Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Duration of Device-Based Fever Prevention after Cardiac Arrest.

BACKGROUND: Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking. METHODS: We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months. RESULTS: A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events. CONCLUSIONS: Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited. METHODS: In a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months. RESULTS: A total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P = 0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups. CONCLUSIONS: Targeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Oxygen Targets in Comatose Survivors of Cardiac Arrest.

BACKGROUND: The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown. METHODS: In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days. RESULTS: A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P = 0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 µg per liter in the restrictive-target group and 18 µg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Prediction of Shock-Refractory Ventricular Fibrillation During Resuscitation of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Out-of-hospital cardiac arrest due to shock-refractory ventricular fibrillation (VF) is associated with relatively poor survival. The ability to predict refractory VF (requiring ≥3 shocks) in advance of repeated shock failure could enable preemptive targeted interventions aimed at improving outcome, such as earlier administration of antiarrhythmics, reconsideration of epinephrine use or dosage, changes in shock delivery strategy, or expedited invasive treatments. METHODS: We conducted a cohort study of VF out-of-hospital cardiac arrest to develop an ECG-based algorithm to predict patients with refractory VF. Patients with available defibrillator recordings were randomized 80%/20% into training/test groups. A random forest classifier applied to 3-s ECG segments immediately before and 1 minute after the initial shock during cardiopulmonary resuscitation was used to predict the need for ≥3 shocks based on singular value decompositions of ECG wavelet transforms. Performance was quantified by area under the receiver operating characteristic curve. RESULTS: Of 1376 patients with VF out-of-hospital cardiac arrest, 311 (23%) were female, 864 (63%) experienced refractory VF, and 591 (43%) achieved functional neurological survival. Total shock count was associated with decreasing likelihood of functional neurological survival, with a relative risk of 0.95 (95% CI, 0.93-0.97) for each successive shock (P<0.001). In the 275 test patients, the area under the receiver operating characteristic curve for predicting refractory VF was 0.85 (95% CI, 0.79-0.89), with specificity of 91%, sensitivity of 63%, and a positive likelihood ratio of 6.7. CONCLUSIONS: A machine learning algorithm using ECGs surrounding the initial shock predicts patients likely to experience refractory VF, and could enable rescuers to preemptively target interventions to potentially improve resuscitation outcome.

Blood Pressure and Oxygen Targets on Kidney Injury After Cardiac Arrest.

BACKGROUND: Acute kidney injury (AKI) represents a common and serious complication to out-of-hospital cardiac arrest. The importance of post-resuscitation care targets for blood pressure and oxygenation for the development of AKI is unknown. METHODS: This is a substudy of a randomized 2-by-2 factorial trial, in which 789 comatose adult patients who had out-of-hospital cardiac arrest with presumed cardiac cause and sustained return of spontaneous circulation were randomly assigned to a target mean arterial blood pressure of either 63 or 77 mm Hg. Patients were simultaneously randomly assigned to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa or a liberal oxygenation target of a Pao2 of 13 to 14 kPa. The primary outcome for this study was AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) classification in patients surviving at least 48 hours (N=759). Adjusted logistic regression was performed for patients allocated to high blood pressure and liberal oxygen target as reference. RESULTS: The main population characteristics at admission were: age, 64 (54-73) years; 80% male; 90% shockable rhythm; and time to return of spontaneous circulation, 18 (12-26) minutes. Patients allocated to a low blood pressure and liberal oxygen target had an increased risk of developing AKI compared with patients with high blood pressure and liberal oxygen target (84/193 [44%] versus 56/187 [30%]; adjusted odds ratio, 1.87 [95% CI, 1.21-2.89]). Multinomial logistic regression revealed that the increased risk of AKI was only related to mild-stage AKI (KDIGO stage 1). There was no difference in risk of AKI in the other groups. Plasma creatinine remained high during hospitalization in the low blood pressure and liberal oxygen target group but did not differ between groups at 6- and 12-month follow-up. CONCLUSIONS: In comatose patients who had been resuscitated after out-of-hospital cardiac arrest, patients allocated to a combination of a low mean arterial blood pressure and a liberal oxygen target had a significantly increased risk of mild-stage AKI. No difference was found in terms of more severe AKI stages or other kidney-related adverse outcomes, and creatinine had normalized at 1 year after discharge. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03141099.

