Loss of Consciousness at SAH Onset Important Risk Marker

Pauline Anderson

November 11, 2015

Loss of consciousness (LOC) at the onset of a subarachnoid hemorrhage (SAH) might signal severe bleeding and increased risk for death or severe disability, a new study suggests.

LOC in this setting has been "underappreciated and under-recognized as an important early feature" of brain injury, said study author Stephan A. Mayer, MD, professor, neurology and neurosurgery, Icahn School of Medicine at Mt Sinai, and director, neuro critical care, Mt Sinai Health System, New York.

"In a way, this study directs and focuses attention to this important phenomenon, and I think it's going to be helpful" especially for frontline emergency department staff, he told Medscape Medical News.

Dr Stephan A. Mayer

"If you're in emergency medicine and you're seeing someone with a bad headache, the worst headache of their life, it's a matter of asking one simple question: Did you pass out? If they did, it's almost certainly going to be a SAH."

The study was published online November 9 in JAMA Neurology.

Researchers retrospectively analyzed 1460 patients with SAH from the Columbia University SAH Outcomes Project (SHOP) who had lost consciousness and were assessed from mid-1996 to mid-2012. The mean age of this study group was 55 years; 33.3% of patients were men and 45.8% were white.

Of these, 40.4% lost consciousness at the onset of SAH. Loss of consciousness was defined as any sudden, abnormal alteration of alertness, awareness, or responsiveness to sensory stimuli at symptom onset during the prehospital phase of illness regardless of duration.

However, starting in 2002, in addition to recording the presence or absence of LOC, researchers evaluated the duration of LOC. Of the 443 patients whose duration of LOC was recorded, 38.1% lost consciousness for less than 10 minutes, 21.0% for 10 to 60 minutes, and 40.9% for longer than 60 minutes.

Longer Duration of LOC

Longer duration of LOC was associated with worse Hunt and Hess scale scores on admission. If LOC lasted less than 10 minutes, the risk of presenting with a Hunt and Hess score of 4 or 5 (stuporous or comatose) was only 16.0% and 6.5%, respectively, but if LOC lasted more than 60 minutes, the risk was 21.5% and 67.4%, respectively.

Loss of consciousness in general was associated with poor clinical grade assessed with the Hunt and Hess scale and the Glasgow Coma Scale, and with higher median Acute Physiology and Chronic Health Evaluation II (APACHE II) physiologic subscores. Headache and vomiting at onset occurred less frequently in patients with LOC, which probably reflects their inability to self-report an accurate history when initial symptoms weren't witnessed, said the authors.

Compared with patients who didn't lose consciousness, those who did had more cisternal and intraventricular blood on computed tomography (CT) , global cerebral edema, parenchymal hematoma hydrocephalus, and acute infarction. They were also more likely to have prehospital tonic-clonic activity (22.7% vs 4.2%; P < .001) and cardiopulmonary arrest (9.7% vs 0.5%; P < .001).

After adjustment for age, admission, Hunt and Hess grade, Acute Physiology and Chronic Health Evaluation (APACHE II) physiologic subscore and aneurysm size, LOC was associated with global cerebral edema, but not with delayed cerebral ischemia (DCI) or rebleeding. A possible explanation for not finding an association with DCI is that the study had reduced sensitivity due to lower event rates, said the authors.

Investigators assessed patients using the modified Rankin Scale (mRS). They imputed 12-month mRS scores from discharge or 3-month outcomes for the 20% of patients who were lost to follow-up.

They found that 51.2% with LOC were dead or severely disabled (mRS score of 4 to 6) at 12 months compared with 17.7% of those who didn't lose consciousness. Death or functional dependence at 12 months was significantly associated with LOC, even after controlling for age, admission clinical grade, APACHE II physiologic subscore, and aneurysm size (adjusted odds ratio, 1.94; 95% confidence interval, 1.38 - 2.72; P < .001).

