Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

An assessment of a sleep aid and sleep promotion practices in hospitalized medical patients.

BACKGROUND: Half of patients admitted to medicine units report sleep disruption, which increases the risk of sleep deprivation. Non-pharmacological interventions are the first step to improving sleep. However, utilization of sleep aids continues to be prevalent. Limited data are available on sleep aid prescribing practices across transitions of care. OBJECTIVES: The aim of this study was to describe the current practices for assessing sleep and prescribing pharmacologic agents to promote sleep in the adult medicine population. METHODS: This study was designed as a single-center, retrospective, observational cohort study of all patients discharged by the general medicine teams over a 3-month period (September 2019- November 2019). Prior to admission, inpatient and discharge prescriptions for sleep aids were recorded, and documentation of sleep assessments and non-pharmacological interventions were evaluated. RESULTS: Of 754 patients included, 211 (28%) were prescribed a sleep aid while inpatient. During hospitalization, 124 (16%) patients had at least one documented sleep assessment, and only 22 (3%) were ordered the institutional non-pharmacological sleep promotion order set. The most prescribed sleep aid in inpatients was melatonin (50%), as well as prior to admission (35%) and at discharge (25%). Overall, the relative reduction in sleep aid prescriptions between admission and discharge was 67%. CONCLUSION: Inpatient sleep aid prescribing is common in medical patients. Despite this, sleep assessments and the standard of care of non-pharmacological interventions are rarely utilized. Future efforts should focus on implementation of strategies to make sleep assessments and non-pharmacological sleep promotion routine and consistent in the inpatient setting.

State-of-the-Art Evaluation of Acute Adult Disorders of Consciousness for the General Intensivist.

OBJECTIVES: To provide a concise review of knowledge and practice pertaining to the diagnosis and initial management of unanticipated adult patient disorders of consciousness (DoC) by the general intensivist. DATA SOURCES: Detailed search strategy using PubMed and OVID Medline for English language articles describing adult patient acute DoC diagnostic evaluation and initial management strategies including indications for transfer. STUDY SELECTION: Descriptive and interventional studies that address acute adult DoC, their evaluation and initial management, indications for transfer, as well as outcome prognostication. DATA EXTRACTION: Relevant descriptions or studies were reviewed, and the following aspects of each manuscript were identified, abstracted, and analyzed: setting, study population, aims, methods, results, and relevant implications for adult critical care practice. DATA SYNTHESIS: Acute adult DoC may be categorized by etiology including structural, functional, infectious, inflammatory, and pharmacologic, the understanding of which drives diagnostic investigation, monitoring, acute therapy, and subsequent specialist care decisions including team-based local care as well as intra- and inter-facility transfer. CONCLUSIONS: Acute adult DoC may be initially comprehensively addressed by the general intensivist using an etiology-driven and team-based approach. Certain clinical conditions, procedural expertise needs, or resource limitations inform transfer decision-making within a complex care facility or to one with greater complexity. Emerging collaborative science helps improve our current knowledge of acute DoC to better align therapies with underpinning etiologies.

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.

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 (ß coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (ß coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (ß 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 (ß coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (ß coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (ß 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.

Sleep-Promotion Bundle Development, Implementation, and Evaluation in Critically Ill Adults: Roles for Pharmacists.

OBJECTIVE: To review evidence for intensive care unit (ICU) sleep improvement bundle use, identify preferred sleep bundle components and implementation strategies, and highlight the role for pharmacists in developing and evaluating bundle efforts. DATA SOURCES: Multiple databases were searched from January 1, 1990, to September 1, 2021, using the MeSH terms sleep, intensive care or critical care, protocol or bundle to identify comparative studies evaluating ICU sleep bundle implementation. STUDY SELECTION AND DATA EXTRACTION: Study screening, data extraction, and risk-of-bias evaluation were conducted in tandem. The ICU quality improvement literature and Institute for Healthcare Improvement bundle improvement guidance were also reviewed to identify recommended strategies for successful sleep bundle use. DATA SYNTHESIS: Nine studies (3 randomized, 1 quasi-experimental, 5 before-and-after) were identified. Bundle elements varied and were primarily focused on nonpharmacological interventions designed to be performed during either the day or night; only 2 studies included a medication-based strategy. Five studies were associated with reduced delirium; 2 studies were associated with improved total sleep time and 2 with improved patient-perceived sleep. Pharmacists were involved directly in 4 studies. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Sleep improvement bundles are recommended for use in all critically ill adults; specific bundle elements and ICU team member roles should be individualized at the institution/ICU level. Pharmacists can help lead bundle development efforts and routinely deliver key elements. CONCLUSIONS: Pharmacists can play an important role in the development and implementation of ICU sleep bundles. Further research regarding the relative benefit of individual bundle elements on relevant patient outcomes is needed.

