Defibrillation Strategies for Refractory Ventricular Fibrillation.

BACKGROUND: Despite advances in defibrillation technology, shock-refractory ventricular fibrillation remains common during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED; rapid sequential shocks from two defibrillators) and vector-change (VC) defibrillation (switching defibrillation pads to an anterior-posterior position) have been proposed as defibrillation strategies to improve outcomes in patients with refractory ventricular fibrillation. METHODS: We conducted a cluster-randomized trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest. Patients were treated with one of these three techniques according to the strategy that was randomly assigned to the paramedic service. The primary outcome was survival to hospital discharge. Secondary outcomes included termination of ventricular fibrillation, return of spontaneous circulation, and a good neurologic outcome, defined as a modified Rankin scale score of 2 or lower (indicating no symptoms to slight disability) at hospital discharge. RESULTS: A total of 405 patients were enrolled before the data and safety monitoring board stopped the trial because of the coronavirus disease 2019 pandemic. A total of 136 patients (33.6%) were assigned to receive standard defibrillation, 144 (35.6%) to receive VC defibrillation, and 125 (30.9%) to receive DSED. Survival to hospital discharge was more common in the DSED group than in the standard group (30.4% vs. 13.3%; relative risk, 2.21; 95% confidence interval [CI], 1.33 to 3.67) and more common in the VC group than in the standard group (21.7% vs. 13.3%; relative risk, 1.71; 95% CI, 1.01 to 2.88). DSED but not VC defibrillation was associated with a higher percentage of patients having a good neurologic outcome than standard defibrillation (relative risk, 2.21 [95% CI, 1.26 to 3.88] and 1.48 [95% CI, 0.81 to 2.71], respectively). CONCLUSIONS: Among patients with refractory ventricular fibrillation, survival to hospital discharge occurred more frequently among those who received DSED or VC defibrillation than among those who received standard defibrillation. (Funded by the Heart and Stroke Foundation of Canada; DOSE VF ClinicalTrials.gov number, NCT04080986.).

Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit.

BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Prognostic Factors Associated With Extubation Failure in Acutely Brain-Injured Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Extubation failure in brain-injured patients is associated with increased morbidity. Our objective was to systematically review prognostic factors associated with extubation failure in acutely brain-injured adult patients receiving invasive ventilation in an ICU. DATA SOURCES: MEDLINE, Embase, and Cochrane Central were searched from inception to January 31, 2022. STUDY SELECTION: Two reviewers independently screened citations and selected English-language cohort studies and randomized trials examining the association of prognostic factors with extubation failure. Studies were considered if they included greater than or equal to 80% adult patients with acute brain injury admitted to the ICU and mechanically ventilated for greater than or equal to 24 hours. DATA EXTRACTION: Two reviewers extracted data on population, prognostic factors, extubation outcomes, and risk of bias (using the quality in prognostic factors tool). DATA SYNTHESIS: In the primary analysis, adjusted odds ratios (aOR) for each prognostic factor were pooled using random-effects models. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. The search identified 7,626 citations, of which 21 studies met selection criteria. Moderate-certainty evidence suggested increased risk of extubation failure with older age (aOR, 3.0 for upper vs lower tertile; 95% CI, 1.78-5.07) and longer duration of mechanical ventilation (aOR, 3.47 for upper vs lower tertile; 95% CI, 1.68-7.19). Presence of cough (aOR, 0.40; 95% CI, 0.28-0.57) and intact swallow (aOR, 0.34; 95% CI, 0.21-0.54) probably decreased risk of extubation failure (moderate certainty). Associations of other factors with extubation failure were informed by low or very low certainty evidence. CONCLUSIONS: Patient age, duration of mechanical ventilation, and airway reflexes were associated with extubation failure in brain-injured patients with moderate certainty. Future studies are needed to determine the optimal application of these variables in clinical practice.

Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials.

Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain. Objective: To determine whether vitamin C improves outcomes for patients with COVID-19. Design, Setting, and Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents. Interventions: Patients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses). Main Outcomes and Measures: The primary outcome was a composite of organ support-free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from -1 organ support-free days for patients experiencing in-hospital death to 22 organ support-free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support-free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility. Results: Enrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support-free days was 7 (IQR, -1 to 17 days) for the vitamin C group vs 10 (IQR, -1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support-free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy. Conclusions and Relevance: In hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support-free days and hospital survival. Trial Registration: ClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP).

