg/mL, p=0.046). Overall obesity was associated with improved survival in septic shock and differences in pattern of infection, fluids, and vasopressors. Importantly, the magnitude of inflammatory IL-6 response is muted in the obese.

Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: An international multicenter cohort study

Article

Full-text available

Apr 2013

Introduction Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients. Methods We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality. Results Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese). Conclusions The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012

Article

Full-text available

Feb 2013

OBJECTIVE:: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN:: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS:: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. RESULTS:: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS:: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

The FINNAKI study group: fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

Article

Full-text available

Oct 2012

Introduction Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality. Methods We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality. Results We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT. Conclusions Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.

1445: THE PHARMACIST ROLE IN FLUID STEWARDSHIP IN A MEDICAL ICU

Article

Jan 2020
CRIT CARE MED

Pathophysiology of Volume Administration in Septic Shock and the Role of the Clinical Pharmacist

Article

Nov 2019

Objective: To review physiological rationale and evidence base surrounding fluid harm to prepare the clinical pharmacist for accountability regarding volume-related outcomes. Data Sources: A PubMed/MEDLINE search was conducted using the following terms: (fluid therapy) AND [(critical care) OR (sepsis)] from 1966 to August 2019 published in English. Study Selection and Data Extraction: A total of 3364 citations were reviewed with only relevant clinical data extracted. Data Synthesis: Although early fluid resuscitation may be a necessary component to decrease mortality in the majority of patients with septic shock admitted to the intensive care unit (ICU), the benefit of continued administration after the first 24 hours is uncertain. Paradoxically, a positive fluid balance secondary to intravenous fluid receipt has been associated with diverse and perpetuating detriment on a multitude of organ systems after the first 24 hours of ICU stay. Continued clinical harm has been demonstrated on patient outcomes such as rates of mortality and length of stay. Despite the growing body of evidence supporting the potential adverse aspects of positive fluid balance, fluid overload remains common during critical care admission. Conclusion: Physiological concerns to overly zealous fluid administration and subsequent volume overload are vast. Relevance to Patient Care and Clinical Practice: Optimization of fluid balance in critically ill patients with sepsis is primed for clinical pharmacy intervention. Critical care pharmacists have the potential to improve patient care by optimizing fluid pharmacotherapy while potentially reducing adverse events, days on mechanical ventilation, and length of ICU stay.

Characterization of changes in medication complexity using a modified scoring tool

Article

Oct 2019

Purpose The purpose of this study was to characterize dynamic changes in medication regimen complexity over time in critically ill adults and to validate a modified version of the medication regimen complexity–intensive care unit (MRC-ICU) scoring tool. Summary A single-center, retrospective, observational chart review was conducted with a primary aim of assessing changes in medication regimen complexity over time, as measured by both the 39-item MRC-ICU scoring tool and a modified version (the mMRC-ICU) containing just 17 items. Secondary aims included validation of the mMRC-ICU and exploration of relationships between medication regimen complexity and ICU length of stay (LOS), inpatient mortality, and patient acuity. Adults admitted to a medical ICU from November 2016 through June 2017 were included. The medication regimens of a total of 130 patients were scored in order to test, modify, and validate the MRC-ICU and mMRC-ICU tools. The modified tool was validated by evaluating correlation of mMRC-ICU scores with MRC-ICU scores and with patient outcomes including patient acuity, ICU LOS, and inpatient mortality. mMRC-ICU scores were collected at 24 and 48 hours after admission and at ICU discharge to evaluate changes over time. Significant changes in medication regimen complexity over time were observed, with the highest scores observed at 24 hours after admission. Conclusion Medication regimen complexity may provide valuable insights into pharmacist activity and resource allocation. Further validation of the MRC-ICU and mMRC-ICU scoring tools in other critically ill populations and at external sites is required.

