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OBJECTIVES: To identify interprofessional staffing pattern clusters used in U.S. ICUs. DESIGN: Latent class analysis. SETTING AND PARTICIPANTS: Adult U.S. ICUs. PATIENTS: None. INTERVENTIONS: None. ANALYSIS: We used data from a staffing survey that queried respondents (n = 596 ICUs) on provider (intensivist and nonintensivist), nursing, respiratory therapist, and clinical pharmacist availability and roles. We used latent class analysis to identify clusters describing interprofessional staffing patterns and then compared ICU and hospital characteristics across clusters. MEASUREMENTS AND MAIN RESULTS: We identified three clusters as optimal. Most ICUs (54.2%) were in cluster 1 ("higher overall staffing") characterized by a higher likelihood of good provider coverage (both intensivist [onsite 24 hr/d] and nonintensivist [orders placed by ICU team exclusively, presence of advanced practice providers, and physicians-in-training]), nursing leadership (presence of charge nurse, nurse educators, and managers), and bedside nursing support (nurses with registered nursing degrees, fewer patients per nurse, and nursing aide availability). One-third (33.7%) were in cluster 2 ("lower intensivist coverage & nursing leadership, higher bedside nursing support") and 12.1% were in cluster 3 ("higher provider coverage & nursing leadership, lower bedside nursing support"). Clinical pharmacists were more common in cluster 1 (99.4%), but present in greater than 85% of all ICUs; respiratory therapists were nearly universal. Cluster 1 ICUs were larger (median 20 beds vs. 15 and 17 in clusters 2 and 3, respectively; p < 0.001), and in larger (> 250 beds: 80.6% vs. 66.1% and 48.5%; p < 0.001), not-for-profit (75.9% vs. 69.4% and 60.3%; p < 0.001) hospitals. Telemedicine use 24 hr/d was more common in cluster 3 units (71.8% vs. 11.7% and 14.1%; p < 0.001). CONCLUSIONS: More than half of U.S. ICUs had higher staffing overall. Others tended to have either higher provider presence and nursing leadership or higher bedside nursing support, but not both.

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RATIONALE: Uncertainty remains regarding the risks associated with single dose use of etomidate. OBJECTIVES: To assess use of etomidate in critically ill patients and compare outcomes for patients who received etomidate versus ketamine. METHODS: We assessed patients who received invasive mechanical ventilation (IMV), admitted to an ICU in the Premier Healthcare Database, 2008-2021. The exposure was receipt of etomidate on the day of IMV initiation and the main outcome was hospital mortality. Using multivariable regression we compared patients who received IMV within the first two days of hospitalization who received etomidate with propensity-score matched patients who received ketamine. We also assessed whether receipt of corticosteroids in the days after intubation modified the association between etomidate and mortality. MEASUREMENTS AND MAIN RESULTS: Of 1,689,945 patients who received IMV, nearly half (738,855; 43.7%) received etomidate. Among those who received IMV in the first two days of hospitalization, we established 22,273 matched pairs given either etomidate or ketamine. In the primary analysis, receipt of etomidate was associated with greater hospital mortality relative to ketamine (21.6% vs 18.7%; absolute risk difference: 2.8%, 95% CI 2.1%, 3.6%; adjusted odds ratio: 1.28, 95% CI 1.21,1.34). This was consistent across subgroups and sensitivity analyses. We found no attenuation of the association with mortality with receipt of corticosteroids in the days following etomidate use. CONCLUSIONS: Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality compared with ketamine. This finding is independent of subsequent treatment with corticosteroids.

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IMPORTANCE: The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. OBJECTIVES: To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. MAIN OUTCOMES AND MEASURES: We assessed whether patients received opioid infusion and the dose of said opioid infusion. RESULTS: We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3-11%) and 39% (95% CI, 28-49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129-1341 µg) in the KPNC cohort and 200 µg (IQR, 0-1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1-7%) and 20% (95% CI, 15-26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. CONCLUSIONS AND RELEVANCE: In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals' analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.

