Validating quantitative pupillometry thresholds for neuroprognostication after out-of-hospital cardiac arrest. A predefined substudy of the Blood Pressure and Oxygenations Targets After Cardiac Arrest (BOX)-trial.

PURPOSE: Out-of-hospital cardiac arrest (OHCA) survivors face significant risks of complications and death from hypoxic-ischemic brain injury leading to withdrawal of life-sustaining treatment (WLST). Accurate multimodal neuroprognostication, including automated pupillometry, is essential to avoid inappropriate WLST. However, inconsistent study results hinder standardized threshold recommendations. We aimed to validate proposed pupillometry thresholds with no false predictions of unfavorable outcomes in comatose OHCA survivors. METHODS: In the multi-center BOX-trial, quantitative measurements of automated pupillometry (quantitatively assessed pupillary light reflex [qPLR] and Neurological Pupil index [NPi]) were obtained at admission (0 h) and after 24, 48, and 72 h in comatose patients resuscitated from OHCA. We aimed to validate qPLR < 4% and NPi ≤ 2, predicting unfavorable neurological conditions defined as Cerebral Performance Category 3-5 at follow-up. Combined with 48-h neuron-specific enolase (NSE) > 60 µg/L, pupillometry was evaluated for multimodal neuroprognostication in comatose patients with Glasgow Motor Score (M) ≤ 3 at ≥ 72 h. RESULTS: From March 2017 to December 2021, we consecutively enrolled 710 OHCA survivors (mean age: 63 ± 14 years; 82% males), and 266 (37%) patients had unfavorable neurological outcomes. An NPi ≤ 2 predicted outcome with 0% false-positive rate (FPR) at all time points (0-72 h), and qPLR < 4% at 24-72 h. In patients with M ≤ 3 at ≥ 72 h, pupillometry thresholds significantly increased the sensitivity of NSE, from 42% (35-51%) to 55% (47-63%) for qPLR and 50% (42-58%) for NPi, maintaining 0% (0-0%) FPR. CONCLUSION: Quantitative pupillometry thresholds predict unfavorable neurological outcomes in comatose OHCA survivors and increase the sensitivity of NSE in a multimodal approach at ≥ 72 h.

Relevance of age and hypertension for blood pressure targets in comatose survivors of cardiac arrest: a BOX-trial sub-study.

AIMS: To assess whether the optimal mean arterial blood pressure (MAP) target after out-of-hospital cardiac arrest (OHCA) is influenced by age and a history of arterial hypertension. METHODS AND RESULTS: A post hoc analysis of data from the Blood Pressure and Oxygenation Targets in Post Resuscitation Care trial. The trial included 789 comatose patients randomized to a MAP target of 63 or 77 mmHg. The primary outcome of this sub-study was 1-year all-cause mortality. Cox proportional hazards regression and restricted cubic splines were used to examine whether prevalent hypertension and age modified the effect of low vs. high MAP target on all-cause mortality. Of the 789 patients randomized, 393 were assigned to a high MAP target, and 396 to a low MAP target. Groups were well-balanced for mean age (high MAP target 63 ± 13 years vs. low 62 ± 14 years) and hypertension (45 vs. 47%, respectively). At 1 year, the primary outcome occurred in 143 patients (36%) with a high MAP target and 138 (35%) with a low MAP target. The risk of the primary outcome increased linearly with increasing age (P < 0.001). The effect of a high vs. low MAP target on the primary outcome was modified by age when tested continuously, potentially favouring a low MAP target in younger patients (P for interaction = 0.03). Prevalent hypertension did not modify the effect of a high vs. low MAP target on the primary outcome (P for interaction = 0.67). CONCLUSION: Among patients resuscitated after OHCA, older patients and those with a history of hypertension did not benefit from a high MAP target.

Does extracorporeal cardiopulmonary resuscitation improve survival with favorable neurological outcome in out-of-hospital cardiac arrest? A systematic review and meta-analysis.

PURPOSE: Extracorporeal cardiopulmonary resuscitation (E-CPR) may improve survival with favorable neurological outcome in patients with refractory out-of-hospital cardiac arrest (OHCA). Unfortunately, recent results from randomized controlled trials were inconclusive. We performed a meta-analysis to investigate the impact of E-CPR on neurological outcome compared to conventional cardiopulmonary resuscitation (C-CPR). METHODS: A systematic research for articles assessing outcomes of adult patients with OHCA either treated with E-CPR or C-CPR up to April 27, 2023 was performed. Primary outcome was survival with favorable neurological outcome at discharge or 30 days. Overall survival was also assessed. RESULTS: Eighteen studies were included. E-CPR was associated with better survival with favorable neurological status at discharge or 30 days (14% vs 7%, OR 2.35, 95% CI 1.61-3.43, I2 = 80%, p < 0.001, NNT = 17) than C-CPR. Results were consistent if the analysis was restricted to RCTs. Overall survival to discharge or 30 days was also positively affected by treatment with E-CPR (OR = 1.71, 95% CI = 1.18-2.46, I2 = 81%, p = 0.004, NNT = 11). CONCLUSIONS: In this meta-analysis, E-CPR had a positive effect on survival with favorable neurological outcome and, to a smaller extent, on overall mortality in patients with refractory OHCA.

