Time to Rethink Prognosis After Prolonged Unconsciousness?

Megan Brooks

March 04, 2021

Most patients who become comatose after experiencing moderate or severe traumatic brain injury (TBI) recover consciousness in the short term — and nearly half regain functional independence, new research suggests.

The study, which included more than 17,000 patients who were hospitalized with moderate and severe TBI over three decades, showed that even when they remained unconscious at the end of their initial acute hospital care and were admitted for subsequent inpatient rehabilitation, 82% recovered consciousness by rehab completion.

"The results of our study, we think, show that caution is warranted in making decisions to withdraw or hold care in patients with these serious brain injuries," lead author Robert G. Kowalski, MBBCh, Department of Neurology, University of Colorado School of Medicine, Aurora, told Medscape Medical News.

"A meaningful recovery is possible, even when loss of consciousness occurs after the brain injury," he added.

The findings were published online March 1 in JAMA Neurology.

Self-fulfilling Prophecy?

TBI sends 2.9 million people to US emergency departments annually. More than half of patients with moderate to severe TBI become unconscious after the initial impact to the brain; and in many cases, this unconsciousness is deep (defined as coma) and persists for many hours, days, or weeks, Kowalski reported.

Historically, the prognosis of recovery for patients who have prolonged unconsciousness or disorders of consciousness (DOC) "has been perceived to be poor, with little hope for a return to independence," he said.

Therefore, in a significant proportion of cases, decisions are made to withdraw or withhold life-sustaining therapies, and the patients subsequently die. "This in turn contributes to the perception of poor prognosis in severe TBI — a so-called 'self-fulfilling prophecy,' " Kowalski noted.

The investigators evaluated the trajectory of, and factors associated with, recovery of consciousness and functional ability in patients with a DOC after moderate to severe TBI, focusing on the acute stage of emergent and critical care and subsequent inpatient rehabilitation.

"We chose this period of care, including the initial hospitalization and subsequent inpatient rehabilitation, because this is the time window during which treating medical teams and families make critical decisions that may prolong life and affect longer-term outcome for these patients, and help determine how successfully they are able to return to independent living," Kowalski said.

The cohort included 17,470 patients with moderate and severe TBI (median age at injury 39 years; 74% men). Of these, 7547 participants (57%) experienced initial loss of consciousness. This "loss of consciousness" state persisted to time of admission to acute rehabilitation (median days post-TBI, 25) in 2058 patients (12%).

However, 1674 comatose patients (82%) recovered consciousness (ability to follow commands) by the end of inpatient rehabilitation (median rehabilitation stay, 33 days). In addition, their trajectory of functional improvement mirrored that of patients with TBI who did not lose consciousness.

The investigators also observed the absence of specific signs of neuroanatomic injury on brain imaging, typically brain CT in the acute phase of treatment, including blood in the ventricles of the brain and severe midline shift of cerebral structures. This absence portends better prospects for recovery of consciousness and functional ability for these patients, the researchers note.

"These findings may provide specific imaging thresholds upon which decisions can be made, using tools available to treating teams of TBI in most cases," Kowalski said.

"We think the results support the value of pursuing inpatient rehabilitation after initial hospital care for these patients, both in terms of recovery of consciousness and to aid a return to independence in daily life," he added.

Overly Nihilistic

In an accompanying editorial, Jennifer Kim, MD, PhD, and Kevin Sheth, MD, Division of Neurocritical Care, Yale School of Medicine, New Haven, Connecticut, note that the study "further challenges our potential toward overly nihilistic notions of who may, or may not, ultimately recover consciousness long term" by showing that a large proportion of patients with persistent DOC recover during acute rehabilitation.

"Other studies that followed up patients long term (not restricted to the inpatient rehabilitation period) corroborate the observation that recovery in TBI can occur 6 to 12 months after injury," they write.

The current study used one of the largest cohorts of patients with TBI available to assess recovery in the rehabilitation setting, and the "remarkable rate of recovery should give pause to practitioners who counsel families about potential recovery of DoC," write Kim and Sheth.

"If there are no concerning radiographic features, then practitioners should communicate the potential for delayed DoC recovery," they add.

Echoing the investigators, the editorialists write that this study "adds to the TBI literature cautioning against withdrawal of life-sustaining therapy even when faced with prolonged DoC during hospitalization because there remains significant potential for recovery."

"Defining both good and poor prognostic risk factors is critical to portending recovery. Future work must refine biomarker identification and use in patients with DoC to improve physician prognostication and avoid self-fulfilling prophecy," they conclude.

The study had no commercial funding. Kowalski reported receiving grants from the National Institute on Disability, Independent Living, and Rehabilitation Research during the conduct of the study. Sheth reported receiving grants from the National Institutes of Health (NIH), the American Heart Association, Bard, Hyperfine, Biogen, and Novartis; other support from Zoll DSMB Chair and Alva Equity; and personal fees from NControl outside the submitted work. Kim reported receiving grants from the NIH, American Academy of Neurology, and Swebilius Foundation.

JAMA Neurol. Published March 1, 2021. Abstract, Editorial

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