Additive Impact of Interleukin 6 and Neuron Specific Enolase for Prognosis in Patients With Out-of-Hospital Cardiac Arrest - Experience From the HAnnover COoling REgistry.

Background: Patients after out-of-hospital cardiac arrest (OHCA) are at increased risk for mortality and poor neurological outcome. We assessed the additive impact of interleukin 6 (IL-6) at admission to neuron-specific enolase (NSE) at day 3 for prognosis of 30-day mortality and long-term neurological outcome in OHCA patients. Methods: A total of 217 patients from the HAnnover COoling REgistry with return of spontaneous circulation (ROSC) after OHCA and IL-6 measurement immediately after admission during 2017-2020 were included to investigate the prognostic value and importance of IL-6 in addition to NSE obtained on day 3. Poor neurological outcome was defined by cerebral performance category (CPC) ≥ 3 after 6 months. Results: Patients with poor outcome showed higher IL-6 values (30-day mortality: 2,224 ± 524 ng/l vs 186 ± 15 ng/l, p < 0.001; CPC ≥ 3 at 6 months: 1,440 ± 331 ng/l vs 180 ± 24 ng/l, p < 0.001). IL-6 was an independent predictor of mortality (HR = 1.013/ng/l; 95% CI 1.007-1.019; p < 0.001) and poor neurological outcome (HR = 1.004/ng/l; 95% CI 1.001-1.007; p = 0.036). In ROC-analysis, AUC for IL-6 was 0.98 (95% CI 0.96-0.99) for mortality, but only 0.76 (95% CI 0.68-0.84) for poor neurological outcome. The determined cut-off value for IL-6 was 431 ng/l for mortality (NPV 89.2%). In patients with IL-6 > 431 ng/l, the combination with NSE < 46 µg/l optimally identified those individuals with potential for good neurological outcome (CPC ≤ 2). Conclusion: Elevated IL-6 levels at admission after ROSC were closely associated with 30-day mortality. The combination of IL-6 and NSE provided clinically important additive information for predict poor neurological outcome at 6 months.

Computed-Tomography as First-line Diagnostic Procedure in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Mortality after out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC) remains high despite numerous efforts to improve outcome. For patients with suspected coronary cause of arrest, coronary angiography is crucial. However, there are other causes and potentially life-threatening injuries related to cardiopulmonary resuscitation (CPR), which can be detected by routine computed tomography (CT). MATERIALS AND METHODS: At Hannover Medical School, rapid coronary angiography and CT are performed in successfully resuscitated OHCA patients as a standard of care prior to admission to intensive care. We analyzed all patients who received CT following OHCA with ROSC over a three-year period. RESULTS: There were 225 consecutive patients with return of spontaneous circulation following out-of-hospital cardiac arrest. Mean age was 64 ± 13 years, 75% were male. Of them, 174 (77%) had witnessed arrest, 145 (64%) received bystander CPR, and 123 (55%) had a primary shockable rhythm. Mean time to ROSC was 24 ± 20 min. There were no significant differences in CT pathologies in patients with or without ST-segment elevations in the initial ECG. Critical CT findings qualifying as a potential cause for cardiac arrest were intracranial bleeding (N = 6), aortic dissection (N = 5), pulmonary embolism (N = 17), pericardial tamponade (N = 3), and tension pneumothorax (N = 11). Other pathologies were regarded as consequences of CPR and relevant for further treatment: aspiration (N = 62), rib fractures (N = 161), sternal fractures (N = 50), spinal fractures (N = 11), hepatic bleeding (N = 12), and intra-abdominal air (N = 3). CONCLUSION: Early CT fallowing OHCA uncovers a high number of causes and consequences of OHCA and CPR. Those are relevant for post-arrest care and are frequently life-threatening, suggesting that CT can contribute to improving prognosis following OHCA.

High rate of critical coronary stenosis in comatose patients with Non-ST-elevation out-of-hospital cardiac arrest (NSTE-OHCA) undergoing therapeutic hypothermia-Experience from the HAnnover COoling REgistry (HACORE).