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.

Normal value of neuron-specific enolase for predicting good neurological outcomes in comatose out-of-hospital cardiac arrest survivors.

Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 µg/L) and guideline-suggested (NSE < 60 µg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 µg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 µg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 µg/L, and 87.34% and 82.24% of NSE < 60 µg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction.

Grey-to-White Matter Ratio Values in Early Head Computed Tomography (CT) as a Predictor of Neurologic Outcomes in Survivors of Out-of-Hospital Cardiac Arrest Based on Severity of Hypoxic-Ischemic Brain Injury.

BACKGROUND: Hypoxic-ischemic brain injury (HIBI) is a common complication of out-of-hospital cardiac arrest (OHCA). OBJECTIVES: We investigated whether grey-to-white matter ratio (GWR) values, measured using early head computed tomography (HCT), were associated with neurologic outcomes based on the severity of HIBI in survivors of OHCA. METHODS: This retrospective multicenter study included adult comatose OHCA survivors who underwent an HCT scan within 2 h after the return of spontaneous circulation. HIBI severity was assessed using the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) scale (low, moderate, and severe). Poor neurologic outcomes were defined as Cerebral Performance Categories 3 to 5 at 6 months after OHCA. RESULTS: Among 354 patients, 27% were women and 224 (63.3%) had poor neurologic outcomes. The distribution of severity was 19.5% low, 47.5% moderate, and 33.1% severe. The area under the receiver operating curves of the GWR values for predicting rCAST severity (low, moderate, and severe) were 0.52, 0.62, and 0.79, respectively. The severe group had significantly higher predictive performance than the moderate group (p = 0.02). Multivariate logistic regression analysis revealed a significant association between GWR values and poor neurologic outcomes in the moderate group (adjusted odds ratio = 0.012, 95% CI 0.0-0.54, p = 0.02). CONCLUSIONS: In this cohort study, GWR values measured using early HCT demonstrated variations in predicting neurologic outcomes based on HIBI severity. Furthermore, GWR in the moderate group was associated with poor neurologic outcomes.

Landiolol for refractory ventricular fibrillation in out-of-hospital cardiac arrest: A randomized, double-blind, placebo-controlled, pilot trial.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) complicated by refractory ventricular fibrillation (VF) is associated with poor outcome. Beta-1-receptor selective blockade might overcome refractory VF and improve survival. This trial investigates the efficacy and safety of prehospital landiolol in OHCA and refractory VF. METHODS: In this randomized, double-blind, placebo-controlled pilot trial, patients with OHCA and recurrent or refractory VF (at least 3 defibrillation attempts and last rhythm shockable), pretreated with epinephrine and amiodarone, were allocated to receive add-on treatment with landiolol or placebo. Landiolol was given as a 20 mg bolus infusion. The primary efficacy outcome was time from trial drug infusion to sustained return of spontaneous circulation (ROSC). Safety outcomes included the onset of bradycardia and asystole. RESULTS: A total of 36 patients were enrolled, 19 were allocated to the landiolol group and 17 to the placebo group. Time from trial drug infusion to sustained ROSC was similar between treatment groups (39 min [landiolol] versus 41 min [placebo]). Sustained ROSC was numerically lower in the landiolol group compared with the placebo group (7 patients [36.8%] versus 11 patients [64.7%], respectively). Asystole within 15 min of trial drug infusion occurred significantly more often in the landiolol group than in the placebo group (7 patients [36.8%] and 0 patients [0.0%], respectively). CONCLUSION: In patients with OHCA and refractory VF who are pretreated with epinephrine and amiodarone, add-on bolus infusion of landiolol 20 mg did not lead to a shorter time to sustained ROSC compared with placebo. Landiolol might be associated with bradycardia and asystole.

Effects of mild hypercapnia on myocardial injury after out-of-hospital cardiac arrest. A sub-study of the TAME trial.