Angiotensin II and Vasopressin for Vasodilatory Shock: A Critical Appraisal of Catecholamine-Sparing Strategies.

Vasodilatory shock is a serious medical condition that increases the morbidity and mortality of perioperative and critically ill patients. Norepinephrine is an established first-line therapy for this condition, but at high doses, it may lead to diminishing returns. Oftentimes, secondary noncatecholamine agents are required in those whose hypotension persists. Angiotensin II and vasopressin are both noncatecholamine agents available for the treatment of hypotension in vasodilatory shock. They have distinct modes of action and unique pharmacologic properties when compared to norepinephrine. Angiotensin II and vasopressin have shown promise in certain subsets of the population, such as those with acute kidney injury, high Acute Physiology and Chronic Health Evaluation II scores, or those receiving cardiac surgery. Any benefit from these drugs must be weighed against the risks, as overall mortality has not been shown to decrease mortality in the general population. The aims of this narrative review are to provide insight into the historical use of noncatecholamine vasopressors and to compare and contrast their unique modes of action, physiologic rationale for administration, efficacy, and safety profiles.

Continuation of Opioid Therapy at Transitions of Care in Critically Ill Patients.

PURPOSE: Opioids are one of the high-risk medication classes that are administered to critically ill patients during their intensive care unit (ICU) stay. However, little attention has been given to inpatient opioid prescribing practices, especially in critically ill patients. The purpose of our study was to characterize opioid prescribing practices across 2 transitions of care during an inpatient hospital stay: medical ICU (MICU)/intermediate care unit (IMC) to floor and floor to hospital discharge and identify potential patient-specific factors that impact opioid continuation. METHODS: This is a retrospective cohort study evaluating opioid-naive adult patients with new opioid therapy initiated in MICU/IMC at a tertiary care academic medical center from December 1, 2016, to November 30, 2017. Opioid continuation rate was assessed twice: transition 1 (MICU/IMC to floor) and transition 2 (floor to hospital discharge). RESULTS: In total, 112 opioid-naive patients with initial opioid administration in the MICU/IMC were included. Opioid therapy was continued in 56.1% (37/66) at transition 1 and 56.8% of patients (21/37) at transition 2. Patients with opioids continued at transition 1 had a longer hospital length of stay compared to those not continued on opioids, 22 (interquartile range [IQR] 11-36) vs 8 (IQR 6-14; P = .0004). Among the patients continued on opioids at hospital discharge, intubation during hospital stay and cumulative opioid dosage were greater than those not continued on opioids (17 [80.9%] vs 7 [43.8%], P = .019; and 3482 mcg [IQR 1690-9530] vs 732.5 mcg [IQR 187.5-1360.9], P = .0018, respectively). CONCLUSIONS: Opioid-naive patients receiving opioid therapy in the MICU/IMC had a continuation rate of >56% during transitions of care, including hospital discharge. Factors that contributed to the continuation of opioids at transitions of care included longer hospital length of stay, intubation, and cumulative hospital opioid dosage. These findings may help to provide health systems with guidance on targeted opioid stewardship programs.

Antimicrobial Therapy in Septic Shock Is Conservative During Resuscitation and Maintenance Phases.

