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Treatment Options for Early Asphyxia in Hypoxic Ischemic Encephalopathy


It is not always clear at birth which baby will recover completely from hypoxic ischemic encephalopathy (HIE) especially in mild cases. At the minimum, oxygen is given for breathing support while other organ systems are closely monitored. More severe forms of asphyxia may require ‘high frequency’ mechanical ventilations via a breathing tube attached to a machine, fluid intravenously, medication to prevent seizures and control blood pressure, and inhaled nitric oxide to help dilate blood vessels in the lungs to treat pulmonary hypertension to help oxygenate the blood in the lungs for transport to the other organs. In many cases of moderate to severe HIE in term or near-term (36 weeks and beyond) infants, hypothermia is used to cool the core body temperature to approximately 91 degrees F to prevent brain damage during the second phase of asphyxia which is when the blood flow to the brain is restored. An advanced form of support and therapy is extracorporeal membrane oxygenation (ECMO) which means that a heart-lung machine (outside of the body) provides the baby’s lungs and heart a rest and time to heal.

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Initial Resuscitation and Stabilization

Elk & Elk

Strict guidelines exist which use the standard neonatal Resuscitation Program (NRP) guidelines and specifically include oxygen therapy and delivery method, perfusion status, avoidance of hypoglycemia, hyperglycemia, and hypothermia. The decision to use 100% oxygen has been abandoned after multiple studies revealed that room air (21% oxygen concentration) is just as effective in resuscitation. It has been shown that less oxidative stress markers are found in infants who receive room air levels versus 100% oxygen. The time for the baby’s return to normal circulation has not been studied with room air. Based on this, international committees and the NRP guidelines are now recommending 21% oxygen unless the ventilation parameters do not improve. In this case, higher concentrations of oxygen should be given and monitored.

Supportive Care for Infants with HIE

In severe cases of HIE, most infants need ventilator support for a few days. Although some animal studies indicate that allowing increased carbon dioxide levels may be neuroprotective, no studies are available to show this in human newborns. The usual standards are to maintain the blood levels of oxygen and carbon dioxide in the normal physiologic ranges and correct any acid-base abnormalities. Removing too much carbon dioxide may lead to under perfusion of the brain and an increase base (pH) results in cellular alkalosis which results in a worse neurodevelopmental outcomes. The concentration level of inspired oxygen during the first 6 hours of life is important during hypothermia therapy. Studies show worse outcomes with increased oxygen levels. This further reinforces that room air is the best initial resuscitation tactic.

Blood Pressure and Perfusion Management

Low blood pressure is common in infants with HIE which is due to cardiac muscle dysfunction, leaky capillaries, and low blood volume. This leads to a decreased blood supply to the brain. Therefore, medications such as dopamine and dobutamine might be used to increase the heart’s pumping ability and increase the output of blood to the brain. It is essential to avoid the opposite effect such as unintentional high blood pressure.

Fluid and Electrolyte Management

Managing fluid volume which maintains blood volume and perfusion of vital organs is important and must be individualized based on clinical parameters such as changes in weight, urine output, blood serum levels of electrolytes (potassium, sodium, chloride, magnesium, calcium, phosphorus), and renal function studies. Electrolytes measure the acidity of the blood, the amount of water in the body, and muscle function. The kidneys are subject to acute tubular necrosis (ATN) and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion which means that fluid restriction may be necessary. Theophylline may be given preventatively to help reduce kidney dysfunction in HIE. In small studies, improved filtration, decreased protein spillage, and increased clearance of creatinine were noted. Avoiding low or high blood sugar is important. Exceptionally low blood sugar (hypoglycemia) is associated with significant adverse outcomes. Both high and low blood sugar can worsen brain damage.

Hyperthermia Avoidance

Increases in body temperature have an adverse effect in neonates with moderate to severe HIE. For every 1 degree C increase in temperature, there was a 3.6 to 4 –fold risk of death.

Hypothermia Treatment

Lowering the body temperature to 3-4 degrees C (mild hypothermia) for a few hours within 6 hours of birth has been shown to be neuroprotective in near-term and full-term infants. The possible explanation is not well understood, but could be due to a reduced metabolic rate and energy depletion, decreased production of stress hormones, reduced fluctuations in electrolyte movement, reduced oxidative and inflammatory free radical release, reduced swelling, reduced cellular death, and reduced vascular leaks. It may help keep the blood-brain barrier from being disrupted. Over 1500 infants who met criteria for moderate to severe HIE have been enrolled in multiple studies showing the benefit of controlled hypothermia. In 2013, the Cochrane review looked at 11 randomized trials of 1505 infants and found that hypothermia resulted in a reduction in mortality and neurodevelopmental disability at 18 months and survivors. Long-term follow-up revealed that in those babies in the control group (untreated) died 445 compared to 28% in the hypothermia group. IQ at age 6-7 was below 70 in 62% of untreated versus 47% in the treated group.

Future considerations include studies to determine the optimal duration of cooling which is currently set at 72 hours. For hospitals whose nursery lacks such technology, the ICE trial confirmed that a less complicated cooling method can be used by referring hospitals while awaiting transfer to tertiary centers. This involves using widely available ice packs for infant transport. It is believed that the more severe cases of asphyxia warrant longer periods of hypothermia. The addition of medications and EEG monitoring during hypothermia are also being evaluated to determine if improved outcomes can be attained with a multi-modal approach.

Adverse effects of hypothermia might theoretically include abnormalities of coagulation studies, white blood cell malfunctions, pulmonary hypertension, cardiac rhythm disturbances, or acidosis. However, the Cochrane review revealed that sinus bradycardia (slow heartbeat) and low platelets were the only significant findings and this was considered reassuring for the continued use of this therapy.