Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

Clinical Impact of the Implementation Strategies Used to Apply the 2013 Pain, Agitation/Sedation, Delirium or 2018 Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption Guideline Recommendations: A Systematic Review and Meta-Analysis.

OBJECTIVES: To summarize the effectiveness of implementation strategies for ICU execution of recommendations from the 2013 Pain, Agitation/Sedation, Delirium (PAD) or 2018 PAD, Immobility, Sleep Disruption (PADIS) guidelines. DATA SOURCES: PubMed, CINAHL, Scopus, and Web of Science were searched from January 2012 to August 2023. The protocol was registered with PROSPERO (CRD42020175268). STUDY SELECTION: Articles were included if: 1) design was randomized or cohort, 2) adult population evaluated, 3) employed recommendations from greater than or equal to two PAD/PADIS domains, and 4) evaluated greater than or equal to 1 of the following outcome(s): short-term mortality, delirium occurrence, mechanical ventilation (MV) duration, or ICU length of stay (LOS). DATA EXTRACTION: Two authors independently reviewed articles for eligibility, number of PAD/PADIS domains, quality according to National Heart, Lung, and Blood Institute assessment tools, implementation strategy use (including Assess, prevent, and manage pain; Both SAT and SBT; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; Family engagement and empowerment [ABCDEF] bundle) by Cochrane Effective Practice and Organization of Care (EPOC) category, and clinical outcomes. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. DATA SYNTHESIS: Among the 25 of 243 (10.3%) full-text articles included ( n = 23,215 patients), risk of bias was high in 13 (52%). Most studies were cohort ( n = 22, 88%). A median of 5 (interquartile range [IQR] 4-7) EPOC strategies were used to implement recommendations from two (IQR 2-3) PAD/PADIS domains. Cohort and randomized studies were pooled separately. In the cohort studies, use of EPOC strategies was not associated with a change in mortality (risk ratio [RR] 1.01; 95% CI, 0.9-1.12), or delirium (RR 0.92; 95% CI, 0.82-1.03), but was associated with a reduction in MV duration (weighted mean difference [WMD] -0.84 d; 95% CI, -1.25 to -0.43) and ICU LOS (WMD -0.77 d; 95% CI, -1.51 to 0.04). For randomized studies, EPOC strategy use was associated with reduced mortality and MV duration but not delirium or ICU LOS. CONCLUSIONS: Using multiple implementation strategies to adopt PAD/PADIS guideline recommendations may reduce mortality, duration of MV, and ICU LOS. Further prospective, controlled studies are needed to identify the most effective strategies to implement PAD/PADIS recommendations.

Role of a Pharmacist in Postdischarge Care for Patients With Kidney Disease: A Scoping Review.

OBJECTIVE: The objective was to explore and describe the role of pharmacists in providing postdischarge care to patients with kidney disease. DATA SOURCES: PubMed, Embase (Elsevier), CINAHL (Ebscohost), Web of Science Core Collection, and Scopus were searched on January 30, 2023. Publication date limits were not included. Search terms were identified based on 3 concepts: kidney disease, pharmacy services, and patient discharge. Experimental, quasi-experimental, observational, and qualitative studies, or study protocols, describing the pharmacist's role in providing postdischarge care for patients with kidney disease, excluding kidney transplant recipients, were eligible. STUDY SELECTION AND DATA EXTRACTION: Six unique interventions were described in 10 studies meeting inclusion criteria. DATA SYNTHESIS: Four interventions targeted patients with acute kidney injury (AKI) during hospitalization and 2 evaluated patients with pre-existing chronic kidney disease. Pharmacists were a multidisciplinary care team (MDCT) member in 5 interventions and were the sole provider in 1. Roles commonly identified include medication review, medication reconciliation, medication action plan formation, kidney function assessment, drug dose adjustments, and disease education. Some studies showed improvements in diagnostic coding, laboratory monitoring, medication therapy problem (MTP) resolution, and patient education; prevention of hospital readmission was inconsistent. Limitations include lack of standardized reporting of kidney disease, transitions of care processes, and differences in outcomes evaluated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review identifies potential roles of a pharmacist as part of a postdischarge MDCT for patients with varying degrees of kidney disease. CONCLUSIONS: The pharmacist's role in providing postdischarge care to patients with kidney disease is inconsistent. Multidisciplinary care teams including a pharmacist provided consistent identification and resolution of MTPs, improved patient education, and increased self-awareness of diagnosis.