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).

Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation.

BACKGROUND: Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest. However, the benefits of early coronary angiography and revascularization in resuscitated patients without electrocardiographic evidence of ST-segment elevation are unclear. METHODS: In this multicenter trial, we randomly assigned 554 patients with successfully resuscitated out-of-hospital cardiac arrest of possible coronary origin to undergo either immediate coronary angiography (immediate-angiography group) or initial intensive care assessment with delayed or selective angiography (delayed-angiography group). All the patients had no evidence of ST-segment elevation on postresuscitation electrocardiography. The primary end point was death from any cause at 30 days. Secondary end points included a composite of death from any cause or severe neurologic deficit at 30 days. RESULTS: A total of 530 of 554 patients (95.7%) were included in the primary analysis. At 30 days, 143 of 265 patients (54.0%) in the immediate-angiography group and 122 of 265 patients (46.0%) in the delayed-angiography group had died (hazard ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.63; P = 0.06). The composite of death or severe neurologic deficit occurred more frequently in the immediate-angiography group (in 164 of 255 patients [64.3%]) than in the delayed-angiography group (in 138 of 248 patients [55.6%]), for a relative risk of 1.16 (95% CI, 1.00 to 1.34). Values for peak troponin release and for the incidence of moderate or severe bleeding, stroke, and renal-replacement therapy were similar in the two groups. CONCLUSIONS: Among patients with resuscitated out-of-hospital cardiac arrest without ST-segment elevation, a strategy of performing immediate angiography provided no benefit over a delayed or selective strategy with respect to the 30-day risk of death from any cause. (Funded by the German Center for Cardiovascular Research; TOMAHAWK ClinicalTrials.gov number, NCT02750462.).

Effect of prehospital high-dose glucocorticoid on hemodynamics in patients resuscitated from out-of-hospital cardiac arrest: a sub-study of the STEROHCA trial.

BACKGROUND: Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients. METHODS: The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times. RESULTS: A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference - 0.04 mcg/kg/min, 95% CI - 0.07 to - 0.01, p = 0.02). Moreover, after 12-24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from - 4.2 to - 3.8, 95% CIs from - 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from - 0.10 to - 0.07, 95% CIs from - 0.16 to - 0.01), while there were no major differences in heart rate (mean differences from - 4 to - 3, 95% CIs from - 11 to 3). These treatment differences between groups were also present 30-48 h post-admission but to a smaller extent and with increased statistical uncertainty. No differences were found in pulmonary artery catheter measurements between groups. CONCLUSIONS: Prehospital treatment with high-dose glucocorticoid was associated with reduced norepinephrine use in resuscitated OHCA patients. TRIAL REGISTRATION: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www. CLINICALTRIALS: gov ; Unique Identifier: NCT04624776.

Acute kidney injury after out-of-hospital cardiac arrest.

