Perinatal Asphyxia Syndrome
Perinatal asphyxia syndrome (PAS), also termed hypoxic ischemic syndrome (HIS), describes the clinical consequences of reduced oxygen delivery to tissues. The clinical effects of asphyxia can be widespread and can involve many systems including the nervous system, kidneys, gastrointestinal tract, and cardiopulmonary system.
The nervous system is the most commonly affected. The pathophysiology and clinical features of nervous system disease can be found in the Neonatal Encephalopathy section in Chapter 17. The renal system is the second most common system affected by asphyxia. In most affected foals the impact is relatively small, with reduced glomerular filtration and mild tubular disease, resulting in few abnormal clinical or laboratory findings. The most common laboratory derangement is persistent elevation in creatinine concentration or an increased level that is slow to normalize. In a small number of animals there is significant acute tubular necrosis resulting in anuria or oliguria, widespread edema, persistent and worsening elevation in serum creatinine concentration, and abnormal fractional excretion of electrolytes. Tissue edema can develop quickly, particularly if high rates of sodium-rich fluids are used. It is recommended to err on the side of fluid restriction rather than fluid excess when managing foals at risk for complications from PAS.97 See Chapter 17 for fluid therapy guidelines in neonatal foals. Nephrotoxic drugs such as gentamicin or amikacin should be avoided if possible, unless therapeutic drug monitoring is available.The management of oliguria or anuria can be difficult. Strategies to promote diuresis include a constant rate infusion (CRI) of dopamine at a rate of 2 to 5 μg/kg/min or furosemide at a CRI (0.25 to 2.0 mg/kg/h) or frequent boluses (1 mg/kg). The two treatments can be used concurrently.98 Use of mannitol remains controversial but can be considered if oliguria persists.
Once urine flow is established, the use of diuretics and vasoactive drugs should be revised and serum electrolyte concentrations and blood pH monitored. Overuse of diuretics can promote excessive fluid and electrolyte losses.The gastrointestinal tract is another common target for asphyxial injury. The clinical signs are often related to gastro- paresis and intestinal ileus. These include colic, recurrent gastric reflux, abdominal distention due to accumulation of intestinal gas and fluid, intestinal impaction, and diarrhea. In severe cases there is marked edema of the bowel wall, epithelial necrosis, and hemorrhage into the lumen. Damage to mucosal integrity can lead to translocation of bacteria with generalized peritonitis and systemic sepsis. The syndrome of necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality in preterm human infants.99 The disease involves intestinal coagulative necrosis, bacterial overgrowth, Pneumatosis intestinalis, and a marked inflammatory response. Although controversial, intestinal hypoxia or ischemia and infection with certain bacteria, such as Clostridium perfringens, may be important contributing factors.99 A similar syndrome has been reported in foals associated with birth hypoxia and Clostridium species.100,101
The recognition that intestinal complications of asphyxia should promote preventative strategies, including avoidance of overfeeding, monitoring of gastric and intestinal volume and wall movement with ultrasound, monitoring for increases in abdominal circumference using a soft tape measure, and avoidance of antiacid medications. Decreased gastric acidity may be a partial explanation as to why preterm human infants are at heightened risk of NEC.99 A small volume of milk is often fed to at-risk foals to promote intestinal health (so-called “trophic feeding”), but this falls short of what is required in terms of minimal caloric requirements.102 Trophic feeding is often around 12 to 24 mL/kg/day in human neonates, with full enteral feeding described as 150 to 180 mL/kg/day.103,104 Other strategies that have been used to reduce the risk of NEC in human preterm infants include recombinant erythropoietin (rEPO), probiotics, and lactoferrin105; none of these have been described in at-risk foals.
Recombinant EPO was originally used to treat anemia of prematurity but also exerts a trophic effect on the intestine.105 Calorie supplementation of foals with parenteral nutrition is strongly recommended, particularly when gastric reflux or hemorrhagic diarrhea is present and no enteral feeding can be used.Foals that have experienced an episode of hypoxia or ischemia are at increased for secondary infection and should be on broadspectrum antibiotics. The use of aminoglycosides should be reconsidered if therapeutic monitoring is not available due to likely altered renal function. Immunoglobulin prophylaxis is recommended when serum IgG concentration is less than 800 gm/dL (8 gm/L), although there are no data that document decreased infection or improved survival with plasma therapy in at-risk foals. Plasma does have benefits in addition to immunotherapy, including improvement of osmotic pressure and provision of coagulation factors and a buffer base.97 Glucose homeostasis is commonly disturbed in postasphyxiated foals, and concentrations should be monitored frequently. Hypoglycemia is frequently noted at the time of admission, but hyperglycemia is also common in responsive to modest replacement therapy. In some foals glucose intolerance can be managed by insulin therapy (see Chapter 17).
Respiratory failure is uncommon in PAS foals, but periods of hypoxemia and/or hypercapnia are not uncommon. Intranasal delivery of humidified oxygen is often helpful in the early stages of treatment. Rates of 2 to 5 L/min are commonly used with the goal of raising the arterial oxygen concentration (PaO2) above 80 mm Hg. This should be achieved along with maintenance of tissue perfusion, using judicious fluid therapy and vasopressive agents as needed. Hypercapnia should be treated only if there is a poorly compensated respiratory acidosis. This can be managed using positive pressure ventilation or respiratory stimulants, such as doxapram or caffeine.
The short-term prognosis for foals with PAS is dependent on several factors, including the degree and duration of oxygen deprivation, as well as the organ systems involved, and the preparedness and training of attending personnel. The prognosis for most foals is good to excellent with survival rates commonly reported around 75%.106,107