Prevention and management of antibiotic associated acute kidney injury in critically ill patients: new insights.

PURPOSE OF REVIEW: Drug associated kidney injury (D-AKI) occurs in 19-26% of hospitalized patients and ranks as the third to fifth leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Given the high use of antimicrobials in the ICU and the emergence of new resistant organisms, the implementation of preventive measures to reduce the incidence of D-AKI has become increasingly important. RECENT FINDINGS: Artificial intelligence is showcasing its capabilities in early recognition of at-risk patients for acquiring AKI. Furthermore, novel synthetic medications and formulations have demonstrated reduced nephrotoxicity compared to their traditional counterparts in animal models and/or limited clinical evaluations, offering promise in the prevention of D-AKI. Nephroprotective antioxidant agents have had limited translation from animal studies to clinical practice. The control of modifiable risk factors remains pivotal in avoiding D-AKI. SUMMARY: The use of both old and new antimicrobials is increasingly important in combating the rise of resistant organisms. Advances in technology, such as artificial intelligence, and alternative formulations of traditional antimicrobials offer promise in reducing the incidence of D-AKI, while antioxidant medications may aid in minimizing nephrotoxicity. However, maintaining haemodynamic stability using isotonic fluids, drug monitoring, and reducing nephrotoxic burden combined with vigilant antimicrobial stewardship remain the core preventive measures for mitigating D-AKI while optimizing effective antimicrobial therapy.

Interventions, Barriers, and Proposed Solutions Associated With the Implementation of a Protocol That Uses Clinical Decision Support and a Stress Biomarker Test to Identify ICU Patients at High-Risk for Drug Associated Acute Kidney Injury.

BACKGROUND: Damage biomarkers are helpful in early identification of patients who are at risk of developing acute kidney injury (AKI). Investigations are ongoing to identify the optimal role of stress/damage biomarkers in clinical practice regarding AKI risk prediction, surveillance, diagnosis, and prognosis. OBJECTIVE: To determine the impact of utilizing a clinical decision support system (CDSS) to guide stress biomarker testing in intensive care unit (ICU) patients at risk for drug-induced acute kidney injury (D-AKI). METHODS: A protocol was designed utilizing a clinical decision support system (CDSS) alert to identify patients that were ordered 3 or more potentially nephrotoxic medications, suggesting risk for progressing to AKI from nephrotoxic burden. Once alerted to these high-risk patients, the pharmacist determined if action was needed by ordering a stress biomarker test, tissue inhibitor of metalloproteinase-2-insulin-like growth factor-binding protein 7 (TIMP-2•IGFBP7). If the biomarker test result was elevated, the pharmacist provided nephrotoxin stewardship recommendations to the team. Pharmacists recorded the response to the clinical decision support alert, ordering, and interpreting the TIMP-2•IGFBP7, and information regarding clinical interventions. An alert in conjunction with TIMP-2•IGFBP7 as a strategy for AKI risk prediction and stimulant for patient care management was assessed. In addition, barriers and solutions to protocol implementation were evaluated. RESULTS: There were 394 total activities recorded by pharmacists for 345 unique patients. Ninety-three (93/394; 23.6%) actionable alerts resulted in a TIMP-2•IGFBP7 test being ordered. Thirty-one TIMP-2•IGFBP7 results were >0.3 (31/81; 38.3%), suggesting a high-risk of progression to AKI, which prompted 191 pharmacist/team interventions. On average, there were 1.64 interventions per patient in the low-risk patients, 3.43 in high-risk patients, and 3.75 in the highest-risk patients. CONCLUSION AND RELEVANCE: Stress biomarkers can be used in conjunction with CDSS alerts to affect therapeutic decisions in ICU patients at high-risk for D-AKI.

Moving toward a contemporary classification of drug-induced kidney disease.