BACKGROUND: Acute kidney injury (AKI) is a significant risk factor associated with reduced survival following out-of-hospital cardiac arrest (OHCA). Whether the severity of AKI simply serves as a surrogate measure of worse peri-arrest conditions, or represents an additional risk to long-term survival remains unclear. METHODS: This is a sub-study derived from a randomized trial in which 789 comatose adult OHCA patients with presumed cardiac cause and sustained return of spontaneous circulation (ROSC) were enrolled. Patients without prior dialysis dependent kidney disease and surviving at least 48 h were included (N = 759). AKI was defined by the kidney disease: improving global outcome (KDIGO) classification, and patients were divided into groups based on the development of AKI and the need for continuous kidney replacement therapy (CKRT), thus establishing three groups of patients-No AKI, AKI no CKRT, and AKI CKRT. Primary outcome was overall survival within 365 days after OHCA according to AKI group. Adjusted Cox proportional hazard models were used to assess overall survival within 365 days according to the three groups. RESULTS: In the whole population, median age was 64 (54-73) years, 80% male, 90% of patients presented with shockable rhythm, and time to ROSC was median 18 (12-26) min. A total of 254 (33.5%) patients developed AKI according to the KDIGO definition, with 77 requiring CKRT and 177 without need for CKRT. AKI CKRT patients had longer time-to-ROSC and worse metabolic derangement at hospital admission. Overall survival within 365 days from OHCA decreased with the severity of kidney injury. Adjusted Cox regression analysis found that AKI, both with and without CKRT, was significantly associated with reduced overall survival up until 365 days, with comparable hazard ratios relative to no AKI (HR 1.75, 95% CI 1.13-2.70 vs. HR 1.76, 95% CI 1.30-2.39). CONCLUSIONS: In comatose patients who had been resuscitated after OHCA, patients developing AKI, with or without initiation of CKRT, had a worse 1-year overall survival compared to non-AKI patients. This association remains statistically significant after adjusting for other peri-arrest risk factors. TRIAL REGISTRATION: The BOX trial is registered at ClinicalTrials.gov: NCT03141099.

Association of hyperfibrinolysis with poor prognosis in refractory circulatory arrest: implications for extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Identifying candidates for extracorporeal cardiopulmonary resuscitation (eCPR) is challenging, and novel predictive markers are urgently needed. Hyperfibrinolysis is linked to tissue hypoxia and is associated with poor outcomes in out-of-hospital cardiac arrest (OHCA). Rotational thromboelastometry (ROTEM) can detect or rule out hyperfibrinolysis, and could, therefore, provide decision support for initiation of eCPR. We explored early detection of hyperfibrinolysis in patients with refractory OHCA referred for eCPR. METHODS: We analysed ROTEM results and resuscitation parameters of 57 adult patients with ongoing OHCA who presented to our ICU for eCPR evaluation. RESULTS: Hyperfibrinolysis, defined as maximum lysis ≥15%, was present in 36 patients (63%) and was associated with higher serum lactate, lower arterial blood pH, and increased low-flow intervals. Of 42 patients who achieved return of circulation, 28 had a poor 30-day outcome. The incidence of hyperfibrinolysis was higher in the poor outcome group compared with patients with good outcomes (75% [21 of 28] vs 7.1% [1 of 14]; P<0.001). The ratio of EXTEM A5 to lactate concentration showed good predictive value in detecting hyperfibrinolysis (AUC of 0.89 [95% confidence interval 0.8-1]). CONCLUSIONS: Hyperfibrinolysis was common in patients with refractory cardiac arrest, and was associated with poor prognosis. The combination of high lactate with early clot firmness values, such as EXTEM A5, appears promising for early detection of hyperfibrinolysis. This finding could facilitate decisions to perform eCPR, particularly for patients with prolonged low-flow duration but lacking hyperfibrinolysis.

Thrombolytics in Cardiac Arrest from Pulmonary Embolism: A Systematic Review and Meta Analysis.

BACKGROUND: During cardiopulmonary resuscitation, intravenous thrombolytics are commonly used for patients whose underlying etiology of cardiac arrest is presumed to be related to pulmonary embolism (PE). METHODS: We performed a systematic review and meta-analysis of the existing literature that focused on the use of thrombolytics for cardiac arrest due to presumed or confirmed PE. Outcomes of interest were return of spontaneous circulation (ROSC), survival to hospital discharge, neurologically-intact survival, and bleeding complications. RESULTS: Thirteen studies with a total of 803 patients were included in this review. Most studies included were single-armed and retrospective. Thrombolytic agent and dose were heterogeneous between studies. Among those with control groups, intravenous thrombolysis was associated with higher rates of ROSC (OR 2.55, 95% CI = 1.50-4.34), but without a significant difference in survival to hospital discharge (OR 1.41, 95% CI = 0.79-2.41) or bleeding complications (OR 2.21, 0.95-5.17). CONCLUSIONS: Use of intravenous thrombolytics in cardiac arrest due to confirmed or presumed PE is associated with increased ROSC but not survival to hospital discharge or change in bleeding complications. Larger randomized studies are needed. Currently, we recommend continuing to follow existing consensus guidelines which support use of thrombolytics for this indication.

