Head down tilt 15° in experimental intracerebral hemorrhage: a randomized non-inferiority safety trial

Background: Head down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the pre-hospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage. Methods: Intracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized non-inferiority trial design was used to assign rats to HDT15° or flat position (n=64). HDT15° was applied for 1 hour during the time window of hematoma expansion. The primary outcome was hematoma volume at 24 hours. Secondary outcomes were mass effect, mortality and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth and cardiorespiratory parameters in separate sets of randomized animals (n=32). Results: HDT15° achieved the specified criteria of non-inferiority for hematoma volume at 24 hours. Mass effect, mortality and functional deficit at 24 hours showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pre-treatment values (+ 2.91 +/- 1.76 mmHg). HDT15° had a neutral effect on MRI-based analysis of hematoma growth and cardiorespiratory parameters. Conclusions: Application of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.