Drug-induced kidney disease (DIKD) accounts for about one-fourth of all cases of acute kidney injury (AKI) in hospitalized patients, especially in critically ill setting. There is no standard definition or classification system of DIKD. To address this, a phenotype definition of DIKD using expert consensus was introduced in 2015. Recently, a novel framework for DIKD classification was proposed that incorporated functional change and tissue damage biomarkers. Medications were stratified into four categories, including "dysfunction without damage," "damage without dysfunction," "both dysfunction and damage," and "neither dysfunction nor damage" using this novel framework along with predominant mechanism(s) of nephrotoxicity for drugs and drug classes. Here, we briefly describe mechanisms and provide examples of drugs/drug classes related to the categories in the proposed framework. In addition, the possible movement of a patient's kidney disease between certain categories in specific conditions is considered. Finally, opportunities and barriers to adoption of this framework for DIKD classification in real clinical practice are discussed. This new classification system allows congruencies for DIKD with the proposed categorization of AKI, offering clarity as well as consistency for clinicians and researchers.

Developing a Knowledge Graph for Pharmacokinetic Natural Product-Drug Interactions.

BACKGROUND: Pharmacokinetic natural product-drug interactions (NPDIs) occur when botanical or other natural products are co-consumed with pharmaceutical drugs. With the growing use of natural products, the risk for potential NPDIs and consequent adverse events has increased. Understanding mechanisms of NPDIs is key to preventing or minimizing adverse events. Although biomedical knowledge graphs (KGs) have been widely used for drug-drug interaction applications, computational investigation of NPDIs is novel. We constructed NP-KG as a first step toward computational discovery of plausible mechanistic explanations for pharmacokinetic NPDIs that can be used to guide scientific research. METHODS: We developed a large-scale, heterogeneous KG with biomedical ontologies, linked data, and full texts of the scientific literature. To construct the KG, biomedical ontologies and drug databases were integrated with the Phenotype Knowledge Translator framework. The semantic relation extraction systems, SemRep and Integrated Network and Dynamic Reasoning Assembler, were used to extract semantic predications (subject-relation-object triples) from full texts of the scientific literature related to the exemplar natural products green tea and kratom. A literature-based graph constructed from the predications was integrated into the ontology-grounded KG to create NP-KG. NP-KG was evaluated with case studies of pharmacokinetic green tea- and kratom-drug interactions through KG path searches and meta-path discovery to determine congruent and contradictory information in NP-KG compared to ground truth data. We also conducted an error analysis to identify knowledge gaps and incorrect predications in the KG. RESULTS: The fully integrated NP-KG consisted of 745,512 nodes and 7,249,576 edges. Evaluation of NP-KG resulted in congruent (38.98% for green tea, 50% for kratom), contradictory (15.25% for green tea, 21.43% for kratom), and both congruent and contradictory (15.25% for green tea, 21.43% for kratom) information compared to ground truth data. Potential pharmacokinetic mechanisms for several purported NPDIs, including the green tea-raloxifene, green tea-nadolol, kratom-midazolam, kratom-quetiapine, and kratom-venlafaxine interactions were congruent with the published literature. CONCLUSION: NP-KG is the first KG to integrate biomedical ontologies with full texts of the scientific literature focused on natural products. We demonstrate the application of NP-KG to identify known pharmacokinetic interactions between natural products and pharmaceutical drugs mediated by drug metabolizing enzymes and transporters. Future work will incorporate context, contradiction analysis, and embedding-based methods to enrich NP-KG. NP-KG is publicly available at https://doi.org/10.5281/zenodo.6814507. The code for relation extraction, KG construction, and hypothesis generation is available at https://github.com/sanyabt/np-kg.

Comparison of COVID-19 Preprint and Peer-Reviewed Versions of Studies on Therapies for Critically Ill Patients.