Outcome prediction in comatose cardiac arrest patients with initial shockable and non-shockable rhythms.

BACKGROUND: Prognosis after out-of-hospital cardiac arrest (OHCA) is presumed poorer in patients with non-shockable than shockable rhythms, frequently leading to treatment withdrawal. Multimodal outcome prediction is recommended 72 h post-arrest in still comatose patients, not considering initial rhythms. We investigated accuracy of outcome predictors in all comatose OHCA survivors, with a particular focus on shockable vs. non-shockable rhythms. METHODS: In this observational NORCAST sub-study, patients still comatose 72 h post-arrest were stratified by shockable vs. non-shockable rhythms for outcome prediction analyzes. Good outcome was defined as cerebral performance category 1-2 within 6 months. False positive rate (FPR) was used for poor and sensitivity for good outcome prediction accuracy. RESULTS: Overall, 72/128 (56%) patients with shockable and 12/50 (24%) with non-shockable rhythms had good outcome (p < .001). For poor outcome prediction, absent pupillary light reflexes (PLR) and corneal reflexes (clinical predictors) 72 h after sedation withdrawal, PLR 96 h post-arrest, and somatosensory evoked potentials (SSEP), all had FPR <0.1% in both groups. Unreactive EEG and neuron-specific enolase (NSE) >60 µg/L 24-72 h post-arrest had better precision in shockable patients. For good outcome, the clinical predictors, SSEP and CT, had 86%-100% sensitivity in both groups. For NSE, sensitivity varied from 22% to 69% 24-72 h post-arrest. The outcome predictors indicated severe brain injury proportionally more often in patients with non-shockable than with shockable rhythms. For all patients, clinical predictors, CT, and SSEP, predicted poor and good outcome with high accuracy. CONCLUSION: Outcome prediction accuracy was comparable for shockable and non-shockable rhythms. PLR and corneal reflexes had best precision 72 h after sedation withdrawal and 96 h post-arrest.

High-sensitivity troponin T for detection of culprit lesions in patients with out-of-hospital cardiac arrest.

BACKGROUND: Patients with an out-of-hospital cardiac arrest (OHCA) often undergo coronary angiography, although a culprit lesion is found in only 30%-40% of patients. The aim of this study was to investigate high-sensitivity troponin T (hsTnT) levels in post cardiac arrest patients with and without coronary culprit lesions; factors affecting hsTnT levels after return of spontaneous circulation (ROSC); and the diagnostic ability of hsTnT in identifying patients with culprit lesions. We hypothesized that peak hsTnT levels were higher during the initial 48 h after cardiac arrest in patients with a coronary culprit lesion. METHODS: This was a retrospective observational study, which included patients admitted to the Intensive Care Unit after an OHCA and who received a coronary angiography. Peak values and dynamic changes in hsTnT were analyzed in relation to the presence of a culprit lesion at coronary angiography. RESULTS: A total of 238 patients were studied, of whom 140 had a culprit lesion. HsTnT levels during the initial 48 h were higher in patients with culprit lesions, longer time to ROSC and an unwitnessed cardiac arrest. At 6 to 12 h after ROSC, a hsTnT cut-off level of 1690 ng/L had a sensitivity of 64% and specificity of 84% to identify a culprit lesion. In patients without ST-elevations, hsTnT measured between 6 and 12 h after ROSC had a specificity above 90%, with a sensitivity of 46%. CONCLUSION: HsTnT levels after cardiac arrest are higher in patients with coronary culprit lesions. Presence of a culprit lesion, witnessed status and the duration of CPR are important factors affecting hsTnT levels. Repeated measurement of hsTnT within the first 12 h after admission improved diagnostic accuracy but the value of hsTnT as a predictor of culprit lesions early after OHCA is limited.

