Facilitators and Barriers Influencing Antipsychotic Medication Prescribing and Deprescribing Practices in Critically Ill Adult Patients: a Qualitative Study.

BACKGROUND: Antipsychotic medications do not alter the incidence or duration of delirium, but these medications are frequently prescribed and continued at transitions of care in critically ill patients when they may no longer be necessary or appropriate. OBJECTIVE: The purpose of this study was to identify and describe relevant domains and constructs that influence antipsychotic medication prescribing and deprescribing practices among physicians, nurses, and pharmacists that care for critically ill adult patients during and following critical illness. DESIGN: We conducted qualitative semi-structured interviews with critical care and ward healthcare professionals including physicians, nurses, and pharmacists to understand antipsychotic prescribing and deprescribing practices for critically ill adult patients during and following critical illness. PARTICIPANTS: Twenty-one interviews were conducted with 11 physicians, five nurses, and five pharmacists from predominantly academic centres in Alberta, Canada, between July 6 and October 29, 2021. MAIN MEASURES: We used deductive thematic analysis using the Theoretical Domains Framework (TDF) to identify and describe constructs within relevant domains. KEY RESULTS: Seven TDF domains were identified as relevant from the analysis: Social/Professional role and identity; Beliefs about capabilities; Reinforcement; Motivations and goals; Memory, attention, and decision processes; Environmental context and resources; and Beliefs about consequences. Participants reported antipsychotic prescribing for multiple indications beyond delirium and agitation including patient and staff safety, sleep management, and environmental factors such as staff availability and workload. Participants identified potential antipsychotic deprescribing strategies to reduce ongoing antipsychotic medication prescriptions for critically ill patients including direct communication tools between prescribers at transitions of care. CONCLUSIONS: Critical care and ward healthcare professionals report several factors influencing established antipsychotic medication prescribing practices. These factors aim to maintain patient and staff safety to facilitate the provision of care to patients with delirium and agitation limiting adherence to current guideline recommendations.

Impact of Ketamine on Analgosedative Consumption in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to synthesize evidence available on continuous infusion ketamine versus nonketamine regimens for analgosedation in critically ill patients. DATA SOURCES: A search of MEDLINE, EMBASE, CINAHL, CDSR, and ClinicalTrials.gov was performed from database establishment to November 2021 using the following search terms: critical care, ICU, ketamine, sedation, and anesthesia. All studies included the primary outcome of interest: daily opioid and/or sedative consumption. STUDY SELECTION AND DATA EXTRACTION: Relevant human studies were considered. Randomized controlled trials (RCT), quasi-experimental studies, and observational cohort studies were eligible. Two reviewers independently screened articles, extracted data, and appraised studies using the Cochrane RoB and ROBINS-I tools. DATA SYNTHESIS: A total of 13 RCTs, 5 retrospective, and 1 prospective cohort study were included (2255 participants). The primary analysis of six RCTs demonstrated reduced opioid consumption with ketamine regimens (n = 494 participants, -13.19 µg kg-1 h-1 morphine equivalents, 95% CI -22.10 to -4.28, P = 0.004). No significant difference was observed in sedative consumption, duration of mechanical ventilation (MV), ICU or hospital length of stay (LOS), intracranial pressure, and mortality. Small sample size of studies may have limited ability to detect true differences between groups. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This meta-analysis examining ketamine use in critically ill patients is the first restricting analysis to RCTs and includes up-to-date publication of trials. Findings may guide clinicians in consideration and dosing of ketamine for multimodal analgosedation. CONCLUSION: Results suggest ketamine as an adjunct analgosedative has the potential to reduce opioid exposure in postoperative and MV patients in the ICU. More RCTs are required before recommending routine use of ketamine in select populations.

A scoping review of perceptions from healthcare professionals on antipsychotic prescribing practices in acute care settings.

