Post-resuscitation strategies to avoid ongoing injury following intrapartum hypoxia–ischemia
Introduction
The consequences of interruption of placental blood flow that occurs during labor, particularly when severe or prolonged, can affect cerebral and systemic function. Thus, acute hypoxia that is sufficient to result in neonatal encephalopathy almost always involves multiple organs and not just the brain.1, 2 Multisystem involvement can include renal failure, cardiac damage, hepatic injury, respiratory complications, acute bowel injury, and hematologic abnormalities.1, 2, 3 Thus, post-resuscitation strategies should focus on both the management of systemic organ dysfunction and on methods to prevent ongoing brain injury. This chapter reviews the pathophysiology associated with interruption of placental blood flow, systemic organ injury, metabolic disturbances, potential adverse cerebral consequences, treatment strategies directed at modulating systemic organ dysfunction, and methods of preventing ongoing injury with modest hypothermia.
Section snippets
Pathophysiology
The pathophysiology attributed to brain and systemic organ injury is initiated as a consequence of the circulatory changes that accompany the interruption of placental blood flow. This is frequently referred to as ‘asphyxia’, which is a biochemical term describing progressive hypoxia, hypercarbia, and acidosis. It is generally accepted that an umbilical cord arterial pH < 7.00 (a state referred to as severe or pathologic fetal academia) reflects a degree of acidemia below which the risk of brain
Systemic organ injury and management
As noted above, systemic organ involvement is common when interruption of placental blood flow is severe or prolonged. Thus, in one study, approximately 60% of ‘asphyxiated’ term infants exhibited single or multiple organ injury.1 In another study, severe central nervous system involvement always occurred with the involvement of one or more organs.3 Thus, to reduce the severity of long-term morbidity, post-resuscitative management should focus on optimizing supportive care that will facilitate
Ventilator management
Most infants who have a suffered a moderate to severe insult are likely to receive ventilator support during the first days of life. As pCO2 levels influence cerebral blood flow, with hypercarbia causing cerebral vasodilation and hypocarbia causing a reduction in cerebral blood flow, close attention to ventilator support is important. Appropriate support can be guided through assessment of serial arterial blood gases. Both hypocapnia and hypercapnia appear to increase the risk of brain injury
Blood pressure and fluid administration
Blood pressure is a key component to maintaining cerebral perfusion. In turn, cerebral perfusion is influenced by the venous pressure, and is reflected in the following relationship:
Some studies suggest that for term infants a mean blood pressure > 35–40 mm Hg is necessary to avoid a decrease in cerebral perfusion pressure.10, 11, 12 However, this issue has not been subjected to randomized studies. Nonetheless, blood pressure
Renal status
Oliguria (defined as urine output < 1 cc/kg/h) is a common finding and can complicate the fluid management of infants. The mechanisms for oliguria are not entirely clear. One pathway relates to the release of adenosine, which acts as a vasoconstrictive metabolite contributing to a fall in glomerular filtration rate. This vasoconstriction can be blocked by theophylline, a non-specific adenosine antagonist. In two small, randomized, placebo-controlled studies,15, 16 ‘asphyxiated’ infants [(n = 24)15;
Electrolyte imbalance
During the post-resuscitative phase, infants frequently develop electrolyte abnormalities, including hyponatremia, hypocalcemia, or hypomagnesemia. These parameters should be monitored closely and treated as clinically indicated.
As mentioned above, hyponatremia is likely to be due to impaired renal function and/or inappropriate release of antidiuretic hormone. The treatment of hyponatremia is fluid restriction until an improvement of urine output and a decrease in weight is noted.
Hypocalcemia
Glucose management
Experimental studies suggest that in the context of cerebral hypoxia–ischemia, both hyperglycemia and hypoglycemia can accentuate brain damage. In adult experimental animal models, as well as in humans, brain damage is accentuated with hyperglycemia. However, in immature animals subjected to cerebral hypoxia–ischemia, hyperglycemia to blood glucose concentration of 600 mg/dL entirely prevents the occurrence of brain damage.18 The effects of hypoglycemia in experimental animals vary and are
Seizures
Hypoxic–ischemic cerebral injury is the most common cause of early-onset neonatal seizures. Although seizures are a consequence of the underlying brain injury, seizure activity in itself might contribute to ongoing injury. Experimental evidence strongly suggests that repetitive seizures disturb brain growth and development, and also increase the risk for subsequent epilepsy.20, 21 Despite the potential adverse effects of seizures, the question of which infants should be treated remains
Potential neuroprotective strategies aimed at ameliorating secondary brain injury
Supportive care as outlined above, while important in the overall management of infants with HIE, is clearly not focused on the more relevant and specific issue, i.e. the prevention of the secondary phase of brain injury. Interventions currently under investigation include the use of modest hypothermia, excitatory amino acid antagonists, i.e. magnesium sulfate, erythropoeitin and minocillin.
