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The number of patients maintained on buprenorphine is steadily increasing. To date, no study has reported buprenorphine management practices for these patients during critical illness, nor its relationship with supplemental full‐agonist opioid administration during their hospital stay. In this single‐center retrospective study, we have explored the incidence of buprenorphine continuation during critical illness among patients receiving buprenorphine for the treatment of opioid use disorder. Additionally, we investigated the relationship between nonbuprenorphine opioid exposure and buprenorphine administration during the intensive care unit (ICU) and post‐ICU phases of care. Our study included adults maintained on buprenorphine for opioid use disorder admitted to the ICU between December 1, 2014, and May 31, 2019. Nonbuprenorphine, full agonist opioid doses were converted to fentanyl equivalents (FEs). Fifty‐one (44%) patients received buprenorphine during the ICU phase of care, with an average dose of 8 (8–12) mg/day. During the post‐ICU phase of care, 68 (62%) received buprenorphine, with an average dose of 10 (7–14) mg/day. Lack of mechanical ventilation and acetaminophen use were also associated with buprenorphine use. Full agonist opioid use was more frequent on days when buprenorphine was not given (odds ratio [OR], 6.2 [95% CI, 2.3–16.4]; P <.001). Additionally, the average cumulative dose of opioids given on nonbuprenorphine administration days was significantly higher both in the ICU (OR, 1803 [95% CI, 1271–2553] vs OR, 327 [95% CI, 152–708] FEs/day; P < 0.001) and after ICU discharge (OR, 1476 [95% CI, 962–2265] vs OR, 238 [95% CI, 150‐377] FEs/day; P <.001). Given these findings, buprenorphine continuation during critical illness should be considered, as it is associated with significantly decreased full agonist opioid use. [ABSTRACT FROM AUTHOR]

In fact, SETPOINT2 compared early tracheostomy with a "standard" approach of weaning with a goal of extubation and an option for tracheostomy after day 10, if necessary. Comment & Response B In Reply b In response to the Letters about SETPOINT2,[1] we agree with Mr Li and Dr Zhou that the location and extent of the brain lesion(s) may be more related to tracheostomy need and timing than the exact vascular pathophysiology. Early vs Standard Approach to Tracheostomy and Functional Outcome Among Patients With Severe Stroke Receiving Mechanical Ventilation - Reply. [Extracted from the article]

Background: Sedation and analgesia are recommended during targeted temperature management (TTM) after cardiac arrest, but there are few data to provide guidance on dosing to bedside clinicians. We evaluated differences in patient-level sedation and analgesia dosing in an international multicenter TTM trial to better characterize current practice and clinically important outcomes. Methods: A total 950 patients in the international TTM trial were randomly assigned to a TTM of 33 °C or 36 °C after resuscitation from cardiac arrest in 36 intensive care units. We recorded cumulative doses of sedative and analgesic drugs at 12, 24, and 48 h and normalized to midazolam and fentanyl equivalents. We compared number of medications used, dosing, and titration among centers by using multivariable models, including common severity of illness factors. We also compared dosing with time to awakening, incidence of clinical seizures, and survival. Results: A total of 614 patients at 18 centers were analyzed. Propofol (70%) and fentanyl (51%) were most frequently used. The average dosages of midazolam and fentanyl equivalents were 0.13 (0.07, 0.22) mg/kg/h and 1.16 (0.49, 1.81) µg/kg/h, respectively. There were significant differences in number of medications (p < 0.001), average dosages (p < 0.001), and titration at all time points between centers (p < 0.001), and the outcomes of patients in these centers were associated with all parameters described in the multivariate analysis, except for a difference in the titration of sedatives between 12 and 24 h (p = 0.40). There were associations between higher dosing at 48 h (p = 0.003, odds ratio [OR] 1.75) and increased titration of analgesics between 24 and 48 h (p = 0.005, OR 4.89) with awakening after 5 days, increased titration of sedatives between 24 and 48 h with awakening after 5 days (p < 0.001, OR > 100), and increased titration of sedatives between 24 and 48 h with a higher incidence of clinical seizures in the multivariate analysis (p = 0.04, OR 240). There were also significant associations between decreased titration of analgesics and survival at 6 months in the multivariate analysis (p = 0.048). Conclusions: There is significant variation in choice of drug, dosing, and titration when providing sedation and analgesics between centers. Sedation and analgesia dosing and titration were associated with delayed awakening, incidence of clinical seizures, and survival, but the causal relation of these findings cannot be proven. [ABSTRACT FROM AUTHOR]

Hypotension after cardiac arrest could aggravate prolonged hypoxic ischemic encephalopathy. The association of circulatory shock at hospital admission with outcome after cardiac arrest has not been well studied. The objective of this study was to investigate the independent association of circulatory shock at hospital admission with neurologic outcome, and to evaluate whether cardiovascular comorbidities interact with circulatory shock. 4004 adult patients with out-of-hospital cardiac arrest enrolled in the International Cardiac Arrest Registry 2006–2017 were included in analysis. Circulatory shock was defined as a systolic blood pressure below 90 mmHg and/or medical or mechanical supportive measures to maintain adequate perfusion during hospital admission. Primary outcome was cerebral performance category (CPC) dichotomized as good, (CPC 1–2) versus poor (CPC 3–5) outcome at hospital discharge. 38% of included patients were in circulatory shock at hospital admission, 32% had good neurologic outcome at hospital discharge. The adjusted odds ratio for good neurologic outcome in patients without preexisting cardiovascular disease with circulatory shock at hospital admission was 0.60 [0.46–0.79]. No significant interaction was detected with preexisting comorbidities in the main analysis. We conclude that circulatory shock at hospital admission after out-of-hospital cardiac arrest is independently associated with poor neurologic outcome. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality.Methods: The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years.Discussion: The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome.Trial Registration: ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021. [ABSTRACT FROM AUTHOR]

Late chemokine response is associated with poor outcomes in patients after cardiac arrest. [Display omitted] • Circulating chemokines demonstrate different temporal dynamics after cardiac arrest. • CCL23 and neutrophil count are related to clinical outcomes after cardiac arrest. • Late neutrophil activation may promote ongoing tissue injury after cardiac arrest. • Cardiac arrest neutrophil activation and migration to brain tissue in mouse model. Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled. Quantitative antibody array, chemokines, and endotoxin quantification were performed using the patients blood. Analysis of CCL23 production in neutrophils obtained from CA patients and injected into immunodeficient mice after CA and cardiopulmonary resuscitation (CPR) were done using flow cytometry. The levels of CCL2, CCL4, and CCL23 are increased in CA patients. Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a delayed elevation in CCL23 at forty-eight hours after CA. A high level of CCL23 was associated with an increased number of neutrophils, neuron-specific enolase (NSE), worse cerebral performance category (CPC) score, and higher mortality. To investigate the role of neutrophil activation locally in injured brain tissue, we used a mouse model of CA/CPR. CCL23 production was increased in human neutrophils that infiltrated mouse brains compared to those in the peripheral circulation. It is known that an early intense inflammatory response (within hours) is associated with poor outcomes after CA. Our data indicate that late activation of neutrophils in brain tissue may also promote ongoing injury via the production of CCL23 and impair recovery after cardiac arrest. [ABSTRACT FROM AUTHOR]

