**4. Risk factors for neurologic injury**

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

#### **4.1 Pre-ECMO**

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 puts one at further risk of adverse cerebrovascular events.

### **4.2 ECMO-related**

Animal models have demonstrated the effects of carotid artery and jugular vein cannulation and ligation on cerebral blood flow [18, 19]. Adults with atherosclerosis may develop emboli during arterial cannulation. ECMO cannulae and circuits expose a patient to prothrombotic surfaces and the foreign materials often incite an inflammatory response. Platelets are consumed in the circuit components leading to thrombocytopenia, putting a patient at increased risk of bleeding. Maintaining patency of the circuits requires the use of anticoagulation, which needs to be closely monitored to avoid complications such as bleeding, or thrombosis and embolism. Reperfusion injury is another risk factor after adequate oxygenation and blood flow delivery have been ensured following a period of severe hypoxemia. VA ECMO cannulation for cardiogenic shock is also associated with non-pulsatile flow which is not physiologic. Neurologic exams are often limited for patients on ECMO, confounded by sedation and limited mobility, which can lead to delayed diagnosis and recognition. A precannulation lactate greater than 10 mmol/L was found to be associated with increased odds for ischemic strokes in adults [8]. A history of pre ECMO cardiac arrest, need for renal replacement therapy and elevated bilirubin levels were associated with increased odds of neurologic injury [3]. A study of neonates found that birth weight less than 3 kg, gestational age less than 34 weeks, a history of prior ECMO cannulation and severe acidosis were risk factors for neurologic injury [5].

### **4.3 Veno-arterial (VA) versus veno-venous (VV)**

VA ECMO carries with it the increased risk of embolization as blood is directly pumped into the arterial system, unlike in VV ECMO where the oxygenated blood is returned to the venous system where the lungs can filter thrombi. However, a study by Zahraa found that there was no difference in central nervous system complications between pediatric respiratory failure patients supported on VA versus VV ECMO [20]. Differential hypoxia, where the arterial oxygen tension is lower in the upper half of the body than in the lower half, is a phenomenon occasionally seen in patients supported on peripheral VA ECMO that causes cerebral ischemia [21]. For pediatric patients on VA ECMO, the incidence of stroke was much lower for transthoracic or central cannulation compared to peripheral cannulation [22]. VA ECMO is also unique in that poor cardiac function results in absence of pulsatile flow, with potential implications for cerebral autoregulation and vascular reactivity.

#### **4.4 Carotid repair**

The right carotid artery and internal jugular vein are commonly sacrificed during ECMO cannulation. Taylor et al. showed the feasibility of vascular repair with antegrade flow, without increasing the incidence of embolic phenomenon [23]. A larger, more recent study of neonates on VA ECMO, showed over 84% patency of repaired vessels. While 43% of all patients had a severe brain lesion after ECMO, there was no difference in early neurologic outcomes between the groups that underwent carotid repair versus carotid ligation [24].

#### **4.5 Extracorporeal cardiopulmonary resuscitation (ECPR)**

ECPR is the rapid deployment of VA ECMO for a patient in cardiac arrest, with ongoing CPR, prior to the return of spontaneous circulation. A systematic review of adult ECPR data showed that a shockable rhythm and duration of CPR were significantly associated with a favorable neurologic outcome [25]. A study of the

**205**

*Neurologic Complications and Neuromonitoring on ECMO*

ELSO registry looking at pediatric patients that received ECPR found an overall incidence of acute neurologic injury in 22% of patients [26]. The in-hospital mortality was high for these patients at 89%. An analysis of neonatal and pediatric ECPR events from a multicenter, national registry showed that while only 43.7% of patients survived to hospital discharge, the majority of survivors had favorable neurologic outcomes [27]. Another study comparing survivors of ECPR and those with return of circulation after conventional CPR found comparable neurologic outcomes between the two groups, with total duration of cardiac arrest being the

**5. Types of neurological complications and their management**

There is a wide variety of neurological injuries that are noted after ECMO including embolic strokes, hypoxic-ischemic encephalopathy, cerebral infarction, intracranial and subarachnoid hemorrhages, seizures, cerebral edema and even brain death. Other complications, such as critical illness myopathy, neuropathies, delirium, hearing loss, vocal cord paralysis etc. are related to prolonged hospitalization and ICU stays, need for prolonged mechanical ventilation or tracheostomy, prolonged exposure to sedation, and limited mobility that often accompany ECMO runs. In this section of the chapter, we will look at some of the more common neurologic complications experienced by patients treated with ECMO.