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Importance: Guidelines recommend an analgesia-first strategy for sedation during mechanical ventilation, but associations between opioids provided during mechanical ventilation and posthospitalization opioid-related outcomes are unclear. Objective: To evaluate associations between an intravenous opioid dose received during mechanical ventilation and postdischarge opioid-related outcomes in medical (nonsurgical) patients. Design, Setting, and Participants: This retrospective cohort study evaluated adults receiving mechanical ventilation lasting 24 hours or more for acute respiratory failure and surviving hospitalization. Participants from 21 Kaiser Permanente Northern California hospitals from January 1, 2012, to December 31, 2019, were included. Data were analyzed from October 1, 2020, to October 31, 2023. Exposures: Terciles of median daily intravenous fentanyl equivalents during mechanical ventilation. Main Outcomes and Measures: The primary outcome was the first filled opioid prescription in 1 year after discharge. Secondary outcomes included persistent opioid use and opioid-associated complications. Secondary analyses tested for interaction between opioid doses during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Estimates were based on multivariable-adjusted time-to-event analyses, with death as a competing risk, and censored for hospice or palliative care referral, rehospitalization with receipt of opioid, or loss of Kaiser Permanente plan membership. Results: The study included 6746 patients across 21 hospitals (median age, 67 years [IQR, 57-76 years]; 53.0% male). Of the participants, 3114 (46.2%) filled an opioid prescription in the year prior to admission. The median daily fentanyl equivalent during mechanical ventilation was 200 µg (IQR, 40-1000 µg), with terciles of 0 to 67 µg, more than 67 to 700 µg, and more than 700 µg. Compared with patients who did not receive opioids during mechanical ventilation (n = 1013), a higher daily opioid dose was associated with opioid prescriptions in the year after discharge (n = 2942 outcomes; tercile 1: adjusted hazard ratio [AHR], 1.00 [95% CI, 0.85-1.17], tercile 2: AHR, 1.20 [95% CI, 1.03-1.40], and tercile 3: AHR, 1.25 [95% CI, 1.07-1.47]). Higher doses of opioids during mechanical ventilation were also associated with persistent opioid use after hospitalization (n = 1410 outcomes; tercile 3 vs no opioids: odds ratio, 1.44 [95% CI, 1.14-1.83]). No interaction was observed between opioid dose during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Conclusions and Relevance: In this retrospective cohort study of patients receiving mechanical ventilation, opioids administered during mechanical ventilation were associated with opioid prescriptions following hospital discharge. Additional studies to evaluate risks and benefits of strategies using lower opioid doses are warranted.

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BACKGROUND: The last national estimates of US ICU physician staffing are 25 years old and lack information about interprofessional teams. RESEARCH QUESTION: How are US adult ICUs currently staffed? STUDY DESIGN AND METHODS: We conducted a cross-sectional survey (May 4, 2022-February 2, 2023) of adult ICU clinicians (targeting nurse/physician leadership) contacted using 2020 American Hospital Association (AHA) database information and, secondarily, through professional organizations. The survey included questions about interprofessional ICU staffing availability and roles at steady state (pre-COVID-19). We linked survey data to hospital data in the AHA database to create weighted national estimates by extrapolating ICU staffing data to nonrespondent hospitals based on hospital characteristics. RESULTS: The cohort consisted of 596 adult ICUs (response rates: AHA contacts: 2.1%; professional organizations: unknown) with geographic diversity and size variability (median, 20 beds; interquartile range, 12-25); most cared for mixed populations (414 [69.5%]), yet medical (55 [9.2%]), surgical (70 [11.7%]), and specialty (57 [9.6%]) ICUs were well represented. A total of 554 (93.0%) had intensivists available, with intensivists covering all patients in 75.6% of these and onsite 24 h/d in one-half (53.3% weekdays; 51.8% weekends). Of all ICUs, 69.8% had physicians-in-training and 77.7% had nurse practitioners/physician assistants. For patients on mechanical ventilation, nurse to patient ratios were 1:2 in 89.6% of ICUs. Clinical pharmacists were available in 92.6%, and respiratory therapists were available in 98.8%. We estimated 85.1% (95% CI, 85.7%-84.5%) of hospitals nationally had ICUs with intensivists, 51.6% (95% CI, 50.6%-52.5%) had physicians-in-training, 72.1% (95% CI, 71.3%-72.9%) had nurse practitioners/physician assistants, 98.5% (95% CI, 98.4%-98.7%) had respiratory therapists, and 86.9% (95% CI, 86.4%-87.4%) had clinical pharmacists. For patients on mechanical ventilation, 86.4% (95% CI, 85.8%-87.0%) used 1:2 nurses/patients. INTERPRETATION: We found that intensivist presence in adult US ICUs has greatly increased over 25 years. Intensivists, respiratory therapists, and clinical pharmacists are commonly available, and each nurse usually provides care for two patients on mechanical ventilation. However, team composition and workload vary.

