**7. Therapeutic hypothermia**

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

**6.5 Cerebral near infra-red spectroscopy (NIRS)**

obtained in real time to influence management.

**6.7 Somato-sensory evoked potentials (SSEPs)**

**6.8 Optic nerve sheath diameter (ONSD)**

back by moving red blood cells in the blood vessels. The difference in frequencies of emitted and reflected waves is proportional to the cerebral blood flow. Studies have found that TCD velocities (TCDV) are much lower for pediatric patients on ECMO when compared to normative values for healthy and critically-ill children [15, 61]. While there was no significant association between global TCDV (systolic flow velocity, diastolic flow velocity, mean flow velocity) and neurologic injury, increased pulsatility index and regional increases in velocities or asymmetries might be predictive of neurologic injury.

NIRS monitoring is a non-invasive technology that uses near-infrared wavelength

of light that penetrates brain tissue via a scalp electrode. It provides a continuous measurement of regional tissue oxygen saturation (rSO2), which is a marker of the balance between oxygen delivery and demand in the tissues. When the probe is placed on the forehead, it measures cerebral oximetry. An analysis of adult patients on VA ECMO showed that cerebral desaturation was common and mortality higher for patients with cerebral desaturation compared to those without [21]. A sudden decrease in cerebral saturation can be associated with an acute neurological event, prompting further investigation. It can also serve as an early predictor of inadequate oxygenation and cardiac output especially peri-cannulation [62]. It can influence management by prompting a need for increased flows in VA ECMO or alternate cannulation strategies if there is differential hypoxia. A very high rSO2 could also be

suggestive of very poor oxygen extraction and poor neurologic outcomes.

Several plasma proteins have been evaluated as potential markers for brain injury [63]. These biomarkers include substances associated with glial injury (glial fibrillary acidic protein and s-100b), neuronal injury (neuron-specific enolase and brain-derived neurotrophic factor) and neuro-inflammation (intercellular adhesion molecue-5). Unfavorable neurologic outcomes have been associated with higher biomarker concentrations [64], with combinations of biomarkers providing higher sensitivities and specificities for detection of neurologic injury. These tests are more expensive and require laboratory equipment and processing availability. While not currently a routine component of neuromonitoring on ECMO in most institutions, there is potential for further research and applicability if these results can be

SSEPs measure electrical signals in the somatosensory cortex after a peripheral stimulus, assessing the pathway of neuronal conduction from the peripheral nerve to the cortex. They are assessed as normal, abnormal (increased latency) or absent. ECMO cannulation is not thought to alter the ability to assess SSEPs from the hemispheres [65]. Small studies have shown an association between abnormal SSEPs and poor neurologic outcome after ECMO [66], but the predictive value of evoked potentials remains to be determined. In one study, absence of bilateral SSEPs was associated with progression to brain death for patients treated with ECPR [67].

It is a simple bedside test used to detect elevated intracranial pressure. A cut-off

of 5.2 mm is sensitive and specific for intracranial hypertension [68]. Its use in

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**6.6 Biomarkers**

Therapeutic hypothermia has been shown to be neuroprotective for term neonates at risk of hypoxic ischemic encephalopathy secondary to perinatal asphyxia. However a randomized controlled study out of the United Kingdom did not show an improvement in outcomes for neonates on ECMO treated with mild hypothermia [70]. On the other hand, therapeutic hypothermia has been associated as a risk factor for intracranial hemorrhage and should be avoided [30]. In 2015, the American Heart Association recommended targeted temperature management of 32–36°C for comatose patients with return of spontaneous circulation after cardiac arrest [71]. This was also applied to patients who suffered in- hospital cardiac arrest leading to ECPR. A more recent large, multicenter, randomized control trial failed to show a benefit in survival with favorable neurological outcome for children with in-hospital cardiac arrest. There is no data to support routine therapeutic hypothermia for children undergoing ECPR although maintaining normothermia is still encouraged.