PURPOSE: Significant increases in the volume of preprint articles due to the COVID-19 pandemic, we examined the reliability of preprint articles compared to their peer-reviewed publications. MATERIALS AND METHODS: Preprint articles evaluating experimental studies of select treatment options (anticoagulation, dexamethasone, hydroxychloroquine, remdesivir, and tocilizumab) for COVID-19 in the critically ill, available in a peer-reviewed publication were screened for inclusion within Altmetric (n = 2040). A total of 40 articles met inclusion criteria, with 21 being randomly selected for evaluation. The primary outcome of this evaluation was a change in a study's reported primary outcome or statistical significance between preprint and peer-reviewed articles. Secondary outcomes included changes in primary/secondary outcome effect size and change in study conclusion. RESULTS: One article (4.8%, 95% CI 0.12%-23.8%) had a change in the primary outcome. Seven articles (33.3%, 95% CI 14.6%-57.0%) had a change in the primary outcome's effect measure. Five studies (23.8%, 95% CI 8.2%-47.2%) had changes in statistical significance of at least one secondary outcome. Four studies (19.0%, 95% CI 5.4%-41.9%) had a change in study conclusion. CONCLUSIONS: In preprint articles of COVID-19 treatments, the provided primary outcome is generally reliable, while interpretation of secondary outcomes should be made with caution, while awaiting completion of the peer-review process.

Nephrotoxin Exposure in the 3 Years following Hospital Discharge Predicts Development or Worsening of Chronic Kidney Disease among Acute Kidney Injury Survivors.

INTRODUCTION: Survivors of acute kidney injury (AKI) are at high risk of progression to chronic kidney disease (CKD), for which drugs may be a modifiable risk factor. METHODS: We conducted a population-based cohort study of Olmsted County, MN residents who developed AKI while hospitalized between January 1, 2006, and December 31, 2014, using Rochester Epidemiology Project data. Adults with a hospitalization complicated by AKI who survived at least 90 days after AKI development were included. Medical records were queried for prescription of potentially nephrotoxic medications over the 3 years after discharge. The primary outcome was de novo or progressive CKD defined by either a new diagnosis code for CKD or ≥30% decline in estimated glomerular filtration rate from baseline. The composite of CKD, AKI readmission, or death was also evaluated. RESULTS: Among 2,461 AKI survivors, 2,140 (87%) received a potentially nephrotoxic medication during the 3 years following discharge. When nephrotoxic medication use was analyzed in a time-dependent fashion, those actively prescribed at least one of these drugs experienced a significantly higher risk of de novo or progressive CKD (HR 1.38: 95% CI: 1.24, 1.54). Similarly, active potentially nephrotoxic medication use predicted a greater risk of the composite endpoint of CKD, AKI readmission, or death within 3 years of discharge (HR 1.41: 95% CI: 1.28, 1.56). CONCLUSION: In this population-based cohort study, AKI survivors actively prescribed one or more potentially nephrotoxic medications were at significantly greater risk for de novo or progressive CKD. An opportunity exists to reassess nephrotoxin appropriateness following an AKI episode to improve patient outcomes.

A Pharmacovigilance Study of Adverse Drug Reactions Reported for Cardiovascular Disease Medications Approved Between 2012 and 2017 in the United States Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

PURPOSE: Between 2012 and 2017, the FDA approved 29 therapies for a cardiovascular disease (CVD) indication. Due to the limited literature on patient safety outcomes for recently approved CVD medications, this study investigated adverse drug reports (ADRs) reported in the FDA Adverse Event Reporting System (FAERS). METHODS: A disproportionality analysis of spontaneously reported ADR was conducted. Reports in FAERS from Quarter 1, 2012, through Quarter 1, 2019, were compiled, allowing a 2-year buffer following drug approval in 2017. Top 10 reported ADRs and reporting odds ratios (ROR; confidence interval (CI)), a measure of disproportionality, were analyzed and compared to drugs available prior to 2012 as appropriate. RESULTS: Of 7,952,147 ADR reports, 95,016 (1.19%) consisted of reports for newly approved CVD medications. For oral anticoagulants, apixaban had significantly lower reports for anemia and renal failure compared to dabigatran and rivaroxaban but greater reports for neurological signs/symptoms, and arrhythmias. Evaluating heart failure drugs, sacubitril/valsartan had greater reports for acute kidney injury, coughing, potassium imbalances, and renal impairment but notably, lower for angioedema compared to lisinopril. Assessing familial hypercholesterolemia drugs, alirocumab had greater reports for joint-related-signs/symptoms compared to other agents in this category. A newer pulmonary arterial hypertension treatment, selexipag, had greater reports of reporting for bone/joint-related-signs/symptoms but riociguat had greater reports for hemorrhages and vascular hypotension. CONCLUSION: Pharmacovigilance studies allow an essential opportunity to evaluate the safety profile of CVD medications in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved CVD medications.

