Carbon dioxide dynamics in relation to neurological outcome in resuscitated out-of-hospital cardiac arrest patients: an exploratory Target Temperature Management Trial substudy

Abstract

BackgroundDyscarbia is common in out-of-hospital cardiac arrest (OHCA) patients and its association to neurological outcome is undetermined.MethodsThis is an exploratory post-hoc substudy of the Target Temperature Management (TTM) trial, including resuscitated OHCA patients, investigating the association between serial measurements of arterial partial carbon dioxide pressure (PaCO2) and neurological outcome at 6 months, defined by the Cerebral Performance Category (CPC) scale, dichotomized to good outcome (CPC 1 and 2) and poor outcome (CPC 3–5). The effects of hypercapnia and hypocapnia, and the time-weighted mean PaCO2 and absolute PaCO2 difference were analyzed. Additionally, the association between mild hypercapnia (6.0–7.30 kPa) and neurological outcome, its interaction with target temperature (33 °C and 36 °C), and the association between PaCO2 and peak serum-Tau were evaluated.ResultsOf the 939 patients in the TTM trial, 869 were eligible for analysis. Ninety-six percent of patients were exposed to hypocapnia or hypercapnia. None of the analyses indicated a statistical significant association between PaCO2 and neurological outcome (P = 0.13–0.96). Mild hypercapnia was not associated with neurological outcome (P = 0.78) and there was no statistically significant interaction with target temperature (Pinteraction = 0.95). There was no association between PaCO2 and peak serum-Tau levels 48 or 72 h after return of spontaneous circulation (ROSC).ConclusionsDyscarbia is common after ROSC. No statistically significant association between PaCO2 in the post-cardiac arrest phase and neurological outcome at 6 months after cardiac arrest was detected. There was no significant interaction between mild hypercapnia and temperature in relation to neurological outcome.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2119-5) contains supplementary material, which is available to authorized users.

Physiological interventions in cardiac arrest: passing the pilot phase

“…Other reports have indicated worse outcome with increasing doses of vasopressors, hypotension, hypocapnia, severe hypercapnia and severe hyperoxia [5][6][7]. Also, completely neutral reports have been published [8]. A pilot trial of mild hypercapnia versus normocapnia (standard care) suggested better outcome and lower levels of biomarkers of brain damage with mildly elevated carbon dioxide levels [9].…”

Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan

“…Theoretically, the TTM2 trial interventions are believed to have neuroprotective effects including reductions in metabolic rate and pathologic cell signalling, while the TAME trial interventions are believed to affect cerebral blood flow. Furthermore, we have studied the interaction between PaCO2 and temperature in the TTM trial and there was no statistically significant interaction (P interaction = 0.95) [4]. If we show significant interactions, this will be handled as described under the 'Assessments of underlying statistical assumptions' section.…”

“…Another potential limitation is the planned co-enrolment with the TAME Trial; our results will be difficult to interpret if there are significant interactions between the TTM2 and TAME trial interventions. As mentioned (see the 'Co-enrolment with the TAME trial' section), we have studied the interaction between PaCO 2 and temperature in the TTM trial and found no statistically significant interaction (P interaction = 0.95) [4], and if we show significant interactions, this will be handled (see the 'Assessments of underlying statistical assumptions' section). Co-enrolment with the TAME trial also made it possible to increase the planned sample size from 1200 to 1900 participants.…”

Mild hypercapnia improves brain tissue oxygen tension but not diffusion limitation in asphyxial cardiac arrest: an experimental study in pigs

“…Previous studies found mild hypercapnia increased cerebral oxygenation assessed by near infrared spectroscopy (NIRS) and attenuated the release of serum neuron specific enolase (NSE) [9,11,13]. However, the results were inconsistent and the potential mechanisms are unclear [10,14,15]. In addition, NIRS may not accurately reflect the cerebral oxygenation [16].…”