Prehospital Advanced Airway Management and Ventilation for Out-of-Hospital Cardiac Arrest with Prehospital Return of Spontaneous Circulation: A Prospective Observational Cohort Study in Japan.

BACKGROUND: The relationship among advanced airway management (AAM), ventilation, and oxygenation in patients with out-of-hospital cardiac arrest (OHCA) who achieve prehospital return of spontaneous circulation (ROSC) has not been validated. This study was designed to evaluate ventilation and oxygenation for each AAM technique (supraglottic devices [SGA] or endotracheal intubation [ETI]) using arterial blood gas (ABG) results immediately after hospital arrival. METHODS: This observational cohort study, using data from the Japanese Association for Acute Medicine OHCA Registry, included patients with OHCA with prehospital and hospital arrival ROSC between July 1, 2014, and December 31, 2019. The primary outcomes were the partial pressure of carbon dioxide in the arterial blood (PaCO2) and partial pressure of oxygen in the arterial blood (PaO2) in the initial ABG at the hospital for each AAM technique (SGA or ETI) performed by paramedics. The secondary outcome was favorable neurological outcome (cerebral performance category [CPC] 1 or 2) for specific PaCO2 levels, which were defined as good ventilation (PaCO2 ≤45 mmHg) and insufficient ventilation (PaCO2 >45 mmHg). RESULTS: This study included 1,527 patients. Regarding AAM, 1,114 and 413 patients were ventilated using SGA and ETI, respectively. The median PaCO2 and PaO2 levels were 74.50 mmHg and 151.35 mmHg in the SGA group, while 66.30 mmHg and 173.50 mmHg in the ETI group. PaCO2 was significantly lower in the ETI group than in the SGA group (12.55 mmHg; 95% CI 15.27 to 8.20, P-value < 0.001), while no significant difference was found in PaO2 by multivariate linear regression analysis. After stabilizing inverse probability of weighting (IPW), the adjusted odds ratio for favorable neurological outcome at 1 month was significant in the good ventilation group compared to the insufficient ventilation cohort (adjusted odds ratio = 2.12, 95%CI: 1.40 to 3.19, P value < 0.001). CONCLUSION: The study showed that in OHCA patients with prehospital ROSC, the PaCO2 levels in the initial ABG were lower in the group with AAM by ETI than in the SGA group. Furthermore, patients with prehospital ROSC and PaCO2 ≤45 mmHg on arrival had an increased odds of favorable neurological outcome after stabilized IPW adjustment.

Dynamic Course of Clinical State Transitions in Patients Undergoing Advanced Life Support after Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Studies of out-of-hospital cardiac arrest generally document the presenting (pulseless electrical activity [PEA], ventricular fibrillation/tachycardia (VF/VT), asystole), and the final states (resuming stable spontaneous circulation [s-ROSC], being declared dead). Only a few studies described the transitions between clinical states during advanced life support (ALS). The aim of this study was to describe and analyze the dynamics of state transitions during ALS. METHODS: A retrospective analysis of 464 OHCA events was conducted. Any observed state and its corresponding changing time were documented through continuous electrocardiographic and trans-thoracic impedance recording. RESULTS: When achieved, most s-ROSCs were obtained by 30 min, regardless of the presenting state. After this time point, the persistence of any transient state was associated with a great probability of being declared dead. The most probable change for VF/VT or PEA at any time was the transition to asystole (36.4% and 34.4%, respectively); patients in asystole at any time had a 70% probability of death. Patients achieving s-ROSC mostly came from a VF/VT state.In most cases, the presenting rhythm tended to persist over time during ALS. Asystole was the most stable state; a higher degree of instability was observed when the presenting rhythms were VF/VT or PEA. Transient ROSC episodes occurred mainly as the first transition after the presenting state, especially for initial PEA. CONCLUSIONS: An understanding of the dynamic course of clinical state transitions during ALS may allow treatment strategies to be tailored in patients affected by OHCA.

