The effectiveness of targeted temperature management following cardiac arrest may depend on bystander cardiopulmonary resuscitation rates.

Abstract

Editor, Therapeutic hypothermia and targeted temperature management (TTM) after cardiac arrest can improve outcome, as demonstrated in multiple experimental and clinical studies.1,2 The most recent TTM trials, however, did not find such positive therapeutic effects.3,4 In these trials, the target temperature was reached after more than 7 h (time until randomisation and time to target temperature). There are no experimental data available showing any effectiveness of TTM established more than 7 h following cardiac arrest1 so, in the most recent clinical trials, TTM was applied outside any potential therapeutic window. Moreover, the median duration of cardiac arrest until the start of cardiopulmonary resuscitation (CPR) was 1 min in at least the first TTM study,4 and most probably also in the second TTM trial, but this was not reported there.3 Substantial damage to the brain happens after several minutes of no-flow, so any therapeutic intervention focusing on the brain after only 1 min of cardiac arrest may be senseless and, thus, not effective.1 Most interestingly (and this is the reason for the very short time of cardiac arrest and down time), the bystander CPR rates (∼80%) and survival (∼50%) reported in both of these recent trials3,4 are much higher than that reported from actual cardiac arrest registries.5 Very high bystander CPR rates are good for the outcome of the patients enrolled, but may not reflect reality for most cardiac arrest patients and settings around the world.5 We hypothesised that bystander CPR, which is known to increase the rate of good survival of cardiac arrest patients by two-fold to three-fold,5 may be a key factor influencing the therapeutic effects of other potential therapeutic interventions like TTM in the postresuscitation period. We therefore analysed all available data from larger clinical trials, focusing on therapeutic hypothermia and TTM,2–4 and compared bystander CPR rates and the effects of TTM. Results from the analysis of pooled data from these publications support the hypothesis that populations with lower bystander CPR rates benefit much more from TTM than those with very high bystander-CPR rates (Fig. 1). From our results we thus conclude that therapeutic hypothermia and TTM may not be effective when administered following very short periods of cardiac arrest – due to very high bystander CPR rates – consequently resulting in only mild cerebral insults. In addition, with a very late onset of reaching target temperature,3,4 the application of TTM may have been outside the window of therapeutic opportunities.1 Further studies may investigate this most important relationship.Fig. 1: Association of bystander cardiopulmonary resuscitation (CPR) rates with absolute benefit per 1000 treated patients for the intervention (targeted temperature management) for the outcome parameter ‘survival with good neurological outcome’ in recent important clinical studies evaluating the effect of targeted temperature management