Delayed Intraventricular Hemorrhage: Treatment Target in ICH?

March 19, 2015

The implications of the delayed appearance of intraventricular hemorrhage (IVH) on follow-up imaging in patients who have sustained an intracerebral hemorrhage (ICH) is being debated after the publication of a new study.

A previous study suggested that delayed IVH is associated with an increased risk for unfavorable outcome and so represents a promising target for preventative intervention, but the new study questions this idea.

The new study, published in the March 10 issue of Neurology, was led by Jens Witsch, MD, Columbia University College of Physicians and Surgeons, New York, New York, and colleagues. "In ICH patients, associated IVH on admission imaging is commonly encountered and is associated with poor long-term outcome," they conclude. "In contrast, delayed IVH on subsequent scans is far less common and does not appear to portend worse outcome."

But in an accompanying Comment, Matthew Maas, MD, Northwestern University, Chicago, Illinois, author of the previous study, argues that the new data from Dr Witsch and colleagues should not be interpreted as indicating delayed IVH does not signal worse outcomes. He points out that in the current study, the odds ratio for a bad outcome is similar for early IVH and delayed IVH, and the fact that the delayed IVH result is not significant is probably due to insufficient numbers of patients.

"Just because a result is not significant does not mean there is no effect," he commented to Medscape Medical News.

"Physiologically Intuitive"

"These findings are physiologically intuitive: Why would IVH affect outcomes differently when it occurs a few hours later, or when discovered in a patient who arrives at the hospital a few hours earlier?" Dr Maas writes. "The key message for practicing clinicians is that important pathologic processes continue to evolve while patients are under our observation and care. The challenge ahead lies in elucidating the most effective methods for preventing, detecting, and treating these evolving and harmful processes."

Author of an accompanying editorial, Alejandro A. Rabinstein, MD, Mayo Clinic, Rochester, Minnesota, explained to Medscape Medical News that both studies confirm IVH at presentation is a poor prognostic indicator, but neither fully establishes whether delayed IVH can independently worsen prognosis. "Delayed IVH was most commonly seen in patients having their first CT [computed tomographic] scan very early and then developing substantial hematoma expansion on the repeat CT scan. The question remains whether the association of delayed IVH with poor outcome is simply dependent on expansion of the intraparenchymal hematoma (as suggested by Witsh et al) or a factor worsening prognosis per se (as initially suggested by Maas et al)."

Dr Rabinstein says both studies are underpowered to answer that question conclusively. "At this point there is no evidence that delayed IVH can become a therapeutic target, and further research on a much larger cohort is warranted," he added.

The new study by Dr Witsch and colleagues involved 282 patients with spontaneous ICH, of whom 151 (53.5%) had IVH on initial CT scan. Of the remaining 131 patients, 19 (14.5%) developed IVH after the initial CT scan (delayed IVH).

Results showed that after adjustment for components of the ICH score and hematoma expansion, presence of IVH on initial CT was associated with discharge mortality and poor outcome at 3, 6, and 12 months, but delayed IVH was not significantly associated with any of the outcome measures.

An Artefact of Delayed CT Scanning?

The authors point out that delayed IVH was predominantly seen in those who underwent very early admission CT scans and who had greater hematoma expansion, suggesting that categorization into initial and delayed IVH is mainly driven by CT timing.

Senior author Jan Claassen, MD, Columbia University College of Physicians and Surgeons, elaborated to Medscape Medical News: "IVH, no matter when it happens, is bad news. We found that too. The question is whether delayed IVH is its own entity and happens at all. We think it is primarily an artefact of delayed CT scanning, and if one looks at the timing that CT scans are obtained, which we did but Dr Maas' group did not, then the difference melts away."

He added: "There is clear evidence that shows preventing secondary enlargement of ICH makes a difference but in my mind there is so far no evidence to suggest that delayed IVH is its own clinical entity that requires study and trials."

Dr Maas responded that he does not believe delayed IVH is a distinct phenomenon from initial IVH but rather that both conditions are the same evolving process. However, he notes that it might be stoppable. "Sometimes you catch patients early in the process before extension into the ventricles has happened and thus you have the opportunity to potentially prevent it with interventions like blood pressure control, reversing coagulopathy, et cetera.

"Since some IVH occurs after hospital admission, perhaps it could be a target, but it would only be worth trying to prevent if it is harmful," he added. "The goal of my original paper was to show that delayed IVH was equally harmful as initial IVH. Several of the most widely used models to estimate the risk of death and disability in patients with IVH only consider initial IVH."

Dr Maas objects to his study being dismissed as "no evidence" and says a more reasonable conclusion would be that "there is now potentially conflicting evidence on this issue and larger studies are needed."

Neurology. 2015;84:989-994, 993, 970-971. Abstract Comment Editorial

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