A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial.

Background: The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes. Methods: This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India. Adult patients (≥18 years) with proven or suspected infection as the main diagnosis and needing a continuous intravenous vasopressor infusion were randomized to intravenous vitamin C (50 mg/kg every 6 hours for a maximum of 16 doses) or matching placebo. Primary outcomes were related to protocol adherence and feasibility (enrollment per month). The key secondary outcome was the composite of mortality or persistent organ dysfunction (POD) at day 28 after randomization. Results: 60 patients were screened, 51 were eligible, 32 were randomized, and 30 were included in the analysis (randomized/eligible ratio: 0.63). The overall rate of enrollment was 1.5 patients per month. The median (IQR) age was 63.5 (51.0, 70.0) and 70.0% of the patients were male. In both arms, all patients received ≥90% of scheduled doses of the study drug. No patient received open-label vitamin C and there were no deviations from the glucose monitoring protocol. The composite outcome of mortality or POD at day 28 occurred in 56.3% (9/16) in the vitamin C arm as compared to 42.9% (6/14) in the placebo arm [RR: 1.31 (95% CI: 0.62, 2.76), p = 0.47]. Conclusion: In this pilot feasibility randomized controlled trial of vitamin C for adult patients with sepsis, protocol adherence was excellent and feasibility endpoints were met. Trial registration: CTRI/2020/03/024371. How to cite this article: Vijayaraghavan BKT, Venkataraman R, Ramanathan Y, Margabandhu S, Jayakumar D, Ramachandran P, et al. A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial. Indian J Crit Care Med 2023;27(12):910-916.

Outcomes After Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis.

OBJECTIVES: To compare health service use and clinical outcomes for patients with and without direct discharge to home (DDH) from ICUs in Ontario. DESIGN: Population-based, observational, cohort study using propensity scoring to match patients who were DDH to those not DDH and a preference-based instrumental variable (IV) analysis using ICU-level DDH rate as the IV. SETTING: ICUs in Ontario. PATIENTS: Patients discharged home from a hospitalization either directly or within 48 hours of care in an ICU between April 1, 2015, and March 31, 2017. INTERVENTION: DDH from ICU. MEASUREMENTS AND MAIN RESULTS: Among 76,737 patients in our cohort, 46,859 (61%) were DDH from the ICU. In the propensity matched cohort, the odds for our primary outcome of hospital readmission or emergency department (ED) visit within 30 days were not significantly different for patients DDH (odds ratio [OR], 1.00; 95% CI, 0.96-1.04), and there was no difference in mortality at 90 days for patients DDH (OR, 1.08; 95% CI, 0.97-1.21). The effect on hospital readmission or ED visits was similar in the subgroup of patients discharged from level 2 (OR, 0.98; 95% CI, 0.92-1.04) and level 3 ICUs (OR, 1.02; 95% CI, 0.96-1.09) and in the subgroups with cardiac conditions (OR, 1.03; 95% CI, 0.96-1.12) and noncardiac conditions (OR, 0.98; 95% CI, 0.94-1.03). Similar results were obtained in the IV analysis (coefficient for hospital readmission or ED visit within 30 d = -0.03 ± 0.03 ( se ); p = 0.3). CONCLUSIONS: There was no difference in outcomes for patients DDH compared with ward transfer prior to discharge when two approaches were used to minimize confounding within a large health systemwide observational cohort. We did not evaluate how patients are selected for DDH. Our results suggest that with careful patient selection, this practice might be feasible for routine implementation to ensure efficient and safe use of limited healthcare resources.

Quantitative Assessment of Viral Dispersion Associated with Respiratory Support Devices in a Simulated Critical Care Environment.