Background/Objective: Neurostimulants may improve or accelerate cognitive and functional recovery after intracerebral hemorrhage (ICH), ischemic stroke (IS), or subarachnoid hemorrhage (SAH), but few studies have described their safety and effectiveness in the intensive care unit (ICU). The objective of this study was to describe amantadine and modafinil administration practices during acute stroke care starting in the ICU and to evaluate safety and effectiveness. Methods: Consecutive adult ICU patients treated with amantadine and/or modafinil following acute non-traumatic IS, ICH, or SAH were evaluated. Neurostimulant administration data were extracted from the electronic medication administration record, including medication (amantadine, modafinil, or both), starting dose, time from stroke to initiation, and whether the neurostimulant was continued at hospital discharge. Patients were considered responders if they met two of three criteria within 9 days of neurostimulant initiation: increase in Glasgow coma scale (GCS) score ≥ 3 points from pre-treatment baseline, improved wakefulness or participation documented in caregiver notes, or clinical improvement documented in physical or occupational therapy notes. Potential confounders of the effectiveness assessment and adverse drug effects were also recorded. Results: A total of 87 patients were evaluable during the 3.7-year study period, including 41 (47%) with ICH, 29 (33%) with IS, and 17 (20%) with SAH. The initial neurostimulant administered was amantadine in 71 (82%) patients, modafinil in 13 (15%), or both in 3 (3%) patients. Neurostimulants were initiated a median of 7 (4.25, 12.75) days post-stroke (range 1–27 days) for somnolence (77%), not following commands (32%), lack of eye opening (28%), or low GCS (17%). The most common starting dose was 100 mg twice daily for both amantadine (86%) and modafinil (54%). Of the 79 patients included in the effectiveness evaluation, 42 (53%) were considered responders, including 34/62 (55%) receiving amantadine monotherapy and 8/24 (33%) receiving both amantadine and modafinil at the time they met the definition of a responder. No patient receiving modafinil monotherapy was considered a responder. The median time from initiation to response was 3 (2, 5) days. Responders were more frequently discharged home or to acute rehabilitation compared to non-responders (90% vs 62%, p = 0.006). Among survivors, 63/72 (88%) were prescribed a neurostimulant at hospital discharge. The most common potential adverse drug effect was sleep disruption (16%). Conclusions: Neurostimulant administration during acute stroke care may improve wakefulness. Future controlled studies with a neurostimulant administration protocol, prospective evaluation, and discretely defined response and safety criteria are needed to confirm these encouraging findings. [ABSTRACT FROM AUTHOR]

Background: The American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.Objectives: This study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.Methods: Using the INTCAR (International Cardiac Arrest Registry), the impact of each proposed "unfavorable feature" on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.Results: Seven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age >85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC >30 min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate >7 mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH <7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted <40% survival. Presence of the 3 strongest risk factors (age >85 years, time-to-ROSC >30 min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a ≤10% chance of survival to discharge.Conclusions: Patients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable. [ABSTRACT FROM AUTHOR]

Background: The benefit of emergency coronary angiography after resuscitation from out-of-hospital cardiac arrest is uncertain for patients without ST-segment elevation. The aim of this randomized trial was to evaluate the efficacy and safety of early coronary angiography and to determine the prevalence of acute coronary occlusion in resuscitated patients with out-of-hospital cardiac arrest without ST-segment elevation.Methods: Adult (>18 years) comatose survivors without ST-segment elevation after resuscitation from out-of-hospital cardiac arrest were prospectively randomized in a 1:1 fashion under exception to informed consent regulations to early coronary angiography versus no early coronary angiography in this multicenter study. Early angiography was defined as ≤120 minutes from arrival at the percutaneous coronary intervention-capable facility. The primary end point was a composite of efficacy and safety measures, including efficacy measures of survival to discharge, favorable neurologic status at discharge (Cerebral Performance Category score ≤2), echocardiographic measures of left ventricular ejection fraction >50%, and a normal regional wall motion score of 16 within 24 hours of admission. Adverse events included rearrest, pulmonary edema on chest x-ray, acute renal dysfunction, bleeding requiring transfusion or intervention, hypotension (systolic arterial pressure ≤90 mm Hg), and pneumonia. Secondary end points included the incidence of culprit vessels with acute occlusion.Results: The study was terminated prematurely before enrolling the target number of patients. A total of 99 patients were enrolled from 2015 to 2018, including 75 with initially shockable rhythms. Forty-nine patients were randomized to early coronary angiography. The primary end point of efficacy and safety was not different between the 2 groups (55.1% versus 46.0%; P=0.64). Early coronary angiography was not associated with any significant increase in survival (55.1% versus 48.0%; P=0.55) or adverse events (26.5% versus 26.0%; P=1.00). Early coronary angiography revealed a culprit vessel in 47%, with a total of 14% of patients undergoing early coronary angiography having an acutely occluded culprit coronary artery.Conclusions: This underpowered study, when considered together with previous clinical trials, does not support early coronary angiography for comatose survivors of cardiac arrest without ST elevation. Whether early detection of occluded potential culprit arteries leads to interventions that improve outcomes requires additional study.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02387398. [ABSTRACT FROM AUTHOR]

Amantadine and modafinil are neurostimulants that may improve cognitive and functional recovery post-stroke, but the existing study results vary, and no comprehensive review has been published. This systematic review describes amantadine and modafinil administration practices post-stroke, evaluates timing and impact on clinical effectiveness measures, and identifies the incidence of potential adverse drug effects. A librarian-assisted search of the MEDLINE (PubMed) and EMBASE databases identified all English-language publications with "amantadine" or "modafinil" in the title or abstract from inception through February 1, 2020. Publications meeting predefined Patient, Intervention, Comparator, Outcome (PICO) criteria were included: Patients (≥ 18 years of age post-stroke); Intervention (amantadine or modafinil administration); Comparison (pretreatment baseline or control group); Outcomes (cognitive or functional outcome). Amantadine and modafinil administration practices, cognitive and functional outcomes, and incidence of potential adverse drug effects were collected following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance. Quantitative analyses were not performed due to heterogeneity in the clinical effectiveness measures; descriptive data are presented as number (percent) or median (interquartile range). Of 12,620 publications initially identified, 10 amantadine publications (n = 121 patients) and 12 modafinil publications (n = 120 patients) were included. Amantadine was initiated 39 (16, 385) days post-stroke, with most common initial doses of 100 mg once or twice daily (range 100–200 mg/day), and final daily dose of 200 (188, 200) mg/day. Modafinil was initiated 170 (17, 496) days post-stroke, with initial and final daily doses of 100 (100, 350) mg/day and 200 (100, 350) mg/day, respectively. The most common indication was consciousness disorders for amantadine (n = 3/10 publications; 30%) and fatigue for modafinil (n = 5/12; 42%). Forty unique clinical effectiveness measures (1.8 per study) with 141 domains (6.4 per study) were described across all studies. A positive response in at least one clinical effectiveness measure was reported in 70% of amantadine publications and 83% of modafinil publications. Only one publication each for amantadine (10%; n = 5 patients) and modafinil (8%; n = 21 patients) studied acutely hospitalized or ICU patients; both were randomized studies showing improvements in neurocognitive function for amantadine and fatigue for modafinil. Potential adverse drug effects were reported in approximately 50% of publications, most commonly visual hallucinations with amantadine (2% of patients) and dizziness (5% of patients) and dry eyes or mouth (5% of patients). Amantadine and modafinil may improve cognitive and functional recovery post-stroke, but higher-quality data are needed to confirm this conclusion, especially in the acute care setting. [ABSTRACT FROM AUTHOR]