BACKGROUND: Antipsychotic medications are frequently prescribed in acute care for clinical indications other than primary psychiatric disorders such as delirium. Unfortunately, they are commonly continued at hospital discharge and at follow-ups thereafter. The objective of this scoping review was to characterize antipsychotic medication prescribing practices, to describe healthcare professional perceptions on antipsychotic prescribing and deprescribing practices, and to report on antipsychotic deprescribing strategies within acute care. METHODS: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and Web of Science databases from inception date to July 3, 2021 for published primary research studies reporting on antipsychotic medication prescribing and deprescribing practices, and perceptions on those practices within acute care. We included all study designs excluding protocols, editorials, opinion pieces, and systematic or scoping reviews. Two reviewers screened and abstracted data independently and in duplicate. The protocol was registered on Open Science Framework prior to data abstraction (10.17605/OSF.IO/W635Z). RESULTS: Of 4528 studies screened, we included 80 studies. Healthcare professionals across all acute care settings (intensive care, inpatient, emergency department) perceived prescribing haloperidol (n = 36/36, 100%) most frequently, while measured prescribing practices reported common quetiapine prescribing (n = 26/36, 76%). Indications for antipsychotic prescribing were delirium (n = 48/69, 70%) and agitation (n = 20/69, 29%). Quetiapine (n = 18/18, 100%) was most frequently prescribed at hospital discharge. Three studies reported in-hospital antipsychotic deprescribing strategies focused on pharmacist-driven deprescribing authority, handoff tools, and educational sessions. CONCLUSIONS: Perceived antipsychotic prescribing practices differed from measured prescribing practices in acute care settings. Few in-hospital deprescribing strategies were described. Ongoing evaluation of antipsychotic deprescribing strategies are needed to evaluate their efficacy and risk.

Influence of sedation on delirium recognition in critically ill patients: A multinational cohort study.

BACKGROUND: Guidelines advocate intensive care unit (ICU) patients be regularly assessed for delirium using either the Confusion Assessment Method for the ICU (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC). Single-centre studies, primarily with the CAM-ICU, suggest level of sedation may influence delirium screening results. OBJECTIVE: The objective of this study was to determine the association between level of sedation and delirium occurrence in critically ill patients assessed with either the CAM-ICU or the ICDSC. METHODS: This was a secondary analysis of a multinational, prospective cohort study performed in nine ICUs from seven countries. Consecutive ICU patients with a Richmond Agitation-Sedation Scale (RASS) of -3 to 0 at the time of delirium assessment where a RASS ≤ 0 was secondary to a sedating medication. Patients were assessed with either the CAM-ICU or the ICDSC. Logistic regression analysis was used to account for factors with the potential to influence level of sedation or delirium occurrence. RESULTS: Among 1660 patients, 1203 patients underwent 5741 CAM-ICU assessments [9.6% were delirium positive; at RASS = 0 (3.3% were delirium positive), RASS = -1 (19.3%), RASS = -2 (35.1%); RASS = -3 (39.0%)]. The other 457 patients underwent 3210 ICDSC assessments [11.6% delirium positive; at RASS = 0 (4.9% were delirium positive), RASS = -1 (15.8%), RASS = -2 (26.6%); RASS = -3 (20.6%)]. A RASS of -3 was associated with more positive delirium evaluations (odds ratio: 2.31; 95% confidence interval: 1.34-3.98) in the CAM-ICU-assessed patients (vs. the ICDSC-assessed patients). At a RASS of 0, assessment with the CAM-ICU (vs. the ICDSC) was associated with fewer positive delirium evaluations (odds ratio: 0.58; 95% confidence interval: 0.43-0.78). At a RASS of -1 or -2, no association was found between the delirium assessment method used (i.e., CAM-ICU or ICDSC) and a positive delirium evaluation. CONCLUSIONS: The influence of level of sedation on a delirium assessment result depends on whether the CAM-ICU or ICDSC is used. Bedside ICU nurses should consider these results when evaluating their sedated patients for delirium. Future research is necessary to compare the CAM-ICU and the ICDSC simultaneously in sedated and nonsedated ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02518646.

Proton Pump Inhibitors in the Elderly Hospitalized Patient: Evaluating Appropriate Use and Deprescribing.

Background: Proton pump inhibitors (PPIs) are often prescribed for elderly patients without appropriate indication, or for longer durations than recommended. Objective: To review appropriateness of PPI use prior to and in hospital, and deprescribing rates across different hospital units. Methods: Retrospective analysis of patients ≥65 years admitted to 5 acute care units: intensive care unit, acute care for elderly, orthopedics, surgery, and medicine. Patients who were "non-naive" (prehospital PPI use) or "naive" (new PPI initiated in hospital) users were included. For both groups, demographics, reason for admission, length of stay, comorbidities, name and number of home medications, PPI name, dose and indication, and PPI discharge instructions were collected. For naive patients, duration of in-hospital use and prescriber specialty was recorded. Results: Among non-naive patients (n = 377), for 37 patients (10%), the indication for a PPI was not appropriate, and for 92 patients (24%), the indication was unclear. Most patients had their home PPI continued while in hospital (87%) and at discharge (90%). Among naive (n = 93) patients, for 8 patients (9%), the indication for a PPI was not appropriate, and for 25 (27%) patients, the indication was unclear. PPI was prescribed to only 16 (18%) by the gastrointestinal consult service. Most patients had their new PPI continued at discharge (74%); only 7 (9%) were discharged with a plan to reassess PPI indication. Conclusion: PPIs are infrequently deprescribed during hospital admission, despite inappropriate or unclear indications for use. Thorough medication reconciliation, documentation of PPI indication and duration, and institutional focus on deprescribing are encouraged.

