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

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245210
Author(s):  
Muharrem Akin ◽  
Vera Garcheva ◽  
Jan-Thorben Sieweke ◽  
John Adel ◽  
Ulrike Flierl ◽  
...  

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.

2020 ◽  
Author(s):  
Nilesh Pareek ◽  
Peter Kordis ◽  
Nicholas Beckley-Hoelscher ◽  
Dominic Pimenta ◽  
Spela Tadel Kocjancic ◽  
...  

AimsThe purpose of this study was to develop a practical risk−score to predict poor neurological outcome after out−of−hospital cardiac arrest (OOHCA) for use on arrival to a Heart Attack Centre.Methods and ResultsBetween May 2012 and December 2017, 1055 patients had OOHCA in our region, of whom 373 patients were included in the King's Out of Hospital Cardiac Arrest Registry (KOCAR). We performed prediction modelling with multi-variable logistic regression to identify factors independently predictive of the primary outcome in order to derive a risk score. This was externally validated in two independent cohorts comprising 474 patients. The primary outcome was poor neurological function at 6−month follow−up (Cerebral Performance Category 3-−). Seven independent variables for prediction of outcome were identified: Missed (Unwitnessed) arrest, Initial non-shockable rhythm, non-Reactivity of pupils, Age, Changing intra-arrest rhythms, Low pH<;7.20 and Epinephrine administration. From these variables, the MIRA2CLE2 score was developed which had an AUC of 0.90 in the development and 0.85 and 0.89 in the validation cohorts. 3 risk groups of the MIRA2CLE2 were defined − Low risk (≤2−5.6% risk of poor outcome; Intermediate risk (3−4−55.4% of poor outcome) and high risk (≥5−92.3% risk of poor outcome). The risk-score performance was equivalent in a sub-group of patients referred for early angiography and revascularisation where appropriate.ConclusionsThe MIRA2CLE2 score is a practical risk score for early accurate prediction of poor neurological outcome after OOHCA, which has been developed for simplicity of use on admission to a Heart Attack Centre.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Akin ◽  
V Garcheva ◽  
J T Sieweke ◽  
J Tongers ◽  
L C Napp ◽  
...  

Abstract Purpose To establish cut-offs for neuromarkers such as neuron-specific enolase (NSE) and S-100 predicting good neurological outcome for patients treated with therapeutic hypothermia with out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC) as current cut-offs had been derived from normothermic cohorts. Methods Consecutive data of all patients with OHCA admitted to our institution between 01/2011 and 12/2016 were collected in a database. Patient received standard intensive care according to the Hannover Cardiac Resuscitation Algorithm (HaCRA) including mandatory hypothermia. Neurological markers such as neuron-specific enolase (NSE) and S-100 have been used to assess neurological damage following OHCA. Results Mean age of overall patient population (n=302) was 63±14 [54–74] years with a male predominance (77%). Cardiac arrest was witnessed in 81% and bystander cardiopulmonal resuscitation (CPR) was performed in 67%. Initial rhythm was ventricular fibrillation in 69%. ROSC had been achieved after 24±17 minutes. Hypothermia was applied in all patients. In 95% percutaneous coronary angiography and in 57% of them coronary intervention was performed. After ROSC, STEMI was present in 44%. Mechanical support was required in 19%. 30 day mortality was 44% in the total cohort. Mean NSE was 27±69 μg/l, mean NSE with good neurological outcome was 20±8.7 μg/l, highest NSE with good neurological outcome was 46 μg/l. Mean S-100 was 0.114±2.037μg/l, mean S-100 with good neurological outcome was 0.068±0.067 μg/l, highest S-100 with good neurological outcome was 0.360 μg/l. Conclusion Even when using a strict protocol for OHCA patients and routinely applying therapeutic hypothermia, the cut-offs for NSE and S-100 regarding good neurological outcome are similar to those reported before without therapeutic hypothermia, but they must not be used solitary to withdraw life support as even very high markers can be associated with goof neurological outcome in individual patients.


2021 ◽  
Author(s):  
Nobunaga Okada ◽  
Tasuku Matsuyama ◽  
Yohei Okada ◽  
Asami Okada ◽  
Kenji Kandori ◽  
...  