Background: The absence of the pupillary light reflex (PLR) 3 days after cardiac arrest predicts poor outcome, but quantitative PLR assessment with pupillometry early after recovery of spontaneous circulation (ROSC) and throughout targeted temperature management (TTM) has rarely been evaluated.Methods: Fifty-five adult patients treated with TTM with available pupillometry data from the NeurOptics NPi-200 were studied. Discharge outcome was classified good if the cerebral performance category score was 1-2, poor if 3-5. Pupil size, PLR percent constriction (%PLR), and constriction velocity (CV) were determined at TTM start and 6 (± 2)-h post-ROSC ("early"), and throughout TTM using data from the worst eye at each assessment. The Neurological Pupil index (NPi) was also determined at each pupil assessment; the NPi is scored from 0 (nonreactive) to 5 (brisk) with values < 3 considered sluggish or abnormal. Prognostic performance to predict poor outcome was assessed with receiver operator characteristic curves.Results: All nine patients with ≥ 1 nonreactive pupil (NPi = 0) within 6 (± 2) h after ROSC died, and 12/14 (86%) with sluggish pupils (0 < NPi < 3) had poor outcomes. 15/29 (52%) patients with normal pupil reactivity (NPi ≥ 3) had poor outcomes, four survived with cerebral performance category = 3, three died of cardiac causes, and eight died of neurologic causes. During TTM, 20/21 (95%) patients with nonreactive pupils had poor outcomes, 9/14 (64%) of patients with sluggish pupils had poor outcomes, and 9/20 (45%) with normal pupil reactivity had poor outcomes. Pupil size did not predict outcome, but NPi (AUC = 0.72 [0.59-0.86], p < 0.001), %PLR (AUC = 0.75 [0.62-0.88], p < 0.001) and CV (AUC = 0.78 [0.66-0.91], p < 0.001) at 6 h predicted poor outcome. When nonreactive pupils were first detected, 75% were < 5 mm.Conclusions: Very early after resuscitation from cardiac arrest, abnormal Neurological Pupil index and pupillary light reflex measurements by pupillometer are predictive of poor outcome, and are not usually associated with dilated pupils. [ABSTRACT FROM AUTHOR]

Buprenorphine is highly effective for the treatment of opioid use disorder (OUD), and, in recent years, the rates of patients maintained on buprenorphine requiring critical care have been steadily increasing. Currently, no unified guidance exists for buprenorphine management during critical illness. Likewise, we do not know if patients maintained on buprenorphine for OUD are prescribed medications for OUD (MOUD) following hospital discharge or if buprenorphine management influences mu opioid agonist dispensing. In our cohort of adults over the age of 18 with OUD, receiving buprenorphine formulations in the 3 months preceding their ICU admission, we sought to investigate the relationship between receipt of MOUD and non-MOUD opioid prescribing up to 12 months following hospital discharge. This was a single-center, retrospective cohort study approved by the MaineHealth institutional review board. The study analyzed differences in prescription rates between discharge and subsequent time points using chi square or Fisher's exact test, as appropriate. We performed analyses using SPSS Statistical Software version 28 (IBM SPSS Inc., Armonk, NY) with significance set at p < 0.05. We identified a statistically significant increase in MOUD prescribing 3 months posthospital discharge in patients who received MOUD at time of discharge (87.9 % vs 40 % p = 0.002.) The study found a significant increase in nonbuprenorphine opioid prescribing in patients who did not receive an MOUD prescription at time of discharge (24.2 % vs 70 % p = 0.007). This trend persisted at the 6-month and 12-month time points; however, it did not reach statistical significance. Additionally, the study identified a significant reduction in the incidence of non-MOUD opioid dispensing in patients prescribed MOUD at each time point measured (p = 0.007, p < 0.001. p < 0.001 and p = 0.008 at discharge, 3, 6, and 12 months, respectively). These findings support continuing buprenorphine dispensing following hospital discharge. • MOUD prescribing at hospital discharge associated with increased MOUD dispensing • Outpatient opioid agonist prescribing more likely when MOUD not prescribed at discharge • Decreased opioid agonist dispensing 12 months post-discharge in patients given MOUD [ABSTRACT FROM AUTHOR]

Aim: "Early" withdrawal of life support therapies (eWLST) within the first 3 calendar days after resuscitation from cardiac arrest (CA) is discouraged. We evaluated a prospective multicenter registry of patients admitted to hospitals after resuscitation from CA to determine predictors of eWLST and estimate its impact on outcomes.Methods: CA survivors enrolled from 2012-2017 in the International Cardiac Arrest Registry (INTCAR) were included. We developed a propensity score for eWLST and matched a cohort with similar probabilities of eWLST who received ongoing care. The incidence of good outcome (Cerebral Performance Category of 1 or 2) was measured across deciles of eWLST in the matched cohort.Results: 2688 patients from 24 hospitals were included. Median ischemic time was 20 (IQR 11, 30) minutes, and 1148 (43%) had an initial shockable rhythm. Withdrawal of life support occurred in 1162 (43%) cases, with 459 (17%) classified as eWLST. Older age, initial non-shockable rhythm, increased ischemic time, shock on admission, out-of-hospital arrest, and admission in the United States were each independently associated with eWLST. All patients with eWLST died, while the matched cohort, good outcome occurred in 21% of patients. 19% of patients within the eWLST group were predicted to have a good outcome, had eWLST not occurred.Conclusions: Early withdrawal of life support occurs frequently after cardiac arrest. Although the mortality of patients matched to those with eWLST was high, these data showed excess mortality with eWLST. [ABSTRACT FROM AUTHOR]

Aim: Shivering may interfere with targeted temperature management (TTM) after cardiac arrest, contributing to secondary brain injury. Early identification of shivering is challenging with existing tools. We hypothesized that shivering detected by continuous surface sEMG monitoring would be validated with calorimetry and detected earlier than by intermittent clinical observation.Methods: This prospective observational study enrolled a convenience sample of comatose adult cardiac arrest patients treated with TTM at 33 °C. Clinical shivering was monitored hourly using the Bedside Shivering Assessment Scale (BSAS) by bedside nurses who administered intermittent neuromuscular blockade (NMB) when BSAS ≥ 1. The research team monitored independently for shivering with BSAS every 15 min during continuous blinded monitoring of oxygen consumption (VO2) via indirect calorimetry and sEMG power during the maintenance phase of TTM. A sustained 20% increase in the 5-min rolling average of VO2 above baseline identified the Gold Standard shivering threshold (VO2-20).Results: Among 18 patients, clinical shivering was detected 23 times in 14 patients. Hierarchical models to predict a shiver event determined by the VO2-20 for sEMG power and BSAS revealed an AUC for sEMG power of 0.92 (95%CI = 0.88-0.95), and 0.90 (CI = 0.87-0.94) for BSAS. The optimal threshold of sEMG to predict VO2-20 was 32 decibels (dB), and this was exceeded 38 (29-56) min before nurse-detected shivering.Conclusions: Shivering was detected by sEMG power earlier than by clinical assessment with BSAS, with similar accuracy compared to the indirect calorimetry gold standard. Continuous sEMG monitoring appears useful for clinical assessment and research for shivering during TTM. [ABSTRACT FROM AUTHOR]