BACKGROUND: Myocardial infarction is the most frequent cause for out-of-hospital cardiac arrest (OHCA) in adults. Patients with ST-segment elevations (STE) following return of spontaneous circulation (ROSC) are regularly admitted to the catheterisation laboratory for urgent coronary angiography. Whether patients without obvious STE (NSTE) should receive coronary angiography as part of a standardised diagnostic work-up following OHCA is still debated. METHODS: We analysed a cohort of 517 subsequent OHCA patients admitted at our institution who received a standardised diagnostic work-up including coronary angiography and therapeutic hypothermia. Patients were 63±14 years old, 76% were male. Overall, 180 (35%) had ST-elevation in the post-ROSC ECG, 317 (61%) had shockable rhythm (ventricular fibrillation or tachycardia) at first ECG. ROSC was achieved after 26±21 minutes. RESULTS: Critical coronary stenosis requiring PCI was present in 83% of shockable and 87% of non-shockable STE-OHCA and in 48% of shockable and 22% of non-shockable NSTE-OHCA patients. In-hospital survival was 61% in shockable and 55% in non-shockable STE-OHCA and 60% in shockable and 28% in non-shockable NSTE-OHCA. CONCLUSION: Standardised admission diagnostics in OHCA patients undergoing therapeutic hypothermia with a strict admission protocol incorporating ECG and coronary catheterisation shows a high rate of relevant coronary stenosis in STE-OHCA irrespective of the initial rhythm and in NSTE-OHCA with initial shockable rhythm. Based on the unfavourable outcome and low PCI rate observed in NSTE-OHCA patients with a primary non-shockable ECG rhythm it might be reasonable to restrict routine early coronary angiography to patients with primary shockable rhythms and/or ST-segment elevations after ROSC.

Neuromarkers and neurological outcome in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia-experience from the HAnnover COoling REgistry (HACORE).

BACKGROUND: Neuron-specific enolase (NSE) and S-100b have been used to assess neurological damage following out-of-hospital cardiac arrest (OHCA). Cut-offs were derived from small normothermic cohorts. Whether similar cut-offs apply to patients treated with hypothermia remained undetermined. METHODS: We investigated 251 patients with OHCA treated with hypothermia but without routine prognostication. Neuromarkers were determined at day 3, neurological outcome was assessed after hospital discharge by cerebral performance category (CPC). RESULTS: Good neurological outcome (CPC≤2) was achieved in 41%. Elevated neuromarkers, older age and absence of ST-segment elevation after ROSC were associated with increased mortality. Poor neurological outcome in survivors was additionally associated with history of cerebrovascular events, sepsis and higher admission lactate. Mean NSE was 33µg/l [16-94] vs. 119µg/l [25-406]; p<0.001, for survivors vs. non-survivors, and 21µg/l [16-29] vs. 40µg/l [23-98], p<0.001 for good vs. poor neurological outcome. S-100b was 0.127µg/l [0.063-0.360] vs. 0.772µg/l [0.121-2.710], p<0.001 and 0.086µg/l [0.061-0.122] vs. 0.138µg/l [0.090-0.271], p = 0.009, respectively. For mortality, thresholds of 36µg/l for NSE and 0.128µg/l for S-100b could be determined; for poor neurological outcome 33µg/l (NSE) and 0.123µg/l (S-100b), respectively. Positive predictive value for NSE was 81% (74-88) and 79% (71-85) for S-100b. CONCLUSIONS: Thresholds for NSE and S-100b predicting mortality and poor neurological outcome are similar in OHCA patients receiving therapeutic hypothermia as in those reported before the era of hypothermia. However, both biomarkers do not have enough specificity to predict mortality or poor neurological outcome on their own and should only be additively used in clinical decision making.

Early use of hemoadsorption in patients after out-of hospital cardiac arrest - a matched pair analysis.

BACKGROUND: Pro- and anti-inflammatory mediators are released during and after cardiac arrest, which may be unfavourable. Small case-series and observational studies suggested that unselective hemoadsorption may reduce inadequately high cytokine levels during sepsis or cardiac surgery. We aimed to assess the effect of cytokine adsorbtion on mortality in patients following out-of-hospital cardiac arrest by comparing a patient cohort with hemoadsorption after resuscitation for out-of-hospital cardiac arrest to a control cohort without adsorption within the HAnnover COling REgistry (HACORE). METHODS: We adopted an early routine use of hemoadsorption in patients after out-of-hospital cardiac arrest with increased vasopressor need and performed a 1:2 match according to age, gender, time to return of spontaneous circulation, initial left-ventricular ejection fraction, extracorporeal membrane-oxygenation or left-ventricular unloading by Impella, need for renal replacement therapy, admission lactate, pH, glomerular filtration rate to patients without an adsorber from HACORE. The primary endpoint was 30-day mortality. RESULTS: Twenty-four patients receiving hemoadsorption were matched to 48 patients without hemoadsorption (mean age 62±13 years, 83% male). While there was no significant difference in baseline parameters, 30-day mortality was higher in patients treated with hemoadsorption than in the matched control group (83% vs 65%, Log rank p = 0.011). CONCLUSIONS: Routine use of hemoadsorption did not reduce, but seems to be associated with higher 30-day mortality in patients after OHCA. Prior to routine adoption in daily practice, hemoadsorption should be evaluated in properly sized randomized controlled trials.