Abstract We aimed to estimate the association between PaCO2 level in the patient after out-of-hospital cardiac arrest (OHCA) resuscitation with patient outcome based on a multicenter prospective cohort registry in Japan between June 2014 and December 2015.Based on the PaCO2 within 24-h after return of spontaneous circulation (ROSC), patients were divided into six groups as follow; severe hypocapnia (<25mmHg), mild hypocapnia (25–35mmHg,), normocapnia (35–45mmHg), mild hypercapnia (45–55mmHg), severe hypercapnia (>55mmHg), exposure to both hypocapnia and hypercapnia. Multivariate logistic regression analysis was conducted to calculate the adjusted odds ratios (aORs) and 95% confidence interval (CI) for the 1-month poor neurological outcome (Cerebral Performance Category ≥3). Among the 13491 OHCA patients, 607 were included. Severe hypocapnia, mild hypocapnia, severe hypercapnia, and exposure to both hypocapnia and hypercapnia were associated with a higher rate of 1-month poor neurological outcome compared with mild hypercapnia (aOR 6.68 [95% CI 2.16–20.67], 2.56 [1.30–5.04], 2.62 [1.06–6.47], 5.63 [2.21–14.34]; respectively). There was no significant difference between the outcome of patients with normocapnia and mild hypercapnia. In conclusion, maintaining normocapnia and mild hypercapnia during the 24-h after ROSC was associated with better neurological outcomes than other PaCO2 abnormalities in this study.


Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Yohei Okada ◽  
Takeyuki Kiguchi ◽  
Tetsuhisa Kitamura ◽  
Takashi Kawamura ◽  
Taku Iwami

Background: Our study aim was to identify the association of acidemia with neurological outcome among the out-of-hospital cardiac arrest patients who undergo extracorporeal cardio-pulmonary resuscitation (E-CPR). Method: We analyzed the data from multi-institutional prospective cohort study (CRITICAL study: Comprehensive Registry of Intensive Cares for out-of-hospital cardiac arrest Survival) including 14 emergency departments in Osaka, Japan. We included adult out-of-hospital cardiac arrest patients aged ≥18 years who undergo E-CPR. The exposure of interest was serum pH measured before start to E-CPR on admission, and it was divided to tertiles. The primary outcome was 30-days favorable neurological outcome defined as cerebral performance category 1 or 2. We calculated the adjusted odds ratio (OR) with 95% confidence intervals (CI) using logistic regression model, adjusted by age, sex, witness of collapse, by-stander CPR, cardiac rhythm on hospital arrival, and time to hospital arrival. Results: Among 9,822 patients in Critical study database, 303 patients were included in the analysis. The median (interquartile range) of the age was 62 (48-71) years-old. The range of serum pH in each tertile was as below; Tertile 1[ pH≥7.02, (n=101)], Tertile 2 [pH 6.87-7.02, (n=100)], Tertile 3 [pH <6.87, (n=102)]. The adjusted OR with 95%CI of tertile2, and 3 for favorable neurological outcome were 0.23 (0.09 to 0.58), and 0.18 (0.06 to 0.52) referred to Tertile 1, respectively. Conclusion: Among the out-of-hospital cardiac arrest patients who undergo E-CPR, severe acidemia (pH < 7.02) on arrival was associated with 30-days poor neurological outcome. Serum pH measurement might be useful to consider the indication of E-CPR.


