Effects of respiratory stimulants on cerebral metabolism and blood flow

The cerebral metabolic and circulatory effects of the two main classes of respiratory stimulants used in the apnea of the newborn and premature infant, i.e. methylxanthines and doxapram, have not been studied in great detail. In adult animals and humans, methylxanthines widely increase cerebral metabolic rates and simultaneously decrease cerebral blood flow levels. Thus, these compounds are able to reset the level of coupling between cerebral blood flow and energy metabolism inducing a relative hypoperfusion at a constant metabolic rate. In neonates, methylxanthines induce no change in cerebral blood flow as long as the drop in pCO2 related to drug administration is prevented. Information on doxapram effects on cerebral blood flow and metabolism is very scarse and limited to adult animals. Doxapram does not induce any change in cerebral energy metabolism and transiently decreases cerebral blood flow. In conclusion, it seems that the use of methylxanthines in apneic newborn infants fulfils a good margin of safety with respect to cerebral blood flow as long as no other pathology such as marked hypoxia or seizures is present. The use of doxapram also seems to stay in a good margin of safety in terms of cerebral blood flow and energy metabolism but many more studies are necessary to better understand the effects of this respiratory stimulant on cerebral functional activity.