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Juan Sastre, PhD
Jose Viña, PhD, MD
Department of Physiology
School of Medicine
University of Valencia
46010 Valencia, Spain
To the Editor.—
In a recent article, Rutherford et al1 describe the neuroprotective effect of whole-body cooling and selective head cooling in newly born infants suffering from hypoxic-ischemic encephalopathy. MRI studies of infants receiving either of these therapies showed a lesser degree of basal ganglia and thalamic lesions than nontreated controls, which correlates with a better neurologic prognosis.
However, no description of the resuscitation maneuvers used is present in the article's "Patients and Methods" section. Thus, the authors do not include details on how many infants were given positive pressure ventilation and, especially, what concentration of oxygen was used, if oxygen saturation was controlled by pulse oximetry within physiologic limits, or if blood gases were determined once the resuscitation procedures were concluded and the patients were considered clinically stable. These details undoubtedly are of extreme importance, considering the fact that asphyxia was defined as having an Apgar score of <5 at 5 minutes and cord pH level of <7.1, and it has been previously described that many infants recover without additional neurologic sequelae under these circumstances and may easily reach hyperoxemia during resuscitation.2,3
Mild hypothermia has been shown to be protective to the neonatal brain because it attenuates neuronal energy metabolism, reduces cytotoxic edema, and excitotoxicity, thus improving outcome.4,5 Under these circumstances, neurons preserve their ATP stores for a longer period of time and accumulate less purine derivatives such as hypoxanthine. After reoxygenation, the xanthine oxidase enzymatic complex metabolizes these compounds to uric acid. However, if there is an excess of oxygen in the milieu, xanthine oxidase uses dioxygen as a substrate, producing an outburst of oxygen free radicals.6 These extremely aggressive reactive species not only damage nearby cellular organelles and structures but also act as cellular signaling molecules promoting apoptosis, thus amplifying the initial area of neuronal damage.7,8
The use of room air (21% oxygen concentration) has been shown not only to be suitable for resuscitating asphyxiated newly born infants9 but also to reduce postnatal oxidative stress as measured by the oxidized to reduced glutathione ratio (GSH/GSSG) and other oxidative stress markers such as malondialdehyde, 8-oxo-dihydroguanosine, or antioxidant enzyme activities.10 In fact, the GSH/GSSG ratio not only reflects the pro-oxidant-to-antioxidant balance in the cytoplasm of the cells but, more importantly, it correlates with the intracellular redox status, which is indispensable for the cell maturation, reproduction, and survival, as recently shown by our group.11 Thus, we have reported that newborn infants resuscitated with 100% oxygen had significantly higher GSSG concentration in the first days of postnatal life, which correlated with increased cardiac and renal damage as compared with those who were resuscitated with room air.12 In accordance with these findings, recent meta-analyses have shown an increased mortality in newly born infants resuscitated with 100% oxygen as compared with those resuscitated with room air.13,14
At present, an increasing number of hospitals worldwide are initiating resuscitation of the asphyxiated newly born infant with lower concentrations of oxygen and close control of oxygen saturation. Under these circumstances, it would have been extremely important and informative if Rutherford et al had included in their methodology section a detailed description of the procedures used for the resuscitation of asphyxiated infants, as well as the blood gases obtained when clinical stabilization was achieved. Thus, the oxygen concentration used during the first minutes of life, as well as the PO2, PCO2, and base excess reached within the first minutes of postnatal life, may significantly influence outcome of their patients, as shown in the above-mentioned studies, and bias the results of a specific therapeutic approach such as selective brain cooling or whole-body cooling.
REFERENCES
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