The Effects of Milrinone Systemic Administration on Cerebral Perfusion as Measured with Computed Tomography in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND

Aneurysmal subarachnoid hemorrhage (SAH) prognosis is determined by the occurrence of delayed cerebral ischemia (DCI), which is associated with specific dynamics of perfusion computed tomography (CTP) parameters. Systemic administration of milrinone is proposed to reduce DCI, though underlying mechanisms remain putative.

OBJECTIVE

This study aimed to describe the effects of milrinone intravenous infusion on systemic and cerebral hemodynamics in patients with SAH.

METHODS

We conducted a retrospective observational study including patients diagnosed with aneurysmal SAH and monitored with PiCCO device and CTP. Relationships between milrinone dose, cardiac index (CI), and CTP parameters were assessed.

RESULTS

A total of 17 patients were included, 88% presented cerebral vasospasm, 29% evolved with DCI. CI increased with systemic milrinone dose in the entire population (p < 0.001). Contrarily, cerebral blood flow (CBF) decreased with milrinone in the non-DCI subpopulation (p = 0.002) and was not correlated to it in the DCI one. However, CBF increased with CI in this DCI subpopulation (p = 0.008). Spatial heterogeneity of perfusion, quantified by the global (CoV) and regional (rCoV) coefficients of variation of CBF, decreased with milrinone dose in the non-DCI subpopulation (p < 0.001). While no correlation at the global scale emerged in the DCI subpopulation, rCoV increased with milrinone in DCI regions (p < 0.01).

CONCLUSIONS

Intravenous infusion of milrinone did not seem to improve cerebral perfusion through systemic effects. In non-DCI patients, milrinone seemed to homogenize CBF and prevent evolution towards DCI. We suggest that in patients with DCI, it failed to do so, such that CBF spatial heterogeneity pathologically increased until infarction. We propose that spatiotemporal evolution of CBF heterogeneity is both a biomarker and a pathophysiological feature of DCI that advocates for further theoretical and experimental exploration.