Hypoxia - Reoxygenation in neonatal cardiac arrest: Results from experimental models.

In this review, we summarize the results of studies that investigated the effects of hypoxia and reoxygenation in cardiac arrest, including the use of different fractions of inspired oxygen, in neonatal animals. The studies were heterogenous in terms of anaesthetic regimens, and definitions of cardiac arrest and circulatory recovery. Cardiopulmonary resuscitation with 100% oxygen increased oxidative stress in maturing rats. Studies in fetal/neonatal lambs and post-transitional neonatal piglets indicate no consistent differences between ventilation with 21% vs. 100% oxygen with regards to recovery times, oxygen damage or adverse events. If 21% oxygen is as effective as 100% oxygen in newborn infants with cardiac arrest requiring chest compression, the use of 21% instead of 100% oxygen could reduce morbidity and mortality in asphyxiated infants. Unanswered questions include what is the most optimal cerebral oxygen delivery during reperfusion, as well as oxygenation targets after return of spontaneous circulation.

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.

Tidal volume delivery during continuous chest compressions and sustained inflation.

OBJECTIVE: To determine the distending pressure needed to achieve sufficient tidal volume (VT) delivery during continuous chest compressions (CC) superimposed by sustained inflation (SI) (CC+SI). DESIGN: Randomised animal/manikin trial. SETTING: University laboratory. SUBJECTS: Cadaver piglets/manikin. INTERVENTIONS: SI distending pressures of 5, 10, 15, 20, 25 and 30 cm H2O were delivered in random order during CC+SI for 2 min each. MAIN OUTCOME MEASURES: VT, gas flow and airway pressure. Spearman's r for distending pressure and VT. RESULTS: Distending pressure and VT correlated in cadaver piglets (r=0.83, p<0.001), manikin (r=0.98, p<0.001) and combined data (r=0.49, p<0.001). VT was delivered during chest recoil during CC in both models. In cadaver piglets, a distending pressure ∼25 cm H2O was needed to achieve an adequate VT. CONCLUSIONS: Chest recoil generates VT depending on an adequate distending pressure. This has previously been demonstrated in adult animals. A pressure of ∼25 cm H2O is needed to achieve an adequate VT delivery.