Rationale: Patients with severe coronavirus disease (COVID-19) require supplemental oxygen and ventilatory support. It is unclear whether some respiratory support devices may increase the dispersion of infectious bioaerosols and thereby place healthcare workers at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Objectives: To quantitatively compare viral dispersion from invasive and noninvasive respiratory support modalities.Methods: This study used a simulated ICU room with a breathing-patient simulator exhaling nebulized bacteriophages from the lower respiratory tract with various respiratory support modalities: invasive ventilation (through an endotracheal tube with an inflated cuff connected to a mechanical ventilator), helmet ventilation with a positive end-expiratory pressure (PEEP) valve, noninvasive bilevel positive-pressure ventilation, nonrebreather face masks, high-flow nasal oxygen (HFNO), and nasal prongs.Measurements and Main Results: Invasive ventilation and helmet ventilation with a PEEP valve were associated with the lowest bacteriophage concentrations in the air, and HFNO and nasal prongs were associated with the highest concentrations. At the intubating position, bacteriophage concentrations associated with HFNO (2.66 × 104 plaque-forming units [PFU]/L of air sampled), nasal prongs (1.60 × 104 PFU/L of air sampled), nonrebreather face masks (7.87 × 102 PFU/L of air sampled), and bilevel positive airway pressure (1.91 × 102 PFU/L of air sampled) were significantly higher than those associated with invasive ventilation (P < 0.05 for each). The difference between bacteriophage concentrations associated with helmet ventilation with a PEEP valve (4.29 × 10-1 PFU/L of air sampled) and bacteriophage concentrations associated with invasive ventilation was not statistically significant.Conclusions: These findings highlight the potential differential risk of dispersing virus among respiratory support devices and the importance of appropriate infection prevention and control practices and personal protective equipment for healthcare workers when caring for patients with transmissible respiratory viral infections such as SARS-CoV-2.

The evolution of mean arterial pressure in critically ill patients on vasopressors before and during a trial comparing a specific mean arterial pressure target to usual care.

BACKGROUND: In randomized clinical controlled trials, the choice of usual care as the comparator may be associated with better clinician uptake of the study protocol and lead to more generalizable results. However, if care processes evolve to resemble the intervention during the course of a trial, differences between the intervention group and usual care control group may narrow. We evaluated the effect on mean arterial pressure of an unblinded trial comparing a lower mean arterial pressure target to reduce vasopressor exposure, vs. a clinician-selected mean arterial pressure target, in critically ill patients at least 65 years old. METHODS: For this multicenter observational study using data collected both prospectively and retrospectively, patients were recruited from five of the seven trial sites. We compared the mean arterial pressure of patients receiving vasopressors, who met or would have met trial eligibility criteria, from two periods: [1] at least 1 month before the trial started, and [2] during the trial period and randomized to usual care, or not enrolled in the trial. RESULTS: We included 200 patients treated before and 229 after trial initiation. There were no differences in age (mean 74.5 vs. 75.2 years; p = 0.28), baseline Acute Physiology and Chronic Health Evaluation II score (median 26 vs. 26; p = 0.47) or history of chronic hypertension (n = 126 [63.0%] vs. n = 153 [66.8%]; p = 0.41). Mean of the mean arterial pressure was similar between the two periods (72.5 vs. 72.4 mmHg; p = 0.76). CONCLUSIONS: The initiation of a trial of a prescribed lower mean arterial pressure target, compared to a usual clinician-selected target, was not associated with a change in mean arterial pressure, reflecting stability in the net effect of usual clinician practices over time. Comparing prior and concurrent control groups may alleviate concerns regarding drift in usual practices over the course of a trial or permit quantification of any change.

A Quantitative Study of Particle Dispersion due to Respiratory Support Modalities in PC-12 Aircraft: Prehospital Patient Transport.

OBJECTIVE: It is unclear whether supplemental oxygen and noninvasive ventilation respiratory support devices increase the dispersion of potentially infectious bioaerosols in a pressurized air medical cabin. This study quantitatively compared particle dispersion from respiratory support modalities in an air medical cabin during flight. METHODS: Dispersion was measured in a fixed wing air ambulance during flight with a breathing medical mannequin simulator exhaling nebulized saline from the lower respiratory tract with the following respiratory support modalities: a nasal cannula with a surgical mask, high-flow nasal oxygen (HFNO) with a surgical mask, and noninvasive bilevel positive airway pressure (BiPAP) ventilation. RESULTS: Nasal cannula oxygen with a surgical mask was associated with the highest particle concentrations. In the absence of mask seal leaks, BiPAP was associated with 1 order of magnitude lower particle concentration compared with a nasal cannula with a surgical mask. Particle concentrations associated with HFNO with a surgical mask were lower than a nasal cannula with a surgical mask but higher than BiPAP. CONCLUSIONS: Particle dispersion associated with the use of BiPAP and HFNO with a surgical mask is lower than nasal cannula oxygen with a surgical mask. These findings may assist air medical organizations with operational decisions where little data exist about respiratory particle dispersion.

Using Prior Culture Results to Improve Initial Empiric Antibiotic Prescribing: An Evaluation of a Simple Clinical Heuristic.