Incidence of Serum Creatinine Monitoring and Outpatient Visit Follow-Up among Acute Kidney Injury Survivors after Discharge: A Population-Based Cohort Study.

INTRODUCTION: Acute kidney injury (AKI) affects 20% of hospitalized patients and worsens outcomes. To limit complications, post-discharge follow-up and kidney function testing are advised. The objective of this study was to evaluate the frequency of follow-up after discharge among AKI survivors. METHODS: This was a population-based cohort study of adult Olmsted County residents hospitalized with an episode of stage II or III AKI between 2006 and 2014. Those dismissed from the hospital on dialysis, hospice, or who died within 30 days after discharge were excluded. The frequency and predictors of follow-up, defined as an outpatient serum creatinine (SCr) level or an in-person healthcare visit after discharge were described. RESULTS: In the 627 included AKI survivors, the 30-day cumulative incidence of a follow-up outpatient SCr was 80% (95% confidence interval [CI]: 76% and 83%), a healthcare visit was 82% (95% CI: 79 and 85%), or both was 70% (95% CI: 66 and 73%). At 90 days and 1 year after discharge, the cumulative incidences of meeting both follow-up criteria rose to 82 and 91%, respectively. Independent predictors of receiving both an outpatient SCr assessment and healthcare visit within 30 days included lower estimated glomerular filtration rate at discharge, higher comorbidity burden, longer length of hospitalization, and greater maximum AKI severity. Age, sex, race/ethnicity, education level, and socioeconomic status did not predict follow-up. CONCLUSIONS: Among patients with moderate to severe AKI, 30% did not have follow-up with a SCr and healthcare visit in the 30-day post-discharge interval. Follow-up was associated with higher acuity of illness rather than demographic or socioeconomic factors.

Health system perspectives in acute kidney injury: commitment to kidney health and planning implementation interventions.

PURPOSE OF REVIEW: To discuss a deliberate commitment by health systems to optimize kidney health and outcomes of patients who are at risk for or develop acute kidney injury (AKI) during hospitalization. RECENT FINDINGS: In 2019, the US Department of Health and Human Services set national goals targeted at improving the care and outcomes of patients with kidney disease including prevention by reducing the number of Americans who develop end-stage kidney disease (ESKD) by 25% by 2030. In response to this call to action, there is a need to focus on education to identify patients at high-risk for kidney disease development and progression, active surveillance methods to ensure timely identification, offering better follow-up care after an episode of AKI. A strategic approach to determining the health systems level of commitment and developing a plan for organizational change is discussed in this commentary. Items for consideration are structuring sound implementation projects and selecting implementation interventions. Clinical interventions to consider for implementation include the use of clinical decision support for detecting patients with AKI, novel biomarkers to determine patients at high-risk for AKI and nephrotoxin stewardship to prevent medication safety complications and drug-associated AKI. SUMMARY: There is a national call to action to improve the care and outcomes of patients with kidney disease. Health systems have an opportunity to respond by providing a high level of commitment towards ensuring the best kidney health for all patients equally. Deliberate change that is sustainable and scalable should be considered by all health systems.

Development of a Theory-Informed Behavior Change Intervention to Reduce Inappropriate Prescribing of Nephrotoxins and Renally Eliminated Drugs.

