Influence of Early Indomethacin on Venous Admixture in Infants With HMD

Abstract

Caffeine is an efficient respiratory stimulant during theneonatal period, but its action on respiration beyond this period remains unclear. This study was performed to evaluate the effect of caffeine on ventilation in relation to post-natal maturation. Nineteen lambs divided in 3 groups of different ages were studied;I: 7 lambs with a mean age of 1 week;II: 6 lambs, mean age of 2 112 months and 111: 6 sheep, 6 months old. After a baseline period, saline (as a control infusion) then, 10 minutes later, caffeine 10 mg/kg I.V. were injected to the animals. Ventilation was measured using a mask adapted to the animal's facial contour and connected to a pneumotachograph; on-line values of t~ (minute ventilation), Vt/Ti, (mean inspiratory flow) and Ti/Ttot (timing of respiration) were derived from the flow signal using a computerized system.No response was seen after sa1ine;but in all three groups, VE (ml/min/kg) increased significantly after caffeine; this increase was 36% in groue 1; 46% in group 11; and was 48% in group 111. This increase in VE was due mainly to an increase in Vt/Ti (ml/sec/kg), which increased in groups I,II, 111 by 36,41 and 26%. Ti/Ttot did not change significantly at any time. The plasma concentrations were 9.7.8.8.10.0 mg/l in groups I,II,III. We conclude that: the magnitude of the ventilatory response and the strategy of breathing in response to the therapeutic blood concentration of caffeine persists withoutmajor difference between I week to 6 months of age in lambs. Caffeine is frequently used as a respiratory stimulant in the therapy of infants with apnen.The site of action of caffeine remains unclear and this present study was undertaken to evaluate the role of the chemoreceptors in the increase of ventilation following caffeine therapy. To achieve this goal we decided to study the response to caffeine after carotid body denervation (CBD). Twelve animals were studied, 6 had CBD and 6 had a sham denervation (intact) at a mean age of 13 days. The present study was carried out at a mean age of 80 days in an awake and not sedated state. The caffeine dose used was that recommended for human infants:lO mg/kg I.V. and the plasma concentration achieved was in the therapeutic range;CBO:9.0, intact:8.8 mg/l. The intact lambs responded significantly to caffeine by an increase in tE of 46% from 274+10(+SEM) to 400+21 ml/kg/min at I min. This response gradually faxed,-but at 2,-hours CE was still greater than baseline being 314+21. This increase in ventilation was mainly caused by a change in-vt/~i;from baseline 9.9 ml/kg/min it reached 14.0 at I min and was still increased at 120 min:11.2. In the CBD lambs no increase in VE (from baseline 263225) and VtjTi wasseen. No change in Ti/Ttot was seen in both groups. We concluded that: for the usual therapeutic dose of caffeine, CBD abolishes the increase in ventilation seen in intact lambs. This suggests that the carotid body receptors play an important role in the mediation of the ventilatory response to caffeine. This study was designed to assess the mecha...