Target temperature management after out-of-hospital cardiac arrest—a randomized, parallel-group, assessor-blinded clinical trial—rationale and design

Nielsen, Niklas; Wetterslev, Jørn; Al-Subaie, Nawaf; Andersson, Bertil; Bro-Jeppesen, John; Bishop, Gillian; Brunetti, Iole; Cranshaw, Julius; Cronberg, Tobias; Edqvist, Kristin; Erlinge, David; Gasche, Yvan; Glover, Guy; Hassager, Christian; Horn, Janneke; Hovdenes, Jan; Johnsson, Jesper; Kjærgaard, Jesper; Kuiper, Michael; Langørgen, Jørund; Macken, Lewis; Martinell, Louise; Martner, Patrik; Pellis, Thomas; Pelosi, Paolo; Petersen, P.; Persson, Stefan; Rundgren, Malin; Saxena, Manoj; Svensson, Robert; Stammet, Pascal; Thorén, Anders; Undén, Johan; Walden, Andrew; Wallskog, Jesper; Wanscher, Michael; Wise, Matthew Peter; Wyon, Nicholas; Åneman, Anders; Friberg, Hans

doi:10.1016/j.ahj.2012.01.013

Cited by 142 publications

(124 citation statements)

References 26 publications

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“…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%

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 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%

Serum tau and neurological outcome in cardiac arrest

Mattsson

Zetterberg

Nielsen

et al. 2017

Annals of Neurology

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“…There has been considerable quantity of new re search published in the field of postresus citation care and prognostication. The re sults of the Targeted Temperature Manage ment (TTM) trial [29], which has finished recruitment of 950 patients, will be present ed later this year and will undoubtedly add to the debate about the precise role of tem perature control after cardiac arrest. The current hot topic in resuscitation is prog nostication.…”

Section: The International Liaison Committee On Resuscitation (Ilcor)mentioning

confidence: 99%

The International Liaison Committee on Resuscitation (ILCOR) process for developing guidelines

Nolan

2013

Notfall Rettungsmed

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“…3 Both the 2009 and 2012 Cochrane Reviews concluded: "With conventional cooling methods... patients were 55% more likely to leave the hospital without major brain damage." 4 However, a meta-analysis by Nielson et al 5 (2012) described the overall quality of evidence as low and suggested that a large-scale clinical trial should be conducted. Nielson et al 5 hypothesized that the benefits demonstrated by TTM may come from the prevention of fever rather than from the induction of hypothermia.…”

mentioning

confidence: 99%

“…4 However, a meta-analysis by Nielson et al 5 (2012) described the overall quality of evidence as low and suggested that a large-scale clinical trial should be conducted. Nielson et al 5 hypothesized that the benefits demonstrated by TTM may come from the prevention of fever rather than from the induction of hypothermia. 5 The reviewed study was designed to evaluate whether the degree of temperature reduction affects outcomes.…”

mentioning

confidence: 99%