Background: Hypotension, hyperglycemia, dysoxia, and dyscarbia may contribute to reperfusion injury, and each is independently associated with poor outcome (PO) after cardiac arrest. We investigated whether the combined effects of these physiological derangements are associated with cardiac arrest outcomes.Methods: This institutional review board-approved retrospective cohort study included consecutive resuscitated cardiac arrest patients that received targeted temperature management at Maine Medical Center from 2013 to 2015. We abstracted demographics, intra-arrest factors, and physiological parameters. The primary outcome was dichotomized cerebral performance category (CPC 1-2 vs 3-5) at hospital discharge. After comparing demographics, clinical factors, and persistent post-arrest physiological derangements in patients with good and PO, we constructed a logistic regression model comprised of clinical and demographic factors separately associated with severity, and physiology variables, attempting to evaluate the independent effects of persistent physiological derangements on outcome.Results: Sixty-eight of 222 (31%) patients had CPC 1-2 (good outcome [GO]) at discharge. In bivariate analysis, factors associated with PO included increased time from collapse to resuscitation, non-shockable rhythm, and age-combined Charlson comorbidity index. In multivariate analysis, each persistent physiological derangement incrementally decreased the likelihood of GO [OR GO per derangement 0.71 (interquartile range [IQR] 0.51-0.99), p = 0.042, area under the curve (AUC) for final model 0.769].Conclusions: Uncorrected physiological derangements in the first 24 h after cardiac arrest are independently associated with PO. Although causality cannot be established, these findings support preclinical models suggesting that aggressive normalization of physiology after resuscitation may be a reasonable strategy to decrease reperfusion injury. [ABSTRACT FROM AUTHOR]

Background: No practical tool quantitates the risk of circulatory-etiology death (CED) immediately after successful cardiopulmonary resuscitation in patients without ST-segment-elevation myocardial infarction. We developed and validated a prediction model to rapidly determine that risk and facilitate triage to individualized treatment pathways.Methods: With the use of INTCAR (International Cardiac Arrest Registry), an 87-question data set representing 44 centers in the United States and Europe, patients were classified as having had CED or a combined end point of neurological-etiology death or survival. Demographics and clinical factors were modeled in a derivation cohort, and backward stepwise logistic regression was used to identify factors independently associated with CED. We demonstrated model performance using area under the curve and the Hosmer-Lemeshow test in the derivation and validation cohorts, and assigned a simplified point-scoring system.Results: Among 638 patients in the derivation cohort, 121 (18.9%) had CED. The final model included preexisting coronary artery disease (odds ratio [OR], 2.86; confidence interval [CI], 1.83-4.49; P≤0.001), nonshockable rhythm (OR, 1.75; CI, 1.10-2.77; P=0.017), initial ejection fraction<30% (OR, 2.11; CI, 1.32-3.37; P=0.002), shock at presentation (OR, 2.27; CI, 1.42-3.62; P<0.001), and ischemic time >25 minutes (OR, 1.42; CI, 0.90-2.23; P=0.13). The derivation model area under the curve was 0.73, and Hosmer-Lemeshow test P=0.47. Outcomes were similar in the 318-patient validation cohort (area under the curve 0.68, Hosmer-Lemeshow test P=0.41). When assigned a point for each associated factor in the derivation model, the average predicted versus observed probability of CED with a CREST score (coronary artery disease, initial heart rhythm, low ejection fraction, shock at the time of admission, and ischemic time >25 minutes) of 0 to 5 was: 7.1% versus 10.2%, 9.5% versus 11%, 22.5% versus 19.6%, 32.4% versus 29.6%, 38.5% versus 30%, and 55.7% versus 50%.Conclusions: The CREST model stratified patients immediately after resuscitation according to risk of a circulatory-etiology death. The tool may allow for estimation of circulatory risk and improve the triage of survivors of cardiac arrest without ST-segment-elevation myocardial infarction at the point of care. [ABSTRACT FROM AUTHOR]

Background: Prothrombin complex concentrates (PCCs) have become the first-line therapy for warfarin reversal in the setting of central nervous system (CNS) hemorrhage. Randomized, controlled studies comparing agents for warfarin reversal excluded patients with international normalized ratio (INR) <2, yet INR values of 1.6-1.9 are also associated with poor outcomes.Methods: We retrospectively reviewed our use of a low-dose (15 units/kg) strategy of 4-factor PCC (4F-PCC) on warfarin reversal (INR 1.6-1.9) in the setting of both traumatic and spontaneous intracranial bleeding.Results: A total of 21/134 (15.7%) patients with either spontaneous or traumatic intracranial hemorrhage presented with an INR value of 1.6-1.9. Nine patients (43%) presented with traumatic bleeding and 12 (57%) with spontaneous bleeding. The median (IQR) presenting INR was 1.8 (1.7, 1.9) which decreased to 1.3 (1.2, 1.3) following the administration of low-dose 4F-PCC (median dose = 1062 units; 15.2 units/kg). A total of 19/20 (95%) patients achieved a goal INR value of ≤1.5 on the first check following dosing and 17/20 (85%) achieved an INR value ≤1.3. One patient did not have follow-up INR testing due to withdrawal of life support. No patient experienced hematoma expansion within 48 h of 4F-PCC, and there were no thromboembolic events within 72 h of administration.Conclusions: The administration of low dose (15 units/kg) of 4F-PCC for urgent warfarin reversal in the setting of CNS hemorrhage was effective in correcting the INR in patients presenting with INR values of 1.6-1.9. Further assessment of low-dose PCC for urgent reversal of modest INR elevation is warranted. [ABSTRACT FROM AUTHOR]

Airway management and ventilation are central to the resuscitation of the neurologically ill. These patients often have evolving processes that threaten the airway and adequate ventilation. Furthermore, intubation, ventilation, and sedative choices directly affect brain perfusion. Therefore, Airway, Ventilation, and Sedation was chosen as an Emergency Neurological Life Support protocol. Topics include airway management, when and how to intubate with special attention to hemodynamics and preservation of cerebral blood flow, mechanical ventilation settings and the use of sedative agents based on the patient's neurological status. [ABSTRACT FROM AUTHOR]

Introduction Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development of pneumonia in that population. Methods We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors ≥18 years of age with a GCS < 8 at hospital admission and treated with TTM at 32–34 °C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome. Results 416 of 1240 patients (33.5%) received PRO. Groups were similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p < 0.001) and less sepsis (1.2 vs. 5.7%, p < 0.001) compared to no-PRO patients. ICU length of stay (98 vs. 100 h, p = 0.2) and incidence of a good functional outcome (41.1 vs. 36.6%, p = 0.19) were similar between groups. Backwards stepwise logistic regression demonstrated PRO were independently associated with a lower incidence of pneumonia (OR 0.09, 95% 0.06–0.14, p < 0.001) and a similar incidence of good functional outcome. Conclusions Prophylactic antibiotics were associated with a reduced incidence of pneumonia but a similar rate of good functional outcome. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To determine if early cardiac catheterization (CC) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infarction (STEMI) is absent. Methods: We conducted a retrospective observational study of a prospective cohort of 754 consecutive comatose patients treated with therapeutic hypothermia (TH) following cardiac arrest. Results: A total of 269 (35.7%) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH. Of these, 122 (45.4%) received CC while comatose (early CC). Acute coronary occlusion was discovered in 26.6% of patients treated with early CC compared to 29.3% of patients treated with late CC (p =0.381). Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC (65.6% vs. 48.6%; p =0.017). In a multivariate regression model that included study site, age, bystander CPR, shock on admission, comorbid medical conditions, witnessed arrest, and time to return of spontaneous circulation, early CC was independently associated with a significant reduction in the risk of death (OR 0.35, 95% CI 0.18–0.70, p =0.003). Conclusions: In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality. The incidence of acute coronary occlusion is high, even when STEMI is not present on the postresuscitation electrocardiogram. [Copyright &y& Elsevier]