Association between early lactate-related variables and 6-month neurological outcome in out-of-hospital cardiac arrest patients.

INTRODUCTION: The role of lactate measurement in out-of-hospital cardiac arrest (OHCA) survivors remains controversial. We assessed the association between early lactate-related variables, OHCA characteristics, and long-term neurological outcome. METHODS: In OHCA patients who received targeted temperature management, lactate levels were measured at 0, 12, and 24 h after the return of spontaneous circulation. We calculated lactate clearance and time-weighted cumulative lactate (TWCL), which represent the area under the time-lactate curve. The area under the receiver operating characteristic curve (AUC) and the adjusted odds ratios (AORs) of lactate-related variables for predicting 6-month poor outcome (Cerebral Performance Category 3-5) were evaluated. Interactions between lactate variables and characteristics of OHCA were evaluated by a multivariable logistic model with interaction terms and subgroup analysis. RESULTS: A total of 347 OHCA patients were included. After adjustment, higher lactate levels at the three time points were associated with a poor outcome (AOR 1.10 [95% CI, 1.03-1.18], AOR 1.15 [95% CI, 1.02-1.29], and AOR 1.36 [95% CI, 1.15-1.60], respectively), while TWCL was the only lactate kinetics variable associated with a poor outcome (AOR 1.29 [95% CI, 1.12-1.49]). We identified several interactions between lactate-related variables and OHCA characteristics. In particular, the AUC of TWCL was excellent in cases of noncardiac etiology (AUC 0.92 [95% CI, 0.86-0.96] but only moderate in cardiac etiology (AUC 0.69 [95% CI, 0.62-0.75]). CONCLUSIONS: Early lactate levels, especially at 24 h, and TWCL were independent predictors of neurologic outcome in these patients, whereas lactate clearance was not. The prognostic ability of lactate-related variables varied depending on the OHCA characteristics.

Treatment strategies for patients with out-of-hospital cardiac arrest associated with traumatic brain injury: A case series.

INTRODUCTION: Collapse after out-of-hospital cardiac arrest (OHCA) can cause severe traumatic brain injury (TBI). We aimed to investigate the clinical characteristics and treatment strategies for patients with OHCA and TBI. METHODS: We analyzed a consecutive cohort of patients with intrinsic OHCA retrospectively treated between January 2011 and December 2021 at a single critical care center, and presented a case series of seven patients. Patients with collapse-related TBI were examined for the causes and situations of cardiac arrest, laboratory data, radiological images, targeted temperature management (TTM), coronary angiography (CAG), percutaneous coronary intervention (PCI), and extracorporeal cardiopulmonary resuscitation (ECPR). RESULTS: Of the 197 patients with intrinsic OHCA, 7 (3.6%) had TBI (age range: 49-70 years; 6 men). All seven patients presented with ventricular fibrillation in the initial electrocardiograms, with four refractory cases treated with ECPR. All patients underwent CAG under heparinization, and four underwent PCI with antiplatelet administration. Initial head computed tomography indicated an intracranial hemorrhage (ICH) in three patients. ICH appeared or was exacerbated in six patients after CAG with or without PCI, except in one who underwent delayed PCI. All patients displayed elevated plasma D-dimer levels, and four underwent neurosurgical procedures. Four patients survived (three with cerebral performance category [CPC] 2, one with CPC 3) and three died; two had hypoxic-ischemic brain injury and one had severe TBI. CONCLUSION: Delayed ICH occurred frequently. Individualized management is required based on the extent of brain and cardiac damage, including optimal TTM, PCI procedures, and antiplatelet medications. Early detection of ICH and emergency treatment are critical for multi-disciplinary collaboration.