External Validation of Two Models to Predict Delirium in Critically Ill Adults Using Either the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist for Delirium Assessment.

OBJECTIVES: To externally validate two delirium prediction models (early prediction model for ICU delirium and recalibrated prediction model for ICU delirium) using either the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist for delirium assessment. DESIGN: Prospective, multinational cohort study. SETTING: Eleven ICUs from seven countries in three continents. PATIENTS: Consecutive, delirium-free adults admitted to the ICU for greater than or equal to 6 hours in whom delirium could be reliably assessed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The predictors included in each model were collected at the time of ICU admission (early prediction model for ICU delirium) or within 24 hours of ICU admission (recalibrated prediction model for ICU delirium). Delirium was assessed using the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist. Discrimination was determined using the area under the receiver operating characteristic curve. The predictive performance was determined for the Confusion Assessment Method-ICU and Intensive Care Delirium Screening Checklist cohort, and compared with both prediction models' original reported performance. A total of 1,286 Confusion Assessment Method-ICU-assessed patients and 892 Intensive Care Delirium Screening Checklist-assessed patients were included. Compared with the area under the receiver operating characteristic curve of 0.75 (95% CI, 0.71-0.79) in the original study, the area under the receiver operating characteristic curve of the early prediction model for ICU delirium was 0.67 (95% CI, 0.64-0.71) for delirium as assessed using the Confusion Assessment Method-ICU and 0.70 (95% CI, 0.66-0.74) using the Intensive Care Delirium Screening Checklist. Compared with the original area under the receiver operating characteristic curve of 0.77 (95% CI, 0.74-0.79), the area under the receiver operating characteristic curve of the recalibrated prediction model for ICU delirium was 0.75 (95% CI, 0.72-0.78) for assessing delirium using the Confusion Assessment Method-ICU and 0.71 (95% CI, 0.67-0.75) using the Intensive Care Delirium Screening Checklist. CONCLUSIONS: Both the early prediction model for ICU delirium and recalibrated prediction model for ICU delirium are externally validated using either the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist for delirium assessment. Per delirium prediction model, both assessment tools showed a similar moderate-to-good statistical performance. These results support the use of either the early prediction model for ICU delirium or recalibrated prediction model for ICU delirium in ICUs around the world regardless of whether delirium is evaluated with the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist.

Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically Ill neonates, children and adults: A systematic review of clinical studies.

WHAT IS KNOWN AND OBJECTIVE: Many critically ill patients are exposed to opioids and benzodiazepines at high doses for prolonged periods, and upon discontinuation of these drugs, they may be at risk for iatrogenic withdrawal. Although this syndrome was associated with worse outcomes in the critically ill, limited guidance exists regarding its evaluation, prevention and treatment. This systematic review examined the frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and/or benzodiazepines in critically ill neonates, children and adults. METHODS: The literature search was conducted in PubMed, Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane register of systematic reviews, DARE, CINAHL, Trip database, CMA infobase and NICE evidence from inception to February 2018. Grey literature was examined. We included studies reporting frequency, risk factors or symptomatology of iatrogenic withdrawal of opioids, benzodiazepines (or both) in critically ill patients. We considered all study designs except case reports and case series. We excluded studies on neonatal abstinence syndrome, alcohol withdrawal, studies on chronic opioid and/or benzodiazepine users and studies on prevention or treatment of withdrawal in critical care patients. Two independent reviewers applied the inclusion and exclusion criteria. Pairs of reviewers independently abstracted data and evaluated methodological quality using the Cochrane Collaboration Tool, Newcastle-Ottawa or QUADAS-2. Details regarding study design, outcomes, definition, evaluation and type of withdrawal (opioid, benzodiazepine or mixed) were collected. Cumulative doses and duration of opioids and benzodiazepines were collected. RESULTS AND DISCUSSION: We identified 21 866 unique citations and 153 full texts were assessed for eligibility. Thirty-four studies were included; the majority were observational and few included adults. In prospective studies, mixed withdrawal was observed in 7.5%-100% of patients in paediatric studies and ranged from 16.7% to 55% in adults. Symptomatology of withdrawal was not well described. Risk factors included higher cumulative dose and prolonged administration of opioids and benzodiazepines. WHAT IS NEW AND CONCLUSION: Iatrogenic withdrawal appears to be a frequent syndrome in critical care patients who received regular doses of opioids and/or benzodiazepines for ≥72 hours. Larger studies are required, especially in critically ill adults, to better define the syndrome and its symptomatology.