Background: Maximal dosing of early antimicrobials with high loading and maintenance doses may optimize pharmacokinetic parameters to achieve and maintain therapeutic concentrations at the site of infection in septic shock. Little is known about the current practice of early antimicrobial dosing in septic shock. Objective: To characterize early antimicrobial dosing in patients in the resuscitation phase of septic shock. Methods: This retrospective cohort study included patients admitted to the medical intensive care unit (ICU) with septic shock. The primary outcome was the percentage of early antibiotic orders that were maximal or conservative during the resuscitation (0 to 48 hours) phase based on predefined dosing criteria. The secondary outcomes were the correlations of different dosing strategies on hospital length of stay (LOS), ICU LOS, and hospital mortality. Results: This study evaluated 161 patients and 692 antibiotic orders; 504 (72.8%) of the orders during the resuscitation phase were conservative. There were no differences in mortality (odds ratio = 0.66; 95% confidence interval = 0.35-1.25; P = .20), hospital LOS (median = 20 [interquartile range (IQR) = 10-34] vs 19 [IQR = 11-32] days; P = .93), or ICU LOS (median = 8 [IQR = 5-16] vs 9 [IQR = 5-15] days; P = .63) between maximal and conservative dosing groups, respectively, in the resuscitation phase. Limitations of this study included the use of institution-specific antimicrobial dosing guidelines and its retrospective nature. Conclusions: Early antibiotic dosing is conservative for a majority of patients in septic shock. Future studies are needed to evaluate the impact of dosing strategy on patient-centered outcomes in septic shock.

Experience with integrating pharmacist documenters on cardiac arrest teams to improve quality.

OBJECTIVES: To determine if adding a clinical pharmacist to the cardiac arrest team in a documenter role improves completeness of documentation and quality of advanced cardiovascular life support (ACLS). SETTING: A 1541-bed, tertiary care, academic medical center with an integrated clinical pharmacy practice model. PRACTICE DESCRIPTION: In 2012, we identified documentation of resuscitation activities during cardiac arrest events and compliance with published ACLS guidelines as opportunities for systematic quality improvement at our tertiary care academic medical center. Although clinical pharmacists provided pharmacotherapy support through active participation on multidisciplinary patient care rounds, pharmacists were not routinely accountable for care provided during cardiac arrest events. PRACTICE INNOVATION: We integrated pharmacists on the cardiac arrest team in the unique role of documenter and pharmacotherapy consultant. The pharmacist documenter was responsible for recording all activities (e.g., medication administered, endotracheal intubation, vital signs), providing real-time quality assurance during the event, and assisting with any clinical or operational needs of the team. Participating pharmacists received didactic lectures, practical assessments, and a written examination to ensure baseline competency in ACLS and teamwork principles. EVALUATION: Using a before-and-after study design, we conducted a retrospective chart review to evaluate our pilot program. All cardiac arrest events requiring activation of the cardiac arrest team from January 2012 through December 2013 were included (n = 80). RESULTS: Pharmacists attended all cardiac arrest team events in the postintervention period during the scheduled coverage hours. The percentage of forms with all documentation components complete increased from 0% at baseline to 28% postintervention (P = 0.002). ACLS compliance also increased from 8% preintervention to 31% postintervention (P = 0.024). CONCLUSION: Implementation of a dedicated pharmacist for documentation and pharmacotherapy consultation during cardiac arrest events is associated with improved documentation completeness and ACLS compliance. This was achieved without funding or additional pharmacist resources.

Next generation of critical care pharmacist practice studies: Beyond essential.

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.

Critical care pharmacist perspectives on optimal practice models and prioritization of professional activities: A cross-sectional survey.

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: Critical care pharmacists (CCPs) are essential members of the multidisciplinary critical care team. Professional activities of the CCP are outlined in a 2020 position paper on critical care pharmacy services. This study looks to characterize CCP perspectives for priorities in optimizing pharmacy practice models and professional activities. METHODS: This was a cross-sectional survey conducted from July 24 to September 20, 2023. A 41-question survey instrument was developed to assess 7 domains: demographics, CCP resource utilization, patient care, quality improvement, research and scholarship, training and education, and professional development. This voluntary survey was sent to members of the American College of Clinical Pharmacy's Critical Care Practice and Research Network. The survey was open for a total of 6 weeks. RESULTS: There was a response rate of 20.7% (332 of 1,605 invitees), with 66.6% of respondents (n = 221) completing at least 90% of the survey questions. Most respondents were clinical specialists (58.2%) and/or practiced at an academic medical center (58.5%). Direct patient care, quality improvement and medication safety, and teaching and precepting were identified as the CCP activities of highest importance to CCPs. The CCP-to-patient ratios considered ideal were 1:11-15 (selected by 49.8% of respondents) and 1:16-20 (33.9% of respondents). The ideal percentage of time dedicated to direct patient care activities, as identified by survey respondents, was 50% (interquartile range, 40-50). CONCLUSION: These findings highlight the professional activities viewed as having the highest priority by CCPs. Future research is needed to define optimal CCP practice models for the delivery of patient care in real-world settings.