Conclusions
Post-resuscitative management following delivery should include strategies directed towards potential consequences of systemic organ dysfunction, e.g. hypotension and its possible impact on cerebral perfusion and oxygen delivery. Advances in the understanding of ongoing brain injury have facilitated the introduction of a targeted neuroprotective strategy, i.e. modest hypothermia that has improved long-term outcome in a subset of patients. Future strategies are likely to include hypothermia as a
Conflict of interest
The authors have no conflicts of interest to disclose.
References (70)
- et al.
Neonatal organ injury in acute asphyxia sufficient to result in neonatal encephalopathy
Obstet Gynecol
(2002) - et al.
Multiple organ involvement inperinatal asphyxia
J Pediatr
(1995) - et al.
Hypoxic-ischemic brain injury in the term infant- current concepts
Early Hum Dev
(2004) - et al.
Hypoxic-ischemic brain injury in the newborn: cellular mechanisms and potential strategies for neuroprotection
Clin Perinatol
(1997) - et al.
Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trail
J Pediatr
(2006) Hypoglycemic injury to the immature brain
Clin Perinatol
(2002)Consensus and controversy in the clinical management of neonatal seizures
Clin Perinatol
(1989)- et al.
Use of barbiturate therapy in severe perinatal asphyxia: a randomized controlled trial
J Pediatr
(1986) - et al.
Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial
Lancet
(2005) - et al.
Moderate hypothermia in neonatal encephalopathy: efficacy outcomes
Pediatr Neurol
(2005)
Neuroprotection against hypoxia-ischemia in neonatal rat brain by novel superoxide dismutase mimetics
Neurosci Lett
Hypoxic-ischemic encephalopathy, therapeutic approaches against microvascular injury, and role of neutrophils, PAF, and free radicals
Clin Perinatol
Pathogenesis of hypoxic-ischemic cerebral injury in the term infant current concepts
Clin Perinatol
Magnesium protects against neurological deficit after brain injury
Brain Res
Enhancing adenosine A1 receptor binding reduces hypoxic-ischemic brain injury in newborn rats
Brain Res
Erythropoietin exerts neuroprotective effect in neonatal rat model of hypoxic-ischemic brain injury
Brain Dev
Acute systemic organ injury in term infants after asphyxia
Am J Dis Child
Dalayed seconday cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continues 48-hour studies by phosphorus magnetic resonance spectroscopy
Pediatr Res
Hypocapnia and other ventilation-related risk factors for cerebral palsy in low birth weight infants
Pediatr Res
Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants
J Perinatol
Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants
Pediatrics
Intracranial and cerebral perfusion pressure: methodology and clinical considerations
Med Instrum
Continuous measurement of subarachnoid pressure in the severly asphyxiated newborn
Arch Dis Child
Value of intracranial pressure monitoring of asphyxiated newborn infants
Dev Med Child Neurol
Randomized trail of volume infusion during resuscitation of asphyxiated neonatal piglets
Pediatr Res
Use of volume expansion during delivery room resuscitation in near-term and term infants
Pediatrics
A randomized, double-blind, placebo controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia
Pediatrics
Neonatal hypoglycemia in infants with birth asphyxia
Pediatrics
Initial hypoglycemia and neonatal brain injury in term infants with severe fetal acidemia
Pediatrics
Seizures accelerate anoxia-induced neuronal death in the neonatal rat hippocampus
Ann Neurol
Consequences of neonatal seizures in the rat: morphological and behavioral effects
Ann Neurol
Electrographic seizures in preterm and fullterm infants neonates: clinical correlates associated brain lesions and risk for neurologic sequelae
Pediatrics
High-dose phenobarbital therapy in term newborn infants with severe perinatal asphyxia: a randomized prospective study with three-year follow-up
J Pediatr
Influence of mild hypothermia on hypoxic-ischemic brain damage in the immature rat
Pediatr Res
Modest hypothermia provides partial neuroprotection for ischemic neonatal brain
Pediatr Res
Cited by (27)
Neonatal multiple organ failure after perinatal asphyxia
2022, Anales de PediatriaSpring into action
2019, Journal of Neonatal NursingGeneral Supportive Management of the Term Infant With Neonatal Encephalopathy Following Intrapartum Hypoxia-Ischemia
2018, Neurology: Neonatology Questions and ControversiesHypoxic-Ischemic Encephalopathy (HIE): A Review for the Bedside Nurse of a Complex Clinical Problem
2016, Newborn and Infant Nursing ReviewsCitation Excerpt :In HIE, temperature management is key to optimizing outcomes. Care should be taken to make sure that the infant is not overheated during resuscitation/stabilization.17–20 If the infant needs to be transported to a tertiary care center, passive cooling on a radiant warmer to a body temperature of 36 °C axilla until the transport team arrives is recommended.
Subacute Hypoxia-Ischemia and the Timing of Injury in Treatment With Therapeutic Hypothermia
2015, Pediatric NeurologyEarly hyperglycemia is associated with poor gross motor outcome in asphyxiated term newborns
2014, Pediatric Neurology