Delirium prediction in the intensive care unit: comparison of two delirium prediction models.

BACKGROUND: Accurate prediction of delirium in the intensive care unit (ICU) may facilitate efficient use of early preventive strategies and stratification of ICU patients by delirium risk in clinical research, but the optimal delirium prediction model to use is unclear. We compared the predictive performance and user convenience of the prediction  model for delirium (PRE-DELIRIC) and early prediction model for delirium (E-PRE-DELIRIC) in ICU patients and determined the value of a two-stage calculation. METHODS: This 7-country, 11-hospital, prospective cohort study evaluated consecutive adults admitted to the ICU who could be reliably assessed for delirium using the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist. The predictive performance of the models was measured using the area under the receiver operating characteristic curve. Calibration was assessed graphically. A physician questionnaire evaluated user convenience. For the two-stage calculation we used E-PRE-DELIRIC immediately after ICU admission and updated the prediction using PRE-DELIRIC after 24 h. RESULTS: In total 2178 patients were included. The area under the receiver operating characteristic curve was significantly greater for PRE-DELIRIC (0.74 (95% confidence interval 0.71-0.76)) compared to E-PRE-DELIRIC (0.68 (95% confidence interval 0.66-0.71)) (z score of - 2.73 (p < 0.01)). Both models were well-calibrated. The sensitivity improved when using the two-stage calculation in low-risk patients. Compared to PRE-DELIRIC, ICU physicians (n = 68) rated the E-PRE-DELIRIC model more feasible. CONCLUSIONS: While both ICU delirium prediction models have moderate-to-good performance, the PRE-DELIRIC model predicts delirium better. However, ICU physicians rated the user convenience of E-PRE-DELIRIC superior to PRE-DELIRIC. In low-risk patients the delirium prediction further improves after an update with the PRE-DELIRIC model after 24 h. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02518646 . Registered on 21 July 2015.

Iatrogenic Opioid Withdrawal in Critically Ill Patients: A Review of Assessment Tools and Management.

OBJECTIVE: To (1) provide an overview of the epidemiology, clinical presentation, and risk factors of iatrogenic opioid withdrawal in critically ill patients and (2) conduct a literature review of assessment and management of iatrogenic opioid withdrawal in critically ill patients. DATA SOURCES: We searched MEDLINE (1946-June 2017), EMBASE (1974-June 2017), and CINAHL (1982-June 2017) with the terms opioid withdrawal, opioid, opiate, critical care, critically ill, assessment tool, scale, taper, weaning, and management. Reference list of identified literature was searched for additional references as well as www.clinicaltrials.gov . STUDY SELECTION AND DATA EXTRACTION: We restricted articles to those in English and dealing with humans. DATA SYNTHESIS: We identified 2 validated pediatric critically ill opioid withdrawal assessment tools: (1) Withdrawal Assessment Tool-Version 1 (WAT-1) and (2) Sophia Observation Withdrawal Symptoms Scale (SOS). Neither tool differentiated between opioid and benzodiazepine withdrawal. WAT-1 was evaluated in critically ill adults but not found to be valid. No other adult tool was identified. For management, we identified 5 randomized controlled trials, 2 prospective studies, and 2 systematic reviews. Most studies were small and only 2 studies utilized a validated assessment tool. Enteral methadone, α-2 agonists, and protocolized weaning were studied. CONCLUSION: We identified 2 validated assessment tools for pediatric intensive care unit patients; no valid tool for adults. Management strategies tested in small trials included methadone, α-2 agonists, and protocolized sedation/weaning. We challenge researchers to create validated tools assessing specifically for opioid withdrawal in critically ill children and adults to direct management.

The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness.

