The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest

Dragancea, Irina; Rundgren, Malin; Englund, Elisabet; Friberg, Hans; Cronberg, Tobias

doi:10.1016/j.resuscitation.2012.09.015

Cited by 286 publications

(228 citation statements)

References 32 publications

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“…Gaining an understanding of how, when, and why patients die after initial resuscitation regardless of the use of TH is critical to enable the design and execution of therapeutic trials and also for delivery of care systems in patients with the recently recognized "post-cardiac arrest syndrome" (2). The results of our observational study differ significantly from the existing literature (42,43) in that our use of a stringent definition for brain injury leading to death (declaration of brain death) eliminated potential confounders, biases, and ambiguity. This is crucial, as without a clear understanding of the mechanisms and circumstances leading to death and poor outcomes, we cannot conceive new therapeutic interventions and processes to intervene in appropriate steps of the pathophysiologic process.…”

Section: Discussioncontrasting

confidence: 95%

“…The high rate and early timing of WLST in the TH group render comparisons between the two groups very difficult; however, the aim of the present study is not to compare these groups but rather to highlight the inadequacies of prognostication at 72 hours after TH. This study is also one of the few to describe the time to awakening of patients treated with and without TH, as well as the proportion of patients who progress to brain death, and one of the first to describe time to withdrawal of care (28,31,32,40,42,43).This study and the majority of clinical trials and studies on the subject have been unable to accurately account for the multiple effects of TH in postcardiac arrest-be it the mechanisms of neuroprotection or the delay in awakening. It is important for the resuscitation community to consider that without a solid physiopathologic understanding of the effects of the intervention on our patients, many of these questions are unlikely to be answered satisfactorily.…”

mentioning

confidence: 99%

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Awakening and Withdrawal of Life-Sustaining Treatment in Cardiac Arrest Survivors Treated With Therapeutic Hypothermia

Mulder

Gibbs

Smith

et al. 2015

Survey of Anesthesiology

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Objectives-To characterize the prevalence of withdrawal of life-sustaining treatment, as well as the time to awakening, short-term neurologic outcomes, and cause of death in comatose survivors of out-of-hospital resuscitated cardiopulmonary arrests treated with therapeutic hypothermia.Design-Single center, prospective observational cohort study of consecutive patients with outof-hospital cardiopulmonary arrests. Setting-Academic HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptPatients-Adults with witnessed, nontraumatic, out-of-hospital cardiopulmonary arrests regardless of initial electrocardiographic rhythm with return of spontaneous circulation who were admitted to an ICU. Interventions-None.Measurements and Main Results-The study cohort included 154 comatose survivors of witnessed out-of-hospital cardiopulmonary arrests who were admitted to an ICU during the 54-month study period. One hundred eighteen patients (77%) were treated with therapeutic hypothermia. The mean age was 59 years, 104 (68%) were men, and 83 (54%) had an initial rhythm of ventricular tachycardia or fibrillation. Only eight of all 78 patients (10%) who died qualified as brain dead; and 81% of all patients (63 of 78) who died did so after withdrawal of lifesustaining treatment. Twenty of 56 comatose survivors (32%) treated with hypothermia who awoke (as defined by Glasgow Motor Score of 6) and had good neurologic outcomes (defined as Cerebral Performance Category 1-2) did so after 72 hours.Conclusions-Our study supports delaying prognostication and withdrawal of life-sustaining treatment to beyond 72 hours in cases treated with therapeutic hypothermia. Larger multicenter prospective studies are needed to better define the most appropriate time frame for prognostication in comatose cardiac arrest survivors treated with therapeutic hypothermia. These data are also consistent with the notion that a majority of out-of-hospital cardiopulmonary arrest survivors die after a decision to withdrawal of life-sustaining treatment and that very few of these survivors progress to brain death. Keywordsbrain death; cardiac arrest; outcome; prognostication; therapeutic hypothermia; withdrawal of lifesustaining treatmentOut-of-hospital cardiopulmonary arrests (OHCA) pose a significant public health burden, with an estimated annual prevalence of over 380,000 arrests evaluated by emergency medical services in the United States alone (1-4). In the decade following the 2002 landmark trials of therapeutic hypothermia (TH) to improve outcomes in comatose cardiac arrest survivors, little additional progress has been made in finding and implementing successful new neuroprotective interventions (5, 6). Therefore, TH remains the only proven neuroprotective strategy available and the focus of the resuscitation community. A number of factors explain this lack of progress: a lack of understanding of the mechanisms and circumstances leading to poor outcomes, lead time and selection biases, as well as funding and ethical co...

