Trimethylamine-N-oxide (TMAO) predicts short- and long-term mortality and poor neurological outcome in out-of-hospital cardiac arrest patients

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.

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.


2020 ◽  
Vol 9 (5) ◽  
pp. 1405 ◽  
Author(s):  
Naemi Herzog ◽  
Rahel Laager ◽  
Emanuel Thommen ◽  
Madlaina Widmer ◽  
Alessia M. Vincent ◽  
...  

Background: Studies have suggested that taurine may have neuro- and cardio-protective functions, but there is little research looking at taurine levels in patients after out-of-hospital cardiac arrest (OHCA). Our aim was to evaluate the association of taurine with mortality and neurological deficits in a well-defined cohort of OHCA patients. Methods: We prospectively measured serum taurine concentration in OHCA patients upon admission to the intensive care unit (ICU) of the University Hospital Basel (Switzerland). We analyzed the association of taurine levels and in-hospital mortality (primary endpoint). We further evaluated neurological outcomes assessed by the cerebral performance category scale. We calculated logistic regression analyses and report odds ratios (OR) and 95% confidence intervals (CI). We calculated different predefined multivariable regression models including demographic variables, comorbidities, initial vital signs, initial blood markers and resuscitation measures. We assessed discrimination by means of area under the receiver operating curve (ROC). Results: Of 240 included patients, 130 (54.2%) survived until hospital discharge and 110 (45.8%) had a favorable neurological outcome. Taurine levels were significantly associated with higher in-hospital mortality (adjusted OR 4.12 (95%CI 1.22 to 13.91), p = 0.02). In addition, a significant association between taurine concentration and a poor neurological outcome was observed (adjusted OR of 3.71 (95%CI 1.13 to 12.25), p = 0.03). Area under the curve (AUC) suggested only low discrimination for both endpoints (0.57 and 0.57, respectively). Conclusion: Admission taurine levels are associated with mortality and neurological outcomes in OHCA patients and may help in the risk assessment of this vulnerable population. Further studies are needed to assess whether therapeutic modulation of taurine may improve clinical outcomes after cardiac arrest.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Stephan Seewald ◽  
Jan Wnent ◽  
Barbara Jakisch ◽  
Andreas Bohn ◽  
Matthias Fischer ◽  
...  

Introduction: Cardiac arrest is a common event and one of the leading causes of death. Especially within the elderly judgment on if the treatment will be in favor of the patient is a major challenge for the medical team. We evaluated the influence of the age on short and long-term survival after out-of- hospital cardiac arrest (OHCA). Hypothesis: Elderly people survive an out-of-hospital cardiac arrest with good neurological outcome. Methods: For this purpose, we analyzed data of 24,686 out-of-hospital cardiac arrest patients prospectively registered between 2008 and 2017 within the German Resuscitation Registry (GRR). The data records were divided according to different age groups and within the age group after shockable and non-shockable rhythms. The data sets were examined with regard to short and long-term survival. Short term survival was measured by expected and observed return-of-spontaneous circulation based on the RACA-score. The RACA-score is a previously published score to predict ROSC based on readily available variables after arrival of the emergency medical service (EMS) on scene. Long-term survival was differentiated in 24-hour survival, 30-day survival and hospital discharge with good neurological outcome (Cerebral Performance Category 1 and 2). Results: (Table 1) Conclusions: Our data shows that shockable rhythm and younger age are important factors of good neurological outcome after OHCA. Nevertheless, the few cases with shockable rhythms (411 out of 3227) in the elderly (>85 years) showed a favorable neurological outcome in 12.2% (77,2% of all patients with hospital discharge). In the non-shockable group 1.4% (58,3%) of the >85 year old had a good outcome. Data show that a resuscitation attempt in the elderly is not futile, especially if a shockable rhythm is detected. Further studies are necessary to maintain this decision.


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.


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.