BACKGROUND: Patients with 2009 pandemic influenza A(H1N1pdm09)-related critical illness were frequently treated with systemic corticosteroids. While observational studies have reported significant corticosteroid-associated mortality after adjusting for baseline differences in patients treated with corticosteroids or not, corticosteroids have remained a common treatment in subsequent influenza outbreaks, including avian influenza A(H7N9). Our objective was to describe the use of corticosteroids in these patients and investigate predictors of steroid prescription and clinical outcomes, adjusting for both baseline and time-dependent factors. METHODS: In an observational cohort study of adults with H1N1pdm09-related critical illness from 51 Canadian ICUs, we investigated predictors of steroid administration and outcomes of patients who received and those who did not receive corticosteroids. We adjusted for potential baseline confounding using multivariate logistic regression and propensity score analysis and adjusted for potential time-dependent confounding using marginal structural models. RESULTS: Among 607 patients, corticosteroids were administered to 280 patients (46.1%) at a median daily dose of 227 (interquartile range, 154-443) mg of hydrocortisone equivalents for a median of 7.0 (4.0-13.0) days. Compared with patients who did not receive corticosteroids, patients who received corticosteroids had higher hospital crude mortality (25.5% vs 16.4%, p = 0.007) and fewer ventilator-free days at 28 days (12.5 ± 10.7 vs 15.7 ± 10.1, p < 0.001). The odds ratio association between corticosteroid use and hospital mortality decreased from 1.85 (95% confidence interval 1.12-3.04, p = 0.02) with multivariate logistic regression, to 1.71 (1.05-2.78, p = 0.03) after adjustment for propensity score to receive corticosteroids, to 1.52 (0.90-2.58, p = 0.12) after case-matching on propensity score, and to 0.96 (0.28-3.28, p = 0.95) using marginal structural modeling to adjust for time-dependent between-group differences. CONCLUSIONS: Corticosteroids were commonly prescribed for H1N1pdm09-related critical illness. Adjusting for only baseline between-group differences suggested a significant increased risk of death associated with corticosteroids. However, after adjusting for time-dependent differences, we found no significant association between corticosteroids and mortality. These findings highlight the challenges and importance in adjusting for baseline and time-dependent confounders when estimating clinical effects of treatments using observational studies.

Analgesic, sedative, antipsychotic, and neuromuscular blocker use in Canadian intensive care units: a prospective, multicentre, observational study.

PURPOSE: Our aim was to describe analgo-sedation and antipsychotic and neuromuscular blocking drug (NMBD) use in critically ill patients, management strategies, and variables associated with these practice patterns. METHODS: This prospective observational study in 51 intensive care units (ICUs) included all patients who underwent invasive mechanical ventilation (MV) over a two-week period during 2008-2009. RESULTS: We included 712 patients representing 3,620 patient-days. Median MV duration was 3.0 days (interquartile range 2-6). During MV, 92% of patients received analgo-sedation, 32% an adjunct agent (e.g., acetaminophen), 18% NMBDs, and 10% antipsychotics. Opioids were used more frequently than benzodiazepines or propofol (84.8% vs 62.2% vs 10.1% patients, respectively, P < 0.0001). Independent predictors of opioid and benzodiazepine use were a longer MV duration, assessment scales, physical restraints, and university-affiliated hospital. Although more than 50% of ICUs reported that assessment tools, protocols, and daily sedation interruption (DSI) were available for use, application was modest: sedation scale 53.0%, pain scale 19.1%, delirium scale 5.2%, protocol 25.0%, DSI 42.1%. Accidental device removal occurred in 4.6% of patients, with 75.8% of events during DSI. Daily sedation interruption was associated with protocol use, physical restraints, university-affiliated hospital, and short-duration MV. Variables associated with protocol use included assessment scales, longer MV duration, lack of physical restraints, and admission to a community hospital. CONCLUSION: Nearly all MV patients received analgo-sedation. Opioids were used more often than sedatives despite infrequent use of pain scales. Few patients received antipsychotic therapy, but physical restraint was common. Protocol use was poor compared to DSI. Duration of MV predicted the use of either.

Venous thromboembolism in critically ill adult patients with hematologic malignancy: a population-based cohort study.

PURPOSE: The aim of this study was to describe the incidence of venous thromboembolism (VTE) and major bleeding among hospitalized patients with hematologic malignancy, assessing its association with critical illness and other baseline characteristics. METHODS: We conducted a population-based cohort study of hospitalized adults with a new diagnosis of hematologic malignancy in Ontario, Canada, between 2006 and 2017. The primary outcome was VTE (pulmonary embolism or deep venous thrombosis). Secondary outcomes were major bleeding and in-hospital mortality. We compared the incidence of VTE between intensive care unit (ICU) and non-ICU patients and described the association of other baseline characteristics and VTE. RESULTS: Among 76,803 eligible patients (mean age 67 years [standard deviation, SD, 15]), 20,524 had at least one ICU admission. The incidence of VTE was 3.7% in ICU patients compared to 1.2% in non-ICU patients (odds ratio [OR] 3.08; 95% confidence interval [CI] 2.77-3.42). The incidence of major bleeding was 7.6% and 2.4% (OR 3.33; 95% CI 3.09-3.58), respectively. The association of critical illness and VTE remained significant after adjusting for potential confounders (OR 2.92; 95% CI 2.62-3.25). We observed a higher incidence of VTE among specific subtypes of hematologic malignancy and patients with prior VTE (OR 6.64; 95% CI 5.42-8.14). Admission more than 1 year after diagnosis of hematologic malignancy (OR 0.64; 95% CI 0.56-0.74) and platelet count ≤ 50 × 109/L at the time of hospitalization (OR 0.63; 95% CI 0.48-0.84) were associated with a lower incidence of VTE. CONCLUSION: Among patients with hematologic malignancy, critical illness and certain baseline characteristics were associated with a higher incidence of VTE.