Objectives: Sedation and neuromuscular blockade protocols in patients undergoing targeted temperature management after cardiac arrest address patient discomfort and manage shivering. These protocols vary widely between centers and may affect outcomes.Design: Consecutive patients admitted to 20 centers after resuscitation from cardiac arrest were prospectively entered into the International Cardiac Arrest Registry between 2006 and 2016. Additional data about each center's sedation and shivering management practice were obtained via survey. Sedation and shivering practices were categorized as escalating doses of sedation and minimal or no neuromuscular blockade (sedation and shivering practice 1), sedation with continuous or scheduled neuromuscular blockade (sedation and shivering practice 2), or sedation with as-needed neuromuscular blockade (sedation and shivering practice 3). Good outcome was defined as Cerebral Performance Category score of 1 or 2. A logistic regression hierarchical model was created with two levels (patient-level data with standard confounders at level 1 and hospitals at level 2) and sedation and shivering practices as a fixed effect at the hospital level. The primary outcome was dichotomized Cerebral Performance Category at 6 months.Setting: Cardiac arrest receiving centers in Europe and the United states from 2006 to 2016 PATIENTS:: Four-thousand two-hundred sixty-seven cardiac arrest patients 18 years old or older enrolled in the International Cardiac Arrest Registry.Interventions: None.Measurements and Main Results: The mean age was 62 ± 15 years, 36% were female, 77% out-of-hospital arrests, and mean ischemic time was 24 (± 18) minutes. Adjusted odds ratio (for age, return of spontaneous circulation, location of arrest, witnessed, initial rhythm, bystander cardiopulmonary resuscitation, defibrillation, medical history, country, and size of hospital) was 1.13 (0.74-1.73; p = 0.56) and 1.45 (1.00-2.13; p = 0.046) for sedation and shivering practice 2 and sedation and shivering practice 3, respectively, referenced to sedation and shivering practice 1.Conclusion: Cardiac arrest patients treated at centers using as-needed neuromuscular blockade had increased odds of good outcomes compared with centers using escalating sedation doses and avoidance of neuromuscular blockade, after adjusting for potential confounders. These findings should be further investigated in prospective studies. [ABSTRACT FROM AUTHOR]

Background: Tracheostomy in mechanically ventilated patients with severe stroke can be performed surgically or dilationally. Prospective data comparing both methods in patients with stroke are scarce. The randomized Stroke-Related Early Tracheostomy vs Prolonged Orotracheal Intubation in Neurocritical Care Trial2 (SETPOINT2) assigned 382 mechanically ventilated patients with stroke to early tracheostomy versus extubation or standard tracheostomy. Surgical tracheostomy (ST) was performed in 41 of 307 SETPOINT2 patients, and the majority received dilational tracheostomy (DT). We aimed to compare ST and DT in these patients with patients., Methods: All SETPOINT2 patients with ST were compared with a control group of patients with stroke undergoing DT (1:2), selected by propensity score matching that included the factors stroke type, SETPOINT2 randomization group, Stroke Early Tracheostomy score, patient age, and premorbid functional status. Successful decannulation was the primary outcome, and secondary outcome parameters included functional outcome at 6 months and adverse events attributable to tracheostomy. Potential predictors of decannulation were evaluated by regression analysis., Results: Baseline characteristics were comparable in the two groups of patients with stroke undergoing ST (n = 41) and matched patients with stroke undergoing DT (n = 82). Tracheostomy was performed significantly later in the ST group than in the DT group (median 9 [interquartile range {IQR} 5-12] vs. 9 [IQR 4-11] days after intubation, p = 0.025). Patients with ST were mechanically ventilated longer (median 19 [IQR 17-24] vs.14 [IQR 11-19] days, p = 0.008) and stayed in the intensive care unit longer (median 23 [IQR 16-27] vs. 17 [IQR 13-24] days, p = 0.047), compared with patients with DT. The intrahospital infection rate was significantly higher in the ST group compared to the DT group (14.6% vs. 1.2%, p = 0.002). At 6 months, decannulation rates (56% vs. 61%), functional outcomes, and mortality were not different. However, decannulation was performed later in the ST group compared to the DT group (median 81 [IQR 66-149] vs. 58 [IQR 32-77] days, p = 0.004). Higher baseline Stroke Early Tracheostomy score negatively predicted decannulation., Conclusions: In ventilated patients with severe stroke in need of tracheostomy, surgical and dilational methods are associated with comparable decannulation rate and functional outcome at 6 months. However, ST was associated with longer time to decannulation and higher rates of early infections, supporting the dilational approach to tracheostomy in ventilated patients with stroke., (© 2024. The Author(s).)

Objective: We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest., Methods: We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests., Results: After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group., Conclusion: We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

Importance: Protein binding of valproate varies among ICU patients, altering the biologically active free valproate concentration (VPAC). Free VPAC is measured at few laboratories and is often discordant with total VPAC. Existing equations to predict free VPAC are either not validated or are inaccurate in ICU patients., Objectives: We designed this study to derive and validate a novel equation to predict free VPAC using data from ICU patients and to compare its performance to published equations., Design: Retrospective cohort study., Setting: Two academic medical centers., Participants: Patients older than 18 years old with concomitant free and total VPACs measured in the ICU were included in the derivation cohort if admitted from 2014 to 2018, and the validation cohort if admitted from 2019 to 2022., Main Outcomes and Measures: Multivariable linear regression was used to derive an equation to predict free VPAC. Modified Bland-Altman plots and the rate of therapeutic concordance between the measured and predicted free VPAC were compared., Results: Demographics, median free and total VPACs, and valproate free fractions were similar among 115 patients in the derivation cohort and 147 patients in the validation cohort. The Bland-Altman plots showed the new equation performed better (bias, 0.3 [95% limits of agreement, -13.6 to 14.2]) than the Nasreddine (-9.2 [-26.5 to 8.2]), Kodama (-9.7 [-30.0 to 10.7]), Conde Giner (-7.9 [-24.9 to 9.1]), and Parent (-9.9 [-30.7 to 11.0]) equations, and similar to Doré (-2.0 [-16.0 to 11.9]). The Doré and new equations had the highest therapeutic concordance rate (73%)., Conclusions and Relevance: For patients at risk of altered protein binding such as ICU patients, existing equations to predict free VPAC are discordant with measured free VPAC. A new equation had low bias but was imprecise. External validation should be performed to improve its precision and generalizability. Until then, monitoring free valproate is recommended during critical illness., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: The CREST model is a prediction model, quantitating the risk of circulatory-etiology death (CED) after cardiac arrest based on variables available at hospital admission, and intend to guide the triage of comatose patients without ST-segment-elevation myocardial infarction after successful cardiopulmonary resuscitation. This study assessed performance of the CREST model in the Target Temperature Management (TTM) trial cohort., Methods: We retrospectively analyzed data from resuscitated out-of-hospital cardiac arrest (OHCA) patients in the TTM-trial. Demographics, clinical characteristics, and CREST variables (history of coronary artery disease, initial heart rhythm, initial ejection fraction, shock at admission and ischemic time > 25 min) were assessed in univariate and multivariable analysis. The primary outcome was CED. The discriminatory power of the logistic regression model was assessed using the C-statistic and goodness of fit was tested according to Hosmer-Lemeshow., Results: Among 329 patients eligible for final analysis, 71 (22%) had CED. History of ischemic heart disease, previous arrhythmia, older age, initial non-shockable rhythm, shock at admission, ischemic time > 25 min and severe left ventricular dysfunction were variables associated with CED in univariate analysis. CREST variables were entered into a logistic regression model and the area under the curve for the model was 0.73 with adequate calibration according to Hosmer-Lemeshow test (p = 0.602)., Conclusions: The CREST model had good validity and a discrimination capability for predicting circulatory-etiology death after resuscitation from cardiac arrest without ST-segment elevation myocardial infarction. Application of this model could help to triage high-risk patients for transfer to specialized cardiac centers., (© 2023. The Author(s).)

