Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

Nielsen, Niklas; Wetterslev, Jørn; Cronberg, Tobias; Erlinge, David; Gasche, Yvan; Hassager, Christian; Horn, Janneke; Hovdenes, Jan; Kjærgaard, Jesper; Kuiper, Michael; Pellis, Tommaso; Stammet, Pascal; Wanscher, Michael; Wise, Matthew Peter; Åneman, Anders; Al-Subaie, Nawaf; Boesgaard, Søren; Bro-Jeppesen, John; Brunetti, Iole; Bugge, J. F.; Hingston, Christopher D.; Juffermans, Nicole P.; Koopmans, Matty; Køber, Lars; Langørgen, Jørund; Lilja, Gisela; Møller, Jacob Eifer; Rundgren, Malin; Rylander, Christian; Šmíd, Ondřej; Werer, Christophe; Winkel, Per; Friberg, Hans; Act, Abstr

doi:10.1056/nejmoa1310519

Cited by 2,465 publications

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“…Because neurological outcome did not differ by intervention arm,2 and the overall aim was to test associations between tau and outcome, the analyses were done on the pooled sample. However, we adjusted the results for intervention arm, as described below.…”

Section: Resultsmentioning

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.…”

Section: Methodsmentioning

confidence: 99%

“…The length of ICU stay is increasing, but rates of mortality and neurological morbidity due to anoxic brain injury remain very high 2. There is a need for early and accurate prognostication methods, both to avoid prolonged treatment of patients where continued life‐supporting measures is futile, and to ensure that patients with potential for recovery receive optimal management 3.…”

mentioning

confidence: 99%

“…We used a novel version of the single‐molecule detection assay to quantify serum tau in a nested cohort within the Target Temperature Management (TTM) trial, which is a large prospective cardiac arrest study 2. We aimed to evaluate tau as a predictor of neurological outcome and death.…”

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confidence: 99%

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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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Section: Resultsmentioning

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.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Serum tau and neurological outcome in cardiac arrest

Mattsson

Zetterberg

Nielsen

et al. 2017

Annals of Neurology

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“…There are promising clinical treatments, such as therapeutic hypothermia, ischemic postconditioning, and controlled reperfusion, which improve survival in preclinical studies and are hypothesized to address postresuscitation metabolic disorders 10, 11, 12, 13. However, there are a number of randomized controlled clinical trials that show no benefit,14, 15, 16, 17, 18 in part as a result of the lack of an ability to differentiate patients with treatable metabolic injury, patients who might live with proper treatment, from patients who do not have a metabolic injury, patients who will live, or from patients with untreatable metabolic injury, patients who will not live 4, 19, 20, 21…”

Section: Introductionmentioning

confidence: 99%

Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post–Cardiac Arrest Rat: A Novel Metabolic Phenotype

Shinozaki

Becker

Saeki³

et al. 2018

JAHA

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BackgroundThe concept that resuscitation from cardiac arrest (CA) results in a metabolic injury is broadly accepted, yet patients never receive this diagnosis. We sought to find evidence of metabolic injuries after CA by measuring O2 consumption and CO2 production (VCO 2) in a rodent model. In addition, we tested the effect of inspired 100% O2 on the metabolism.Methods and ResultsRats were anesthetized and randomized into 3 groups: resuscitation from 10‐minute asphyxia with inhaled 100% O2 (CA–fraction of inspired O2 [FIO2] 1.0), with 30% O2 (CA‐FIO 2 0.3), and sham with 30% O2 (sham‐FIO 2 0.3). Animals were resuscitated with manual cardiopulmonary resuscitation. The volume of extracted O2 (VO 2) and VCO 2 were measured for a 2‐hour period after resuscitation. The respiratory quotient (RQ) was RQ=VCO 2/VO 2. VCO 2 was elevated in CA‐FIO 2 1.0 and CA‐FIO 2 0.3 when compared with sham‐FIO 2 0.3 in minutes 5 to 40 after resuscitation (CA‐FIO 2 1.0: 16.7±2.2, P<0.01; CA‐FIO 2 0.3: 17.4±1.4, P<0.01; versus sham‐FIO 2 0.3: 13.6±1.1 mL/kg per minute), and then returned to normal. VO 2 in CA‐FIO 2 1.0 and CA‐FIO 2 0.3 increased gradually and was significantly higher than sham‐FIO 2 0.3 2 hours after resuscitation (CA‐FIO 2 1.0: 28.7±6.7, P<0.01; CA‐FIO 2 0.3: 24.4±2.3, P<0.01; versus sham‐FIO 2 0.3: 15.8±2.4 mL/kg per minute). The RQ of CA animals persistently decreased (CA‐FIO 2 1.0: 0.54±0.12 versus CA‐FIO 2 0.3: 0.68±0.05 versus sham‐FIO 2 0.3: 0.93±0.11, P<0.01 overall).Conclusions CA altered cellular metabolism resulting in increased VO 2 with normal VCO 2. Normal VCO 2 suggests that the postresuscitation Krebs cycle is operating at a presumably healthy rate. Increased VO 2 in the face of normal VCO 2 suggests a significant alteration in O2 utilization in postresuscitation. Several RQ values fell well outside the normally cited range of 0.7 to 1.0. Higher FIO 2 may increase VO 2, leading to even lower RQ values.

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Fever in Critical Neurologic Illness

Vespa

2014

JAMA

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Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

Abstract: T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 369;23 nejm.org december 5, 2013

Cited by 2,465 publications

References 35 publications

Serum tau and neurological outcome in cardiac arrest

Serum tau and neurological outcome in cardiac arrest

Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post–Cardiac Arrest Rat: A Novel Metabolic Phenotype

Fever in Critical Neurologic Illness

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