Use of sedation and neuromuscular blockers in critically ill adults receiving high-frequency oscillatory ventilation.

BACKGROUND: Nearly all patients receive sedation and neuromuscular blockers (NMBs) during high-frequency oscillatory ventilation (HFOV). OBJECTIVE: To describe analgo-sedation and NMB use prior to and during HFOV in adults with acute respiratory distress syndrome. METHODS: Retrospective single-center study of 131 consecutive adults whose care was managed with HFOV from 2002 to 2011. RESULTS: During the first 4 days of HFOV, 89% and 95% of patients received sedation and opioids, respectively. Upon HFOV initiation, 119 (90.8%) patients received fentanyl doses higher than 200 µg/h; of these, 48 also received more than 20 mg/h of midazolam. Analgo-sedation doses increased significantly over time such that doses were double by day 3. Factors independently associated with fentanyl doses higher than 200 µg/h were NMB ever used (OR 4.43; 95% CI 1.26-15.65, p = 0.02), pH less than 7.15 (OR 2.08; 95% CI 1.22-3.5, p = 0.007), worsening partial pressure of oxygen/fraction of inspired oxygen (OR 1.05; 95% CI 1.00-1.10, p = 0.04), and Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR 0.87; 95% CI 0.79-0.97, p = 0.009). Deep sedation was commonly administered when NMBs were not being used, with 99.2% of sedation-agitation scores of 1 or 2. Eighty-six patients (65.6%) received NMBs and use was greatest on day 1 (59.5%). Train-of-Four was measured every hour for 53.4% of patients; 29.2% of the measurements were 0 of 4. NMB use declined over the 10-year study period. CONCLUSIONS: High analgo-sedation doses were associated with APACHE II scores, worsening gas exchange, and NMB use. Two thirds of patients received NMBs; use was highest on day 1 and subsequently declined. The percentage of patients who received NMB during HFOV in our study was lower than that previously reported. Future research should evaluate patient outcomes with and without use of NMBs, as well as the potential to manage patients with less sedation.

Impacts of antipsychotic medication prescribing practices in critically ill adult patients on health resource utilization and new psychoactive medication prescriptions.

BACKGROUND: Antipsychotic medications are commonly prescribed to critically ill adult patients and initiation of new antipsychotic prescriptions in the intensive care unit (ICU) increases the proportion of patients discharged home on antipsychotics. Critically ill adult patients are also frequently exposed to multiple psychoactive medications during ICU admission and hospitalization including benzodiazepines and opioid medications which may increase the risk of psychoactive polypharmacy following hospital discharge. The associated impact on health resource utilization and risk of new benzodiazepine and opioid prescriptions is unknown. RESEARCH QUESTION: What is the burden of health resource utilization and odds of new prescriptions of benzodiazepines and opioids up to 1-year post-hospital discharge in critically ill patients with new antipsychotic prescriptions at hospital discharge? STUDY DESIGN & METHODS: We completed a multi-center, propensity-score matched retrospective cohort study of critically ill adult patients. The primary exposure was administration of ≥1 dose of an antipsychotic while the patient was admitted in the ICU and ward with continuation at hospital discharge and a filled outpatient prescription within 1-year following hospital discharge. The control group was defined as no doses of antipsychotics administered in the ICU and hospital ward and no filled outpatient prescriptions for antipsychotics within 1-year following hospital discharge. The primary outcome was health resource utilization (72-hour ICU readmission, 30-day hospital readmission, 30-day emergency room visitation, 30-day mortality). Secondary outcomes were administration of benzodiazepines and/or opioids in-hospital and following hospital discharge in patients receiving antipsychotics. RESULTS: 1,388 propensity-score matched patients were included who did and did not receive antipsychotics in ICU and survived to hospital discharge. New antipsychotic prescriptions were not associated with increased health resource utilization or 30-day mortality following hospital discharge. There was increased odds of new prescriptions of benzodiazepines (adjusted odds ratio [aOR] 1.61 [95%CI 1.19-2.19]) and opioids (aOR 1.82 [95%CI 1.38-2.40]) up to 1-year following hospital discharge in patients continuing antipsychotics at hospital discharge. INTERPRETATION: New antipsychotic prescriptions at hospital discharge are significantly associated with additional prescriptions of benzodiazepines and opioids in-hospital and up to 1-year following hospital discharge.

