Death by Neurologic Criteria in Children Undergoing Extracorporeal Cardiopulmonary Resuscitation: Retrospective Extracorporeal Life Support Organization Registry Study, 2017–2021

Abstract

Objectives: To determine factors associated with brain death in children treated with extracorporeal cardiopulmonary resuscitation (E-cardiopulmonary resuscitation). Design: Retrospective database study. Settings: Data reported to the Extracorporeal Life Support Organization (ELSO), 2017–2021. Patients: Children supported with venoarterial extracorporeal membrane oxygenation (ECMO) for E-cardiopulmonary resuscitation. Intervention: None. Measurements and Main Results: Data from the ELSO Registry included patient characteristics, blood gas values, support therapies, and complications. The primary outcome was brain death (i.e., death by neurologic criteria [DNC]). There were 2,209 children (≥ 29 d to < 18 yr of age) included. The reason for ECMO discontinuation was DNC in 138 patients (6%), and other criteria for death occurred in 886 patients (40%). Recovery occurred in 1,109 patients (50%), and the remaining 76 patients (4%) underwent transplantation. Fine and Gray proportional subdistribution hazards’ regression analyses were used to examine the association between variables of interest and DNC. Age greater than 1 year (p < 0.001), arterial blood carbon dioxide tension (Paco 2) greater than 82 mm Hg (p = 0.022), baseline lactate greater than 15 mmol/L (p = 0.034), and lactate 24 hours after cannulation greater than 3.8 mmol/L (p < 0.001) were independently associated with greater hazard of subsequent DNC. In contrast, the presence of cardiac disease was associated with a lower hazard of subsequent DNC (subdistribution hazard ratio 0.57 [95% CI, 0.39–0.83] p = 0.004). Conclusions: In children undergoing E-cardiopulmonary resuscitation, older age, pre-event hypercarbia, higher before and during ECMO lactate levels are associated with DNC. Given the association of DNC with hypercarbia following cardiac arrest, the role of Paco 2 management in E-cardiopulmonary resuscitation warrants further studies.

The approach to extracorporeal cardiopulmonary resuscitation (ECPR) in children. A narrative review by the paediatric ECPR working group of EuroELSO

“…Acidosis pre-ECMO and on ECMO are both associated with higher mortality. 28,31,35,39,44 Pre-ECPR pH <7.01 is associated with worse outcome and should be taken into account with other risk factors before deploying ECPR. An initial high lactate and the peak lactate are a reflection of the severity of the arrest and are risk factors for mortality.…”

“…16,85 In these patients, intracranial haemorrhage, hypoxic ischaemic injury, ischaemic stroke, cerebral oedema, and seizures are a frequent cause of death or severe functional impairment. 30,44 With appropriate neuromonitoring and neuroprotective measures neurologic injury can be minimised or detected early. 86 The ELSO guidelines on neuromonitoring recommend frequent cranial ultrasound in infants with an open fontanelle, cranial CT-scan in case of clinical suspicion for neurological complications or abnormal findings on neuromonitoring, to consider continuous cerebral oximetry monitoring with NIRS in all patients undergoing ECMO, and to consider continuous EEG monitoring within 12–24 h of ECMO cannulation for a duration of at least 24–48 h. 87 The use of plasma biomarkers for neurologic injury is appealing, but requires further investigation before it can be clinically applied.…”

“…Median ECMO duration after ECPR varies between 3 and 7 days, but is generally 3–5 days in the larger studies. 17,29–31,33,44,48,89 In the ELSO-registry median duration is 3.5 and 4 days for paediatric and neonatal ECPR respectively. 13 In V-A ECMO in general and also in ECPR patients, increased duration of ECMO is associated with a greater risk of mortality and a poor neurologic outcome.…”

“…Based on the limited outcomes in non-cardiac patients it might be reasonable to limit ECPR to children with witnessed IHCA, to exclude those with known cerebral damage or no chance to bridge to recovery or Single-ventricle physiology [28][29][30][31] Two-ventricle physiology 28-31 Non-cardiac disease 32,33 Cardiac disease 17,37,38 Acquired heart disease 27 White race 36,39 Higher complexity of CHD 28 Post-cardiac surgery 27 Prematurity 33 Younger age (<12 months) 34 Chromosomal abnormalities 35 Neurologic comorbidity 17 Trauma 36 Obesity 36 Gastro-intestinal comorbidity 27 Technology dependence 27 Cardiac arrest and CPR OHCA IHCA Unwitnessed CA 40 Short duration of CCPR 41 Long duration of CCPR 41 Open-chest compressions 27 CCPR interruptions 42 CA in catheterisation lab 24 CCPR location outside ICU 27 PH >7.17 39 High lactate 27,43 Neck/RCA cannulation 28,38 Acidosis, pH <7.01 28 Hypercarbia 44 Sodium bicarbonate bolus 32 Calcium 45 Blood-primed ECMO circuit 35 During ECPR Time to normal lactate 43 Early diagnosis and management of underlying cause [49][50][51][52] Normalization of lactate 27 AKI/Renal failure 28,32,33,35,38,39,46 RRT 31,34 Fluid overload 47 ECMO duration 30 Neurologic complications 28,31,34,35,…”

“…75 An ELSO-registry report showed that hypercarbia prior to initiation of ECMO was associated with death due to neurological criteria in paediatric ECPR. 44 Furthermore, hyperoxia should be avoided because of the possible harmful effects of oxygen free radicals. 76 Hyperoxia after ROSC has been associated with increased mortality and poor neurologic recovery.…”