Head Down Tilt 15 Degrees In Experimental Intracerebral Hemorrhage: A Randomized Noninferiority Safety Trial

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