The critical Role of CO2 on Respiratory Control, PeriodicBreathing and Apnea in Neonates

Background- CO2 is a gas present in the atmosphere. Its linear shaped molecule contains two double bonds linking carbon and oxygen. It was discovered in 1630 by Jan Van Helmont who obtained the CO2 by fermenting grape and burning coal. From the beginning it was clear that CO2 is essential to life due to its warming effect on the planet and its role in photosynthesis. In the beginning of the 20th century Haldane (1905) first suggested that breathing is controlled by a negative feedback system in which CO2 is both the controlled and the controller variable. Phillipson and others have shown that without CO2 breathing is absent. During most of the last century the consensus was that CO2 acted centrally on the rostral ventro-lateral surface of the medulla oblongata (Loeschcke;1958, Mitchell, 1963) Only in the end of the last century this action was located on the respiratory neurons of the Pre-Bötzinger region. These are inspiratory pacemakers neurons highly sensitive to CO2. The dendrites of these neurons are located adjacent to the surface of the medulla previously thought to be responsible for this response. The CO2 receptors of these cells are likely to be located in the dendrites of these neurons, mimicking CO2 receptors described for more primitive species, but this has not yet been documented. Breathing Pattern- CO2 is known to be a powerful regularizer of breathing pattern. Our observations show that the coefficient of variability of tidal volume is much less with CO2 than with other regularizers of breathing, such as O2 or Methylxanthines. The CO 2Threshold-Our data in 16 preterm and 16 term infants (JAP 98:1171–76,2005) suggested that periodic breathing occurs due to a periodic fall in baseline PCO2 below the apneic threshold (CO2 level below which breathing stops). InhaledCO2 to Treat Apnea- When assessed in the clinical laboratory, under strict administration control, both CO2 and theophylline decreased apnea time by 71%, and prolonged apnea (=20s) by 92% (n=20). When measured in the Nursery, in a double blind randomized control trial, inhalation of 1% CO2 and theophylline decreased apnea time by 68% and 49% respectively (Pediat Res: 106, 2, 2007; n=79). Prolonged apneas also decreased by 87% and 33%. The fall was always more pronounced with theophylline. Seven infants with residual lung disease did not respond to CO2, but responded to CPAP. Adverse side effects such as tachypnea, tachycardia, emesis and jitteriness predominated with theophylline. We surmised that CO2 inhalation may be a safe alternative to theophylline in the treatment of apnea of prematurity in infants without residual lung disease.