**2. Epidemiology**

Quantification of the burden of neurologic complications has been difficult due to voluntary and retrospective nature of reporting, variability and lack of consensus on neuromonitoring and heterogeneous populations.

An ELSO registry analysis of neonates on ECMO from 2005 to 2010 showed that 20% had some neurologic complications [5]. Non hemorrhagic complications such as cerebral infarction, brain death and seizures were far less common than intracranial hemorrhage. A look at the subgroup of neonates with congenital heart disease failed to show an association between type of cardiac lesion and CNS injury [6]. The pediatric patient population is more heterogeneous than the neonatal group. A study by Hervey-Jumper et al. looked at children on ECMO from 1990 to 2009 and found that intracranial hemorrhage occurred in 7.4%, cerebral infarction in 5.7% and clinical seizures in 8.4% of all patients [7].

A systematic review of studies from 1990 to 2017 found that intracranial hemorrhage was the most common type of neurologic injury in adults, followed by acute ischemic stroke [8]. Incidence reported varies widely with a range of 2–21% for intracranial hemorrhage and 1–33% for acute ischemic stroke, with a median proportion of 5% of patients experiencing hemorrhages and another 5% with stroke. Seizures had the lowest incidence of about 2%. The study did find that neurologic injury was overall more commonly reported in VA ECMO than VV ECMO. The occurrence of neurologic injury significantly increases the in-hospital mortality with median mortality of 96% for hemorrhages, 84% for ischemic strokes 84, and 40% for seizures.

An analysis of the ELSO registry of almost 5000 adult patients on VV ECMO found an overall incidence of neurologic complications in 7.1% of patients [3]. Injuries included hemorrhage in 42.5%, brain death in 23.5%, stroke in 19.9%, and seizures in 14.1%. This study also found that in-hospital mortality was much higher (75.8% versus 37.8%) for patients with neurological injuries. An analysis of the ELSO registry for adult patients on VA ECMO, by the same group, found similar findings in the venoarterial cohort [9]. A decade's review of the Nationwide Inpatient Sample, that included over 23,000 patients, found that adult patients with acute ischemic stroke and intracranial hemorrhage on ECMO had higher rates of discharge to a long term facility and longer length of stay when compared to patients without neurologic injury [10].

A recent international randomized controlled trial, comparing ECMO to conventional mechanical ventilation for severe ARDS, showed a very low rate of ischemic stroke in the ECMO population [11]. Out of 124 patients randomized to receive ECMO, none had ischemic strokes compared to 5% of the patients initially randomized to conventional therapy, although there was the option of crossover to ECMO for refractory ARDS. It is unclear if this is due to a restrictive inclusion criteria of less than 7 days of mechanical ventilation combined with less severe hypoxemia and acidosis from early ECMO cannulation. However, the rates of hemorrhagic stroke were similar in the two groups.

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*Neurologic Complications and Neuromonitoring on ECMO*

**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

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

Cannulation of cervical vessels relies on a competent Circle of Willis to allow

These can be divided into factors prior to initiation of ECMO and factors inherent to ECMO therapy [17]. There are also risk factors for neurological injury after ECMO such as ligation or anastomosis of cervical blood vessels. Because CNS injury is often multifactorial, and lesions are often detected retrospectively on imaging

The underlying physiologic conditions that necessitate ECMO cannulation, such as labile hemodynamics, severe hypoxemia and acidosis, refractory hypotension, etc., leave the patient vulnerable to neurologic insults. These can alter the mechanisms responsible for maintaining cerebral autoregulation and make the vasculature more susceptible to alterations in systemic blood pressure. Prematurity is associated with an increase in intraventricular and intracranial hemorrhage and can be a contraindication for ECMO cannulation. A prior history of neurologic injury

those without. No patients in this study had cerebral hemorrhage [15].

after ECMO, the exact timing of injury can be difficult to determine.

puts one at further risk of adverse cerebrovascular events.

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 neuro-

*DOI: http://dx.doi.org/10.5772/intechopen.85103*

(CNS) injury [13].

logic outcomes [16].

**4.1 Pre-ECMO**

**4. Risk factors for neurologic injury**

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

group, and information may not be relevant for all ages.

on neuromonitoring and heterogeneous populations.

and clinical seizures in 8.4% of all patients [7].

hemorrhagic stroke were similar in the two groups.

**2. Epidemiology**

populations [4]. The H1N1 influenza pandemic in 2009 is primarily credited for the adoption of ECMO in many adult centers and its use in adults has grown exponentially since. While most of the early data came from neonates, more recent studies on neurologic injuries in adults are informing care of the ECMO patient. As ECMO is becoming more ubiquitously used, this chapter discusses neurologic complications noted across the age spectrum. However risk factors, types of complications and management often vary by patient population, from neonates to adults. Effort has been made to specify if certain descriptions are only applicable to a certain age

Quantification of the burden of neurologic complications has been difficult due to voluntary and retrospective nature of reporting, variability and lack of consensus

An ELSO registry analysis of neonates on ECMO from 2005 to 2010 showed that 20% had some neurologic complications [5]. Non hemorrhagic complications such as cerebral infarction, brain death and seizures were far less common than intracranial hemorrhage. A look at the subgroup of neonates with congenital heart disease failed to show an association between type of cardiac lesion and CNS injury [6]. The pediatric patient population is more heterogeneous than the neonatal group. A study by Hervey-Jumper et al. looked at children on ECMO from 1990 to 2009 and found that intracranial hemorrhage occurred in 7.4%, cerebral infarction in 5.7%

A systematic review of studies from 1990 to 2017 found that intracranial hemorrhage was the most common type of neurologic injury in adults, followed by acute ischemic stroke [8]. Incidence reported varies widely with a range of 2–21% for intracranial hemorrhage and 1–33% for acute ischemic stroke, with a median proportion of 5% of patients experiencing hemorrhages and another 5% with stroke. Seizures had the lowest incidence of about 2%. The study did find that neurologic injury was overall more commonly reported in VA ECMO than VV ECMO. The occurrence of neurologic injury significantly increases the in-hospital mortality with median mortality of 96% for hemorrhages, 84% for ischemic strokes 84, and 40% for seizures. An analysis of the ELSO registry of almost 5000 adult patients on VV ECMO found an overall incidence of neurologic complications in 7.1% of patients [3]. Injuries included hemorrhage in 42.5%, brain death in 23.5%, stroke in 19.9%, and seizures in 14.1%. This study also found that in-hospital mortality was much higher (75.8% versus 37.8%) for patients with neurological injuries. An analysis of the ELSO registry for adult patients on VA ECMO, by the same group, found similar findings in the venoarterial cohort [9]. A decade's review of the Nationwide Inpatient Sample, that included over 23,000 patients, found that adult patients with acute ischemic stroke and intracranial hemorrhage on ECMO had higher rates of discharge to a long term facility and longer length of stay when compared to patients without neurologic injury [10]. A recent international randomized controlled trial, comparing ECMO to conventional mechanical ventilation for severe ARDS, showed a very low rate of ischemic stroke in the ECMO population [11]. Out of 124 patients randomized to receive ECMO, none had ischemic strokes compared to 5% of the patients initially randomized to conventional therapy, although there was the option of crossover to ECMO for refractory ARDS. It is unclear if this is due to a restrictive inclusion criteria of less than 7 days of mechanical ventilation combined with less severe hypoxemia and acidosis from early ECMO cannulation. However, the rates of

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