2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
M Jarakovic ◽  
S Bjelica ◽  
M Kovacevic ◽  
M Petrovic ◽  
S Dimic ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Out-of-hospital cardiac arrest (OHCA) is a major public health challenge and although rate of intrahospital survival increased over the last 40 years, it still remains poor (from 8,6% in 1976-1999 to 9,9% in 2000-2019). Different studies report that introduction of mild therapeutic hypothermia (TTM) improves survival and neurological outcome in comatose patients after OHCA.  Purpose The aim of this research was to evaluate influence of pre-hospital predictors related to cardiopulmonary resuscitation (CPR), neurological status and ECG changes at admission and early percutaneous coronary intervention (PCI) performed within 24h of admission on intrahospital survival and neurological outcome of OHCA patients. Methods The research was conducted as a retrospective cohort study of data taken from the hospital registry on OHCA from January 2007 until November 2019. The analyzed factors were: bystander CPR, duration of CPR until return of ROSC, initial rhythm, responsiveness upon admission defined as Glasgow Coma Score (GCS)&gt;8, presence of ST segment elevation (STEMI) on electrocardiography (ECG) and early PCI. The favorable neurological outcome was defined as a cerebral performance category scale (CPC)≤2. Results The research included 506 survivors of OHCA. Cardiac arrest was witnessed in 412 (81.4%), bystander CPR was performed in 197 (38.9%), CPR lasted ≤20min in 291 (57.5%), initial rhythm was shockable in 304 (60.1%) of patients. At admission 387 (76.5%) were comatose (GCS &lt; 8) and TTM was introduced in 177 (45.7%) of patients. ECG upon admission showed STEMI in 176 (34.8%) and early PCI was performed in 145 (28.6%) of patients. In-hospital mortality in our study group was 281 (55.5%) and 185 (36.6%) of patients had favorable neurological outcome. Multivariate regression analysis showed that initial shockable rhythm (OR 3.391 [2.310-4.977], p &lt; 0.0005), early PCI (OR 0.368 [0.226-0.599], p &lt; 0.0005), duration of CPR ≤20min (OR 4.249 [2.688-6.718], p &lt; 0.0005) and GCS &gt; 8 (OR 0.194 [0.110-0.343], p &lt; 0.0005) were independent predictors of in-hospital survival. Independent predictors of favorable neurological outcome were: initial shockable rhythm (OR 3.301 [2.002-5.441], p&lt; 0.0005), STEMI on ECG upon admission (OR 0.528 [0.326-0.853], p = 0.009), duration of CPR ≤20min (OR 5.144 [3.090-8.565], p&lt; 0.0005) and GCS &gt; 8 (OR 0.152 [0.088-0.260], p&lt; 0.0005). Introduction of TTM improved both intrahospital survival (54.1% vs. 24.4%; p &lt; 0.0005) and neurological outcome (33.5% vs. 11.6%; p &lt; 0.0005) in patients with initial shockable rhythm. Conclusion In our study group of OHCA patients of any origin, initial shockable rhythm, duration of CPR ≤20min and GCS &gt; 8 at admission influenced both intrahospital survival and favorable neurological outcome. Introduction of TTM significantly improved both survival and neurological outcome in comatose patients with initial shockable rhythm.


Author(s):  
Seraina R. Hochstrasser ◽  
Kerstin Metzger ◽  
Alessia M. Vincent ◽  
Christoph Becker ◽  
Annalena K. J. Keller ◽  
...  

AbstractObjectivesPrior research found the gut microbiota-dependent and pro-atherogenic molecule trimethylamine-N-oxide (TMAO) to be associated with cardiovascular events as well as all-cause mortality in different patient populations with cardiovascular disease. Our aim was to investigate the prognostic value of TMAO regarding clinical outcomes in patients after out-of-hospital cardiac arrest (OHCA).MethodsWe included consecutive OHCA patients upon intensive care unit admission into this prospective observational study between October 2012 and May 2016. We studied associations of admission serum TMAO with in-hospital mortality (primary endpoint), 90-day mortality and neurological outcome defined by the Cerebral Performance Category (CPC) scale.ResultsWe included 258 OHCA patients of which 44.6% died during hospitalization. Hospital non-survivors showed significantly higher admission TMAO levels (μmol L−1) compared to hospital survivors (median interquartile range (IQR) 13.2 (6.6–34.9) vs. 6.4 (2.9–15.9), p<0.001). After multivariate adjustment for other prognostic factors, TMAO levels were significantly associated with in-hospital mortality (adjusted odds ratios (OR) 2.1, 95%CI 1.1–4.2, p=0.026). Results for secondary outcomes were similar with significant associations with 90-day mortality and neurological outcome in univariate analyses.ConclusionsIn patients after OHCA, TMAO levels were independently associated with in-hospital mortality and other adverse clinical outcomes and may help to improve prognostication for these patients in the future. Whether TMAO levels can be influenced by nutritional interventions should be addressed in future studies.


Author(s):  
Beata Csiszar ◽  
Zsolt Marton ◽  
Janos Riba ◽  
Peter Csecsei ◽  
Lajos Nagy ◽  
...  

AbstractEarly prediction of the mortality, neurological outcome is clinically essential after successful cardiopulmonary resuscitation. To find a prognostic marker among unselected cardiac arrest survivors, we aimed to evaluate the alterations of the l-arginine pathway molecules in the early post-resuscitation care. We prospectively enrolled adult patients after successfully resuscitated in- or out-of-hospital cardiac arrest. Blood samples were drawn within 6, 24, and 72 post-cardiac arrest hours to measure asymmetric and symmetric dimethylarginine (ADMA and SDMA) and l-arginine plasma concentrations. We recorded Sequential Organ Failure Assessment, Simplified Acute Physiology Score, and Cerebral Performance Category scores. Endpoints were 72 h, intensive care unit, and 30-day mortality. Among 54 enrolled patients [median age: 67 (61–78) years, 48% male], the initial ADMA levels were significantly elevated in those who died within 72 h [0.88 (0.64–0.97) µmol/L vs. 0.55 (0.45–0.69) µmol/L, p = 0.001]. Based on receiver operator characteristic analysis (AUC = 0.723; p = 0.005) of initial ADMA for poor neurological outcome, the best cutoff was determined as > 0.65 µmol/L (sensitivity = 66.7%; specificity = 81.5%), while for 72 h mortality (AUC = 0.789; p = 0.001) as > 0.81 µmol/L (sensitivity = 71.0%; specificity = 87.5%). Based on multivariate analysis, initial ADMA (OR = 1.8 per 0.1 µmol/L increment; p = 0.002) was an independent predictor for 72 h mortality. Increased initial ADMA predicts 72 h mortality and poor neurological outcome among unselected cardiac arrest victims.


