What is the efficacy of targeted temperature management (TTM)?

Updated: Jul 26, 2019
  • Author: Alex Koyfman, MD; Chief Editor: Karlheinz Peter, MD, PhD  more...
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A 2011 meta-analysis of randomized controlled trials found that TTM with conventional cooling methods improves both survival and neurologic outcomes at hospital discharge for patients who experienced cardiac arrest. [14]

In a retrospective cohort study covering 7 years that assessed the impact of TTM on early repolarization (ER) in survivors of cardiac arrest attributed to idiopathic ventricular fibrillation (ID-VF) compared with a control group who experienced coronary artery disease-related VF (CAD-VF), Williams et al found that hypothermia increased the prevalence and mean amplitude of ER in cardiac arrest survivors. [15] ER occurred in all survivors of ID-VF (100%) compared with over two third of survivors of CAD-VF (67%); TTM increased ER amplitude only in CAD-VF survivors. [15]

Two early studies demonstrated improved survival and neurological outcomes with induction of mild therapeutic hypothermia for comatose survivors of out-of-hospital cardiac arrest. The Hypothermia after Cardiac Arrest Study Group showed that, when applied to unconscious out-of-hospital cardiac arrest patients with ROSC (n=274), mild hypothermia (cooling to 32ºC-34ºC) provided significant improvement in functional recovery at hospital discharge (55% vs 39%; number needed to treat [NNT] = 6) and lower 6-month mortality rate when compared with patients who were not cooled (41% vs 55%) (NNT = 7). [16]

The NNT is very low and comparable to other important emergent treatments such as cardiac catheterization for acute coronary syndrome. [17] Bernard examined endpoint of survival to hospital discharge to home or a rehabilitation facility (good outcome) in 77 patients and demonstrated 49% in the hypothermia group compared with 26% in the normothermic group, finding an NNT of 4.5 for death and severe disability. [18]

After studying 133 comatose patients who experienced after out-of-hospital cardiac arrest and were treated with TTM, Kragholm et al found that one year later, most patients who were able to work prior to cardiac arrest were able to return to work. [19]

In a prospective, observational study that investigated the rate of good neurologic outcome based on the duration of resuscitation efforts in 86 out-of-hospital cardiac arrest (OHCA) patients treated with TTM, Kim et al reported a median downtime of 18.5 minutes, with 33 patients (38.0%) having a good neurologic outcome. [20] Good neurologic outcomes were greatest when downtime was shortest: 62.5% at 10 minutes or less, 37% at 11-20 minutes, 25% at 21-30 minutes, and 21.7% at longer than 30 minutes. Interestingly, nearly one quarter of patients (22.9%) had a good neurologic outcome even with downtown longer than 20 minutes, a percentage that increased to 37.5% in patients with an initial shockable rhythm. [20]

A 2013 randomized control trial suggested no change in neurologic outcome and survival at 6 months in OHCA for 33ºC and 36ºC, followed by avoidance of fever for 72 hours. [21] Both groups in the study received some form of temperature management. The investigators found no difference in mortality and no difference in neurologic outcome between the groups. However, unlike the Bernard study, this trial included arrest other than VF/pVT OHCA. [21] Currently, advanced cardiac life support (ACLS) guidelines state that a temperature between 33ºC and 36ºC is recommended for at least 24 hours after achieving the target temperature. [2]

In a more recent systematic review and meta-analysis (2000-2016) that evaluated the effects of TTM on mortality and neurologic outcome, investigators found low-quality evidence supporting in-hospital initiation and maintenance of TTM at 32ºC-36ºC among adult OHCA survivors with an initial shockable rhythm for 18-24 hours. [22]  There was no benefit of TTM for survivors of in-hospital cardiact arrest nor for those of OHCA with a nonshockable rhythm. In addition, there was no difference between endovascular and surface cooling TTM systems, and no benefit of adding feedback control to TTM systems. Moderate quality evidence also revealed no benefit for initiating prehospital TTM. [22]

In a multicenter retrospective study (2008-2013) that evaluated 1-year functional outcome (32ºC-34ºC) in 101 patients following intraoperative cardiac arrest (IOCA), Constant et al noted that less than one third (29.7%) received TTM. [23] Patients treated with TTM had an increased risk of infection but not with hemorrhage, arrhythmia, or metabolic/electrolyte disorders; TTM was not an independent prognosticator of 1-year favorable functional outcome after IOCA. [23]

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