Intracranial hemorrhage (ICH) is one of the most common adverse neurologic events on ECMO, carrying a high mortality rate. It can occur as intraparenchymal, intraventricular or subarachnoid hemorrhages. Gestational age at time of ECMO cannulation, severe acidosis needing correction, sepsis, need for epinephrine, therapeutic hypothermia and need for cardiopulmonary resuscitation (CPR) have been associated with intracranial hemorrhage in neonates [29–31]. A longer duration of ECMO, higher activated clotting times (ACTs), presence of bleeding at other sites, pre-admission antithrombotic therapy, and low platelet counts were associated with hemorrhage in adults [32, 33]. Rapid PaCO2 decrease/correction of hypercapnia and renal failure at ICU admission were associated with increased intracranial hemorrhage in one adult study [13]. In order to detect intracranial hemorrhage while on ECMO, cranial ultrasounds are used in neonates while CT imaging is used in children and adults. In one observational study, 42% of the cohort underwent withdrawal of life sustaining therapy, 18% did not require any intervention and 40% were treated. Treatments included hemostatic interventions, ICP management and surgical interventions with 14% of the cohort uneventfully decannulated [34]. Patients that have clinically significant bleeds, with progression of brain injury and little to no improvement on ECMO ultimately end up with withdrawal of life sustaining therapies due to poor prognosis and risk of progression of the bleed. Patients with very small or clinically insignificant hemorrhages can continue their ECMO courses with close neurological monitoring, decannulation at the earliest feasible time and possibly lowering of anticoagulation parameters while balancing thrombotic risks. Platelets and anti-fibrinolytics may need to be administered. Occasionally ECMO circuits can be trialed without any anticoagulation keeping a close eye on the circuit for clots and fibrin deposition. Life-threatening hemorrhage can be severe enough to warrant a craniotomy [7, 35]. Hematoma evacuation on ECMO is high risk and carries a high mortality although there are reports of patients who survived [34]. There is heterogeneity in practice with drugs used for anticoagulation (heparin versus bivalirudin), tests to assess for anticoagulation (TEG,

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

only predictor of survival [28].

**5.1 Hemorrhagic complications**

*Neurologic Complications and Neuromonitoring on ECMO DOI: http://dx.doi.org/10.5772/intechopen.85103*

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

**4.3 Veno-arterial (VA) versus veno-venous (VV)**

underwent carotid repair versus carotid ligation [24].

**4.5 Extracorporeal cardiopulmonary resuscitation (ECPR)**

Animal models have demonstrated the effects of carotid artery and jugular vein cannulation and ligation on cerebral blood flow [18, 19]. Adults with atherosclerosis may develop emboli during arterial cannulation. ECMO cannulae and circuits expose a patient to prothrombotic surfaces and the foreign materials often incite an inflammatory response. Platelets are consumed in the circuit components leading to thrombocytopenia, putting a patient at increased risk of bleeding. Maintaining patency of the circuits requires the use of anticoagulation, which needs to be closely monitored to avoid complications such as bleeding, or thrombosis and embolism. Reperfusion injury is another risk factor after adequate oxygenation and blood flow delivery have been ensured following a period of severe hypoxemia. VA ECMO cannulation for cardiogenic shock is also associated with non-pulsatile flow which is not physiologic. Neurologic exams are often limited for patients on ECMO, confounded by sedation and limited mobility, which can lead to delayed diagnosis and recognition. A precannulation lactate greater than 10 mmol/L was found to be associated with increased odds for ischemic strokes in adults [8]. A history of pre ECMO cardiac arrest, need for renal replacement therapy and elevated bilirubin levels were associated with increased odds of neurologic injury [3]. A study of neonates found that birth weight less than 3 kg, gestational age less than 34 weeks, a history of prior ECMO cannulation and severe acidosis were risk factors for neurologic injury [5].

VA ECMO carries with it the increased risk of embolization as blood is directly pumped into the arterial system, unlike in VV ECMO where the oxygenated blood is returned to the venous system where the lungs can filter thrombi. However, a study by Zahraa found that there was no difference in central nervous system complications between pediatric respiratory failure patients supported on VA versus VV ECMO [20]. Differential hypoxia, where the arterial oxygen tension is lower in the upper half of the body than in the lower half, is a phenomenon occasionally seen in patients supported on peripheral VA ECMO that causes cerebral ischemia [21]. For pediatric patients on VA ECMO, the incidence of stroke was much lower for transthoracic or central cannulation compared to peripheral cannulation [22]. VA ECMO is also unique in that poor cardiac function results in absence of pulsatile flow, with

potential implications for cerebral autoregulation and vascular reactivity.

The right carotid artery and internal jugular vein are commonly sacrificed during ECMO cannulation. Taylor et al. showed the feasibility of vascular repair with antegrade flow, without increasing the incidence of embolic phenomenon [23]. A larger, more recent study of neonates on VA ECMO, showed over 84% patency of repaired vessels. While 43% of all patients had a severe brain lesion after ECMO, there was no difference in early neurologic outcomes between the groups that

ECPR is the rapid deployment of VA ECMO for a patient in cardiac arrest, with ongoing CPR, prior to the return of spontaneous circulation. A systematic review of adult ECPR data showed that a shockable rhythm and duration of CPR were significantly associated with a favorable neurologic outcome [25]. A study of the

**4.2 ECMO-related**

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**4.4 Carotid repair**

ELSO registry looking at pediatric patients that received ECPR found an overall incidence of acute neurologic injury in 22% of patients [26]. The in-hospital mortality was high for these patients at 89%. An analysis of neonatal and pediatric ECPR events from a multicenter, national registry showed that while only 43.7% of patients survived to hospital discharge, the majority of survivors had favorable neurologic outcomes [27]. Another study comparing survivors of ECPR and those with return of circulation after conventional CPR found comparable neurologic outcomes between the two groups, with total duration of cardiac arrest being the only predictor of survival [28].