Measures for the Core Outcome Set for Research Evaluating Interventions to Prevent and/or Treat Delirium in Critically Ill Adults: An International Consensus Study (Del-COrS).

To gain consensus on measurement methods for outcomes (delirium occurrence, severity, time to resolution, mortality, health-related quality of life [HrQoL], emotional distress including anxiety, depression, acute stress, and post-traumatic stress disorder, and cognition) of our Core Outcome Set (COS) for trials of interventions to prevent and/or treat delirium in critically ill adults. DESIGN: International consensus process. SETTING: Three virtual meetings (April 2021). PATIENTS/SUBJECTS: Critical illness survivors/family, clinicians, and researchers from six Countries. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures (selected based on instrument validity, existing recommendations, and feasibility) and measurement time horizons were discussed. Participants voted on instruments and measurement timing (a priori consensus threshold ≥ 70%). Eighteen stakeholders (28% ICU survivors/family members) participated. We achieved consensus on the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist to measure delirium occurrence and delirium resolution (100%), Hospital Anxiety and Depression Scale for emotional distress (71%), and Montreal Cognitive Assessment-Blind for cognition (83%). We did not achieve consensus on EQ-5D five-level for HrQoL (69%) or its measurement at 6 months. We also did not achieve consensus on the Impact of Event Scale (IES)-Revised or IES-6 for post-traumatic stress (65%) or on measurement instruments for delirium severity incorporating delirium-related emotional distress. We were unable to gain consensus on when to commence and when to discontinue assessing for delirium occurrence and time to resolution, when to determine mortality. We gained consensus that emotional distress and cognition should be measured up to 12 months from hospital discharge. CONCLUSIONS: Consensus was reached on measurement instruments for four of seven outcomes in the COS for delirium prevention or treatment trials for critically ill adults. Further work is required to validate instruments for delirium severity that include delirium-related emotional distress.

New and Persistent Sedative Prescriptions Among Older Adults Following a Critical Illness: A Population-Based Cohort Study.

BACKGROUND: ICU survivors often have complex care needs and can experience insufficient medication reconciliation and polypharmacy. It is unknown which ICU survivors are at risk of new sedative use posthospitalization. RESEARCH QUESTION: For sedative-naive, older adult ICU survivors, how common is receipt of new and persistent sedative prescriptions, and what factors are associated with receipt? STUDY DESIGN AND METHODS: This population-based cohort study included ICU survivors aged ≥ 66 years who had not filled sedative prescriptions within ≤ 6 months before hospitalization (sedative-naive) in Ontario, Canada (2003-2019). Using multilevel logistic regression, demographic, clinical, and hospital characteristics and their association with new sedative prescription within ≤ 7 days of discharge are described. Variation between hospitals was quantified by using the adjusted median OR. Factors associated with persistent prescriptions (≤ 6 months) were examined with a multivariable proportional hazards model. RESULTS: A total of 250,428 patients were included (mean age, 76 years; 61% male). A total of 15,277 (6.1%) filled a new sedative prescription, with variation noted across hospitals (2% [95% CI, 1-3] to 44% [95% CI, 3-57]); 8,458 (3.4%) filled persistent sedative prescriptions. Adjusted factors associated with a new sedative included: discharge to long-term care facility (adjusted OR [aOR], 4.00; 95% CI, 3.72-4.31), receipt of inpatient geriatric (aOR, 1.95; 95% CI, 1.80-2.10) or psychiatry (aOR, 2.76; 95% CI, 2.62-2.91) consultation, invasive ventilation (aOR, 1.59; 95% CI, 1.53-1.66), and ICU length of stay ≥ 7 days (aOR, 1.50; 95% CI, 1.42-1.58). The residual heterogeneity between hospitals (adjusted median OR, 1.43; 95% CI, 1.35-1.49) had a stronger association with new sedative prescriptions than the Charlson Comorbidity Index score or sepsis. Factors associated with persistent sedative use were similar with the addition of female subjects (subdistribution hazard ratio, 1.07; 95% CI, 1.02-1.13) and pre-existing polypharmacy (subdistribution hazard ratio, 0.88; 95% CI, 0.80-0.93). INTERPRETATION: One in 15 sedative-naive, older adult ICU survivors filled a new sedative within ≤ 7 days of discharge; more than one-half of these survivors filled persistent prescriptions. New prescriptions at discharge varied widely across hospitals and represent the potential value of modifying prescription practices, including medication review and reconciliation.