Medication Regimen Complexity is Associated With Pharmacist Interventions and Drug‐Drug Interactions: A Use of the Novel MRC‐ICU Scoring Tool

Article

Jun 2019

Background Clinical pharmacists are established members of the interprofessional patient care team, but limited guidance for the optimal utilization of pharmacy resources is available. Objective measurement of medication regimen complexity offers a novel process for evaluating pharmacist activity. The purpose of this study was to evaluate the relationship between medication regimen complexity, as measured by a novel medication regimen complexity scoring tool (MRC‐ICU), and both pharmacist interventions and drug‐drug interactions (DDIs). Methods This was a multi‐center, prospective, observational study. The electronic medical record was reviewed to collect patient demographics, patient outcomes, and MRC‐ICU and modified MRC‐ICU (mMRC‐ICU) score at 24, 48 hours, and at discharge. Pharmacist interventions were recorded during the patients' intensive care unit (ICU) stay. DDIs were also evaluated at 24, 48 hours, and at discharge. Spearman's rank‐order correlation was used to determine any correlation between the MRC‐ICU score at each time point and the number of pharmacist interventions and DDIs. Results A total of 153 patients were evaluated from both centers. The median MRC‐ICU at 24 hours was 11 (interquartile range [IQR] 7‐15). MRC‐ICU at 24 hours was correlated with interventions at 24 hours ( r s .439, P <.001). Furthermore, MRC‐ICU was correlated with total DDIs ( r s .4, P < .001). A modified version of the MRC‐ICU was also correlated with number of pharmacist interventions ( P < .001) and DDIs ( P < .001). Conclusions Medication regimen complexity showed a relationship with number of pharmacist interventions and number of DDIs.

Impact on Patient Outcomes of Pharmacist Participation in Multidisciplinary Critical Care Teams: A Systematic Review and Meta-Analysis

Article

May 2019
CRIT CARE MED

Objectives: The objective of this systematic review and meta-analysis was to assess the effects of including critical care pharmacists in multidisciplinary ICU teams on clinical outcomes including mortality, ICU length of stay, and adverse drug events. Data sources: PubMed, EMBASE, and references from previous relevant systematic studies. Study selection: We included randomized controlled trials and nonrandomized studies that reported clinical outcomes such as mortality, ICU length of stay, and adverse drug events in groups with and without critical care pharmacist interventions. Data extraction: We extracted study details, patient characteristics, and clinical outcomes. Data synthesis: From the 4,725 articles identified as potentially eligible, 14 were included in the analysis. Intervention of critical care pharmacists as part of the multidisciplinary ICU team care was significantly associated with the reduced likelihood of mortality (odds ratio, 0.78; 95% CI, 0.73-0.83; p < 0.00001) compared with no intervention. The mean difference in ICU length of stay was -1.33 days (95% CI, -1.75 to -0.90 d; p < 0.00001) for mixed ICUs. The reduction of adverse drug event prevalence was also significantly associated with multidisciplinary team care involving pharmacist intervention (odds ratio for preventable and nonpreventable adverse drug events, 0.26; 95% CI, 0.15-0.44; p < 0.00001 and odds ratio, 0.47; 95% CI, 0.28-0.77; p = 0.003, respectively). Conclusions: Including critical care pharmacists in the multidisciplinary ICU team improved patient outcomes including mortality, ICU length of stay in mixed ICUs, and preventable/nonpreventable adverse drug events.

Development and validation of a medication regimen complexity scoring tool for critically ill patients

Article

May 2019

Purpose The purpose of this study was to develop and validate a novel medication regimen complexity–intensive care unit (MRC-ICU) scoring tool in critically ill patients and to correlate MRC with illness severity and patient outcomes. Methods This study was a single-center, retrospective observational chart review of adults admitted to the medical ICU (MICU) between November 2016 and June 2017. The primary aim was the development and internal validation of the MRC-ICU scoring tool. Secondary aims included external validation of the MRC-ICU and exploration of relationships between medication regimen complexity and patient outcomes. Exclusion criteria included a length of stay of less than 24 hours in the MICU, active transfer, or hospice orders at 24 hours. A total of 130 patient medication regimens were used to test, modify, and validate the MRC-ICU tool. Results The 39-line item medication regimen complexity scoring tool was validated both internally and externally. Convergent validity was confirmed with total medications (p < 0.0001). Score discriminant validity was confirmed by lack of association with age (p = 0.1039) or sex (p = 0.7829). The MRC-ICU score was significantly associated with ICU length of stay (p = 0.0166), ICU mortality (p = 0.0193), and patient acuity (p < 0.0001). Conclusion The MRC-ICU scoring tool was validated and found to correlate with length of stay, inpatient mortality, and patient acuity.