BACKGROUND: A patient's prior cultures can inform the subsequent risk of infection from resistant organisms, yet prescribers often fail to incorporate these results into their empiric antibiotic selection. Given that timely initiation of adequate antibiotics has been associated with improved outcomes, there is an urgent need to address this gap. METHODS: In order to better incorporate prior culture results in the selection of empiric antibiotics, we performed a pragmatic, prospective, hospital-wide intervention: (1) empiric antibiotic prescriptions were assessed for clinically significant discordance with the most recent methicillin-resistant Staphylococcus aureus (MRSA) surveillance swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and the most recent culture for a Gram-negative (GN) organism; and (2) if discordant, an antimicrobial stewardship pharmacist provided recommendations for alternative therapy. The impact was analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic, tertiary care institution. RESULTS: Clinically significant discordance was identified 99 times in the preintervention period and 86 times in the intervention period. The proportion of patients that received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = .01). The median time to concordant therapy was shorter in the intervention group than the control group (25 vs 55 hrs, respectively; P < .001; adjusted hazard ratio = 1.95 [95% confidence interval {CI}, 1.37-2.77; P < .001]). The median duration of unnecessary vancomycin therapy was reduced by 1.1 days (95% CI, .5-1.6 days; P < .001). CONCLUSIONS: This intervention improved prescribing, with a shorter time to concordant therapy and an increased proportion of patients receiving empiric therapy concordant with prior culture results. The use of unnecessary vancomycin was also reduced.

Improving Decision Making in Empiric Antibiotic Selection (IDEAS) for Gram-negative Bacteremia: A Prospective Clinical Implementation Study.

BACKGROUND: Timely selection of adequate empiric antibiotics has become increasingly difficult due to rising resistance rates and the competing desire to apply antimicrobial stewardship (AMS) principles. Individualized clinical prediction models offer the promise of reducing broad-spectrum antibiotic use and preserving/improving adequacy of treatment, but few have been validated in the clinical setting. METHODS: Multivariable models were used to predict the probability of susceptibility for gram-negative (GN) bacteria in bloodstream infections (bacteremia) to ceftriaxone, ciprofloxacin, ceftazidime, piperacillin-tazobactam, and meropenem. The models were combined with existing resistance-prediction methods to generate optimized and individualized suggestions for empiric therapy that were provided to prescribers by an AMS pharmacist. De-escalation of empiric antibiotics and adequacy of therapy were analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic tertiary care institution. RESULTS: Episodes of bacteremia (n = 182) were identified in the preintervention and postintervention (n = 201) periods. Patients who received the intervention were more likely to have their therapy de-escalated (29 vs 21%; aOR = 1.77; 95% CI, 1.09-2.87; P = .02). The intervention also increased the proportion of patients who were on the narrowest adequate therapy at the time of culture finalization (44% in the control and 55% in the intervention group; aOR = 2.04; 95% CI, 1.27-3.27; P = .003). Time to adequate therapy was similar in the intervention and control groups (5 vs 4 hours; P = .95). CONCLUSIONS: An AMS intervention, based on individualized predictive models for resistance, can influence empiric antibiotic selections for GN bacteremia to facilitate early de-escalation of therapy without compromising adequacy of antibiotic coverage.

Population-Wide Peer Comparison Audit and Feedback to Reduce Antibiotic Initiation and Duration in Long-Term Care Facilities with Embedded Randomized Controlled Trial.

BACKGROUND: Antibiotic overprescribing in long-term care settings is driven by prescriber preferences and is associated with preventable harms for residents. We aimed to determine whether peer comparison audit and feedback reporting for physicians reduces antibiotic overprescribing among residents. METHODS: We employed a province wide, difference-in-differences study of antibiotic prescribing audit and feedback, with an embedded pragmatic randomized controlled trial (RCT) across all long-term care facilities in Ontario, Canada, in 2019. The study year included 1238 physicians caring for 96 185 residents. In total, 895 (72%) physicians received no feedback; 343 (28%) were enrolled to receive audit and feedback and randomized 1:1 to static or dynamic reports. The primary outcomes were proportion of residents initiated on an antibiotic and proportion of antibiotics prolonged beyond 7 days per quarter. RESULTS: Among all residents, between the first quarter of 2018 and last quarter of 2019, there were temporal declines in antibiotic initiation (28.4% to 21.3%) and prolonged duration (34.4% to 29.0%). Difference-in-differences analysis confirmed that feedback was associated with a greater decline in prolonged antibiotics (adjusted difference -2.65%, 95% confidence interval [CI]: -4.93 to -.28%, P = .026), but there was no significant difference in antibiotic initiation. The reduction in antibiotic durations was associated with 335 912 fewer days of treatment. The embedded RCT detected no differences in outcomes between the dynamic and static reports. CONCLUSIONS: Peer comparison audit and feedback is a pragmatic intervention that can generate small relative reductions in the use of antibiotics for prolonged durations that translate to large reductions in antibiotic days of treatment across populations. Clinical Trials Registration. NCT03807466.

