**3. Cerebral blood flow and oxygenation on ECMO**

Cerebral autoregulation is the term used to describe the ability of cerebral arterioles to maintain steady cerebral blood flow across a wide range of cerebral blood pressure. This is achieved through dilation and constriction of cerebral blood vessels in response to fluctuations in mean arterial pressure. This is a complex process mediated through neurogenic regulation, involving sympathetic and cholinergic mechanisms, myogenic regulation involving smooth muscle tone, and metabolic regulation influenced by local concentration of metabolites [12]. Cerebral autoregulation can become disrupted focally or globally in pathological conditions leading to cerebral ischemia, hemorrhage or edema. These conditions associated with ECMO include vasospasm, severe acidosis, low cardiac output states, hypotension and hypertension, reperfusion injury and absence of pulsatile flow in VA ECMO. Hypercapnia is associated with cerebral vasodilation while hypocapnia causes cerebral vasoconstriction. A rapid decline in paCO2 after initiation of VV ECMO has been associated with central nervous system (CNS) injury [13].

A study by O'Brien using transcranial Doppler (TCD) showed that in patients that did not have neurologic injury, cerebral blood flow velocities on ECMO were much lower than predicted and returned closer to baseline after decannulation. However in patients that did have cerebral hemorrhage on ECMO, supranormal flows were noted in the days preceding the event [14]. A more recent multicenter study by the same author confirmed lower flow velocities on ECMO but did not show a difference in flow velocities in children with cerebral ischemia compared to those without. No patients in this study had cerebral hemorrhage [15].

Cannulation of cervical vessels relies on a competent Circle of Willis to allow for cerebral perfusion of both hemispheres. Occlusion of vessels can cause ipsilateral venous stasis and this venous congestion can lead to venous hypertension and decreased cerebral perfusion. Changes in cerebral blood flow rate and volume can contribute to altered cerebral oxygenation as demonstrated by cerebral oximetry [12]. Impairments in cerebral autoregulation, based on wavelet transform coherence, are associated with findings on neuroimaging and neurologic outcomes [16].
