Management of Multi Organ Dysfunction in Neonatal Encephalopathy

Abstract

Neonatal Encephalopathy (NE) describes neonates with disturbed neurological function in the first post-natal days of life. NE is an overall term that does not specify the etiology of the encephalopathy although it often involves hypoxia-ischaemia. In NE, although neurological dysfunction is part of the injury and is most predictive of long-term outcome, these infants may also have multiorgan injury and compromise, which further contribute to neurological impairment and long-term morbidities. Therapeutic hypothermia (TH) is the standard of care for moderate to severe NE. Infants with NE may have co-existing immune, respiratory, endocrine, renal, hepatic, and cardiac dysfunction that require individualized management and can be impacted by TH. Non-neurological organ dysfunction not only has a negative effect on long term outcome but may also influence the efficacy of treatments in the acute phase. Post resuscitative care involves stabilization and decisions regarding TH and management of multi-organ dysfunction. This management includes detailed neurological assessment, cardio-respiratory stabilization, glycaemic and fluid control, sepsis evaluation and antibiotics, seizure identification, and monitoring and responding to biochemical and coagulation derangements. The emergence of new biomarkers of specific organ injury may have predictive value and improve the definition of organ injury and prognosis. Further evidence-based research is needed to optimize management of NE, prevent further organ dysfunction and reduce neurodevelopmental impairment.

Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia

“…While these higher concentrations were not associated with known adverse outcomes compared to neonates with HIE who did not receive aminophylline( 12 ), assessment of toxicity is difficult in this population who frequently have multi-organ failure including central nervous system derangements and seizures. ( 16 ) Our center has since implemented in clinical care the optimized dosing strategy supported by this study. In addition, theophylline trough concentrations are monitored before the fourth maintenance dose.…”

“…A decrease in clearance of theophylline in term neonates with HIE receiving hypothermia may be due in part to organ dysfunction, changes in blood flow, the effect of hypothermia, and/or other unknown factors. ( 15 , 16 ) In our study, markers of disease severity (inotropic support, invasive ventilatory support, acute kidney injury, and/or seizures) and hypothermia were examined and not found to be predictors of clearance. However, our study likely had low power to detect predictors of clearance given the small sample size and lack of a control group.…”

“…liver and kidney) and potential effects of hypothermia itself on drug pharmacokinetics. ( 15 , 16 ) Several previous pharmacokinetic studies in neonates with HIE receiving hypothermia have demonstrated altered pharmacokinetics and unique dose needs for critical medications including morphine, gentamicin, phenobarbital, and midazolam. ( 17 – 20 ) As theophylline is advanced as a renal protective therapy in neonates with HIE receiving hypothermia, an understanding of its pharmacokinetics will be essential to guide dosing.…”

Altered distributions and functions of natural killer T cells and γδ T cells in neonates with neonatal encephalopathy, in school-age children at follow-up, and in children with cerebral palsy

“…The incidence of NE ranges from 2 to 5 per 1000 live term births in advanced countries and up to 26 per 1000 live births in less developed countries (Kurinczuk et al, 2010). NE carries an overall mortality during postnatal period of 28% and approximately a third of surviving infants exhibit permanent neurodevelopmental delay in the form of cerebral palsy (CP), cognitive disabilities, or epilepsy (Kurinczuk et al, 2010;Korzeniewski et al, 2018;O'Dea et al, 2020). Affected new-borns may exhibit multiorgan dysfunction (Shah et al, 2004;O'Dea et al, 2020).…”

Creatinine Trends and Patterns in Neonates Undergoing Whole Body Hypothermia: A Systematic Review

“…This is because the initial cardiovascular response to oxygen depletion results in organ-specific vasoconstriction. This subsequently results in the redistribution of oxygen from non-vital organs to the heart and brain, while other organs, such as the intestines, liver, or kidneys, are underperfused [11][12][13]. As vasoreactive organs, the kidneys are very sensitive to oxygen deprivation, and this commonly (39-42%) results in oliguric or non-oliguric acute kidney injury (AKI) in this setting [14].…”