Discordances Between Factors Associated With Withholding Extubation and Extubation Failure After a Successful Spontaneous Breathing Trial.

OBJECTIVES: To identify whether factors associated with withholding extubation in the ICU also predict the risk of extubation failure. DESIGN: Retrospective cohort study. SETTING: Eight medical-surgical ICUs in Toronto. PATIENTS: Adult patients receiving invasive mechanical ventilation, with a first successful spontaneous breathing trial within 28 days of initial ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary end point had three mutually exclusive levels, including: 1) withholding extubation after a successful spontaneous breathing trial, 2) extubation failure within 48 hours, and 3) successful extubation. Among 9,910 patients, 38% of patients were not extubated within 24 hours of their first successful spontaneous breathing trial. A total of 12.9% of patients who were promptly extubated failed within the next 48 hours. Several discrepancies were evident in the association of factors with risk of withholding extubation and extubation failure. Specifically, both age and female sex were associated with withholding extubation (odds ratio, 1.07; 95% CI, 1.03-1.11; and odds ratio, 1.13; 95% CI, 1.02-1.26, respectively) but not a higher risk of failed extubation (odds ratio, 0.99; 95% CI, 0.93-1.05; and odds ratio, 0.93; 95% CI, 0.77-1.11, respectively). Conversely, both acute cardiovascular conditions and intubation for hypoxemic respiratory failure were associated with a higher risk of failed extubation (odds ratio, 1.32; 95% CI, 1.06-1.66; and odds ratio, 1.46; 95% CI, 1.16-1.82, respectively) but not a higher odds of a withheld extubation attempt (odds ratio, 0.79; 95% CI, 0.68-0.91; and odds ratio, 1.07; 95% CI, 0.93-1.23, respectively). CONCLUSIONS: Several factors showed discordance between the decision to withhold extubation and the risk of extubation failure. This discordance may lead to longer duration of mechanical ventilation or higher reintubation rates. Improving the decision-making behind extubation may help to reduce both exposure to invasive mechanical ventilation and extubation failure.

Long-Term Sustainability and Acceptance of Antimicrobial Stewardship in Intensive Care: A Retrospective Cohort Study.

OBJECTIVES: To evaluate long-term uptake of an antimicrobial stewardship audit-and-feedback program along with potential predictors of stewardship suggestions and acceptance across a diverse ICU population. DESIGN: A retrospective cohort study. SETTING: An urban, academic medical institution. PATIENTS: Patients admitted to an ICU who received an antimicrobial stewardship program suggestion between June 2010 and September 2019. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The antimicrobial stewardship program provided 7,749 antibiotic assessments over the study period and made a suggestion to alter therapy in 2,826 (36%). Factors associated with a higher likelihood of receiving a suggestion to alter therapy included shorter hospital length of stay prior to antimicrobial stewardship program review (odds ratio 1.15 for ≤ 5 d; 95% CI 1.00-1.32), admission to cardiovascular (1.37; 1.06-1.76) or burn surgery (1.88; 1.50-2.36) versus general medicine, and preceding duration of antibiotic use greater than 5 days (1.33; 1.10-1.60). Assessment of aminoglycosides (2.91; 1.85-4.89), carbapenems (1.93; 1.54-2.41), and vancomycin (2.71; 2.19-3.36) versus ceftriaxone was more likely to result in suggestions to alter therapy. The suggestion acceptance rate was 67% (1,895/2,826), which was stable throughout the study period. Admission to a level 3 ICU was associated with higher likelihood of acceptance of suggestions (1.50; 1.14-1.97). Factors associated with lower acceptance rates were admission to burn surgery (0.64; 0.45-0.91), treatment of pneumonia (0.64; 0.42-0.97 for community-acquired and 0.65; 0.44-0.94 for ventilator-acquired), unknown source of infection (0.66; 0.48-0.92), and suggestion types of "narrow spectrum" (0.65; 0.45-0.94), "change formulation of antibiotic" (0.42; 0.27-0.64), or "change agent of therapy" (0.63; 0.40-0.97) versus "change of dose". CONCLUSIONS: An antimicrobial stewardship program implemented over a decade resulted in sustained suggestion and acceptance rates. These findings support the need for a persistent presence of audit-and-feedback over time with more frequent suggestions to alter potentially nephrotoxic agents, increased efforts toward specialized care units, and further work approaching infectious sources that are typically treated without pathogen confirmation and identification.