1513: FLUID STEWARDSHIP

Article

Jan 2019
CRIT CARE MED

Deresuscitation of Patients With Iatrogenic Fluid Overload Is Associated With Reduced Mortality in Critical Illness

Article

Jul 2018
CRIT CARE MED

Objectives: To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness. Design: Retrospective cohort study. Setting: Ten ICUs in the United Kingdom and Canada. Patients: Adults receiving invasive mechanical ventilation for a minimum of 24 hours. Interventions: None. Measurements and main results: Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07-1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater fluid balance included treatment in a Canadian site. Conclusions: Fluid balance is a practice-dependent and potentially modifiable risk factor for adverse outcomes in critical illness. Negative fluid balance achieved with deresuscitation on day 3 of ICU stay is associated with improved patient outcomes. Minimization of day 3 fluid balance by limiting maintenance fluid intake and drug diluents, and using deresuscitative measures, represents a potentially beneficial therapeutic strategy which merits investigation in randomized trials.

Impact of Quality Bundle Enforcement by a Critical Care Pharmacist on Patient Outcome and Costs

Article

Nov 2017
CRIT CARE MED

Objectives: Surgical and medical ICU patients are at high risk of mortality and provide a significant cost to the healthcare system. The aim of this study is to describe the effect of pharmacist-led interventions on drug therapy and clinical strategies on ICU patient outcome and hospital costs. Design: Before and after study in two French ICUs (16 and 10 beds). Patients: ICU patients. Intervention: From January 1, 2013, to June 30, 2015, a pharmacist observation period was compared with an intervention period in which a critical care pharmacist provided recommendations to clinicians regarding sedative drugs and doses, choice of mechanical ventilation mode and related settings, antimicrobial de-escalation, and central venous and urinary catheters removal. Differences in ICU and hospital length of stay, duration of mechanical ventilation, mortality rate, and hospital costs per patient were quantified between groups with patients matched for severity of illness (Simplified Acute Physiology Score II) at admission. Measurements and main results: From the 1,519 and 1,268 admitted patients during the observation and intervention periods, respectively, 1,164 patients were evaluable in both groups after matching for Simplified Acute Physiology Score II score. The intervention period was associated with mean (95% CI) reductions in patient hospital length of stay (3.7 d [5.2-2.3 d]; p < 0.001), ICU length of stay (1.4 d [2.3-0.5 d]; p < 0.005), duration of mechanical ventilation (1.2 d [2.1-0.3 d]; p < 0.01), and hospital costs per stay (2,560 euros [3,728-1,392 euros]; p < 0.001). The overall cost savings were 10,840 euros (10,727-10,952 euros) per month, mostly due to reduced consumption of sedatives and antimicrobials. No impact on mortality rate was identified. Conclusions: Critical care pharmacist-led interventions were associated with decreases in ICU and hospital length of stays and ICU drug costs.

Initial fluid resuscitation following adjusted body weight dosing is associated with improved mortality in obese patients with suspected septic shock

Article

Aug 2017
J CRIT CARE

Objective: The optimal initial fluid resuscitation strategy for obese patients with septic shock is unknown. We evaluated fluid resuscitation strategies across BMI groups. Materials and methods: Retrospective analysis of 4157 patients in a multicenter activation pathway for treatment of septic shock between 2014 and 2016. Results: 1293 (31.3%) patients were obese (BMI≥30). Overall, higher BMI was associated with lower mortality, however this survival advantage was eliminated in adjusted analyses. Patients with higher BMI received significantly less fluid per kilogram at 3h than did patients with lower BMI (p≤0.001). In obese patients, fluid given at 3h mimicked a dosing strategy based on actual body weight (ABW) in 780 (72.2%), adjusted body weight (AdjBW) in 95 (8.8%), and ideal body weight (IBW) in 205 (19.0%). After adjusting for condition- and treatment-related variables, dosing based on AdjBW was associated with improved mortality compared to ABW (OR 0.45; 95% CI [0.19, 1.07]) and IBW (OR 0.29; 95% CI [0.11,0.74]). Conclusions: Using AdjBW to calculate initial fluid resuscitation volume for obese patients with suspected shock may improve outcomes compared to other weight-based dosing strategies. The optimal fluid dosing strategy for obese patients should be a focus of future prospective research.

