Protein biosynthesis is halted. Calcium also enters the cells by glutamate-regulated ion channels as glutamate, an excitatory neurotransmitter, is released from pre-synaptic vesicles following anoxic cellular depolarization. Once the insulting event is over, protein synthesis remains inhibited in specific areas of the brain and returns to normal in less vulnerable areas of the brain. Loss of protein synthesis appears to be an early indicator of cell death due to the primary hypoxic/ anoxic event. A second wave of neuronal cell death occurs during the ‘reperfusion’ phase and is thought to be similar to classically described ‘post-ischemic reperfusion injury’ in that damage is due to production of and release of oxygen radicals, synthesis of nitric oxide (NO) and inflammatory reactions and is thought be associated with the neurotoxicity of glutamate and aspartate excitatory neurotransmitters. There is some evidence that this excitotoxic cascade extends over several days from the time of insult and is modifiable. The activation of the Nmethyl-D-aspartate (NMDA) subtype of glutamate receptors is implicated in the pathophysiology of traumatic brain injury and is suspected to play a role in NE/PAS. Magnesium and many drugs that control seizures have been demonstrated to block these receptors.
Treatment Therapy for the various manifestations of PAS involves: Control of seizures General cerebral support Correction of metabolic abnormalities Maintenance of normal arterial blood gas values Maintenance of tissue perfusion Maintenance of renal function Treatment of gastrointestinal dysfunction Prevention/recognition/early treatment of secondary infections General supportive care It is important that seizures be controlled as cerebral oxygen consumption increases five-fold during seizures. Diazepam and midazolam can be used for emergency control of seizures. If seizures are not readily stopped with diazepam or midazolam, or more than two seizures are recognized, then www.faep.net
diazepam should be replaced with either phenobarbital given to effect or a midazolam constant rate infusion (CRI). In cases of HIE, ketamine and xylazine should be avoided because of their association with increased intracranial pressure. It is important to protect the foal from injury during a seizure and also to ensure the patency of their airway to prevent the onset of negative pressure pulmonary edema or aspiration pneumonia. The most important therapeutic interventions are aimed at maintaining cerebral perfusion. Cerebral interstitial edema is only truly present in the most severe cases and, if suspected, can be treated with mannitol administration. Both mannitol and hypertonic saline infusions are minimally effective treating cellular edema. Thiamine supplementation in the intravenous fluids can be administered to support metabolic processes. Only if cellular necrosis and vasogenic edema are present are drugs such as mannitol and dimethylsulfoxide (DMSO) indicated. The author rarely uses DMSO, has not used it at for the last decade and has not recognized any change in outcome by discontinuing its use. There is evidence suggesting that naloxone increases ischemic injury in neonatal rats, making use of this compound controversial. GABAergic agonists (gabapentin) are being used by some practitioners in the managements of PAS/NE in foals, based on evidence showing neuroprotection when used in ischemia, both alone and in combination with NMDA antagonists like magnesium. There is no good quality evidence for the use of allopurinol, a xanthine oxidase inhibitor. Foals with PAS often have a variety of metabolic problems. The normal period of hypoglycemia that occurs postpartum should not be forgotten and should not be treated aggressively for fear of worsening the neurologic injury due to transient hyperglycemia. Foals suffering from PAS will also have frequent recurrent bouts of hypoxemia and occasional bouts of hypercapnia. INO2 is generally needed in these cases both as a preventative therapy and as direct treatment. Additional respiratory support, particularly in those foals with centrally mediated hypoventilation and periods of apnea or abnormal breathing patterns, include caffeine (per os or per rectum) or doxapram CRI. Foals requiring positive pressure ventilation or with severe respiratory disorders should be referred to a hospital. When evaluating these cases and considering alternatives for treatment, pH is important. If the respiratory acidosis is not so severe as to adversely affect the patient (generally > 70 mmHg), and the pH is within normal limits, hypercapnia may be tolerated. Maintaining tissue perfusion and oxygen delivery to tissues is a cornerstone of therapy. Oxygen carrying capacity of the blood should be maintained; some foals will require transfusions to maintain a PCV >20%. Adequate vascular volume is important, but care should be taken to avoid fluid or sodium overloading. Early evidence of fluid overload is subtle accumulation of ventral edema between the front legs and over the distal limbs. The kidney is a target for injury in these patients and it is not unusual for renal compromise to play a significant role in the demise of these foals. These foals present with signs of fluid overload and generalized edema. It is important that The Practitioner 7
Published on Feb 25, 2013