Use of extracorporeal membrane oxygenation for eCPR in the emergency room in patients with refractory out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) refractory to conventional high-quality cardiopulmonary resuscitation (CPR) may be rescued by extracorporeal CPR (eCPR) using veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Even when trying to identify eCPR candidates based on criteria assumed to be associated with a favourable neurological outcome, reported survival rates are frequently below 10%. METHODS: All patients undergoing implantation of V-A ECMO for eCPR between January 2018 and December 2019 (N = 40) were analysed (age 53±13 years; 75% male). Patients with refractory OHCA and potentially favourable circumstances (initial shockable rhythm, witnessed arrest, bystander CPR, absence of limiting comorbidities, age <75 years) were transported under mechanical chest compression. Candidates for eCPR should have a pH ≥6.9, arterial lactate ≤15 mmol/L and time-to-ECMO should be ≤60 minutes. RESULTS: Overall 30-day survival was 12.5%, with 3 of 5 survivors having a favourable neurological outcome (cerebral performance category (CPC) 1 or 2), representing 7.5% of the total eCPR population. No patient selected for eCPR met all pre-defined criteria (median of unfavourable criteria: 3). Importantly, time-to-ECMO most often (39/40) exceeded 60 minutes (mean 102 ±32 min.), and lactate was >15mmol/L in 30 out of 40 patients. Moreover, 22 out of 40 patients had a non-shockable rhythm on the first ECG. CONCLUSIONS: Despite our intention to select patients with potentially advantageous circumstances to achieve acceptable eCPR outcomes, the imminent deadly consequence of withholding eCPR obviously prompted individual physicians to perform the procedure also in presumably more unfavourable settings, resulting in similar mortality rates of eCPR as reported before.

Mortality in Patients With Out-of-Hospital Cardiac Arrest Undergoing a Standardized Protocol Including Therapeutic Hypothermia and Routine Coronary Angiography: Experience From the HACORE Registry.

OBJECTIVES: This study sought to analyze the impact of mandatory therapeutic hypothermia and cardiac catheterization in the absence of overt noncardiac cause of arrest as part of the Hannover Cardiac Resuscitation Algorithm before intensive care admission. BACKGROUND: Despite advanced therapies, out-of-hospital cardiac arrest (OHCA) is still associated with high mortality rates. Recently, the TTM (Target Temperature Management 33°C Versus 36°C After Out-of-Hospital Cardiac Arrest)-trial caused severe uncertainty about the efficacy of and need for therapeutic hypothermia. Furthermore, the role of early coronary angiography in OHCA survivors without ST-segment elevation remains undetermined. METHODS: In the HACORE (HAnnover Cooling REgistry) we investigated 233 consecutive patients (median age 64 [interquartile range: 53 to 74] years) with OHCA admitted to our institution between January 2011 and December 2015 who were treated according to the algorithm. RESULTS: A total of 73% had ventricular fibrillation as primary rhythm. Return of spontaneous circulation was achieved after 20 (interquartile range: 10 to 30) min. Immediate percutaneous coronary angiography was performed in 96% and coronary angioplasty in 59% of all cases. ST-segment elevation was present in 47%. Critical coronary stenosis requiring percutaneous coronary intervention was present in 67% of patients with and 52% of patients without ST-segment elevation. Overall 30-day intrahospital mortality in this real-world registry was 37%. Patients in our local registry who matched the inclusion/exclusion criteria of the TTM-trial (n = 145) had a markedly lower 30-day mortality (27%) compared with the published trial (44%). CONCLUSIONS: Standardized treatment of patients with OHCA following a strict protocol incorporating computed tomography, cardiac catheterization and revascularization, liberal use of active hemodynamic support in presence of shock, and mandatory therapeutic hypothermia results in mortality rates lower than previously reported.