Aspects of intensive care after cardiac arrest

Background: Cardiovascular disease, and in particular cardiac arrest with the subsequent associated brain injury, is the most common cause of death in many countries. Annually, around 6000 people suffer from Out-of-Hospital Cardiac Arrest (OHCA) in Sweden and only around 10% survive to hospital discharge. Apart from early cardiopulmonary resuscitation (CPR) and defibrillation, it has been difficult to find interventions that can increase survival in OHCA, in particular in the post-resuscitation phase.

Methods and results: Study I. A national observational retrospective study, evaluating the adherence to Targeted Temperature Management (TTM) guidelines in Sweden after the publication of the TTM trial, and if the change in targeted temperature level (from 33 oC to 36 oC) influences 6-month survival. In total, 2899 OHCA patients were included, and of those, 1038 were treated by means of TTM. The proportion of patients with initial shockable rhythm receiving any TTM, i.e., following international guidelines, decreased after publication of the TTM trial (from 70.5% to 54.5%). There was no difference in 6-month survival between the TTM33 (47.2%) and the TTM36 (47.3%) groups (adjusted odds OR 1.12, 95% CI 0.80–1.56).

Study II. A sub-analysis of the PRINCESS trial, in which 677 OHCA patients were randomized to trans-nasal intra-arrest cooling initiated by the emergency medical services (EMS) or cooling started after hospital arrival. In this sub-analysis, the association between early initiation of intra-arrest cooling and neurological outcome was evaluated. Early cooling (intervention group, n=150) was defined as cooling initiated ≤ 20 minutes from collapse, and these patients were propensity score-matched with comparable controls (n=150). The primary outcome was survival with good neurological outcome (defined as Cerebral Performance Category [CPC] 1–2) at 90 days. The proportion of cases with CPC 1–2 at 90 days was 23.3% in the intervention group vs. 16% in the control group (OR 1.92, 95% CI 0.95–3.85). In patients with shockable rhythm the corresponding figures were 50.9% (intervention) vs. 29.8% (control) (OR 3.25, 95% CI 1.06–9.97).

Study III. A nationwide observational retrospective study, evaluating the association between different levels of hyperoxemia at Intensive Care Unit (ICU) arrival after cardiac arrest, and 30-day survival. Partial oxygen pressure (PaO2) was recorded in a standardized way at ICU admission (± one hour). Hyperoxemia was defined as mild (13.4–20 kPa), moderate (20.1–30 kPa), severe (30.1–40 kPa) or extreme (>40 kPa). Normoxaemia was defined as PaO2 8–13.3 kPa and hypoxemia as PaO2 <8 kPa. In total, 9735 patients were included. Of these, 44.6% were hyperoxemic, 44.8% were normoxaemic and 10.5% were hypoxemic. Compared with the normoxemia group, the adjusted risk ratios (RRs) for 30-day survival in the hyperoxemia groups were: mild 0.91 (95% CI 0.85–0.91), moderate 0.88 (95% CI 0.82–0.95), severe 0.79 (95% CI 0.7– 0.89), and extreme 0.68 (95% CI 0.58–0.79).

Study IV. A post-hoc analysis of the TTM2 trial, in which 1900 resuscitated OHCA patients were randomized to either hypothermia (TTM of 33 oC) or normothermia (<37.8 oC) groups for 28 hours. This sub-analysis was carried out to evaluate if there is any association between the cooling method used, i.e., intravascular (IC) vs. surface cooling (SFC), in the TTM 33oC group, and neurological outcome. The primary outcome was survival with good neurological outcome (defined as modified Rankin scale [mRS] result of 0–3) at six months. In total, 876 patients were included in this study, in which 30% were treated by means of IC and 70% by SFC. At six months, after propensity score matching, 53.0% of the patients in the IC group and 42.3% of the patients in the SFC group were alive, with mRS scores of 0–3 (OR 1.5, 95% CI 1.05–2.15). The IC group demonstrated better cooling speed and precision compared with the SFC group.

Conclusions: After publication of the TTM trial, fewer OHCA patients in Sweden received any TTM and this change of practice did not affect six-month survival among patients who underwent TTM. In the PRINCESS trial, intra-arrest cooling started within 20 minutes of arrest, compared with cooling started after hospital admission, was not associated with a significantly better neurological outcome. In the subgroup with shockable rhythms, early cooling was associated with better neurological outcome. Among resuscitated OHCA patients, hyperoxaemia at ICU admission, compared with normoxemia, was associated with lower 30-day survival. The association was stronger in connection with higher PaO2 levels. In OHCA patients in the TTM2 trial treated by means of TTM 33 oC, intravascular cooling, compared with surface cooling, was associated with better cooling performance and better neurological outcomes after six months.

List of scientific papers

I. Abazi L, Awad A, Nordberg P, Jonsson M, Taccone FS, Wickerts CJ, Svensson L, Hollenberg J, Ringh M, Forsberg S. Long-term survival in out-of-hospital cardiac arrest patients treated with targeted temperature control at 33 degrees C or 36 degrees C: A national registry study. Resuscitation. 2019;143:142-7.
https://doi.org/10.1016/j.resuscitation.2019.08.029

II. Awad A, Taccone FS, Jonsson M, Forsberg S, Hollenberg J, Truhlar A, Ringh M, Abella BS, Becker LB, Vincent JL, Svensson L, Nordberg P. Time to intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest patients and its association with neurologic outcome: a propensity matched sub-analysis of the PRINCESS trial. Intensive Care Med. 2020.
https://doi.org/10.1007/s00134-020-06024-3

III. Awad A, Nordberg P, Jonsson M, Hofmann R, Ringh M, Hollenberg J, Olson Joelsson-Alm E. Hyperoxemia after reperfusion in cardiac arrest patients – A potential dose-response association with 30-day survival. Crit Care. 2023;27(1):86.
https://doi.org/10.1186/s13054-023-04379-9

IV. Awad A, Dankiewicz J, Jonsson M, Hollenberg J, Ringh M, Nielsen N, Nordberg P. Intravascular versus surface cooling in out-of-hospital cardiac arrest patients receiving hypothermia after hospital arrival - a post hoc analysis of the TTM2 trial. [Manuscript]