Background: Cumulative research show association of neutrophils and neutrophil extracellular traps (NETs) with poor outcomes in severe COVID-19. However, to date, there is no curative intent therapy able to block neutrophil/NETs-mediated progression of multi-organ dysfunction. Because of emerging neutrophil heterogeneity, the study of subsets of circulating NET-forming neutrophils [NET + Ns] as mediators of multi-organ failure progression among patients with COVID-19 is critical to identification of therapeutic targets., Methods: We conducted a prospective observational study of circulating levels of CD11b + [NET + N] immunotyped for dual endothelin-1/signal peptide receptor (DEspR ±) expression by quantitative immunofluorescence-cytology and causal mediation analysis. In 36 consented adults hospitalized with mod-severe COVID-19, May to September 2020, we measured acute multi-organ failure via SOFA-scores and respiratory failure via SaO2/FiO2 (SF)-ratio at time points t1 (average 5.5 days from ICU/hospital admission) and t2 (the day before ICU-discharge or death), and ICU-free days at day28 (ICUFD). Circulating absolute neutrophil counts (ANC) and [NET + N] subset-specific counts were measured at t1. Spearman correlation and causal mediation analyses were conducted., Results: Spearman correlation analyses showed correlations of t1-SOFA with t2-SOFA ( rho r S  = 0.80) and ICUFD ( r S  = -0.76); circulating DEspR + [NET + Ns] with t1-SOFA ( r S  = 0.71), t2-SOFA ( r S  = 0.62), and ICUFD ( r S  = -0.63), and ANC with t1-SOFA ( r S  = 0.71), and t2-SOFA ( r S  = 0.61).Causal mediation analysis identified DEspR + [NET + Ns] as mediator of 44.1% [95% CI:16.5,110.6] of the causal path between t1-SOFA (exposure) and t2-SOFA (outcome), with 46.9% [15.8,124.6] eliminated when DEspR + [NET + Ns] were theoretically reduced to zero. Concordantly, DEspR + [NET + Ns] mediated 47.1% [22.0,72.3%] of the t1-SOFA to ICUFD causal path, with 51.1% [22.8,80.4%] eliminated if DEspR + [NET + Ns] were reduced to zero. In patients with t1-SOFA > 1, the indirect effect of a hypothetical treatment eliminating DEspR + [NET + Ns] projected a reduction of t2-SOFA by 0.98 [0.29,2.06] points and ICUFD by 3.0 [0.85,7.09] days. In contrast, there was no significant mediation of SF-ratio through DEspR + [NET + Ns], and no significant mediation of SOFA-score through ANC., Conclusions: Despite equivalent correlations, DEspR + [NET + Ns], but not ANC, mediated progression of multi-organ failure in acute COVID-19, and its hypothetical reduction is projected to improve ICUFD. These translational findings warrant further studies of DEspR + [NET + Ns] as potential patient-stratifier and actionable therapeutic target for multi-organ failure in COVID-19., Supplementary Information: The online version contains supplementary material available at 10.1186/s41231-023-00143-x., Competing Interests: Competing interestsBoston University holds awarded patents on DEspR as novel therapeutic approach for cancer, stroke, COVID-19, NETosis and activated neutrophils. VLMH and NRO are co-inventors in patents filed by Boston University., (© The Author(s) 2023.)

Objective: SARS-CoV-2 infection has been shown to result in increased circulating levels of adenosine triphosphate and adenosine diphosphate and decreased levels of adenosine, which has important anti-inflammatory activity. The goal of this pilot project was to assess the levels of soluble CD73 and soluble Adenosine Deaminase (ADA) in hospitalized patients with COVID-19 and determine if levels of these molecules are associated with disease severity., Methods: Plasma from 28 PCR-confirmed hospitalized COVID-19 patients who had varied disease severity based on WHO classification (6 mild/moderate, 10 severe, 12 critical) had concentrations of both soluble CD73 and ADA determined by ELISA. These concentrations were compared to healthy control plasma that is commercially available and was biobanked prior to the start of the pandemic. Additionally, outcomes such as WHO ordinal scale for disease severity, ICU admission, needed for invasive ventilation, hospital length of stay, and development of thrombosis during admission were used as markers of disease severity., Results: Our results show that both CD73 and ADA are decreased during SARS-CoV-2 infection. The level of circulating CD73 is directly correlated to the severity of the disease defined by the need for ICU admission, invasive ventilation, and hospital length of stay. Low level of CD73 is also associated with clinical thrombosis, a severe complication of SARS-CoV-2 infection., Conclusion: Our study indicates that adenosine metabolism is down-regulated in patients with COVID-19 and associated with severe infection. Further large-scale studies are warranted to investigate the role of the adenosinergic anti-inflammatory CD73/ADA axis in protection against COVID-19.

Aim: Describe community consultation and surrogate consent rates for two Exception From Informed Consent (EFIC) trials for out-of-hospital cardiac arrest (OOHCA) - before and during the COVID-19 pandemic., Methods: The PEARL study (2016-2018) randomized OOHCA patients without ST-elevation to early cardiac catheterization or not. Community consultation included flyers, radio announcements, newspaper advertisements, mailings, and in-person surveys at basketball games and ED waiting rooms. The PROTECT trial (2021-present) randomizes OOHCA survivors to prophylactic ceftriaxone or placebo; the community consultation plan during the pandemic included city council presentations, social media posts, outpatient flyers, but no in-person encounters. Demographics for PROTECT community consultation were compared to PEARL and INTCAR registry data, with p-value < 0.05 considered significant., Results: PEARL surveyed 1,362 adults, including 64 % ≥60 years old, 96 % high school graduates or beyond; research acceptance rate was 92 % for the community and 76 % for personal level. PROTECT initially obtained 221 surveys from electronic media - including fewer males (28 % vs 72 %,p < 0.001) and those > 60 years old (14 % vs 53 %;p < 0.001) compared to INTCAR. These differences prompted a revised community consultation plan, targeting 79 adult in-patients with cardiac disease which better matched PEARL and INTCAR data: the majority were ≥ 60 years old (66 %) and male (54 %). Both PEARL and PROTECT enrolled more patients using surrogate consent vs EFIC (57 %, 61 %), including 71 % as remote electronic consents during PROTECT., Conclusions: Community consultation for EFIC studies changed with the COVID-19 pandemic, resulting in different demographic patterns. We describe effective adaptations to community consultation and surrogate consent during the pandemic., (© 2022 The Author(s).)