BACKGROUND: Goals of managing patients with acute kidney injury (AKI) are mitigating disease progression and ensuring safety while providing supportive care because no effective treatment exists. One strategy recommended in guidelines to meet these goals is optimizing medication management. Unfortunately, guideline implementation appears to be lacking as observed by the frequent occurrence of medication errors and adverse drug events. OBJECTIVE: To address this performance gap in the care of hospitalized patients receiving nephrotoxins and renally eliminated drugs, we sought to provide a potential intervention based on theory-informed behavior change. METHODS: Formative research with a qualitative analysis identifying what needs to change in patient care was completed by obtaining clinician opinion and expert opinion and reviewing the published literature. Frontline providers, including 8 physicians, 4 pharmacists, and a multiprofessional group of authors, provided insight into possible barriers to appropriate prescribing. Capability, Opportunity, Motivation and Behavior model and Theoretical Domain Framework were applied to characterize behavior change interventions and inform a potential implementation intervention for changing inappropriate prescribing behaviors. RESULTS: Lack of knowledge about appropriate drug management in patients at risk for adverse outcomes was provided as a major barrier. Other reported barriers included a lack of: (1) tools to assist with drug management, (2) motivation to make changes, (3) routinization, and (4) an accountable clinician. CONCLUSIONS AND RELEVANCE: Assigning a designated clinician to execute a stepwise, routine care process following the checklist provided is a recommended intervention to overcome barriers. The intended impact is behavior change that reduces inappropriate prescribing.

A Systemwide Approach for Navigating the Dilemma of Oral Factor Xa Inhibitor Interference With Unfractionated Heparin Anti-Factor Xa Concentrations.

BACKGROUND: Oral factor Xa inhibitors are known to significantly increase heparin anti-Xa concentrations, which leads to inaccuracies when monitoring intravenous unfractionated heparin (IV UFH). Guidance for managing this laboratory interference is lacking, creating substantial uncertainty in clinical practice. OBJECTIVE: To describe a strategy used by a large academic institution for managing the controversy of laboratory interference in the setting of oral factor Xa inhibitor use and provide effectiveness and safety data for this approach. METHODS: In December 2016, a new Heparin IV Direct Oral Anticoagulant (DOAC) Interference PowerPlan (a comprehensive order set) was made available in the electronic health record (Cerner, North Kansas City, MO) throughout the health system. We retrospectively examined 169 patients with events reported in the error reporting system, RISKMASTER, and evaluated reports with and without the use of the PowerPlan. Effectiveness was determined through evaluation of thrombosis. The Naranjo criteria for causality were applied to assess thrombotic events. RESULTS: Of 56 events that were reported with apixaban when the PowerPlan was not ordered, 4 (7%) thrombotic events occurred within 7 days of UFH initiation. One out of the 4 events (25%) that occurred when the PowerPlan was not appropriately initiated was considered probable using the Naranjo Scale. Three additional events (75%) were possible using the Naranjo Scale. CONCLUSION AND RELEVANCE: The Heparin IV DOAC Interference PowerPlan appears to be conducive to positive patient outcomes when evaluating voluntary reported events and may assist clinicians with managing the therapeutic dilemma of this laboratory interference.

Sedation, Analgesia, and Paralysis in COVID-19 Patients in the Setting of Drug Shortages.

The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global pandemic. The 2019 coronavirus disease (COVID-19) presents with a spectrum of symptoms ranging from mild to critical illness requiring intensive care unit (ICU) admission. Acute respiratory distress syndrome is a major complication in patients with severe COVID-19 disease. Currently, there are no recognized pharmacological therapies for COVID-19. However, a large number of COVID-19 patients require respiratory support, with a high percentage requiring invasive ventilation. The rapid spread of the infection has led to a surge in the rate of hospitalizations and ICU admissions, which created a challenge to public health, research, and medical communities. The high demand for several therapies, including sedatives, analgesics, and paralytics, that are often utilized in the care of COVID-19 patients requiring mechanical ventilation, has created pressure on the supply chain resulting in shortages in these critical medications. This has led clinicians to develop conservation strategies and explore alternative therapies for sedation, analgesia, and paralysis in COVID-19 patients. Several of these alternative approaches have demonstrated acceptable levels of sedation, analgesia, and paralysis in different settings but they are not commonly used in the ICU. Additionally, they have unique pharmaceutical properties, limitations, and adverse effects. This narrative review summarizes the literature on alternative drug therapies for the management of sedation, analgesia, and paralysis in COVID-19 patients. Also, this document serves as a resource for clinicians in current and future respiratory illness pandemics in the setting of drug shortages.