Use of Hydrocortisone, Ascorbic Acid, and Thiamine in Adults with Septic Shock.

Rationale: In December 2016, a single-center study describing significant improvements in mortality among a small group of patients with severe sepsis and septic shock treated with hydrocortisone, high-dose ascorbic acid, and thiamine (HAT therapy) was published online.Objectives: This study aims to describe the administration of HAT therapy among U.S. adults with septic shock before and after study publication and to compare outcomes between patients who received and did not receive HAT therapy.Methods: We performed a retrospective cohort study of 379 acute care hospitals in the Premier Healthcare Database including patients discharged from October 1, 2015, to September 30, 2018. Exposure was quarter year of hospital discharge; postpublication was defined as January 2017 onward (July 2017 for effectiveness analyses). The primary outcome was receipt of HAT at least once during hospitalization. We conducted unadjusted segmented regression analyses to examine temporal trends in HAT administration. In patients with early septic shock, we compared the association of early HAT therapy (within 2 d of hospitalization) with hospital mortality using multivariable modeling and propensity score matching.Measurements and Main Results: Among 338,597 patients, 3,574 (1.1%) received HAT therapy, 98.7% in the postpublication period. HAT administration increased from 0.03% of patients (95% confidence interval [CI], 0.02-0.04) before publication to 2.65% (95% CI, 2.46-2.83) in the last quarter, with a significant step up in use after December 2016 (P < 0.001). Receipt of early HAT was associated with higher hospital mortality (28.2% vs. 19.7%; P < 0.001; adjusted odds ratio, 1.17 [95% CI, 1.02-1.33]; primary propensity-matched model adjusted odds ratio, 1.19 [95% CI, 1.02-1.40]).Conclusions: Publication of a single-center retrospective study was associated with significantly increased administration of HAT. Among patients with early septic shock, receipt of HAT was not associated with mortality benefit.

New Opioid Use after Invasive Mechanical Ventilation and Hospital Discharge.

Rationale: Patients who receive invasive mechanical ventilation (IMV) are usually exposed to opioids as part of their sedation regimen. The rates of posthospital prescribing of opioids are unknown.Objectives: To determine the frequency of persistent posthospital opioid use among patients who received IMV.Methods: We assessed opioid-naive adults who were admitted to an ICU, received IMV, and survived at least 7 days after hospital discharge in Ontario, Canada over a 26-month period (February, 2013 through March, 2015). The primary outcome was new, persistent opioid use during the year after discharge. We assessed factors associated with persistent use by multivariable logistic regression. Patients receiving IMV were also compared with matched hospitalized patients who did not receive intensive care (non-ICU).Measurements and Main Results: Among 25,085 opioid-naive patients on IMV, 5,007 (20.0%; 95% confidence interval [CI], 19.5-20.5) filled a prescription for opioids in the 7 days after hospital discharge. During the next year, 648 (2.6%; 95% CI, 2.4-2.8) of the IMV cohort met criteria for new, persistent opioid use. The patient characteristic most strongly associated with persistent use in the IMV cohort was being a surgical (vs. medical) patient (adjusted odds ratio, 3.29; 95% CI, 2.72-3.97). The rate of persistent use was slightly higher than for matched non-ICU patients (2.6% vs. 1.5%; adjusted odds ratio, 1.37 [95% CI, 1.19-1.58]).Conclusions: A total of 20% of IMV patients received a prescription for opioids after hospital discharge, and 2.6% met criteria for persistent use, an average of 300 new persistent users per year in a population of 14 million. Receipt of surgery was the factor most strongly associated with persistent use.

Educational initiatives for electroencephalography in the critical care setting: a systematic review and meta-analysis.