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Section: Discussioncontrasting

confidence: 95%

mentioning

confidence: 99%

Awakening and Withdrawal of Life-Sustaining Treatment in Cardiac Arrest Survivors Treated With Therapeutic Hypothermia

Mulder

Gibbs

Smith

et al. 2015

Survey of Anesthesiology

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“…Haemodynamic failure was considered to be the cause of death in a majority of patients (55 %) with neurological cause as the runner-up (43 %). These results differ from other published studies [7,8] including those from the TTM trial, where a majority of deaths were considered to be of a neurological cause [6]. …”

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confidence: 99%

Therapeutic hypothermia and coronary angiography are mandatory after out-of-hospital cardiac arrest: No

Friberg

Nielsen

2014

Intensive Care Med

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Sudden out-of-hospital cardiac arrest is a major health problem throughout the world and in spite of increased awareness in society and improved pre-hospital and hospital care, overall survival remains around 10 % [1,2]. An impressive effort to create a prospective populationbased registry covering all out-of-hospital cardiac arrest patients in greater Paris was made and the results from the first 2 years are published in this issue of the journal [3]. The high quality registry study excluded cardiac arrest of obvious non-cardiac aetiology resulting in 3,816 patients in whom a resuscitation attempt was made, which translates into a yearly incidence of 0.6 % per inhabitant, similar to what has previously been reported [4]. Admission rate to hospital was impressively high, 35 %, while 8 % were discharged alive. The size and quality of this registry make it unique, including the systematic collection of pre-hospital and in-hospital background and treatment data. A retrospective control was performed in a sample of intensive care units (ICUs) indicating that an outstanding 99 % of all cardiac arrest patients admitted alive were identified during the study period [3], which is notably higher than in previous reports [5]. It is encouraging that the pre-hospital factors strongly associated with survival to discharge remain the same as earlier identified-initial shockable rhythm, younger age, bystander CPR and cardiac arrest in a public place-suggesting ways to improve pre-hospital performance by educating more lay people, deployment of defibrillators and by engaging fire-fighters, police, taxi drivers etc.The recently published target temperature management after cardiac arrest trial (TTM trial) included basically the same patient group as captured in the present French study [6]. The TTM trial randomly assigned 950 out-ofhospital cardiac arrest patients of cardiac aetiology to a target temperature of either 33 or 36°C with no difference in survival (Fig. 1) or neurological outcome between groups. Compared to the present registry study, patients in the TTM trial had an early angiography performed approximately as often (63 % versus 58 %) while the use of temperature control differed (100 % versus 58 %). In the present study, 22 % of patients admitted alive to hospital were eventually discharged alive; almost all (96 %) with a good neurological outcome. Haemodynamic failure was considered to be the cause of death in a majority of patients (55 %) with neurological cause as the runner-up (43 %). These results differ from other published studies [7,8] including those from the TTM trial, where a majority of deaths were considered to be of a neurological cause [6].

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“…This suggests that even in people with good prognosis after cardiac arrest there may be an initial transient release of tau, which does not reflect irreversible neurological injury or poor outcome. An alternative explanation is that people who die very soon after cardiac arrest (during the first 2–3 days) are more likely to die from cardiac causes or multiorgan failure (which may not correlate directly with high tau), whereas people who die later are more likely to die from causes related to their brain injury 20, 27. There may also be a pathophysiological delay until a significant amount of tau has been released from injured neurons and axons, which make the later samples more reliable to measure brain injury.…”

Section: Discussionmentioning

confidence: 99%

“…The design19 and main results2 of the TTM trial have been published. Neurological prognostication and criteria for withdrawal of life‐sustaining therapy were parts of the protocol 20. Twenty‐nine European centers participated in the biobank part of the TTM trial, and 819 patients were consecutively recruited at these sites between November 2010 and January 2013.…”

Section: Methodsmentioning

confidence: 99%

Serum tau and neurological outcome in cardiac arrest

Mattsson

Zetterberg

Nielsen

et al. 2017

Annals of Neurology

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ObjectiveTo test serum tau as a predictor of neurological outcome after cardiac arrest.MethodsWe measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3–5 at 6 months.ResultsIncreased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7–245ng/l in poor vs median = 1.5, IQR = 0.7–2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false‐positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1–4%) with sensitivity = 66% (95% CI = 61–70%). Tau had higher accuracy than serum neuron‐specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow‐up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest.InterpretationSerum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665–675

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The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest

Cited by 286 publications

References 32 publications

Awakening and Withdrawal of Life-Sustaining Treatment in Cardiac Arrest Survivors Treated With Therapeutic Hypothermia

Awakening and Withdrawal of Life-Sustaining Treatment in Cardiac Arrest Survivors Treated With Therapeutic Hypothermia

Therapeutic hypothermia and coronary angiography are mandatory after out-of-hospital cardiac arrest: No

Serum tau and neurological outcome in cardiac arrest

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