"We're saying that even when you account for all of that, this historical element of passing out adds further significant prognostic information because it's capturing an aspect of the illness that the other variables don't," said Dr Mayer.

The proportion of patients assessed as Hunt and Hess grade 3 was nearly identical among those who did and did not lose consciousness (25.4% and 25.5%, respectively). This, said the authors, suggests that LOC at symptom onset implies an increased risk for severe rather than mild brain injury.

The most common mechanism underlying LOC at SAH onset is likely reduced cerebral perfusion pressure in the setting of elevated intracranial pressure, seizures, or neurogenic cardiopulmonary dysfunction, manifesting as hypotension or frank cardiac arrest. A nearly instantaneous increase in intracranial pressure can occur in less than 1 minute after SAH.

"In that case, you can't get any blood to your brain; there's so much pressure in your skull that the blood can't get in," said Dr. Mayer. "This early brain injury concept is kind of like this flash blast injury to the brain that is going to set up this whole cascade of downstream events."

The new study should remind emergency department physicians and others that loss of consciousness could signal brain injury and could help direct diagnosis.

Such a reminder might be needed; another study by Dr Mayer several years ago that looked at intensive care unit patients with a ruptured brain aneurysm found that one in five were initially misdiagnosed. He described a "classic" case of a man who turned out to have SAH being brought to the emergency department. Because empty bottles were found and no one could get a headache history, the initial assumption was that this was an overdose.

"Eventually it gets figured out, but these patients can deteriorate neurologically, they can rebleed, they can have a worse outcome a year later," he said.

Information on LOC might "create a sense of urgency right up front," he added. "It's papers like this that can help make this become part of the dogma — like, whenever you evaluate a headache you have to ask, did you pass out?"

If the answer is yes, that patient might be immediately moved into a high-risk category with high priority for CT and neurologic expertise, said Dr Mayer.

New Lessons

In an accompanying editorial, R. Loch Macdonald, MD, PhD, Division of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada, noted that the findings are consistent with similar prior reports but that it did add some "new lessons."

"The data provide an important confirmation of the existing studies and solidify the finding that LOC is a prognostic factor for outcome after SAH," writes Dr Macdonald. "The series includes about 4 times as many patients as the prior studies and thus, the findings may be more robust than prior studies."

How LOC is defined is "an important point," he said. "The main question is how to separate the effect of LOC from neurologic grade."

One way to overcome the fact that patients with a poor neurologic grade are unconscious would be to include only those with a good neurologic grade in the effect of LOC. In the current study, researchers examined the effect of LOC in patients with Hunt and Hess grades 1 to 3, and after excluding patients with prehospital cardiac arrest and those with witnessed tonic-clonic activity.

"It is reasonable to exclude the latter 2 events as they could lead to LOC by different mechanisms than the SAH itself. Even in this group, LOC was significantly related to poor outcome," Dr Macdonald writes.

Because patients with Hunt and Hess grade 3 are on the verge of unconsciousness and may not remember an episode of LOC, "it would be interesting to conduct the analysis only on patients assessed as Hunt and Hess grades 1 and 2."

The lack of association between LOC and DCI in the study may be due to statistics as well as to lower event rates, says Dr. Macdonald. "It might be that LOC covaries or interacts in some way with other predictors of DCI (subarachnoid clot volume, neurologic grade, smoking, so that only 1 or 2 of these variables end up reaching the level of statistical significance."

Dr Macdonald concluded that, overall, the study "solidifies the finding that LOC at the time of SAH is an independent predictor of poor outcome, highlighting the importance pf acute reductions in cerebral perfusion and probably of subarachnoid blood since these patients tend to have a larger SAH."

Dr Mayer reported receiving grant-in-aid from the American Heart Association. This study was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr Mayer is a consultant for Edge Therapeutics and Actelion Pharmaceuticals. Dr Macdonald has disclosed no relevant financial relationships.

JAMA Neurol. Published online November 9, 2015. Full text Editorial

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