PURPOSE: We systematically reviewed existing critical care electroencephalography (EEG) educational programs for non-neurologists, with the primary goal of reporting the content covered, methods of instruction, overall duration, and participant experience. Our secondary goals were to assess the impact of EEG programs on participants' core knowledge, and the agreement between non-experts and experts for seizure identification. SOURCE: Major databases were searched from inception to 30 August 2020. Randomized controlled trials, cohort studies, and descriptive studies were all considered if they reported an EEG curriculum for non-neurologists in a critical care setting. Data were presented thematically for the qualitative primary outcome and a meta-analysis using a random effects model was performed for the quantitative secondary outcomes. PRINCIPAL FINDINGS: Twenty-nine studies were included after reviewing 7,486 citations. Twenty-two studies were single centre, 17 were from North America, and 16 were published after 2016. Most EEG studies were targeted to critical care nurses (17 studies), focused on processed forms of EEG with amplitude-integrated EEG being the most common (15 studies), and were shorter than one day in duration (24 studies). In pre-post studies, EEG programs significantly improved participants' knowledge of tested material (standardized mean change, 1.79; 95% confidence interval [CI], 0.86 to 2.73). Agreement for seizure identification between non-experts and experts was moderate (Cohen's kappa = 0.44; 95% CI, 0.27 to 0.60). CONCLUSIONS: It is feasible to teach basic EEG to participants in critical care settings from different clinical backgrounds, including physicians and nurses. Brief training programs can enable bedside providers to recognize high-yield abnormalities such as non-convulsive seizures.

RéSUMé: OBJECTIF: Nous avons réalisé une revue systématique des programmes éducatifs d'électroencéphalographie (EEG) en soins intensifs s'adressant aux non-neurologues, avec pour but principal de rapporter le contenu couvert, les méthodes d'enseignement, la durée globale et l'expérience des participants. Nos objectifs secondaires étaient d'évaluer l'impact des programmes d'EEG sur les connaissances de base des participants, et l'accord entre non-experts et experts pour l'identification des convulsions. MéTHODE: Les principales bases de données ont été consultées depuis leur création jusqu'au 30 août 2020. Les études randomisées contrôlées, les études de cohorte et les études descriptives ont toutes été prises en compte si elles décrivaient un programme de formation en EEG pour les non-neurologues en milieu de soins intensifs. Les données ont été présentées thématiquement en ce qui touchait notre critère d'évaluation principal qualitatif, et une méta-analyse utilisant un modèle à effets aléatoires a été exécutée pour les critères secondaires quantitatifs. CONSTATATIONS PRINCIPALES: Vingt-neuf études ont été incluses après avoir examiné 7486 citations. Vingt-deux études étaient monocentriques, 17 provenaient d'Amérique du Nord et 16 avaient été publiées après 2016. La plupart des études sur l'EEG visaient le personnel infirmier en soins intensifs (17 études); elles se concentraient sur les formes analysées d'EEG; l'EEG à amplitude intégrée était le thème le plus fréquemment abordé (15 études), et la plupart duraient moins d'un jour (24 études). Dans les études avant-après, les programmes d'EEG ont considérablement amélioré les connaissances des participants du matériel testé (changement moyen normalisé, 1,79; intervalle de confiance [IC] à 95 %, 0,86 à 2,73). L'accord en matière d''identification des convulsions entre non-experts et experts était modéré (kappa de Cohen = 0,44; IC 95 %, 0,27 à 0,60). CONCLUSION: Il est possible d'enseigner l'EEG de base dans des milieux de soins intensifs à des participants provenant de différents milieux cliniques, y compris les médecins et le personnel infirmier. De brefs programmes de formation peuvent permettre aux fournisseurs de soins au chevet de reconnaître les anomalies à haut impact comme par exemple des crises épileptiques non convulsives.

Evaluating satisfaction with the quality and provision of end-of-life care for patients from diverse ethnocultural backgrounds.

