Post-resuscitation strategies to avoid ongoing injury following intrapartum hypoxia–ischemia

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Summary

The interruption of placental blood flow during labor with redistribution of cardiac output resulting in increased flow to brain, heart, and adrenal glands at the expense of flow to kidney, gut, and skin can result in systemic organ as well as cerebral injury. Thus, post-resuscitation strategies should focus on both the management of potential systemic organ dysfunction and on methods of preventing ongoing brain injury in high-risk infants. General management strategies should include ventilator management to maintain pCO2 values in the normal range, close attention to blood pressure to avoid hypotension, striving to avoid hypoglycemia, and control of seizures. Modest hypothermia administered within the first 6 hours has been shown to reduce neurodevelopmental deficits and death in those infants at highest-risk infants for developing hypoxic–ischemic brain injury.

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:Cerebral perfusion pressure=mean arterial blood pressurevenous pressure

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.

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