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Invasive resuscitation therapy and moderate cooling after resuscitation both missed the mark in clinical trials, highlighting opportunities for improvement in prehospital and hospital care for out-of-hospital cardiac arrest (OHCA).

A "hyperinvasive" approach to refractory OHCA -- featuring early transport to hospital under mechanical CPR, extracorporeal CPR (venoarterial extracorporeal membrane oxygenation [VA ECMO]), and immediate invasive evaluation -- was not significantly better than standard advanced cardiovascular life support, according to the Prague OHCA study, which had nevertheless been stopped prematurely due to benefit shown in secondary outcomes.

In CAPITAL CHILL, the colder of two target temperatures in therapeutic hypothermia did not improve outcomes for comatose survivors of OHCA, and in fact were associated with harm.

Both trials were presented as late-breakers at the American College of Cardiology (ACC) virtual meeting.

Prague OHCA Study

The hyperinvasive approach had favorable results when tested in patients with refractory OHCA of presumed cardiac cause, but ultimately failed to meet the primary endpoint in a Czech study.

Odds of survival with good brain function (Cerebral Performance Category 1 or 2) at 180 days numerically favored OHCA patients randomized on scene during ongoing chest compressions to the hyperinvasive strategy (31.5% vs 22.0%).

The benefit over controls did not reach statistical significance, however (P=0.09), reported Jan Belohlavek, MD, PhD, of Charles University and General University Hospital in Prague.

Secondary outcomes of neurological recovery at 30 days (30.6% vs 18.2%, P=0.02) and survival at 180 days (approximately 33% vs 25%, log-rank P=0.014) did give the hyperinvasive strategy an advantage.

Rates of cardiac recovery at 30 days again favored the hyperinvasive strategy without reaching statistical significance (43.5% vs 34.1%, P=0.12).

Belohlavek concluded that the hyperinvasive approach is a "feasible and effective" therapy in refractory OHCA.

However, the prerequisites include good prehospital care, widespread bystander CPR, dispatch center-directed CPR, and close cooperation with an experienced hospital -- protocol training alone for the hyperinvasive approach greatly improved outcomes, according to Belohlavek.

"For 2 years, we have been training before we started the randomized trial," he said, suggesting that may be one reason his group couldn't show a significant benefit in the primary endpoint: survivors in both arms of the study were double what investigators initially expected.

"There's clearly a very important trend" favoring the "hyperinvasive" package of resuscitation therapies tested in this study, commented ACC session discussant Julia Indik, MD, PhD, of the University of Arizona in Tucson.

From a pool of 4,345 OHCA patients screened for trial eligibility, 264 met full inclusion criteria -- e.g., witnessed collapse, no return of spontaneous circulation (ROSC) at scene -- and were randomized on scene during ongoing chest compressions. Ultimately, 256 individuals (median age around 57 years, 83% of whom were men) received the assigned treatment and were included in the main analysis.

OHCA had occurred in a public place in nearly 40% of cases. Initial rhythm was ventricular fibrillation in about 60% of cases; the rest split between asystole and pulseless electrical activity.

Bystander CPR was performed in about 99% of the people -- a "phenomenal" rate that was highlighted by Indik. Average bystander CPR in cardiac arrest is well over 80% in Prague, Belohlavek noted.

Time from collapse to EMS arrival took about 9 minutes, and time to randomization, 25 minutes.

Compared with controls, the hyperinvasive group had significantly more patients admitted to hospital (99.2% vs 65.9%). Patients were also transported faster (26 vs 33 min) and underwent CPR for longer (58 vs 46 min).

The hyperinvasive strategy was associated with more bleeding (31.0% vs 14.5%) and shock gut (42.3% vs 20.3%).

Belohlavek reported only three minor technical complications from the hyperinvasive protocol.

CAPITAL CHILL

In a separate study, moderate hypothermia using an endovascular cooling device did not improve clinical outcomes of comatose survivors of OHCA.

The first randomized trial to evaluate cooling at 31°C (87.8°F) for this population showed no difference in all-cause mortality or pool neurological outcome (Disability Ratings Scale >5) at 180 days (48.4% vs 45.4% with cooling at 34°C [93.2°F], RR 1.07, 95% CI 0.86-1.33), according to Michel Le May, MD, of the University of Ottawa Heart Institute in Ontario.

Bringing the target temperature down to 31°C was associated with numerical increases in both individual endpoints of mortality (43.5% vs 41.0%, RR 1.06, 95% CI 0.83-1.35) and poor neurologic outcome (4.9% vs 4.4%, RR 1.12, 95% CI 0.44-2.84).

There also were numerically more cases of pneumonia, seizures, and strokes with this strategy, along with significantly longer cardiac intensive care unit stays.

During the ACC session, Jeanne Poole, MD, of the University of Washington Medical Center in Seattle, noted that patients cooled longer tend to be ventilated longer, which may have contributed to poorer outcomes with the 31°C group.

"Your study may have taken off the table very low temperatures," she concluded, adding, though, that it has "been over 20 years since the landmark studies of therapeutic hypothermia, and lots of questions remain to be answered."

For one, there is the question of whether target temperature in hypothermia should be tailored to ischemic time or other factors, Poole suggested.

"We may not be able to simply see that it's one particular temperature for an entire population. We may have to consider many factors," agreed Le May. "We need to move on in future trials to understand how the brain is deprived [in OHCA] ... in trying to individualize [temperature] on a personal basis."

The single-center CAPITAL CHILL trial randomized 389 people with OHCA of presumed cardiac cause who were resuscitated but unconscious. In the end, 367 patients (mean age 62, over 80% of whom were men) were included in the modified intention-to-treat analysis.

Bystander CPR had been performed in two-thirds of these OHCA survivors. Time from cardiac arrest to ROSC was a median 23 vs 20 minutes between the moderate- and mild-cooling groups.

Nearly all patients received coronary angiography, and nearly 60% underwent percutaneous coronary intervention. The lower-temperature group had a median 73 minutes from arrival at cardiac center to balloon inflation (vs 60 minutes in the milder-cooling group).

Both study groups underwent 24 hours of target temperature cooling, 24 hours of rewarming (a shorter 12 hours for the 34°C group), and another 24 hours of normothermia.

The upcoming trial is expected to fill in some blanks on questions left unanswered by CAPITAL CHILL.

"There's clearly a very important trend" favoring the "hyperinvasive" package of resuscitation therapies tested in this study, Indik said.

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