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BACKGROUND: The best approaches to supplemental oxygen administration during surgery remain unclear, which may contribute to variation in practice. This study aimed to assess determinants of oxygen administration and its variability during surgery. METHODS: Using multivariable linear mixed-effects regression, the study measured the associations between intraoperative fraction of inspired oxygen and patient, procedure, medical center, anesthesiologist, and in-room anesthesia provider factors in surgical cases of 120 min or longer in adult patients who received general anesthesia with tracheal intubation and were admitted to the hospital after surgery between January 2016 and January 2019 at 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. RESULTS: The sample included 367,841 cases (median [25th, 75th] age, 59 [47, 69] yr; 51.1% women; 26.1% treated with nitrous oxide) managed by 3,836 anesthesiologists and 15,381 in-room anesthesia providers. Median (25th, 75th) fraction of inspired oxygen was 0.55 (0.48, 0.61), with 6.9% of cases less than 0.40 and 8.7% greater than 0.90. Numerous patient and procedure factors were statistically associated with increased inspired oxygen, notably advanced American Society of Anesthesiologists classification, heart disease, emergency surgery, and cardiac surgery, but most factors had little clinical significance (less than 1% inspired oxygen change). Overall, patient factors only explained 3.5% (95% CI, 3.5 to 3.5%) of the variability in oxygen administration, and procedure factors 4.4% (95% CI, 4.2 to 4.6%). Anesthesiologist explained 7.7% (95% CI, 7.2 to 8.2%) of the variability in oxygen administration, in-room anesthesia provider 8.1% (95% CI, 7.8 to 8.4%), medical center 23.3% (95% CI, 22.4 to 24.2%), and 53.0% (95% CI, 52.4 to 53.6%) was unexplained. CONCLUSIONS: Among adults undergoing surgery with anesthesia and tracheal intubation, supplemental oxygen administration was variable and appeared arbitrary. Most patient and procedure factors had statistical but minor clinical associations with oxygen administration. Medical center and anesthesia provider explained significantly more variability in oxygen administration than patient or procedure factors.

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Importance: Central venous catheters (CVCs) are commonly used but are associated with complications. Quantifying complication rates is essential for guiding CVC utilization decisions. Objective: To summarize current rates of CVC-associated complications. Data Sources: MEDLINE, Embase, CINAHL, and CENTRAL databases were searched for observational studies and randomized clinical trials published between 2015 to 2023. Study Selection: This study included English-language observational studies and randomized clinical trials of adult patients that reported complication rates of short-term centrally inserted CVCs and data for 1 or more outcomes of interest. Studies that evaluated long-term intravascular devices, focused on dialysis catheters not typically used for medication administration, or studied catheters placed by radiologists were excluded. Data Extraction and Synthesis: Two reviewers independently extracted data and assessed risk of bias. Bayesian random-effects meta-analysis was applied to summarize event rates. Rates of placement complications (events/1000 catheters with 95% credible interval [CrI]) and use complications (events/1000 catheter-days with 95% CrI) were estimated. Main Outcomes and Measures: Ten prespecified complications associated with CVC placement (placement failure, arterial puncture, arterial cannulation, pneumothorax, bleeding events requiring action, nerve injury, arteriovenous fistula, cardiac tamponade, arrhythmia, and delay of ≥1 hour in vasopressor administration) and 5 prespecified complications associated with CVC use (malfunction, infection, deep vein thrombosis [DVT], thrombophlebitis, and venous stenosis) were assessed. The composite of 4 serious complications (arterial cannulation, pneumothorax, infection, or DVT) after CVC exposure for 3 days was also assessed. Results: Of 11 722 screened studies, 130 were included in the analyses. Seven of 15 prespecified complications were meta-analyzed. Placement failure occurred at 20.4 (95% CrI, 10.9-34.4) events per 1000 catheters placed. Other rates of CVC placement complications (per 1000 catheters) were arterial canulation (2.8; 95% CrI, 0.1-10), arterial puncture (16.2; 95% CrI, 11.5-22), and pneumothorax (4.4; 95% CrI, 2.7-6.5). Rates of CVC use complications (per 1000 catheter-days) were malfunction (5.5; 95% CrI, 0.6-38), infection (4.8; 95% CrI, 3.4-6.6), and DVT (2.7; 95% CrI, 1.0-6.2). It was estimated that 30.2 (95% CrI, 21.8-43.0) in 1000 patients with a CVC for 3 days would develop 1 or more serious complication (arterial cannulation, pneumothorax, infection, or DVT). Use of ultrasonography was associated with lower rates of arterial puncture (risk ratio [RR], 0.20; 95% CrI, 0.09-0.44; 13.5 events vs 68.8 events/1000 catheters) and pneumothorax (RR, 0.25; 95% CrI, 0.08-0.80; 2.4 events vs 9.9 events/1000 catheters). Conclusions and Relevance: Approximately 3% of CVC placements were associated with major complications. Use of ultrasonography guidance may reduce specific risks including arterial puncture and pneumothorax.