Critical Care Staffing in Pandemics and Disasters: A Consensus Report From a Subcommittee of the Task Force for Mass Critical Care - Systems Strategies to Sustain the Health Care Workforce.

BACKGROUND: The COVID-19 pandemic has led to unprecedented mental health disturbances, burnout, and moral distress among health care workers, affecting their ability to care for themselves and their patients. RESEARCH QUESTION: In health care workers, what are key systemic factors and interventions impacting mental health and burnout? STUDY DESIGN AND METHODS: The Workforce Sustainment subcommittee of the Task Force for Mass Critical Care (TFMCC) utilized a consensus development process, incorporating evidence from literature review with expert opinion through a modified Delphi approach to determine factors affecting mental health, burnout, and moral distress in health care workers, to propose necessary actions to help prevent these issues and enhance workforce resilience, sustainment, and retention. RESULTS: Consolidation of evidence gathered from literature review and expert opinion resulted in 197 total statements that were synthesized into 14 major suggestions. These suggestions were organized into three categories: (1) mental health and well-being for staff in medical settings; (2) system-level support and leadership; and (3) research priorities and gaps. Suggestions include both general and specific occupational interventions to support health care worker basic physical needs, lower psychological distress, reduce moral distress and burnout, and foster mental health and resilience. INTERPRETATION: The Workforce Sustainment subcommittee of the TFMCC offers evidence-informed operational strategies to assist health care workers and hospitals plan, prevent, and treat the factors affecting health care worker mental health, burnout, and moral distress to improve resilience and retention following the COVID-19 pandemic.

Canadian survey of critical care pharmacists' views and involvement in clinical research.

BACKGROUND: The involvement of Canadian critical care pharmacists in clinical research is not well documented. OBJECTIVE: To describe the clinical research experience of Canadian critical care pharmacists, describe their views about clinical research, and identify factors that facilitate their involvement in clinical research. METHODS: A cross-sectional electronic survey of Canadian critical care pharmacists was developed through an iterative process and conducted from July to October 2010. We invited 325 pharmacists from 129 hospitals across Canada to participate. Surveys with more than 30% of questions unanswered were discarded. RESULTS: Analyzable response rate was 66.2%. Overall, 33 pharmacists (15.7%) were highly involved in research, 54 (25.7%) were moderately involved, and 123 (58.6%) were minimally involved. Most respondents (97.2%) believed that critical care pharmacist involvement in research was desirable, and many (80.4%) expressed interest to be more involved in research. Nearly all respondents (99.5%) agreed that more support should be provided to pharmacists interested in conducting research. Pharmacists currently involved in research have obtained higher academic degrees (adjusted OR 11.23; p < 0.001), express a strong interest in research (adjusted OR 7.44; p < 0.001), report a higher level of training for involvement in research (adjusted OR 2.23; p = 0.047), and practice more often in a university hospital (adjusted OR 3.68; p = 0.004) within an intensive care unit where involvement in research is valued (adjusted OR 5.61; p < 0.001). Support from pharmacy departments is not related to involvement in research (adjusted OR 1.22; p = 0.633). CONCLUSIONS: Canadian critical care pharmacists are involved to varying degrees in clinical research and are very interested in initiating and supporting research activities. Opportunities are present but significant barriers exist. The value of pharmacist-initiated research needs recognition as a priority within hospital pharmacy administration.

Melatonin for Insomnia in Medical Inpatients: A Narrative Review.

In this narrative review, we describe what is known about non-pharmacological and pharmacological treatments for insomnia in medical inpatients, with a focus on melatonin. Hospital-acquired insomnia is common, resulting in shortened total sleep time and more nighttime awakenings. Sleep disturbance has been shown to increase systemic inflammation, pain, and the likelihood of developing delirium in hospital. Treatment for insomnia includes both non-pharmacological and pharmacological interventions, the latter of which requires careful consideration of risks and benefits given the known adverse effects. Though benzodiazepines and non-benzodiazepine benzodiazepine receptor agonists are commonly prescribed (i.e., sedative-hypnotics), they are relatively contraindicated for patients over the age of 65 due to the risk of increased falls, cognitive decline, and potential for withdrawal symptoms after long-term use. Exogenous melatonin has a comparatively low likelihood of adverse effects and drug-drug interactions and is at least as effective as other sedative-hypnotics. Though more research is needed on both its effectiveness and relative safety for inpatients, small doses of melatonin before bedtime may be an appropriate choice for inpatients when insomnia persists despite non-pharmacological interventions.