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NEWS FROM THE AAN ANNUAL MEETING: Long-Term Cognitive Outcomes Look Good After Therapeutic Hypothermia for Cardiac Arrest Study Points to Benefits of Early, Aggressive Intervention

Rukovets, Olga

doi: 10.1097/01.NT.0000432288.39622.cb
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Investigators reported that long-term cognitive outcomes were good for cardiac arrest patients who had undergone therapeutic hypothermia.

What happens to the cognitive status of patients after cardiac arrest and subsequent treatment with therapeutic hypothermia? Many of these patients maintain normal cognition and the ability to work, according to new research presented at the AAN annual meeting in San Diego and published in the May 17 online edition of Neurology.

Much of the current medical literature focuses on endpoints such as hospital discharge disposition, functional scales related to level of dependence, or recovery of consciousness, study author Samuel Arthur Moore, MD, of the Mayo Clinic in Rochester, MN, told Neurology Today. “Our goal was to evaluate the long-term cognitive outcome in out-of-hospital cardiac arrest patients who underwent therapeutic hypothermia,” he said.

“We were able to demonstrate in a large cohort that a significant proportion of patients undergoing therapeutic hypothermia for out-of-hospital cardiac arrest can have a good cognitive outcome, reflected by formal cognitive testing as well as their ability to return to work once they have recovered from their time in the hospital,” Dr. Moore said.

“While we are unable to define the specific impact of therapeutic hypothermia, this study adds further evidence to the growing body of literature in support of early intervention and resuscitation playing a key role in returning to a meaningful, functional life,” he added.

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The researchers reviewed the medical records and recorded the results of brain imaging, serum neuron-specific enolase (NSE) measurements, and electroencephalograms (EEGs) of cardiac arrest survivors who underwent therapeutic hypothermia between June 2006 and May 2011. They assessed cognitive status using the Telephone Interview for Cognitive Status (TICS-m), a phone screening measure for identifying those with and without amnestic mild cognitive impairment. [See “Values for the Telephone Interview for Cognitive Status (TICS-M)” for scoring information.] In their assessment, an education-adjusted score ≥ 32 (out of 50) was considered normal. “Detailed information was obtained from the paramedic records regarding time to return of spontaneous circulation, which was defined as per practice standards,” according to Dr. Moore.

Seventy-seven (58 percent) of the 133 patients who met these criteria were alive at a mean follow-up of 21 months (range 2-59 months). Eighteen patients were excluded because they did not respond to multiple attempts at contact; three patients were excluded because they did not speak English; and one patient was excluded from the cognitive test because of ongoing aphasia.

The investigators interviewed 56 patients (73 percent of those alive), with a median age of 67 years. They found that fifty-one patients (91 percent) were living independently and had median TICS-m scores was of 33 (range 16-41). Thirty-three (60 percent) were considered cognitively normal and 22 (40 percent) were cognitively impaired. The time-to-assessment was not significant for cognitive outcome status (p=0.557). The median duration of coma was two days, which possibly indicated that patients with severe anoxic injury were not included, according to the study.

Eighteen patients were not working at the time of their cardiac arrest (17 retired, 1 unemployed). Thirty-eight patients were working up to the time of the cardiac arrest, and 30 (79 percent) of them returned to work after treatment. The researchers also noted that cognitive outcome was not associated with age, time to return of spontaneous circulation, brain atrophy, leukoaraiosis, or NSE level.

Dr. Moore noted there were some limitations to the study. For instance, the time to telephone assessment was not uniform among the patients. “As such, it remains possible that cognitive abilities improve during the years following a cardiac arrest,” he said. Also, those several patients who did not respond to multiple attempts at telephone contact and were excluded from the analysis, he continued, may have skewed the results if “the patients who were lost to follow-up were more cognitively impaired than the ones that were interviewed.”

In addition, Dr. Moore said that because of the short duration of post-arrest coma and lack of malignant EEGs in these patients, “our results may not be generalizable to a population of patients with more severe brain anoxia. Finally, while the TICS-m score is a validated tool for screening for dementia, we recognize that this is not necessarily a substitute for formal neurocognitive assessment, which may provide evidence of more subtle cognitive problems than we were able to assess.”