Management of Hyperglycemic Crises

Article

May 2017

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are the most serious and life-threatening hyperglycemic emergencies in diabetes. DKA is more common in young people with type 1 diabetes and HHS in adult and elderly patients with type 2 diabetes. Features of the 2 disorders with ketoacidosis and hyperosmolality may coexist. Both are characterized by insulinopenia and severe hyperglycemia. Early diagnosis and management are paramount. Treatment is aggressive rehydration, insulin therapy, electrolyte replacement, and treatment of underlying precipitating events. This article reviews the epidemiology, pathogenesis, diagnosis, and management of hyperglycemic emergencies.

Intra-Abdominal Hypertension and Abdominal Compartment Syndrome: An Underappreciated Cause of Acute Kidney Injury

Article

May 2016

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome are increasingly recognized in both medical and surgical critically ill patients and are predictive of death and the development of acute kidney injury. Although there are many risk factors for the development of IAH, in the era of goal-directed therapy for shock, brisk volume resuscitation and volume overload are the most common contributors. Abdominal examination is an unreliable predictor of intra-abdominal pressure (IAP), but IAP can be easily measured in a reproducible and reliable manner by a number of simple bedside techniques. Prompt recognition and intervention to decrease IAP and improve vital organ perfusion are essential to minimize the negative effects of IAH on somatic and visceral organ functions.

Volume Overload: Prevalence, Risk Factors and Functional Outcome in Survivors of Septic Shock

Article

Sep 2015

Rationale: Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown. Objectives: This study describes patterns of fluid management both during and after septic shock, and examines factors associated with volume overload on intensive care unit (ICU) discharge. We then examine associations between volume overload on ICU discharge and mobility limitation and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes. Methods: We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital from June 2009 to April 2012, who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subject's admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression. Measurements and main results: Eighty-six percent of patients had a positive fluid balance and 35% had volume overload on ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.33-5.27, p=0.01) after adjusting for pre-existing conditions and severity of illness. Only 42% of patients received at least one dose of diuretic during their hospitalization. Volume overload on ICU discharge was independently associated with inability to ambulate on hospital discharge (OR 2.29, 95% CI 1.24-4.25, p=0.01) and, in patients admitted from home, discharge to a healthcare facility (OR 2.34, 95% CI 1.1-4.98, p=0.03). Conclusions: Volume overload is independently associated with impaired mobility and discharge to a healthcare facility in survivors of septic shock. Prevention and treatment of volume overload in patients with septic shock warrants further investigation.

Surviving Sepsis Campaign

Article

Feb 2013
CRIT CARE MED

Objective: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. Design: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Results: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Conclusions: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Fluid Overload in Patients With Severe Sepsis and Septic Shock Treated With Early Goal-Directed Therapy Is Associated With Increased Acute Need for Fluid-Related Medical Interventions and Hospital Death

Article

Sep 2014
SHOCK

Early-goal-directed therapy (EGDT) consists of early, aggressive fluid resuscitation and is known to improve survival in sepsis. It is unknown how often EGDT leads to subsequent fluid overload and whether post-EGDT fluid overload affects patients' outcomes. Our hypothesis was that septic patients treated with EGDT were at risk for fluid overload and that fluid overload would be associated with adverse outcomes. We conducted a retrospective cohort of 405 consecutive patients admitted with severe sepsis and septic shock to the medical intensive care unit of a tertiary care academic hospital from January 2008 to December 2009. Baseline demographics, daily weights, fluid status, clinical or radiographic evidence of fluid overload, and medical interventions (thoracentesis, paracentesis, diuretic use, and ultrafiltration) were abstracted and associations explored using univariate and multivariate logistic and linear regression analyses. At day 1, 67% of patients developed evidence of fluid overload and in 48% fluid overload persisted to day three. Inter-rater agreement for presence of fluid overload was substantial (kappa=0.7). An increased trend in weight was noted in those with persistent clinical and radiologic evidence of fluid overload, but not with recorded positive fluid balance. When adjusted for baseline severity of illness, fluid overload was associated with increased use of fluid-related medical interventions (thoracentesis and diuretics) and hospital mortality (OR 1.92 [1.16-3.22]). In patients with severe sepsis and septic shock treated with EGDT, clinical evidence of persistent fluid overload is common and is associated with increased use of medical interventions and hospital mortality.