2020 ◽  
Vol 41 (47) ◽  
pp. 4508-4517 ◽  
Author(s):  
Nilesh Pareek ◽  
Peter Kordis ◽  
Nicholas Beckley-Hoelscher ◽  
Dominic Pimenta ◽  
Spela Tadel Kocjancic ◽  
...  

Abstract Aims The purpose of this study was to develop a practical risk score to predict poor neurological outcome after out-of-hospital cardiac arrest (OOHCA) for use on arrival to a Heart Attack Centre. Methods and results From May 2012 to December 2017, 1055 patients had OOHCA in our region, of whom 373 patients were included in the King’s Out of Hospital Cardiac Arrest Registry (KOCAR). We performed prediction modelling with multivariable logistic regression to identify predictors of the primary outcome to derive a risk score. This was externally validated in two independent cohorts comprising 473 patients. The primary endpoint was poor neurological outcome at 6-month follow-up (Cerebral Performance Category 3–5). Seven independent predictors of outcome were identified: missed (unwitnessed) arrest, initial non-shockable rhythm, non-reactivity of pupils, age (60–80 years—1 point; &gt;80 years—3 points), changing intra-arrest rhythms, low pH &lt;7.20, and epinephrine administration (2 points). The MIRACLE2 score had an area under the curve (AUC) of 0.90 in the development and 0.84/0.91 in the validation cohorts. Three risk groups were defined—low risk (MIRACLE2 ≤2—5.6% risk of poor outcome); intermediate risk (MIRACLE2 of 3–4—55.4% of poor outcome); and high risk (MIRACLE2 ≥5—92.3% risk of poor outcome). The MIRACLE2 score had superior discrimination than the OHCA [median AUC 0.83 (0.818–0.840); P &lt; 0.001] and Cardiac Arrest Hospital Prognosis models [median AUC 0.87 (0.860–0.870; P = 0.001] and equivalent performance with the Target Temperature Management score [median AUC 0.88 (0.876–0.887); P = 0.092]. Conclusions The MIRACLE2 is a practical risk score for early accurate prediction of poor neurological outcome after OOHCA, which has been developed for simplicity of use on admission.


2020 ◽  
Author(s):  
Sabina Hunziker ◽  
Adrian Quinto ◽  
Maja Ramin-Wright ◽  
Christoph Becker ◽  
Katharina Beck ◽  
...  

Abstract Background: A recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent validation study and to investigate whether NfL improves the prognostic value of two cardiac arrest risk scores.Methods: This prospective, single-center study included 164 consecutive adult cardiac arrest patients upon intensive care unit admission. We calculated two clinical risk scores (OHCA, CAHP) and measured NfL on admission using the single molecule array NF-light® assay. The primary endpoint was neurological outcome at hospital discharge assessed with the cerebral performance category (CPC) score.Results: Poor neurological outcome (CPC≥3) was found in 60% (98/164) of patients, and 55% (91/164) died. Compared to patients with favorable outcome, NfL was 14-times higher in patients with poor neurological outcome (685±1787 vs. 49±111pg/mL), with an adjusted odds ratio of 3.4 (95%CI 2.1 to 5.6, p<0.001) and an area under the curve (AUC) of 0.82. Adding NfL to the clinical risk scores significantly improved discrimination of both the OHCA score (from AUC 0.82 to 0.89, p<0.001) and CAHP score (from AUC 0.89 to 0.92, p<0.05). Admission NfL showed better outcome prediction compared to neuron-specific enolase (NSE) (AUC 0.84 vs.0.69, p=0.01).Conclusions: This study confirms the high performance of admission NfL alone and in combination with two clinical risk scores to prognosticate clinical outcome in patients after cardiac arrest. NfL should be considered as a standard laboratory measures in the evaluation of cardiac arrest patients.


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