Development and validation of a clinico-biological score to predict outcomes in patients with drowning-associated cardiac arrest.

BACKGROUND: While several scoring systems have been developed to predict short-term outcome in out-of-hospital cardiac arrest patients, there is currently no dedicated prognostic tool for drowning-associated cardiac arrest (DACA) patients. METHODS: Patients experiencing DACA from two retrospective multicenter cohorts of drowning patients were included in the present study. Among the patients from the development cohort, risk-factors for day-28 mortality were assessed by logistic regression. A prediction score was conceived and assessed in patients from the validation cohort. RESULTS: Among the 103 included patients from the development cohort, the day-28 mortality rate reached 51% (53/103). Identified independent early risk-factors for day-28 mortality included cardiopulmonary resuscitation duration longer than 20 min (OR 6.40 [95% CI 1.88-23.32]; p = 0.003), temperature at Intensive Care Unit admission <34 °C (OR 8.84 [95% CI 2.66-32.92]; p < 0.001), need for invasive mechanical ventilation (OR 6.83 [95% CI 1.47-40.87]; p = 0.02) and lactate concentration > 7 mmol/L (OR 3.56 [95% CI 1.01-13.07]; p = 0.04). The Area Under the ROC Curve (AUC) of the developed score based on those variables reached 0.91 (95% CI, 0.86-0.97). The optimal cut-off for predicting poor outcomes was 4 points with a sensitivity of 92% (95% CI, 82-98%), a specificity of 82% (95% CI, 67-91%), a positive predictive value (PPV) of 84% (95% CI, 72-95%) and a negative predictive value (NPV) of 91% (95% CI, 79-96%). The assessment of this score on the validation cohort of 81 patients exhibited an AUC of 0.82. Using the same 4 points threshold, sensitivity, specificity, PPV and NPV values of the validation cohort were: 81%, 67%, 72% and 77%, respectively. CONCLUSION: In patients suffering from drowning induced initial cardiac arrest admitted to ICU with a DACA score ≥ 4, the likelihood of survival at day-28 is significantly lower. Prospective validation of the DACA score and assessment of its usefulness are warranted in the future.

Association between quantitative analysis of cerebral edema using CT imaging and neurological outcomes in cardiac arrest survivors.

BACKGROUND: To determine if the density distribution proportion of Hounsfield unit (HUdp) in head computed tomography (HCT) images can be used to quantitatively measure cerebral edema in survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective observational study included adult comatose OHCA survivors who underwent HCT within 6 h (first) and 72-96 h (second), all performed using the same CT scanner. Semi-automated quantitative analysis was used to identify differences in HUdp at specific HU ranges across the intracranial component based on neurological outcome. Cerebral edema was defined as the increased displacement of the sum of HUdp values (ΔHUdp) at a specific range between two HCT scans. Poor neurological outcome was defined as cerebral performance categories 3-5 at 6 months after OHCA. RESULTS: Twenty-three (42%) out of 55 patients had poor neurological outcome. Significant HUdp differences were observed between good and poor neurological outcomes in the second HCT scan at HU = 1-14, 23-35, and 39-56 (all P < 0.05). Only the ΔHUdp = 23-35 range showed a significant increase and correlation in the poor neurological outcome group (4.90 vs. -0.72, P < 0.001) with the sum of decreases in the other two ranges (r = 0.97, P < 0.001). Multivariate logistic regression analysis demonstrated a significant association between ΔHUdp = 23-35 range and poor neurological outcomes (adjusted OR, 1.12; 95% CI: 1.02-1.24; P = 0.02). CONCLUSION: In this cohort study, the increased displacement in ΔHUdp = 23-35 range is independently associated with poor neurological outcome and provides a quantitative assessment of cerebral edema formation in OHCA survivors.