Novel interventions to reduce oxidative-stress related brain injury in neonatal asphyxia.

Perinatal asphyxia-induced brain injury may present as hypoxic-ischemic encephalopathy in the neonatal period, and disability including cerebral palsy in the long term. The brain injury is secondary to both the hypoxic-ischemic event and the reoxygenation-reperfusion following resuscitation. Early events in the cascade of brain injury can be classified as either inflammation or oxidative stress through the generation of free radicals. The objective of this paper is to present efforts that have been made to limit the oxidative stress associated with hypoxic-ischemic encephalopathy. In the acute phase of ischemia/hypoxia and reperfusion/reoxygenation, the outcomes of asphyxiated infants can be improved by optimizing the initial delivery room stabilization. Interventions include limiting oxygen exposure, and shortening the time to return of spontaneous circulation through improved methods for supporting hemodynamics and ventilation. Allopurinol, melatonin, noble gases such as xenon and argon, and magnesium administration also target the acute injury phase. Therapeutic hypothermia, N-acetylcysteine2-iminobiotin, remote ischemic postconditioning, cannabinoids and doxycycline target the subacute phase. Erythropoietin, mesenchymal stem cells, topiramate and memantine could potentially limit injury in the repair phase after asphyxia. To limit the injurious biochemical processes during the different stages of brain injury, determination of the stage of injury in any particular infant remains essential. Currently, therapeutic hypothermia is the only established treatment in the subacute phase of asphyxia-induced brain injury. The effects and side effects of oxidative stress reducing/limiting medications may however be difficult to predict in infants during therapeutic hypothermia. Future neuroprotection in asphyxiated infants may indeed include a combination of therapies. Challenges include timing, dosing and administration route for each neuroprotectant.

Assessment of gas flow waves for endotracheal tube placement in an ovine model of neonatal resuscitation.

AIM: Clinical assessment and end-tidal CO(2) (ETCO(2)) detectors are routinely used to verify correct endotracheal tube (ETT) placement. However, ETCO(2) detectors may mislead clinicians by failing to correctly identify placement of an ETT under a variety of circumstances. A flow sensor measures and displays gas flow in and out of an ETT. We compared endotracheal flow sensor recordings with a colorimetric CO(2)-detector (Pedi-Cap) to detect endotracheal intubation in a preterm sheep model of neonatal resuscitation. METHODS: Six preterm lambs were intubated and ventilated immediately after delivery. At 5 min the oesophagus was also intubated with a similar tube. The endotracheal tube and oesophageal tubes were attached to a Pedi-Cap and flow sensor in random order. Two observers, blinded to the positions of the tubes, used a ETCO(2) detector and the flow sensor recording to determine whether the tube was in the trachea or oesophagus. The experiment was repeated 10 times for each animal. In the last three animals (30 recordings) the number of inflations required to correctly identify the tube placement was noted. RESULTS: The Pedi-Cap and the flow sensor correctly identified tube placement in all studies. Thus, the sensitivity, specificity, and positive and negative predictive values of both devices were 100%. At least three, and up to 10, inflations were required to identify tube location with the Pedi-Cap compared to one or two inflations with the flow sensor. CONCLUSION: A flow sensor correctly identifies tube placement within the first two inflations. The Pedi-Cap required more inflations to correctly identify tube placement.