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Rationale: The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. Objectives: To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. Methods: A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Measurements and Main Results: Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). Conclusions: In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.

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Rationale: Sepsis is a frequent cause of ICU admission and mortality. Objectives: To evaluate temporal trends in the presentation and outcomes of patients admitted to the ICU with sepsis and to assess the contribution of changing case mix to outcomes. Methods: We conducted a retrospective cohort study of patients admitted to 261 ICUs in the United Kingdom during 1988-1990 and 1996-2019 with nonsurgical sepsis. Measurements and Main Results: A total of 426,812 patients met study inclusion criteria. The patients had a median (interquartile range) age of 66 (53-75) years, and 55.6% were male. The most common sites of infection were respiratory (60.9%), genitourinary (11.5%), and gastrointestinal (10.3%). Compared with patients in 1988-1990, patients in 2017-2019 were older (median age, 66 vs. 63 yr), were less acutely ill (median Acute Physiology and Chronic Health Evaluation II acute physiology score, 14 vs. 20), and more often had genitourinary sepsis (13.4% vs. 2.0%). Hospital mortality decreased from 54.6% (95% confidence interval [CI], 51.0-58.1%) in 1988-1990 to 32.4% (95% CI, 32.1-32.7%) in 2017-2019, with an adjusted odds ratio of 0.64 (95% CI, 0.54-0.75). The adjusted absolute hospital mortality reduction from 1988-1990 to 2017-2019 was 8.8% (95% CI, 5.6-12.1). Thus, of the observed 22.2-percentage point reduction in hospital mortality, 13.4 percentage points (60% of total reduction) were explained by case mix changes, whereas 8.8 percentage points (40% of total reduction) were not explained by measured factors and may be a result of improvements in ICU management. Conclusions: Over a 30-year period, mortality for ICU admissions with sepsis decreased substantially. Although changes in case mix accounted for the majority of observed mortality reduction, there was an 8.8-percentage point reduction in mortality not explained by case mix.

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PURPOSE: Antipsychotic agents, which may increase the risk of infection through dopaminergic dysregulation, are prescribed to a fraction of patients following critical illness. We compared the rate of recurrent sepsis among patients who filled a prescription for antipsychotics with high- or low-D2 affinity. METHODS: Population-based cohort with active comparator design. We included sepsis survivors older than 65 years with intensive care unit admission and new prescription of antipsychotics in Ontario 2008-2019. The primary outcome were recurrent sepsis episodes within 1 year of follow-up. Patients who filled a prescription within 30 days of hospital discharge for high-D2 affinity antipsychotics (e.g., haloperidol) were compared with patients who filled a prescription within 30 days of hospital discharge for low-D2 affinity antipsychotics (e.g., quetiapine). Multivariable zero-inflated Poisson regression models with robust standard errors adjusting for confounding at baseline were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: Overall, 1879 patients filled a prescription for a high-D2, and 1446 patients filled a prescription for a low-D2 affinity antipsychotic. Patients who filled a prescription for a high-D2 affinity antipsychotic did not present a higher rate of recurrent sepsis during 1 year of follow-up, compared with patients who filled a prescription for a low-D2 affinity antipsychotic (IRR: 1.12; 95% CI: 0.94, 1.35). CONCLUSIONS: We did not find conclusive evidence of a higher rate of recurrent sepsis associated with the prescription of high-D2 affinity antipsychotics (compared with low-D2 affinity antipsychotics) by 1 year of follow-up in adult sepsis survivors with intensive care unit admission.