PURPOSE: Mild hypercapnia did not improve neurological outcomes for resuscitated out-of-hospital cardiac arrest (OHCA) patients in the Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial. However, the effects of hypercapnic acidosis on myocardial injury in patients with cardiac arrest is unexplored. We investigated whether mild hypercapnia compared to normocapnia, following emergency coronary intervention, increased myocardial injury in comatose OHCA-patients with AMI. METHODS: Single-centre, prospective, pre-planned sub-study of the TAME trial. Patients were randomised to targeted mild hypercapnia (PaCO2 = 6.7-7.3 kPa) or normocapnia (PaCO2 = 4.7-6.0 kPa) for 24 h. Myocardial injury was assessed with high-sensitive cardiac troponin T (hs-cTnT) measured at baseline, 24, 48 and 72 h. Haemodynamics were assessed with right heart catheterisation and blood-gas analyses every 4th hour for 48 h. RESULTS: We included 125 OHCA-patients. 57 (46%) had an AMI, with 31 and 26 patients randomised to hypercapnia and normocapnia, respectively. Median peak hs-cTnT in AMI-patients was 58% lower in the hypercapnia-group: 2136 (IQR: 861-4462) versus 5165 ng/L (IQR: 2773-7519), p = 0.007. Lower average area under the hs-cTnT curve was observed in the hypercapnia-group: 2353 (95% CI 1388-3319) versus 4953 ng/L (95% CI 3566-6341), P-group = 0.002. Hypercapnia was associated with increased cardiac power output (CPO) and lower lactate levels in patients with AMI (P-group < 0.05). hs-cTnT, lactate and CPO were not significantly different between intervention groups in OHCA-patients without AMI (p > 0.05). CONCLUSIONS: Mild hypercapnia was not associated with increased myocardial injury in resuscitated OHCA-patients. In AMI-patients, mild hypercapnia was associated with lower hs-cTnT and lactate, and improved cardiac performance. TRIAL REGISTRATION NUMBER: NCT03114033.

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.

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.

Ghrelin for Neuroprotection in Post-Cardiac Arrest Coma: A Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations. Objective: To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest. Design, Setting, and Participants: A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria. Interventions: Patients were randomized to receive intravenous acyl-ghrelin, 600 µg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care. Main Outcomes and Measures: Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3. Results: A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] µg/L vs 56 [13] µg/L; P = .04) and on day 3 (28 [6] µg/L vs 52 [14] µg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, -2% to 29%; P = .08). Conclusions and Relevance: In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence. Trial Registration: Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.

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.

Impact of pandemic-related movement restriction on public access defibrillation in Japan: a retrospective cohort study.

OBJECTIVES: To analyse monthly changes in public access defibrillation (PAD) incidence and outcomes of out-of-hospital cardiac arrest (OHCA) during the 2020-2021 COVID-19 pandemic compared with those during the 2016-2019 prepandemic period with consideration of pandemic-related movement restriction. DESIGN: Retrospective cohort study. SETTING: An extended database was created by combining and reconciling the nationwide Utstein-style OHCA and the emergency medical service (EMS) transportation databases in Japan. PARTICIPANTS: We analysed 226 182 EMS-witnessed, non-newborn and out-of-home OHCA cases in Japan. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the PAD incidence and neurologically favourable 1-month survival rate. The secondary outcomes were bystander cardiopulmonary resuscitation (CPR) provision and dispatcher-assisted CPR attempts. RESULTS: The proportion of out-of-home OHCA cases slightly decreased during the pandemic (from 33.7% to 31.9%). Although the pandemic was associated with a decreased PAD incidence, 2-year trend analyses by an interaction test showed that the PAD incidence was lower during the first nationwide declaration of a state of emergency (p<0.001) and in the pandemic's second year (p<0.01). Regardless of location, delays in basic life support (BLS) actions and EMS contact with patients were more common and the rate of PAD-induced return of spontaneous circulation was lower during the pandemic. PAD incidence reduction was significant only in locations with a recommendation of automated external defibrillator placement (p<0.001). In other locations, a pronounced delay in BLS was found during the pandemic. The neurologically favourable survival rate was reduced in parallel with the reduced PAD incidence during the pandemic (r=0.612, p=0.002). CONCLUSIONS: Prolonged and repeated movement restrictions during the COVID-19 pandemic worsened the OHCA outcomes concurrently with disturbed BLS actions, including the reduced PAD incidence in out-of-home settings. Maintaining BLS training, re-arranging automated external defibrillator placement and establishing a local alert system for recruiting well-trained citizens to the scene are essential.

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.

Observer-reported cognitive decline in out-of-hospital cardiac arrest survivors and its association with long-term survivor and relative outcomes.