Dexmedetomidine for Facilitating Mechanical Ventilation Extubation in Difficult-to-Wean ICU Patients: Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Agitation and delirium are common in mechanically ventilated adult intensive care unit (ICU) patients and may contribute to delayed extubation times. Difficult-to-wean ICU patients have been associated with an increased risk of longer ICU length of stays and mortality. The purpose of this systematic review and meta-analysis is to evaluate the evidence of dexmedetomidine facilitating successful mechanical ventilation extubation in difficult-to-wean ICU patients and clinical outcomes. METHODS: A literature search was conducted using MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Global Health, Cochrane Central Register of Controlled Trials, Clinical Trial Registries, and the Health Technology Assessment Database from inception to December 5, 2019. Randomized controlled trials evaluating dexmedetomidine with the intended purpose to facilitate mechanical ventilation liberation in adult ICU patients (≥18 years) experiencing extubation failure were included. The primary outcome of time to extubation was evaluated using the weighted mean difference (WMD), with a random effects model. Secondary analyses included hospital and ICU length of stay, in-hospital mortality, hypotension, and bradycardia. RESULTS: A total of 6 trials (n = 306 patients) were included. Dexmedetomidine significantly reduced the time to extubation (WMD: -11.61 hours, 95% CI: -16.5 to -6.7, P = .005) and ICU length of stay (WMD: -3.04 days; 95% CI: -4.66 to -1.43). Hypotension risk was increased with dexmedetomidine (risk ratio [RR]: 1.62, 95% CI: 1.05-2.51), but there was no difference in bradycardia risk (RR: 3.98, 95% CI: 0.70-22.78). No differences were observed in mortality rates (RR: 1.30, 95% CI: 0.45-3.75) or hospital length of stay (WMD: -2.67 days; 95% CI: -7.73 to 2.39). CONCLUSIONS: Dexmedetomidine was associated with a significant reduction in the time to extubation and shorter ICU stay in difficult-to-wean ICU patients. Although hypotension risk was increased with dexmedetomidine, no differences in other clinical outcomes were observed.

Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference.

In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). The guideline was derived from evidence available through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing AKI. In April of 2019, KDIGO held a controversies conference entitled Acute Kidney Injury with the following goals: determine best practices and areas of uncertainty in treating AKI; review key relevant literature published since the 2012 KDIGO AKI guideline; address ongoing controversial issues; identify new topics or issues to be revisited for the next iteration of the KDIGO AKI guideline; and outline research needed to improve AKI management. Here, we present the findings of this conference and describe key areas that future guidelines may address.

Coronavirus Disease 2019 Pandemic Measures: Reports From a National Survey of 9,120 ICU Clinicians.

IMPORTANCE: Recent reports identify that among hospitalized coronavirus disease 2019 patients, 30% require ICU care. Understanding ICU resource needs remains an essential component of meeting current and projected needs of critically ill coronavirus disease 2019 patients. OBJECTIVES: This study queried U.S. ICU clinician perspectives on challenging aspects of care in managing coronavirus disease 2019 patients, current and anticipated resource demands, and personal stress. DESIGN, SETTING, AND PARTICIPANTS: Using a descriptive survey methodology, an anonymous web-based survey was administered from April 7, 2020, to April 22, 2020 (email and newsletter) to query members of U.S. national critical care organizations. MEASUREMENTS AND MAIN RESULTS: Through a 16-item descriptive questionnaire, ICU clinician perceptions were assessed regarding current and emerging critical ICU needs in managing the severe acute respiratory syndrome coronavirus 2 infected patients, resource levels, concerns about being exposed to severe acute respiratory syndrome coronavirus 2, and perceived level of personal stress. A total of 9,120 ICU clinicians responded to the survey, representing all 50 U.S. states, with 4,106 (56.9%) working in states with 20,000 or more coronavirus disease 2019 cases. The 7,317 respondents who indicated their profession included ICU nurses (n = 6,731, 91.3%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 4.5%), physicians (n = 212, 2.9%), respiratory therapists (n = 31, 0.4%), and pharmacists (n = 30, 0.4%). A majority (n = 6,510, 88%) reported having cared for a patient with presumed or confirmed coronavirus disease 2019. The most critical ICU needs identified were personal protective equipment, specifically N95 respirator availability, and ICU staffing. Minimizing healthcare worker virus exposure during care was believed to be the most challenging aspect of coronavirus disease 2019 patient care (n = 2,323, 30.9%). Nurses report a high level of concern about exposing family members to severe acute respiratory syndrome coronavirus 2 (median score of 10 on 0-10 scale). Similarly, the level of concern reached the maximum score of 10 in ICU clinicians who had provided care to coronavirus disease 2019 patients. CONCLUSIONS: This national ICU clinician survey identifies continued concerns regarding personal protective equipment supplies with the chief issue being N95 respirator availability. As the pandemic continues, ICU clinicians anticipate a number of limited resources that may impact ICU care including personnel, capacity, and surge potential, as well as staff and subsequent family members exposure to severe acute respiratory syndrome coronavirus 2. These persistent concerns greatly magnify personal stress, offering a therapeutic target for professional organization and facility intervention efforts.