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The clinical trajectory of survivors of critical illness after hospital discharge can be complex and highly unpredictable. Assessing long-term outcomes after critical illness can be challenging because of possible competing events, such as all-cause death during follow-up (which precludes the occurrence of an event of particular interest). In this perspective, we explore challenges and methodological implications of competing events during the assessment of long-term outcomes in survivors of critical illness. In the absence of competing events, researchers evaluating long-term outcomes commonly use the Kaplan-Meier method and the Cox proportional hazards model to analyze time-to-event (survival) data. However, traditional analytical and modeling techniques can yield biased estimates in the presence of competing events. We present different estimands of interest and the use of different analytical approaches, including changes to the outcome of interest, Fine and Gray regression models, cause-specific Cox proportional hazards models, and generalized methods (such as inverse probability weighting). Finally, we provide code and a simulated dataset to exemplify the application of the different analytical strategies in addition to overall reporting recommendations.

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Importance: The ability to provide invasive mechanical ventilation (IMV) is a mainstay of modern intensive care; however, whether rates of IMV vary among countries is unclear. Objective: To estimate the per capita rates of IMV in adults across 3 high-income countries with large variation in per capita intensive care unit (ICU) bed availability. Design, Setting, and Participants: This cohort study examined 2018 data of patients aged 20 years or older who received IMV in England, Canada, and the US. Exposure: The country in which IMV was received. Main Outcomes and Measures: The main outcome was the age-standardized rate of IMV and ICU admissions in each country. Rates were stratified by age, specific diagnoses (acute myocardial infarction, pulmonary embolus, upper gastrointestinal bleed), and comorbidities (dementia, dialysis dependence). Data analyses were conducted between January 1, 2021, and December 1, 2022. Results: The study included 59 873 hospital admissions with IMV in England (median [IQR] patient age, 61 [47-72] years; 59% men, 41% women), 70 250 in Canada (median [IQR] patient age, 65 [54-74] years; 64% men, 36% women), and 1 614 768 in the US (median [IQR] patient age, 65 [54-74] years; 57% men, 43% women). The age-standardized rate per 100 000 population of IMV was the lowest in England (131; 95% CI, 130-132) compared with Canada (290; 95% CI, 288-292) and the US (614; 95% CI, 614-615). Stratified by age, per capita rates of IMV were more similar across countries among younger patients and diverged markedly in older patients. Among patients aged 80 years or older, the crude rate of IMV per 100 000 population was highest in the US (1788; 95% CI, 1781-1796) compared with Canada (694; 95% CI, 679-709) and England (209; 95% CI, 203-214). Concerning measured comorbidities, 6.3% of admitted patients who received IMV in the US had a diagnosis of dementia (vs 1.4% in England and 1.3% in Canada). Similarly, 5.6% of admitted patients in the US were dependent on dialysis prior to receiving IMV (vs 1.3% in England and 0.3% in Canada). Conclusions and Relevance: This cohort study found that patients in the US received IMV at a rate 4 times higher than in England and twice that in Canada in 2018. The greatest divergence was in the use of IMV among older adults, and patient characteristics among those who received IMV varied markedly. The differences in overall use of IMV among these countries highlight the need to better understand patient-, clinician-, and systems-level choices associated with the varied use of a limited and expensive resource.

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In this article, the authors review the origins of palliative care within the critical care context and describe the evolution of symptom management, shared decision-making, and comfort-focused care in the ICU from the 1970s to the early 2000s. The authors also review the growth of interventional studies in the past 20 years and indicate areas for future study and quality improvement for end-of-life care among the critically ill.

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