New Test Identifies 'Late Awakeners' After Cardiac Arrest

March 20, 2018

Patients who are still comatose more than 7 days after a cardiac arrest represent a major ethical dilemma for neurologists and intensive care staff regarding whether or not to withdraw care. 

But now a new study suggests that diffusion tensor MRI can be used to predict outcome with a high degree of accuracy in such patients, which should save many lives as well as reduce suffering and costs, researchers say.

The study, published online in the Lancet Neurology on February 27, was conducted by an international group led by Lionel Velly, MD, Aix Marseille Université, France.

They explain that latest guidelines recommend delaying a decision on prognosis for comatose patients after cardiac arrest for at least 72 hours after rewarming, which corresponds to days 5 to 7 after arrest in most cases. But they note that "late awakeners" have been described as long as 25 days after arrest.

In their current study of 200 patients who were still comatose at day 7, 22% had made a good recovery by 6 months, but these patients had not been identified by current recommended tests, including review of clinical symptoms, electroencephalography (EEG), and conventional MRI.

But by using quantitative measurements of whole-brain white matter anisotropy, which measures the degree of water diffusion through the brain, they were able to identify patients with a poor outcome with 100% specificity and 90% sensitivity.

Although noting that these results need confirmation from future large-scale trials, the researchers conclude, "Our results are relevant in the clinical setting because they might provide reliable outcome predictors and could possibly improve diagnosis of late awakeners in survivors after cardiac arrest who were still unresponsive to simple orders after 7 days."

Study "Will Undoubtedly Save Lives"

The author of an accompanying comment  in Lancet Neurology, Tobias Cronberg, MD, Lund University, Sweden, told Medscape Medical News that "This study is of great importance and if confirmed will undoubtedly save lives."

"It is a common and very challenging problem for neurologists to try to decide the prognosis of a patient in a coma after a cardiac arrest," explained Cronberg, who is coauthor of the European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for postresuscitation care.

"Intensive care physicians will withdraw care leading to death of the patient on our assessment of prognosis, so this a very heavy duty for us."

He noted that current guidelines set out many different methods for making these assessments, including clinical examination, EEG analysis, and radiologic tests, but most of these are focused on the first few days.

"But while we can give a good or bad prognosis to many patients in the first few days, there are a large subset — maybe up to about one third of patients — who we are still uncertain about, and what to do with these patients is a big problem," he said. "We know very little about how to assess the situation at a week or later. So this study — which involved patients about whom the prognosis is still uncertain after a week — gives very valuable information."

He explained that the current study measured anisotropy in the white matter, which reflects the degree of edema.   

"While we already knew higher levels of edema were bad news, this had not been quantified and validated before.  Higher anisotropy is a temporal development, with the gray matter being affected first and the white matter affected later.  It seems these researchers have identified the correct time window to perform this particular examination."

On the results showing 100% specificity for a poor outcome, he commented: "So with this test we can be certain that these patients are not going to recover. That is of great importance as then care can be withdrawn with confidence. This minimizes the distress for everyone involved."

"The sensitivity was also high — at almost 90% — which means we can make a decision one way or another in the vast majority of cases."   

These results need confirmation, he added, "but if this happens, this test will make a big difference to how we care for these patients who we are still uncertain about at 1 week or more. While most of these patients will have a bad outcome, there are some who will make a recovery and is of great importance that we can identify them accurately."

At present, such decisions are made on a subjective basis, he said, and a recent US study in which researchers propensity-matched patients for whom care was withdrawn or continued has suggested that many patients for whom care was withdrawn may have survived if they had waited longer. "This test could avoid that situation."

Cronberg also pointed out that the use of an automated process in this study to measure anisotropy was "a novel and important factor as it means there is no subjective interpretation of the results."

He added that they were also able to show consistent results using different MRI machines at different hospitals, with each MRI machine being calibrated separately, "another valuable finding."

The study was funded by the French Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia. Some of the study authors report holding a share of a patent that partly covers the reported research.  

Lancet Neurology. Published online February 27, 2018. Abstract, Comment  

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