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HOUSTON -- The risk of re-bleeding after intracranial hemorrhage did not increase when patients received early prophylaxis for venous thromboembolism (VTE), results of a retrospective review showed.

Re-bleeding or hematoma expansion within 24 hours occurred in 5% to 6% of patients, irrespective of the timing of VTE prophylaxis.

Early prophylaxis also did not significantly reduce the risk of VTE as compared with delayed treatment (0.7% versus 3.1%, P=0.17), but patients who developed VTEs had a longer delay from admission to first dose of prophylactic therapy, Andrew Faust, MD, reported here at the Society of Critical Care Medicine meeting.

"Pharmacologic VTE prophylaxis within 48 hours appears safe, which is pretty consistent with the literature, but it didn't decrease the risk of VTE," said Faust, of Methodist University Hospital of Memphis, Tenn. "However, delaying VTE prophylaxis may actually place the patient at risk for further development of VTE."

"We found that patients who did develop VTEs had about a 40-hour greater delay in the time to first dose of pharmacologic prophylaxis, compared with patients who did not develop VTEs," he added.

VTE occurs frequently in neurologic and neurosurgical patients admitted to ICUs. Though VTE prophylaxis is widely practiced, strategies and protocols vary just as widely, primarily because of a paucity of data from randomized trials, Faust said.

The value of published studies has been limited by the observational and retrospective nature of many investigations, the small numbers of patients, lack of consistency in approaches to VTE prophylaxis, and limited clinical data on patients.

American Heart Association/American Stroke Association clinical guidelines for intracranial hemorrhage include a recommendation to initiate VTE prophylaxis with low-dose heparin within one to four days of admission (Stroke 2010; 41: 2108-2129). Guidelines for subarachnoid hemorrhage made no mention of VTE prophylaxis (Stroke 2009; 40: 994-1025).

Continuing the evaluation of VTE prophylaxis in intracranial hemorrhage, Faust and colleagues reviewed records of 793 patients admitted to a neurologic ICU for management of primary intracranial hemorrhage during 2007 to 2010. They excluded patients who died within 72 hours or did not receive any VTE prophylaxis.

The final analysis comprised 400 patients who received pharmacologic prophylaxis for VTE within the first 30 days after intracranial hemorrhage. Of those, 142 (35.5%) started pharmacologic prophylaxis within 48 hours, which Faust acknowledged as an arbitrary cutoff to define early versus late prophylaxis.

Published studies have generally used 48- or 72-hour cutoffs for evaluation of VTE prophylaxis timing. Both cutoffs are consistent with evidence that hematoma expansion on CT rarely occurs after 24 hours (Stroke 1996; 27: 1783-1787).

The primary outcomes were re-bleeding or hematoma expansion and objectively diagnosed VTE during hospitalization. The principal secondary endpoint was readmission for VTE within 30 days after discharge.

More than 90% of patients in the early and delayed-prophylaxis groups received heparin every eight to 12 hours. The remaining patients received enoxaparin at a dose of 40 mg daily.

The most notable difference in baseline characteristics was stroke severity, as patients who received early VTE prophylaxis had a Glasgow Coma Score of 14 versus 11 in the delayed-therapy group (P<0.05).

The delayed group had more severe bleeding associated with the primary intracranial hemorrhage, as reflected by higher rates of intraventricular hemorrhage, midline shift, hematoma diameter, and need for ventriculostomy (P<0.05 for all).

The re-bleeding/hematoma rates were virtually identical: 5.6% with early VTE prophylaxis and 5% with delayed prophylaxis. The 30-day readmission rates also were similar (3% versus 2.6%).

The 21 patients who had re-bleeding or hematoma expansion had a numerically longer time to VTE prophylaxis (74 versus 63 hours), but the difference did not reach statistical significance.

However, time to first dose of VTE prophylaxis was significantly delayed in the nine patients who subsequently developed VTE (108 versus 63 hours, P=0.005).

In multivariate analyses, no independent predictors of re-bleeding emerged. In the VTE analysis, only the time to first dose of prophylactic therapy predicted an increased risk.

In response to a question from the audience, Faust said the decision to initiate VTE prophylaxis was "clinician specific. We did not have a protocol in place for when to start prophylaxis, how to control blood pressure, and issues such as that."

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