AIM: Long-term cognitive decline after out-of-hospital cardiac arrest (OHCA) is still poorly understood. This study describes long-term observer-reported cognitive decline among Danish OHCA survivors, including differences in years since the event, and investigates characteristics and self-reported outcomes associated with observer-reported cognitive decline. METHODS: Adults who survived an OHCA from 2016 to 2019, and their relatives, completed the national DANish Cardiac Arrest Survivorship survey. Relatives completed the Informant Questionnaire on Cognitive Decline in the Elderly, Cardiac Arrest version (IQCODE-CA), the Hospital Anxiety and Depression Scale (HADS) and the World Health Organisation-Five Well-being index; and survivors completed the Two Simple Questions (everyday activities and mental recovery), the Modified Fatigue Impact Scale, HADS, and the Short World Health Organisation Disability Assessment Schedule 2.0. Potential associations between survivor characteristics and the IQCODE-CA were investigated using a multivariable logistic regression model. Self-reported outcomes among survivors and relatives, and the association with IQCODE-CA scores were investigated using separate logistic regression models. RESULTS: Total median IQCODE-CA score was 3.04 (IQR: 3.00-3.27), with 47% having possible cognitive decline (score ≥ 3.04), consistent across time groups. Increasing age (OR 0.98, 95% CI: 0.97-0.99) and worse self-reported mental and physical outcomes for survivors and relatives, except 'everyday activities' were significantly associated with possible cognitive decline among survivors. CONCLUSIONS: Nearly half of OHCA survivors may suffer long-term cognitive decline. Worse self-reported mental and physical outcomes among survivors and their relatives are associated with potential cognitive decline emphasising the need for post-OHCA care to include systematic neurocognitive assessment, tailored support and effective rehabilitation.

Invasive mechanical ventilation in cardiogenic shock complicating acute myocardial infarction: A contemporary Danish cohort analysis.

PURPOSE: Invasive mechanical ventilation (IMV) is widely used in patients with cardiogenic shock following acute myocardial infarction (AMICS), but evidence to guide practice remains sparse. We sought to evaluate trends in the rate of IMV utilization, applied settings, and short term-outcome of a contemporary cohort of AMICS patients treated with IMV according to out-of-hospital cardiac arrest (OHCA) at admission. METHODS: Consecutive AMICS patients receiving IMV in an intensive care unit (ICU) at two tertiary centres between 2010 and 2017. Data were analysed in relation to OHCA. RESULTS: A total of 1274 mechanically ventilated AMICS patients were identified, 682 (54%) with OHCA. Frequency of IMV increased during the study period, primarily due to higher occurrence of OHCA admissions. Among 566 patients with complete ventilator data, positive-end-expiratory pressure, inspired oxygen fraction, and minute ventilation during the initial 24 h in ICU were monitored. No differences were observed between 30-day survivors and non-survivors with OHCA. In non-OHCA, these ventilator requirements were significantly higher among 30-day non-survivors (P for all<0.05), accompanied by a lower PaO2/FiO2 ratio (median 143 vs. 230, P < 0.001) and higher arterial lactate levels (median 3.5 vs. 1.5 mmol/L, P < 0.001) than survivors. Physiologically normal PaO2 and pCO2 levels were achieved in all patients irrespective of 30-day survival and OHCA status. CONCLUSION: In the present contemporary cohort of AMICS patients, physiologically normal blood gas values were achieved both in OHCA and non-OHCA in the early phase of admission. However, increased demand of ventilatory support was associated with poorer survival only in non-OHCA patients.

Acute liver failure after out-of-hospital cardiac arrest: An observational study.

RATIONALE: Apart from hypoxic hepatitis (HH), the hepatic consequences of out-of-hospital cardiac arrest (OHCA) have been little studied. This cohort study aimed to investigate the characteristics of liver dysfunction resulting from OHCA and its association with outcomes. METHODS: Among the conventional static liver function tests used to define acute liver failure (ALF), we determined which one correlated more closely with the reference indocyanine green (ICG) clearance test in a series of OHCA patients from the CYRUS trial (NCT01595958). Subsequently, we assessed whether ALF, in addition to HH (i.e., acute liver injury), was an independent risk factor for death in a large cohort of OHCA patients admitted to two intensive care units between 2007 and 2017. RESULTS: ICG clearance, available for 22 patients, was impaired in 17 (77.3%) cases. Prothrombin time (PT) ratio was the only static liver function test that correlated significantly (r = -0.66, p < 0.01) with ICG clearance and was therefore used to define ALF, with the usual cutoff of < 50%. Of the 418 patients included in the analysis (sex ratio: 1.4; median age: 64 [53-75] years; non-shockable rhythm: 73%), 67 (16.0%) presented with ALF, and 61 (14.6%) had HH at admission. On day 28, 337 (80.6%) patients died. Following multivariate analysis, ALF at admission, OHCA occurring at home, absence of bystander, non-cardiac cause of OHCA, low-flow duration ≥ 20 min, and SOFA score excluding liver subscore at admission were independently associated with day 28 mortality. CONCLUSIONS: ALF occurred frequently after OHCA and, unlike HH, was independently associated with day 28 mortality.

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.