Optimizing Pharmacist Team-Integration for ICU Patient Management: Rationale, Study Design, and Methods for a Multicentered Exploration of Pharmacist-to-Patient Ratio.

BACKGROUND: The workload of healthcare professionals including physicians and nurses in the ICU has an established relationship to patient outcomes, including mortality, length of stay, and other quality indicators; however, the relationship of critical care pharmacist workload to outcomes has not been rigorously evaluated and determined. The objective of our study is to characterize the relationship of critical care pharmacist workload in the ICU as it relates to patient-centered outcomes of critically ill patients. METHODS: Optimizing Pharmacist Team-Integration for ICU patient Management is a multicenter, observational cohort study with a target enrollment of 20,000 critically ill patients. Participating critical care pharmacists will enroll patients managed in the ICU. Data collection will consist of two observational phases: prospective and retrospective. During the prospective phase, critical care pharmacists will record daily workload data (e.g., census, number of rounding teams). During the retrospective phase, patient demographics, severity of illness, medication regimen complexity, and outcomes will be recorded. The primary outcome is mortality. Multiple methods will be used to explore the primary outcome including multilevel multiple logistic regression with stepwise variable selection to exclude nonsignificant covariates from the final model, supervised and unsupervised machine learning techniques, and Bayesian analysis. RESULTS: Our protocol describes the processes and methods for an observational study in the ICU. CONCLUSIONS: This study seeks to determine the relationship between pharmacist workload, as measured by pharmacist-to-patient ratio and the pharmacist clinical burden index, and patient-centered outcomes, including mortality and length of stay.

The Prevalence of Drug-Drug Interactions with Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Patients in the Intensive Care Unit.

Background: Persons living with human immunodeficiency virus (HIV) (PWH) on antiretroviral therapy (ART) are frequently admitted to the intensive care unit (ICU). Persons living with HIV on ART may be at higher risk for potential drug-drug interactions (pDDIs) due to polypharmacy in the ICU. We determined the prevalence of pDDI with ART in critically ill PWH. Objectives: The primary outcome was prevalence of pDDI between ART and ICU medications. Secondary outcomes included pDDI per ICU admission, pDDI severity, ICU, and hospital length of stay (LOS). Methods: A single-center, retrospective cohort evaluating PWH ≥ 18 years old admitted to the ICU for > 24 hours who received ART during ICU admission, between January 2013 and 2015 at a tertiary care hospital in the United States. Each ICU admission was counted as a separate encounter. Medication databases and chart review were used to identify pDDI. Results: We included 77 PWH encounters; mean age was 55 ± 9 years and 65% were male. We identified 208 pDDIs among 53/77 (68.8%), with a mean 4 ± 2 pDDI per ICU admission. Antipsychotics (20%), analgesics (20%), and anti-lipemics (11%) were the most common ICU medications with ART-related pDDI. Of the pDDI, 64% were major, 24% moderate, and 12% contraindicated. Median ICU and hospital LOS were 4 days (IQR: 3-5) and 11 days (IQR: 7-31), respectively. Conclusion: Most PWH had at least one pDDI during ICU admission. Collaborations among pharmacists, intensivists, and infectious disease/HIV specialists to develop effective, actionable strategies, such as electronic health record alerts, could reduce pDDIs for PWH on ART in the ICU.

Current Practice Review in the Management of Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) presents as an acute inflammatory lung injury characterized by refractory hypoxemia and non-cardiac pulmonary edema. An estimated 10% of patients in the intensive care unit and 25% of those who are mechanically ventilated are diagnosed with ARDS. Increased awareness is warranted as mortality rates remain high and delays in diagnosing ARDS are common. The COVID-19 pandemic highlights the importance of understanding ARDS management. Treatment of ARDS can be challenging due to the complexity of the disease state and conflicting existing evidence. Therefore, it is imperative that pharmacists understand both pharmacologic and non-pharmacologic treatment strategies to optimize patient care. This narrative review provides a critical evaluation of current literature describing management practices for ARDS. A review of treatment modalities and supportive care strategies will be presented.

Electrolyte considerations in targeted temperature management.