Fluid resuscitation in septic shock: A positive fluid balance and elevated central venous pressure are associated with increased mortality

Article

Oct 2010

To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated with mortality. We conducted a retrospective review of the use of intravenous fluids during the first 4 days of care. Multicenter randomized controlled trial. The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were receiving a minimum of 5 μg of norepinephrine per minute. None. Based on net fluid balance, we determined whether one's fluid balance quartile was correlated with 28-day mortality. We also analyzed whether fluid balance was predictive of central venous pressure and furthermore whether a guideline-recommended central venous pressure of 8-12 mm Hg yielded a mortality advantage. At enrollment, which occurred on average 12 hrs after presentation, the average fluid balance was +4.2 L. By day 4, the cumulative average fluid balance was +11 L. After correcting for age and Acute Physiology and Chronic Health Evaluation II score, a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased mortality. Central venous pressure was correlated with fluid balance at 12 hrs, whereas on days 1-4, there was no significant correlation. At 12 hrs, patients with central venous pressure <8 mm Hg had the lowest mortality rate followed by those with central venous pressure 8-12 mm Hg. The highest mortality rate was observed in those with central venous pressure >12 mm Hg. Contrary to the overall effect, patients whose central venous pressure was <8 mm Hg had improved survival with a more positive fluid balance. A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased risk of mortality in septic shock. Central venous pressure may be used to gauge fluid balance ≤ 12 hrs into septic shock but becomes an unreliable marker of fluid balance thereafter. Optimal survival in the VASST study occurred with a positive fluid balance of approximately 3 L at 12 hrs.

Position paper on critical care pharmacy services. Society of Critical Care Medicine and American College of Clinical Pharmacy Task Force on Critical Care Pharmacy Services

Article

Dec 2000
CRIT CARE MED

The goal of the Task Force on Critical Care Pharmacy Services was to identify and describe the scope of practice that characterizes the critical care pharmacist and critical care pharmacy services. Specifically, the aims were to define the level of clinical practice and specialized skills characterizing the critical care pharmacist as clinician, educator, researcher, and manager; and to recommend fundamental, desirable, and optimal pharmacy services and personnel requirements for the provision of pharmaceutical care to critically ill patients. Hospitals having comprehensive resources as well as those with more limited resources were considered. Consensus opinion of critical care pharmacists from institutions of various sizes providing critical care services within several types of pharmacy practice models was obtained, including community-based and academic practice settings. Existing guidelines and literature describing pharmacy practice and medication use processes were reviewed and adapted for the critical care setting. By combining the strengths and expertise of critical care pharmacy specialists with existing supporting literature, these recommendations define the level of clinical practice and specialized skills that characterize the critical care pharmacist as clinician, educator, researcher, and manager. This Position Paper recommends fundamental, desirable, and optimal pharmacy services as well as personnel requirements for the provision of pharmaceutical care to critically ill patients.

Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state

Jan 2017
587-606

M Fayfman
Pasquel
Fj
G E Umpierrez

Fluid stewardship during critical illness: a call to action

Jan 2019

W A Hawkins
Smith
Se
A S Newsome

Identifying Intravenous Medication Classes Contributing to Intensive Care Unit Fluid Status. American College of Clinical Pharmacists (ACCP) Annual Meeting

Jan 2019

K S Gamble
Sikora Newsome
A Branan

Impact of quality bundle enforcement by a critical care pharmacist on patient outcome and costs

Jan 2018
199-207

G Leguelinel-Blache
Nguyen
Tl
B Louart

1513: Fluid stewardship: identifying hidden fluids as a target for fluid minimization

Jan 2019

A S Newsome
Smith
Se
W A Hawkins

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

Abstract

No full-text available

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