Objectives: The association between opioid therapy during critical illness and persistent opioid use after discharge is understudied relative to ICU opioid exposure and modifiable risk factors. Our objectives were to compare persistent opioid use after discharge among patients with and without chronic opioid use prior to admission (OPTA) and identify risk factors associated with persistent use., Design: Retrospective cohort study., Setting: Medical, trauma/surgical, or neurologic ICU at an academic hospital., Participants: Adult patients surviving hospital admission., Interventions: Opioid use during the ICU and post-ICU stays., Measurements and Main Results: The primary outcome was persistent opioid use accounting for greater than 70% of days 4-6 months after discharge. Among 2,975 included patients, 257 (8.6%) were classified as OPTA, and 305 (10.2%) persistently filled opioid prescriptions, including 186/257 (72%) OPTA and 119/2,718 (4.4%) with no chronic opioid fills prior to admission. Among all patients, OPTA was strongly associated with persistent opioid use (odds ratio, 57.2 [95% CI, 41.4-80.0]). Multivariable logistic regression revealed that male sex, surgical procedure, and ICU opioid-free days were associated with reduced persistent opioid use for OPTA patients. Age and ICU opioid-free days were associated with reduced persistent opioid use for non-OPTA patients. Total ICU opioid dose and dose per day of ICU exposure were not associated with persistent use for either group., Conclusions: In this mixed cohort of ICU patients, 10.2% persistently filled opioid prescriptions 4-6 months after discharge. Although ICU opioid doses were not associated with persistent use, duration of ICU opioid administration is a modifiable risk factor that may reduce persistent opioid use after critical illness., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation., Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation., Design, Setting, and Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020., Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194)., Main Outcomes and Measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death)., Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy., Conclusions and Relevance: Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded., Trial Registration: ClinicalTrials.gov Identifier: NCT02377167.

SARS-CoV-2 infection results in a spectrum of outcomes from no symptoms to widely varying degrees of illness to death. A better understanding of the immune response to SARS-CoV-2 infection and subsequent, often excessive, inflammation may inform treatment decisions and reveal opportunities for therapy. We studied immune cell subpopulations and their associations with clinical parameters in a cohort of 26 patients with COVID-19. Following informed consent, we collected blood samples from hospitalized patients with COVID-19 within 72 h of admission. Flow cytometry was used to analyze white blood cell subpopulations. Plasma levels of cytokines and chemokines were measured using ELISA. Neutrophils undergoing neutrophil extracellular traps (NET) formation were evaluated in blood smears. We examined the immunophenotype of patients with COVID-19 in comparison to that of SARS-CoV-2 negative controls. A novel subset of pro-inflammatory neutrophils expressing a high level of dual endothelin-1 and VEGF signal peptide-activated receptor (DEspR) at the cell surface was found to be associated with elevated circulating CCL23, increased NETosis, and critical-severity COVID-19 illness. The potential to target this subpopulation of neutrophils to reduce secondary tissue damage caused by SARS-CoV-2 infection warrants further investigation., (© 2021. The Author(s).)

Purpose: To provide clinical practice recommendations and generate a research agenda on mechanical ventilation and respiratory support in patients with acute brain injury (ABI)., Methods: An international consensus panel was convened including 29 clinician-scientists in intensive care medicine with expertise in acute respiratory failure, neurointensive care, or both, and two non-voting methodologists. The panel was divided into seven subgroups, each addressing a predefined clinical practice domain relevant to patients admitted to the intensive care unit (ICU) with ABI, defined as acute traumatic brain or cerebrovascular injury. The panel conducted systematic searches and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to evaluate evidence and formulate questions. A modified Delphi process was implemented with four rounds of voting in which panellists were asked to respond to questions (rounds 1-3) and then recommendation statements (final round). Strong recommendation, weak recommendation, or no recommendation were defined when > 85%, 75-85%, and < 75% of panellists, respectively, agreed with a statement., Results: The GRADE rating was low, very low, or absent across domains. The consensus produced 36 statements (19 strong recommendations, 6 weak recommendations, 11 no recommendation) regarding airway management, non-invasive respiratory support, strategies for mechanical ventilation, rescue interventions for respiratory failure, ventilator liberation, and tracheostomy in brain-injured patients. Several knowledge gaps were identified to inform future research efforts., Conclusions: This consensus provides guidance for the care of patients admitted to the ICU with ABI. Evidence was generally insufficient or lacking, and research is needed to demonstrate the feasibility, safety, and efficacy of different management approaches.

Background: Exposure to extreme arterial partial pressures of oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is common and may affect neurological outcome but results of previous studies are conflicting., Methods: Exploratory study of the International Cardiac Arrest Registry (INTCAR) 2.0 database, including 2162 OHCA patients with ROSC in 22 intensive care units in North America and Europe. We tested the hypothesis that exposure to extreme PaO 2 or PaCO 2 values within 24 h after OHCA is associated with poor neurological outcome at discharge. Our primary analyses investigated the association between extreme PaO 2 and PaCO 2 values, defined as hyperoxemia (PaO 2  > 40 kPa), hypoxemia (PaO 2  < 8.0 kPa), hypercapnemia (PaCO 2  > 6.7 kPa) and hypocapnemia (PaCO 2  < 4.0 kPa) and neurological outcome. The secondary analyses tested the association between the exposure combinations of PaO 2  > 40 kPa with PaCO 2  < 4.0 kPa and PaO 2 8.0-40 kPa with PaCO 2  > 6.7 kPa and neurological outcome. To define a cut point for the onset of poor neurological outcome, we tested a model with increasing and decreasing PaO 2 levels and decreasing PaCO 2 levels. Cerebral Performance Category (CPC), dichotomized to good (CPC 1-2) and poor (CPC 3-5) was used as outcome measure., Results: Of 2135 patients eligible for analysis, 700 were exposed to hyperoxemia or hypoxemia and 1128 to hypercapnemia or hypocapnemia. Our primary analyses did not reveal significant associations between exposure to extreme PaO 2 or PaCO 2 values and neurological outcome (P = 0.13-0.49). Our secondary analyses showed no significant associations between combinations of PaO 2 and PaCO 2 and neurological outcome (P = 0.11-0.86). There was no PaO 2 or PaCO 2 level significantly associated with poor neurological outcome. All analyses were adjusted for relevant co-variates., Conclusions: Exposure to extreme PaO 2 or PaCO 2 values in the first 24 h after OHCA was common, but not independently associated with neurological outcome at discharge.

Purpose: Functional outcomes vary between centers after out-of-hospital cardiac arrest (OHCA) and are partially explained by pre-existing health status and arrest characteristics, while the effects of in-hospital treatments on functional outcome are less understood. We examined variation in functional outcomes by center after adjusting for patient- and arrest-specific characteristics and evaluated how in-hospital management differs between high- and low-performing centers., Methods: Analysis of observational registry data within the International Cardiac Arrest Registry was used to perform a hierarchical model of center-specific risk standardized rates for good outcome, adjusted for demographics, pre-existing functional status, and arrest-related factors with treatment center as a random effect variable. We described the variability in treatments and diagnostic tests that may influence outcome at centers with adjusted rates significantly above and below registry average., Results: A total of 3855 patients were admitted to an ICU following cardiac arrest with return of spontaneous circulation. The overall prevalence of good outcome was 11-63% among centers. After adjustment, center-specific risk standardized rates for good functional outcome ranged from 0.47 (0.37-0.58) to 0.20 (0.12-0.26). High-performing centers had faster time to goal temperature, were more likely to have goal temperature of 33 °C, more likely to perform unconscious cardiac catheterization and percutaneous coronary intervention, and had differing prognostication practices than low-performing centers., Conclusions: Center-specific differences in outcomes after OHCA after adjusting for patient-specific factors exist. This variation could partially be explained by in-hospital management differences. Future research should address the contribution of these factors to the differences in outcomes after resuscitation.