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.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Shinichi Ijuin ◽  
Akihiko Inoue ◽  
Nobuaki Igarashi ◽  
Shigenari Matsuyama ◽  
Tetsunori Kawase ◽  
...  

Introduction: We have reported previously a favorable neurological outcome by extracorporeal cardiopulmonary resuscitation (ECPR) for out of hospital cardiac arrest. However, effects of ECPR on patients with prolonged pulseless electrical activity (PEA) are unclear. We analyzed etiology of patients with favorable neurological outcomes after ECPR for PEA with witness. Methods: In this single center retrospective study, from January 2007 to May 2018, we identified 68 patients who underwent ECPR for PEA with witness. Of these, 13 patients (19%) had good neurological outcome at 1 month (Glasgow-Pittsburgh Cerebral Performance Category (CPC):1-2, Group G), and 55 patients (81%) had unfavorable neurological outcome (CPC:3-5, Group B). We compared courses of treatment and causes/places of arrests between two groups. Results are expressed as mean ± SD. Results: Patient characteristics were not different between the two groups. Time intervals from collapse to induction of V-A ECMO were also not significantly different (Group G; 46.1 ± 20.2 min vs Group B; 46.8 ± 21.7 min, p=0.92). Ten patients achieved favorable neurological outcome among 39 (26%) with non-cardiac etiology. In cardiac etiology, only 3 of 29 patients (9%) had a good outcome at 1 month (p=0.08). In particular, 5 patients of 10 pulmonary embolism, and 4 of 4 accidental hypothermia responded well to ECPR with a favorable neurological outcome. Additionally, 6 of 13 (46%), who had in hospital cardiac arrest, had good outcome, whereas 7 of 55 (15%) who had out of hospital cardiac arrest, had good outcome (p=0.02). Conclusions: In our small cohort of cardiac arrest patients with pulmonary embolism or accidental hypothermia and PEA with witness, EPCR contributed to favorable neurological outcomes at 1 month.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Carole Maupain ◽  
Wulfran Bougouin ◽  
Lamhaut Lionel ◽  
Nicolas Deye ◽  
Daniel Jost ◽  
...  

Background: Out-of-hospital cardiac arrest (OHCA) carries a very poor prognosis. Early prognostication of patients admitted in ICU after resuscitated OHCA is a key issue but remains challenging. The aim of that study was to establish a new scoring system to predict poor neurological outcome in these patients. Materials and Methods: The CAHP (Cardiac Arrest Hospital Prognosis) score was developed from the Sudden Death Expertise Center registry (SDEC, Paris, France). Objective risk factors were weighted on the basis of a logistic regression analysis. The primary outcome was poor neurological outcome defined as Cerebral Performance Category 3, 4 or 5. Thresholds were defined to distinguish low, moderate and high-risk groups. The CAHP score was then validated in an external dataset (Parisian OHCA Registry). Score calibration and discrimination characteristics were assessed in the validation dataset. Results: The developmental dataset included 819 patients admitted in ICU from May 2011 to December 2012. After logistic regression, 7 variables were independently associated with poor neurological outcome: age, initial shockable rhythm, time form collapse to basic life support (BLS), time from BLS to return of spontaneous circulation (ROSC), location of cardiac arrest, epinephrine dose during resuscitation and arterial pH at admission. These variables were included in the CAHP score. 3 risks groups were identified: a low risk group (score ≤ 150, 39 % of unfavorable outcome), medium risk group (score 150-200, 81% of unfavorable outcome) and high-risk group (CAHP score ≥ 200, 100 % of unfavorable outcome). AUC of the CAHP score was 0.93. In the external validation dataset, discrimination value of the CAHP score was consistent with an AUC of 0.85. Conclusion: The CAHP score is a simple and objective tool for early assessment of prognosis in patients admitted to ICU after OHCA. Moreover it allows to stratify the probability of poor neurological outcome by identifying a very high-risk category of patients (score ≥ 200).


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