PURPOSE: Targeted temperature management (TTM), including normothermia and therapeutic hypothermia, is used primarily for comatose patients with return of spontaneous circulation after cardiac arrest or following neurological injury. Despite the potential benefits of TTM, risks associated with physiological alterations, including electrolyte shifts, may require intervention. SUMMARY: This review describes the normal physiological balance of electrolytes and temperature-related alterations as well as the impact of derangements on patient outcomes, providing general recommendations for repletion and monitoring of key electrolytes, including potassium, phosphate, and magnesium. CONCLUSION: Frequent monitoring and consideration of patient variables such as renal function and other risk factors for adverse effects are important areas of awareness for clinicians caring for patients undergoing TTM.

Caring for two in the ICU: Pharmacologic management of pregnancy-related complications.

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism.

Caring for two in the ICU: Pharmacotherapy in the critically ill pregnant patient.

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism.

Systematic review and meta-analysis of the correlation between bispectral index (BIS) and clinical sedation scales: Toward defining the role of BIS in critically ill patients.

INTRODUCTION: The bispectral index (BIS) is an attractive approach for monitoring level of consciousness in critically ill patients, particularly during paralysis, when commonly used sedation scales cannot be used. OBJECTIVES: As a first step toward establishing the utility of BIS during paralysis, this review examines the strength of correlation between BIS and clinical sedation scales in a broad population of non-paralyzed, critically ill adults. METHODS: We included studies evaluating the strength of correlation between concurrent assessments of BIS and Richmond Agitation Sedation Scale (RASS), Ramsay Sedation Scale (RSS), or Sedation Agitation Scale (SAS) in critically ill adult patients. Studies involving assessment of depth sedation periperative or procedural time periods, and those reporting BIS and sedation scale assessments conducted >5 min apart or while neuromuscular blocking agents (NMBA) were administered, were excluded. Data were abstracted on sedation scale, correlation coefficients, setting, patient characteristics, and BIS assessment characteristics that could impact the quality of the studies. RESULTS: Twenty-four studies which enrolled 1235 patients met inclusion criteria. The correlation between BIS and RASS, RSS, and SAS overall was 0.68 (95% confidence interval, 0.61-0.74, Ƭ2  = 0.06 I2  = 71.26%). Subgroup analysis by sedation scale indicated that the correlation between BIS and RASS, RSS, and SAS were 0.66 (95% confidence interval 0.58-0.73, Ƭ2  = 0.01 I2  = 30.20%), 0.76 (95% confidence interval 0.69-0.82, Ƭ2  = 0.04 I2  = 67.15%), and 0.53 (95% confidence interval 0.42-0.63, Ƭ2  = 0.01 I2  = 26.59%), respectively. Factors associated with significant heterogeneity included comparator clinical sedation scale, neurologic injury, and the type of intensive care unit (ICU) population. CONCLUSIONS: BIS demonstrated moderate to strong correlation with clinical sedation scales in adult ICU patients, providing preliminary evidence for the validity of BIS as a measure of sedation intensity when clinical scales cannot be used. Future studies should determine whether BIS monitoring is safe and effective in improving outcomes in patients receiving NMBA treatment.

Multicenter Retrospective Review of Ketamine Use in the ICU.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established. OBJECTIVES: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017. MAIN OUTCOMES AND MEASURES: Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after. RESULTS: A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation (n = 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior: 68.9% [66.7-72.6%], 0-24 hr: 78.6% [74.3-82.5%], 25-48 hr: 80.3% [74.6-84.3%]; p < 0.001) and time spent within goal sedation score (24 hr prior: 57.1% [52.5-60.0%], 0-24 hr: 64.1% [60.7-67.2%], 25-48 hr: 68.9% [65.5-79.5%]; p < 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 [25-400], 0-24 hr: 118 [10-363], 25-48 hr: 80 [5-328]; p < 0.005), midazolam (mg) equivalents (24 hr prior: 11 [4-67], 0-24 hr: 6 [0-68], 25-48 hr: 3 [0-57]; p < 0.001), propofol (mg) (24 hr prior: 942 [223-4,018], 0-24 hr: 160 [0-2,776], 25-48 hr: 0 [0-1,859]; p < 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 [276-1,925], 0-24 hr: 285 [0-1,283], 25-48 hr: 0 [0-826]; p < 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% [17.0-47.0%], 0-24 hr: 39.5% [27.0-43.8%], 25-48 hr: 0% [0-43.7%]; p = 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study. CONCLUSIONS AND RELEVANCE: There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased.

Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.