A new study suggests a brighter future for survivors of severe intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) who initially seemed headed for poor long-term functional outcomes.
Investigators analyzed functional outcome trajectories in more than 700 survivors of ICH or IVH, who had shown very poor functional outcomes at day 30 post-event.
More than 40% of these patients achieved favorable outcomes at 1 year, with one-third being functionally independent. Moreover, by 1 year, oral methotrexate for crohn’s disease almost two-thirds had returned home, and quality of life scores showed a significant upward trajectory in all subjects.
The inclusion of hospital events, preexisting conditions, and responses to therapy in prognostic models improved prediction of future recovery.
“The main take-home message of this study is that the approach to many ICH patients needs to change,” senior author Wendy Ziai, MD, MPH, medical director of the neurovascular laboratory and professor of neurology, Johns Hopkins Hospital, Baltimore, Maryland, told Medscape Medical News.
“Our data support longer evaluation periods for ICH patients with observation of in-hospital events and response of therapy to provide better understanding about long-term recovery,” she said.
The study was published online July 25 in JAMA Neurology.
ICH prognostication is historically performed on admission, and most models predict short-term outcomes, the authors note. The majority of studies also do not describe long-term recovery among those with initial severe disability.
Most prognostication models include baseline ICH severity factors but don’t account for comorbidities, hospital interventions, and complications, whereas IVH grading scales typically incorporate only baseline IVH-volume but not IVH expansion, volume reduction, or hydrocephalus, which “may also impact recovery.”
“Most patients with ICH who die in the hospital do so after decisions are made to withdraw life-sustaining measures, due to perceptions by providers of a high likelihood of poor long-term outcomes,” Ziai observed.
“These decisions may result in a self-fulfilling prophecy of poor outcome,” she continued. “Even do-not-resuscitate orders are associated with increased mortality risk and may lower the likelihood of favorable functional outcome when they are instituted early.”
To assess 1-year outcome trajectories after ICH, the researchers performed a longitudinal post-hoc analysis of all 500 patients with spontaneous obstructive IVH randomly assigned to intraventricular alteplase or placebo in the CLEAR-III trial and 499 patients with spontaneous large supratentorial ICH without obstructive IVH randomly assigned to stereotactic thrombolysis or standard medical care in the MISTIE trial.
Both trials were neutral for the primary endpoint of improved functional outcome but found significant reductions in mortality in the active treatment groups at 180 days and 1 year, respectively.
The final pooled cohort included 715 patients who survived to day 30 with a modified Rankin Scale (mRS) score of 4 (29.5%) or 5 (69.5%). Their mean age was 60.3 years, 58% were male, 68.6% were white, 24.3% Black, and 13.7% Hispanic.
Baseline characteristics included age, sex, race, ethnicity, stroke-related comorbidities, Glasgow Coma Scale score, and National Institutes of Health Stroke Scale (NIHSS) score, as well as hematoma volumes (measured upon admission, at ICH and IVH stability, at the end of treatment, and at day 30 from enrollment in both trials).
The primary outcome measure was 1-year mRS, with assessments performed in both trials at days 30, 180, and 365.
Patients were divided into two groups based on a 1-year outcome of “good” (mRS 0 – 3) and “poor” (mRS 4 – 6).
Secondary outcomes were 1-year mortality, withdrawal of life-sustaining treatment, home discharge, and European Quality-of-Life Visual Analog Scale score.
Avoid Early Withdrawal of Life-Sustaining Therapies
By 1 year, 18% of participants had died, 43% had achieved mRS scores of 0 – 3, and 64.6% of the survivors had returned home at a median of 98 (52 – 302) days postictus.
Among the 308 patients who recovered to a good outcome by 1 year, 95.4% returned home. Moreover, 41% who had persistent poor outcome at 1 year were also able to return home.
In adjusted models for the combined cohort, the factors in the table below at day 30 were associated with lack of recovery.
|Factor||aOR (95% CI)|
|Diabetes||0.50 (0.26 – 0.96)|
|NIHSS||0.93 (0.90 – 0.96)|
|Severe leukoaraiosis||0.30 (0.16 – 0.54)|
|Pineal gland shift||0.87 (0.76 – 0.99)|
|Acute ischemic stroke||0.44 (0.21 – 0.94)|
|Gastrostomy||0.30 (0.17 – 0.50)|
|Persistent hydrocephalus||0.37 (0.14 – 0.98)|
On the other hand, resolution of ICH (adjusted odds ratio [aOR], 1.82; 95% CI, 1.08 – 3.04) and IVH (aOR, 2.19; 95% CI, 1.02 – 4.68) by day 30 were associated with recovery to good outcome.
Additional factors associated with poor outcome included cerebral perfusion pressure less than 60 mm, sepsis, prolonged mechanical ventilation, and the need for intracranial pressure monitoring.
Thirty-day event-based models “strongly predicted” 1-year outcome (AUC, 0.87; 95% CI, 0.83 – 0.90), with “significantly improved discrimination” over models using baseline severity factors alone (AUC, 0.76; 95% CI, 0.71 – 0.80), the authors report.
“Although there remain no proven interventions for ICH patients which definitely improve outcomes, effective hematoma volume reduction, as studied in these clinical trials, was significantly associated with improved ability to discriminate between patients who made eventual functional recovery at 1 year and those who did not,” Ziai commented.
The findings “highlight the importance of promoting aggressive treatment and avoiding early withdrawal of life-sustaining therapies in the acute phase after ICH,” she said.
Commenting for Medscape Medical News, Magdy Selim, MD, PhD, professor of neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the study results have “practice-changing implications.”
Recovery after ICH is “slow but it is possible for many patients to recover with aggressive care and time,” said Selim, author of an accompanying editorial.
Patients and families “need to be informed that the effects of aggressive measures may not be apparent in the short term and that patients with ICH require patience from their providers and caregivers,” said Selim, who was not involved with the study.
He noted that most deaths after ICH result from early withdrawal of care “because of perceived long-term poor outcome by the treating physicians and family.” The study findings “clearly point out that physicians and families need to exercise caution before limiting aggressive care early on, to maximize the patients’ chances of recovery.”
Ziai reported grants from the National Institutes of Health during the conduct of the study, personal fees from C. R. Bard DMC and for serving as an associate editor for “Neurocritical Care” outside the submitted work. The other authors’ disclosures are listed on the original paper. Selim reported grants from the National Institute of Neurological Disorders and Stroke and the National Institute of Aging; royalties from UpToDate and Cambridge University Press; and serving on the advisory board of MedRhythms Inc.
JAMA Neurol. Published online July 25, 2022. Abstract, Editorial
Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as “Behind the Burqa: Our Lives in Afghanistan” and “How We Escaped to Freedom.”
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