Biomarker-guided management of acute kidney injury.

PURPOSE OF REVIEW: The current narrative review discusses practical applications of stress and damage biomarkers for the management of acute kidney injury (AKI) based on clinical trials and real-world evaluations. RECENT FINDINGS: In 2013 with the discovery and validation study of biomarkers for AKI (Sapphire) advancement in care was provided allowing for the early identification of patients at high risk for developing AKI. It was the combination of new biomarkers and the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for managing patients with AKI that provided an opportunity to improve patient care. In 2017, the PrevAKI study implemented KDIGO guideline management in high-risk patients identified by biomarkers followed in 2018 with the BigPAK study that used a similar approach, both of which demonstrated positive outcomes in patient care. Next, real-world evaluations followed supporting biomarker guided management of AKI in clinical practice. Also, proposals for better nephrotoxin management, a major modifiable exposure to prevent AKI, were provided with the foresight in identifying high-risk patients. SUMMARY: Stress and damage biomarker-based approaches to patient care seem to be promising for identifying patients at high risk for developing AKI and thus offers an opportunity for early management to prevent and ameliorate AKI and drug-associated AKI.

Adverse Hemodynamic Events Associated With Concomitant Dexmedetomidine and Propofol for Sedation in Mechanically Ventilated ICU Patients.

PURPOSE: Nonbenzodiazepines are preferred for continuous sedation in mechanically ventilated intensive care unit (ICU) patients. Although dexmedetomidine and propofol have blood pressure lowering properties, limited data exist about the hemodynamic effects of concomitant administration. The purpose of this study was to compare the adverse hemodynamic event rate with concomitant dexmedetomidine and propofol compared to either agent alone in mechanically ventilated ICU patients. METHODS: This retrospective cohort study was conducted at a university medical center. Adult ICU patients (≥18 years) admitted between October 20, 2015, and January 25, 2018, and administered concurrent dexmedetomidine and propofol or either agent alone for ≥24 hours were included. Mean arterial pressure, heart rate, and sedative dosing requirements were assessed from initiation to 72 hours after initiation. The primary end point was comparing the incidence of hypotension among study groups. Secondary aims compared the incidence of tachycardia and bradycardia as well as clinical outcomes. RESULTS: Overall, 276 patients were included among combination (n = 93), dexmedetomidine (n = 91), and propofol (n = 92) groups. The incidence of hypotension was significantly higher in patients administered concomitant dexmedetomidine and propofol (62.4%) compared to those administered dexmedetomidine (23.1%) or propofol (23.9%) alone (P < .0001). Adjunctive dexmedetomidine with propofol was also associated with higher rates of clinically relevant hypotension requiring treatment (P = .048). The tachycardia incidence in the concomitant, dexmedetomidine, and propofol groups were 30.1%, 28.6%, and 14.1%, respectively (P = 02). Only 1.4% (n = 4) of all study patients developed bradycardia. Concomitant therapy was an independent risk factor of hypotension compared to either dexmedetomidine (odds ratio [OR]: 6.7, 95% confidence interval [CI]: 2.61-17.3, P < .0001) or propofol (OR: 2.89, 95% CI: 1.24-6.74, P = .014) monotherapy. Patients experiencing hypotension were associated with worse clinical outcomes. CONCLUSION: Concomitant dexmedetomidine and propofol use in mechanically ventilated patients increased the risk of hypotensive events. Adjunctive dexmedetomidine with propofol administration in the critically ill warrants caution.