BACKGROUND: Recently immigrated and ethnic minority patients in Ontario, Canada are more likely to receive aggressive life-prolonging treatment at the end of life in comparison to other patients. To explore this finding further, this survey-based observational study aimed to evaluate satisfaction with the quality of end-of-life care for patients from diverse ethnocultural backgrounds. METHODS: The End-of-Life Satisfaction Survey was used to measure satisfaction with the quality of inpatient end-of-life care from the perspective of next-of-kin of recently deceased patients at Sunnybrook Health Sciences Centre in Toronto, Ontario (between March 2012 to May 2019). The primary outcome was the global rating of satisfaction. Associations with patient ethnicity, patient religion, level of religiosity/spirituality, language/communication barriers, and location of death were assessed using univariable and multivariable modified Poisson regression. Secondary outcomes included differences in satisfaction and rates of dying in intensive care units (ICU) among patient population subgroups, and identification of high priority areas for quality-of-care improvement. RESULTS: There were 1,543 respondents. Patient ethnicities included Caucasian (68.2%), Mediterranean (10.5%), East Asian (7.6%), South Asian (3.5%), Southeast Asian (2.1%) and Middle Eastern (2.0%); religious affiliations included Christianity (66.6%), Judaism (12.3%) and Islam (2.1%), among others. Location of death was most commonly in ICU (38.4%), hospital wards (37.0%) or long-term care (20.0%). The mean(SD) rating of satisfaction score was 8.30(2.09) of 10. After adjusting for other covariates, satisfaction with quality of end-of-life care was higher among patients dying in ICU versus other locations (relative risk [RR] 1.51, 95%CI 1.05-2.19, p=0.028), lower among those who experienced language/communication barriers (RR 0.49 95%CI 0.23-1.06, p=0.069), and lower for Muslim patients versus other religious affiliations (RR 0.46, 95%CI 0.21-1.02, p=0.056). Survey items identified as highest priority areas for quality-of-care improvement included communication and information giving; illness management; and healthcare provider characteristics such as emotional support, doctor availability and time spent with patient/family. CONCLUSION: Satisfaction with quality-of-care at the end of life was higher among patients dying in ICU and lower among Muslim patients or when there were communication barriers between families and healthcare providers. These findings highlight the importance of measuring and improving end-of-life care across the ethnocultural spectrum.

Compliance With Evidence-Based Processes of Care After Transitions Between Staff Intensivists.

OBJECTIVES: We sought to evaluate the impact of transitions of care among staff intensivists on the compliance with evidence-based processes of care. DESIGN: Cohort study using data from the Toronto Intensive Care Observational Registry. SETTING: Seven academic ICUs in Toronto, Ontario. PATIENTS: Critically ill mechanically ventilated adult patients. INTERVENTIONS: We explored the effects of the weekly transition of care among staff intensivists on compliance with three evidence-based processes of care (spontaneous breathing trials, lung-protective ventilation, and neuromuscular blocking agents). Two practices that are less guided by evidence (early discontinuation of antibiotics and extubation attempts) served as positive controls. We conducted the analysis using generalized estimating equations to account for clustering at the patient level. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 10,570 patients admitted between June 2014 and August 2018. Compliance varied for each practice (63.6%, 42.5%, and 21.1% for lung-protective ventilation, spontaneous breathing trials, and neuromuscular blockade, respectively). There was no effect of transitions of care on compliance with spontaneous breathing trials (odds ratio, 1.00; 95% CI, 0.95-1.07), lung-protective ventilation (odds ratio, 1.07, 95% CI, 0.90-1.26), or neuromuscular blockade use (odds ratio, 0.95; 95% CI, 0.75-1.20). However, early antibiotic discontinuation was more likely (odds ratio, 1.23; 95% CI, 1.06-1.42) and extubation attempts were less frequent (odds ratio, 0.77; 95% CI, 0.65-0.93) after a transition of care. CONCLUSIONS: We observed no significant impact of transitions of care between individual staff physicians on evidence-based processes of care for mechanically ventilated adult patients. However, transitions were associated with a lower likelihood of extubation and higher odds of earlier discontinuation of antibiotics.

Determining Associations and Estimating Effects with Regression Models in Clinical Anesthesia.

There are an increasing number of "big data" studies in anesthesia that seek to answer clinical questions by observing the care and outcomes of many patients across a variety of care settings. This Readers' Toolbox will explain how to estimate the influence of patient factors on clinical outcome, addressing bias and confounding. One approach to limit the influence of confounding is to perform a clinical trial. When such a trial is infeasible, observational studies using robust regression techniques may be able to advance knowledge. Logistic regression is used when the outcome is binary (e.g., intracranial hemorrhage: yes or no), by modeling the natural log for the odds of an outcome. Because outcomes are influenced by many factors, we commonly use multivariable logistic regression to estimate the unique influence of each factor. From this tutorial, one should acquire a clearer understanding of how to perform and assess multivariable logistic regression.