Purpose of Review: Because the whole-body ischemia-reperfusion insult associated with cardiac arrest often results in brain injury, neurologists perform an important role in postresuscitation cardiac arrest care. This article provides guidance for the assessment and management of brain injury following cardiac arrest., Recent Findings: Neurologists have many roles in postresuscitation cardiac arrest care: (1) early assessment of brain injury severity to help inform triage for invasive circulatory support or revascularization; (2) advocacy for the maintenance of a neuroprotective thermal, hemodynamic, biochemical, and metabolic milieu; (3) detection and management of seizures; (4) development of an accurate, multimodal, and conservative approach to prognostication; (5) application of shared decision-making paradigms around the likely outcomes of therapy and the goals of care; and (6) facilitation of the neurocognitive assessment of survivors. Therefore, optimal management requires early neurologist involvement in patient care, a detailed knowledge of postresuscitation syndrome and its complex interactions with prognosis, expertise in bringing difficult cases to their optimal conclusions, and a support system for survivors with cognitive deficits., Summary: Neurologists have a critical role in postresuscitation cardiac arrest care and are key participants in the treatment team from the time of first restoration of a perfusing heart rhythm through the establishment of rehabilitation services for survivors.

Objectives: Community consultation (CC) is fundamental to the Exception from Informed Consent (EFIC) process for emergency research, designed to inform and receive feedback from the target study population about potential risks and benefits. To better understand the effectiveness of different techniques for CC, we evaluated EFIC processes at two centers participating in a trial of early cardiac catheterization following out-of-hospital cardiac arrest., Methods: We studied the Institutional Review Board-approved CC activities at Maine Medical Center (MMC) and University of Arizona (AZ) in support of NCT02387398. In Maine, the public was consulted by survey at a professional basketball game and in the emergency department waiting room (in-person group), by multimedia direction to an online website (online group), and by mail (mailing group). Arizona respondents were either approached at a county fair (in-person group) or were directed to an online survey (online group) via social media advertising., Results: Among 2185 survey respondents, approval rates were high for community involvement and personal participation without individual consent. Community consultation using in-person, online, and mailed surveys offered slightly different approval rates, and the rate of responses by modality differed by age and education level but not ethnicity. Print advertising was the least cost effective at $442 per completed survey., Conclusions: Canvassing at public events was the most efficient mode of performing CC, with approval rates similar to mailings, online surveys, and canvassing in other locations. Print advertisements in local papers had a low yield and cost more than other approaches., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This manuscript describes the state of neurocritical care fellowship training, compares its written standards to those of other critical care fellowship programs, and discusses how programmatic oversight by the United Council for Neurological Subspecialties should evolve to meet American College of Graduate Medical Education standards. This review is a work product of the Society of Critical Care Medicine Neuroscience section and was reviewed and approved by the Council of the Society of Critical Care Medicine., Data Sources: We evaluated the published training criteria and requirements of American College of Graduate Medical Education Critical Care subspecialty fellowships programs of Internal Medicine, Surgery, and Anesthesia and compared them with the training criteria and required competencies for neurocritical care., Study Selection: We have reviewed the published training standards from American College of Graduate Medical Education as well as the United Council for Neurologic Subspecialties subspecialty training documents and clarified the definition and responsibilities of an intensivist with reference to the Leapfrog Group, the National Quality Forum, and the Joint Commission., Data Extraction: No data at present exist to test the concept of similarity across specialty fellowship critical care training programs., Data Synthesis: Neurocritical care training differs in its exposure to clinical entities that are directly associated to other critical care subspecialties. However, the core critical care knowledge, procedural skills, and competencies standards for neurocritical care appears to be similar with some important differences compared with American College of Graduate Medical Education critical care training programs., Conclusions: The United Council for Neurologic Subspecialties has developed a directed program development strategy to emulate American College of Graduate Medical Education standards with the goal to have standards that are similar or identical to American College of Graduate Medical Education standards.

Objectives: The aim of this study was to compare outcomes and coronary angiographic findings in post-cardiac arrest patients with and without ST-segment elevation myocardial infarction (STEMI)., Background: The 2013 STEMI guidelines recommend performing immediate angiography in resuscitated patients whose initial electrocardiogram shows STEMI. The optimal approach for those without STEMI post-cardiac arrest is less clear., Methods: A retrospective evaluation of a post-cardiac arrest registry was performed., Results: The database consisted of 746 comatose post-cardiac arrest patients including 198 with STEMI (26.5%) and 548 without STEMI (73.5%). Overall survival was greater in those with STEMI compared with those without (55.1% vs. 41.3%; p = 0.001), whereas in all patients who underwent immediate coronary angiography, survival was similar between those with and without STEMI (54.7% vs. 57.9%; p = 0.60). A culprit vessel was more frequently identified in those with STEMI, but also in one-third of patients without STEMI (80.2% vs. 33.2%; p = 0.001). The majority of culprit vessels were occluded (STEMI, 92.7%; no STEMI, 69.2%; p < 0.0001). An occluded culprit vessel was found in 74.3% of STEMI patients and in 22.9% of no STEMI patients. Among cardiac arrest survivors discharged from the hospital who had presented without STEMI, coronary angiography was associated with better functional outcome (93.3% vs. 78.7%; p < 0.003)., Conclusions: Early coronary angiography is associated with improved functional outcome among resuscitated patients with and without STEMI. Resuscitated patients with a presumed cardiac etiology appear to benefit from immediate coronary angiography., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Triage after resuscitation from cardiac arrest is hindered by reliable early estimation of brain injury. We evaluated the performance of a triage model based on early bispectral index (BIS) findings and cardiac risk classes., Methods: Retrospective evaluation of serial patients resuscitated from cardiac arrest, unable to follow commands, and undergoing hypothermia. Patients were assigned to a cardiac risk group: STEMI, VT/VF shock, VT/VF no shock, or PEA/asystole, and to a neurological dysfunction group, based on the BIS score following first neuromuscular blockade (BISi), and classified as BISi>20, BISi 10-20, or BISi<10. Cause of death was described as neurological or circulatory., Results: BISi in 171 patients was measured at 267(±177)min after resuscitation and 35(±1.7)°C. BISi<10 suffered 82% neurological-cause and 91% overall mortality, BISi 10-20 35% neurological and 55% overall mortality, and BISi>20 12% neurological and 36% overall mortality. 33 patients presented with STEMI, 15 VT/VF-shock, 41 VT/VF-no shock, and 80 PEA/asystole. Among BISi>20 patients, 75% with STEMI underwent urgent cardiac catheterization (cath) and 94% had good outcome. When BISi>20 with VT/VF and shock, urgent cath was infrequent (33%), and 4 deaths (44%) were uniformly of circulatory etiology. Of 56 VT/VF patients without STEMI, 24 were BISi>20 but did not undergo urgent cath - 5(20.8%) of these had circulatory-etiology death. Circulatory-etiology death also occurred in 26.5% BIS>20 patients with PEA/asystole. When BISi<10, a neurological etiology death dominated independent of cardiac risk group., Conclusions: Neurocardiac triage based on very early processed EEG (BIS) is feasible, and may identify patients appropriate for individualized post-resuscitation care. This and other triage models warrant further study., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

A 45-year-old man was seen in consultation for evaluation of a spiculated right-lower-lobe mass that enlarged over 1 year. The patient had suffered accidental instillation of activated charcoal into the right lung via nasogastric tube 2 years prior to this consultation, with resultant respiratory failure, pneumonia, and pneumothorax. Biopsy of the mass showed anthracosis and granulomatous inflammation. A positron emission tomogram was strongly positive at the lesion, and right-lower-lobectomy with partial diaphragmatic resection was performed. On gross examination of the mass, a charcoal concretion was evident. Histologic examination showed intrinsic and surrounding granulomatous inflammation, but without tumor. The patient recovered uneventfully, and after 1 year had not experienced further complications.