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The effect of caffeine on respiratory control in prematurely born infants

Presented at the Neonatal Society 2016 Autumn Meeting.

Rossor T, Rafferty G, Greenough A

Division of Asthma, Allergy and Lung Biology, King’s College London, London, United Kingdom

Background: Caffeine is used in the treatment of apnoea of prematurity, yet the mechanism by which it reduces apnoea remains unclear. It has been suggested that carbon dioxide (CO2) chemosensitivity may be enhanced by caffeine,(1) but this has not been assessed in infants. We have tested the hypothesis

Methods: Infants born at less that 34 weeks of gestation not requiring respiratory support were recruited on the first day after birth. A steady state hypercarbic challenge was delivered for five minutes via an open circuit, consisting of a non-return valve, a capnograph and a pneumotachograph. Challenges of 0%, 2% and 4% CO2 were delivered in a random order, with a washout period of five minutes between each challenge. The outcome assessed was the CO2sensitivity expressed as the increase in minute ventilation per % change in end tidal CO2. The hypercarbic challenge was repeated weekly until discharge.

Results: Twenty-seven infants, median gestational age of 32 +1 weeks (range 31+1 to 33+5) and median birth weight of 1650g (840-2200g), were recruited into the study. Fourteen infants subsequently required treatment with caffeine. Infants that received caffeine were born earlier median 32+1 weeks (31+1 to 33+4 weeks) versus 32+4 (31+1 to 33+5 weeks), p=0.047) and had a lower median birth weight 1560g (range 840g to 1840g) versus 1850g (range1120g to 2200g),p=0.046). A total of 93 studies were performed with median 4 (range 1-6) assessments per infant. CO2 sensitivity correlated significantly with the corrected gestational age (r=0.38, p<0.001). Linear regression models were developed which treated repeated measurements as independent measurements. Corrected gestational age and caffeine both contributed to the regression model for CO2 sensitivity (p=<0.001; p=0.037 respectively).

Conclusion: The ventilatory response to a hypercarbic challenge significantly increased with increased corrected gestational age and caffeine administration, which may explain why both factors are associated with reduction in the incidence of apnoeas.

Corresponding author: thomas.rossor@kcl.ac.uk

References
Pianosi P, Grondin D, Desmond K, Coates AL, Aranda JV. Effect of caffeine on the ventilatory response to inhaled carbon dioxide. Respiration physiology. 1994;95(3):311-20

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