ANAHEIM, CALIF. (FRONTLINE MEDICAL NEWS) – Withdrawal of life-sustaining systemic therapies in comatose patients after out-of-hospital cardiac arrest as advised in current guidelines often occurs too early, resulting in the death of many patients who could potentially survive with good outcome, according to the results of NORCAST, the Norwegian Cardiorespiratory Arrest Study.

“The take-home message is to be patient and wait. Three days may be too early to make decisions on the patient,” Kjetil Sunde, MD , said in presenting the study findings at the Resuscitation Science Symposium held during the American Heart Association scientific sessions.

Indeed, in NORCAST the mean time from cardiac arrest to awakening from coma with a Glasgow Coma Scale score of 9 or more was 6.2 days in patients who had a good outcome at 6 months as defined by a Cerebral Performance Category ( CPC ) of 1 or 2, noted Dr. Sunde of the University of Oslo.

The European Resuscitation Council and European Society of Intensive Care Medicine have jointly recommended a prognostic algorithm in which a multimodal assessment is made on patients who are still comatose on day 3 after cardiac arrest. But this advice is based on expert opinion and has never been validated. This was the impetus for the prospective NORCAST study.

Current practice in the management of out-of-hospital cardiac arrest patients who are comatose upon hospital admission is to induce therapeutic hypothermia, with targeted temperature management to 33° C for 24 hours under deep sedation. The study hypothesis was that this strategy delays the time to awakening and that, as a consequence, the recommended prognostic tests that are usually done on day 3 after withdrawal of sedation are rendered insufficiently reliable. Thus, decisions to withdraw life-supporting therapies at that point will reduce the survival potential of this population, Dr. Sunde explained.

NORCAST was a prospective observational study that included 259 patients admitted to Oslo University Hospital in a comatose state after out-of-hospital cardiac arrest. In this unselected group, 81% had a cardiac cause for their arrest; the remainder had hypoxic arrest. All patients underwent therapeutic hypothermia, then a period of nonhypothermia followed by sedation withdrawal.

All of the widely used multimodal prognostic tests were ordered, including serial measurement of serum neuron-specific enolase; neurophysiologic testing using EEG and sensory-evoked potential readings obtained both during hypothermia and again at least 3 days after sedation withdrawal; a standardized clinical neurologic exam including assessment of brainstem reflexes and a Glasgow Coma Scale rating 3 days after sedation withdrawal; and a transcranial Doppler study and cerebral MRI on day 5-7. However, the treatment team was blinded to the results of these tests and was encouraged to delay withdrawal of life-supporting therapies as long as possible.

Key findings

Out of 259 patients who were comatose upon admission, 54% were alive at 6 months – and 91% of them had a CPC of 1 or 2.

The final tally at 6 months: 44% of patients were CPC 1, 5.5% were CPC 2, 4% were CPC 3, meaning severely disabled, and 46.5% were CPC 5, which is brain dead.

Withdrawal of life-supporting therapies occurred in 73 patients, or 28%, and 71% of those patients died, few of them in the early days.

Among patients with a CPC score of 1 or 2 at 6 months, only 20% were awake on day 1-3 following admission. Fifty-seven percent awoke on day 4-7, but importantly, 23% of patients with a good outcome at 6 months were not yet awake on day 8.

Three days after withdrawal of sedation, 49% of patients were rated as having a Glasgow Coma Scale score of 3-8, while 51% were Glasgow Coma Scale 9-15. Moreover, at that time 26% of patients with a good outcome as defined by a CPC of 1 or 2 at 6 months were still in a coma.

“So a lot of patients were still affected by their disease or by sedation at that point. That’s an important finding,” Dr. Sunde said.

Some prognostic tests were highly unreliable

A standout in poor performance was the widely utilized standard of a time to return of spontaneous circulation greater than 25 minutes as a predictor of poor cerebral outcome. In fact, it had a 34% false-positive rate.

“I think it’s really useless to use that. I would rather have return to spontaneous circulation after 40 minutes of good-quality CPR than not have it with 25 minutes of lesser-quality CPR,” he commented.

Similarly, a Glasgow Coma Scale score of 9 or less or a Glasgow Coma Scale-Motor score of 1-3 upon assessment 3 days after sedation withdrawal had false-positive rates of 30% and 34%, respectively.

During hypothermia, EEG abnormalities had a high false-positive rate, and sensory-evoked potential findings were difficult to interpret.

Predictors showing utility

Several clinical factors predicted poor cerebral outcome with low false-positive rates: Unwitnessed cardiac arrest had a false-positive rate of only 4%; initial presentation in asystole or with pulseless electrical activity had a false-positive rate of 6%; and no bystander CPR had a false-positive rate of 13%.

Abnormal sensory-evoked potential or EEG findings 3 days after sedation withdrawal had low false-positive rates as prognosticators of poor cerebral outcome. An EEG showing burst suppression or epileptiform activity had a “pretty good” false-positive rate of only 7%, Dr. Sunde noted. Bilaterally absent N20 sensory-evoked potential findings, while uncommon, had a false-positive rate of zero. A serum neuron-specific enolase level greater than 80 mcg/mL had a 3% false-positive rate, in sharp contrast to the previously recommended cutoff of more than 33 mcg/mL, which had an unacceptable 38% false-positive rate.

“We should avoid using single predictors in decision making and be patient, especially if we have a witnessed ventricular fibrillation with bystander CPR, independent of time to return of spontaneous circulation,” he concluded.

Dr. Sunde and his coinvestigators plan to present numerous further follow-up studies from NORCAST, including the results of comprehensive cognitive function testing 6-9 months after cardiac arrest in all survivors, coupled with interviews with their close relatives, as well as cognitive function and quality-of-life measurements 3-6 years after cardiac arrest along with interviews with relatives.

Several audience members rose to declare that they’ve been waiting for data such as this for a long time. Session chair Karl B. Kern, MD , professor of medicine at the University of Arizona, Tucson, and codirector of the University of Arizona Sarver Heart Center, commented, “We’ve been talking about whether 3 days is too early for a number of years, and clearly from your data it is. It was twice as long before most of them woke up.”

Dr. Sunde reported having no financial conflicts of interest regarding the NORCAST study, which was sponsored by Oslo University Hospital.


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