This papercut comes from an editorial in Resuscitation, where they chose four important multi centre RCTs with large sample sizes, published in 2023.... and not necessarily in their journal.
They were:
- The INCEPTION Trial(1): Early initiation of Extracorporeal Life Support in refractory OHCA
- The TAME Trial(2): Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest.
- The ARREST Trial: A Randomised tRial of Expedited transfer to a cardiac arrest centre for non-ST elevation OHCA
- The STEROHCA Trial: STEroid for Out-of-Hospital Cardiac Arrest.
Here is a summary of these four trials.
INCEPTION Trial
Extracorporeal cardiopulmonary resuscitation (ERCP), is sometimes considered to be the new paradigm, that we were looking for in resuscitation. Previous single centre RCT's have found benefit of ECPR.
This was a multicentre, pragmatic (clinical practice was not standardised across hospitals), RCT in the Netherlands that compared extracorporeal cardiopulmonary resuscitation (ERCP) to conventional CPR in adult patients with an initial shockable rhythm and refractory OHCA.
N= 134
In this trial there was a similar rate of survival with favourable neurological outcome at 30 days for ECPR and CPR (20% vs 16% p=0.52). What was different in this trial and what obviously matters in ECPR, is the time to commencement of flow, which was longer in this trial than in previous research, and obviously crucial in its effectiveness. The crucial times are cannulation after arrival to hospital and then time from cannulation to initiation of flow, which were 16 and 20 minutes.
TAME Trial
This was a post arrest trial in comatose patients in ICU which asked the question: Does hypercapnia (PaCO2 50-55 mm Hg) improve outcomes when compared to normocapnia(PaCO2 35-45 mm Hg).
PaCO2 is a regulator of cerebrovascular tone. In previous observational studies (5,6),mild hypercapnia increased cerebral oxygen saturation and was associated with better outcomes. It can however also worsen cerebral oedema and increase intracranial pressure.
This was a multi-centre, RCT in 63 ICU's in 17 countries.
N= 1700
With mild hypercapnia for 24 hours, at 6 months, there was no statistically significant improvement in survival with favourable neurological outcome, or in mortality, in the hypercapnia group.
The ARREST Trial
This trial asked the question: Does transporting patients with ROSC after OHCA and with no ST elevation, to a specialised cardiac centre, improve outcomes when compared to transporting them to the nearest emergency department?
N=862
61% of patients had a cardiac cause for arrest. Of these, 20% had an acute coronary syndrome.
Median time from cardiac arrest to arrival at each centre was:
- 84 minutes to a cardiac arrest hospital
- 77 minutes to the closest hospital.
At 30 days and at 3 months the all-cause mortality in both groups was the same. At 3 months survival with good neurological outcome was also similar between the two groups, although there may have been a higher rate of survival in those patients younger than 57 years going to a cardiac centre.
The STEROHCA Trial
This study looked at whether high dose methylprednisolone in adults with ROSC after OHCA could reduce inflammatory injury and potentially prevent secondary neurological injury.
This was a RCT.
N=158
Patients in the steroid group received 250mg of methylprednisolone as an IV bolus. The control group received placebo.
The inflammatory response was assessed by measuring plasma IL-6 and NSE from admission to 72 hours. The study was not powered to detect mortality difference.
Both groups had similar baseline values of IL-6, however at 24 and 48 hours, there was a significant reduction IL-6 in the intervention group. Values between the two groups was similar at 72 hours. There appeared to be no effect on the brain injury biomarker NSE.
There was a decreased mortality found in the steroid group at 6 months, although the study was not powered to detect a mortality difference.
High dose methyprednislolone was seen to be safe.
References
- Suverein MM, et al. Early extracorporeal CPR for refractory out-of-hospital cardiac arrest. N Engl J Med 2023;388:299–309.
- Eastwood G, et al. Mild hypercapnia or normocapnia after out-of-hospital cardiac arrest. N Engl J Med 2023;389:45–57.
- Patterson T, et al. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial. Lancet 2023;402:1329–37.
- Obling LER, et al. Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial. Intensive Care Med 2023. https://doi.org/10.1007/s00134-023-07247-w.
- Schneider AG, et al. Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest. Resuscitation 2013;84:927–34.
- Vaahersalo J, et al. Arterial blood gas tensions after resuscitation from out-of-hospital cardiac arrest: associations with long-term neurologic outcome. Crit Care Med 2014;42:1463–70.