Overall, he said, the study emphasizes the need for early and aggressive resuscitation efforts in those patients who experience cardiac arrest.

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Eva Katharina Ritzl, MD, assistant professor of neurology at Johns Hopkins Hospital in Baltimore, who was not involved in the study, said: “Fifty-one patients, 91 percent, were living independently [after therapeutic hypothermia] so that's fantastic. If we can show conclusively, like they did here, that there is a large number of positive outcomes associated with hypothermia, that is very important for clinical care.”

Dr. Ritzl said that typically these types of “studies look only at who dies and who lives — and then living is defined very broadly. But what the patients' relatives want to know is: Is my relative going to be the same as they were before?” To this end, their results are very encouraging, she added.

What was interesting, Dr. Ritzl noted, “is that cognitive outcome was not associated with age or time to return to spontaneous circulation — and that's hard to believe.” Dr. Ritzl told Neurology Today that she would have liked to see more specific information on the time to return to spontaneous circulation and how it was defined. “Were the patients cooled so fast that it didn't matter because they shut down metabolism in the brain very early? This is something that I would need to know more about.”

“This study is the first to observe long-term cognitive outcomes of cardiac arrest survivors in the era of hypothermia,” said Julius Gene S. Latorre, MD, MPH, assistant professor of neurology and neurosurgery, chief of the Cerebrovascular Division, director of the department of neurology and neurocritical care service program director at Upstate Medical University in Syracuse, NY.

But some questions remain unanswered, he said. “It is unclear why the authors did not see an association with age and time to return of spontaneous circulation with cognitive outcome. This may be explained by low patient number and inability to correct for additional risk factors,” Dr. Latorre pointed out. However, this may also be a “true effect of therapeutic hypothermia, and once the patient survives hospitalization, outcome is no longer dictated by the usual risk factors during hospitalization.”

We may need larger prospective studies to verify these findings, he said. While the study did not find an association between cognitive outcome and brain atrophy, he said, “it may be interesting to see if volumetric studies on change in brain volume with time using MRI and quantification of leukoaraiosis may be related to the long-term cognitive outcome using more comprehensive neuropsychological testing.”

Quality of life is a very important issue for survivors of cardiac arrest, Dr. Latorre told Neurology Today, and “this study showed important surrogate measures of quality of life (independent living, societal reintegration with return to work) that are frequently lacking in studies of functional outcome.”

TUNE IN: NEUROCRITICAL CARE: How well do patients who have received therapeutic hypothermia after cardiac arrest fare? In a video interview, Kevin N. Sheth, MD, chief of the Division of Neurocritical Care and Emergency Neurology and director of the Neurosciences Intensive Care Unit at Yale New Haven Hospital, discusses a Mayo Clinic study that found that a significant number are able to return to work and have normal cognitive status. He offers an analysis about why these findings on long-term outcomes are important for the field of neurocritical care: Dr. Sheth is a member of the Neurology Today editorial advisory board.

A ‘BEST PAPER’ PICK: Neurology Today editorial advisory board member Kevin N. Sheth, MD, selected this as one of the “best papers” on neurocritical care from the AAN annual meeting. Dr. Sheth is chief of the Division of Neurocritical Care and Emergency Neurology and director of the Neurosciences Intensive Care Unit at Yale New Haven Hospital.

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The TICS-m includes the following items: (1) name, date, age, phone number (worth 9 points); (2) counting backward (worth 2 points); (3) first, a 10-word list learning exercise and then a delayed recall of that word list (both worth 10 points each); (4) subtractions (worth 5 points); (5) responsive naming (worth 4 points); (6) repetition (worth 2 points); (7) current President and Vice President (worth 4 points); (8) finger tapping (worth 2 points), and (9) word opposites (worth 2 points). The total score is 50 points.

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•. Fugate JE, Moore SA, Rabinstein AA, et al. Cognitive outcomes of patients undergoing therapeutic hypothermia after cardiac arrest. Neurology 2013; E-pub 2013 May 17.
•. AAN annual meeting abstract (2013): Cognitive Outcomes of Patients Undergoing Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest:
•. Neurology Today's archives on therapeutic hypothermia:
© 2013 American Academy of Neurology