J.A. Davis

DRY ARTIFICIAL LUNG SURFACTANT AND ITS EFFECT ON VERY PREMATURE BABIES

Artificial lung surfactant prepared with pure dipalmitoylphosphatidylcholine and phosphatidylglycerol in a ratio of 7:3 was made as a dry powder and then blown down an endotracheal tube into the lungs of 22 very premature babies at birth. Only one dose was given. The treated babies did better than their 33 controls. Fewer needed ventilation, and those who did required lower pressures in the first six hours of life. None of the treated babies died, compared with 8 of the controls.

PANCURONIUM PREVENTS PNEUMOTHORACES IN VENTILATED PREMATURE BABIES WHO ACTIVELY EXPIRE AGAINST POSITIVE PRESSURE INFLATION

Preterm infants who were making expiratory efforts against ventilator inflation were randomised to be paralysed with pancuronium or to receive no paralysing agent during ventilation. Pneumothoraces developed in all 11 unparalysed babies but in only 1 of 11 (p less than 0.0004) of those managed with pancuronium, which had no serious side-effects. In 34 infants excluded from the trial because they were not breathing against the ventilator, no pneumothoraces developed.

The therapeutic actions of theophylline in preterm ventilated infants

40 preterm, ventilated infants (gestational ages 24-33 weeks) were entered into a double-blind randomised trial to assess the effect of oral theophylline on lung function and ventilator dependence. Theophylline administration was associated with a significant improvement in compliance (P less than 0.05) and hastened weaning from ventilation (P less than 0.01).

Respiratory reflexes in ventilated premature babies

The respiratory response to therapeutic lung inflation by artificial ventilation in premature babies has been studied. Both the Hering-Breuer and an augmented inspiratory reflex could be provoked by ventilator inflation in neonates as premature as 25 weeks gestational age. No chemo-receptor control was demonstrated on the presence of these reflexes. Augmented inspirations were only seen in the first five postnatal days regardless of gestational age, but the Hering-Breuer reflex persisted throughout the period of study of 11 days. The frequency of elicitation of augmented inspirations was shown to be inversely related to the dynamic compliance. The relative stimulation of these two respiratory reflexes may explain why some infants are easy to ventilate and others difficult.

Provoked augmented inspirations in ventilated premature babies

The stimulating and moderating factors of augmented inspirations provoked by artificial ventilation have been studied in 40 preterm babies on 182 different occasions. Provoked augmented inspirations were demonstrated by recording spontaneous respiratory activity during artificial ventilation by means of an oesophageal balloon and a pneumotachograph. Augmented inspirations were only seen during 18% of the study occasions. The frequency of this reflex was inversely related to the lung compliance as was the ventilator pressure necessary to provoke the augmented inspiration. The inflating volume which stimulated the reflex, when related to body weight, was similar in all the babies. Augmented inspirations were always provoked during the rapid rise in ventilator pressure at the onset of each inflation. Neonates who were recovering from paralysis by pancuronium and others being treated with theophylline both showed an increased frequency of augmented inspirations. It is possible that theophylline could be used to harness this advantageous reflex for the benefit of the ventilated preterm neonate.

Pulmonary surfactant. II. In sudden infant death syndrome

The lung surfactant phospholipid composition of lavage samples from 102 babies dying from Sudden Infant Death Syndrome (SIDS) (one-third with minor signs of inflammation) was compared with that of: 34 babies dying from Hyaline Membrane Disease (HMD), 15 mature babies dying soon after birth, 16 mature babies dying in the same age range as the sudden infant death syndrome cases, 13 babies dying from pneumonia and 6 from septicaemia. The surfactant of the two groups of babies dying from SIDS was identical and approximated that obtained from babies dying from HMD, pneumonia or septicaemia. Compared to that obtained from mature babies, the surfactant of babies dying from SIDS contained significantly lower proportions of phosphatidylcholine (PC) and significantly higher proportions of lyso-PC and sphingomyelin. The proportion of disaturated PC was similar to that of the surfactant of the age-matched mature babies. The surfactant composition of the babies dying from SIDS did not change appreciably after death nor vary with age at death. The surfactant phospholipid composition of postmortem samples from mature babies was similar to that of aspirates from living babies and infants and to that of bronchoalveolar lavage samples from living adults.

Pulmonary surfactant. I. In immature and mature babies

Lung surfactant was obtained by postmortem lavage from: (A) premature babies: 34 dying acutely within 2 days of birth from Hyaline Membrane Disease (HMD), 20 dying several days after birth with HMD and its consequences, 8 dying from causes other than HMD; (B) mature babies: 24 dying stillborn, 15 dying soon after birth and 16 dying between 2 weeks and 1 year of age with minimal lung pathology. The phospholipid composition of the surfactant was analysed. Compared to the surfactant of babies dying acutely from HMD, that of the babies dying later from HMD contained significantly higher proportions of phosphatidylcholine (PC) and significantly lower proportions of sphingomyelin while that of the mature babies contained significantly higher proportions of PC and phosphatidylglycerol but significantly lower proportions of sphingomyelin and combined phosphatidylinositol and phosphatidylserine. The surfactant of premature babies dying of causes other than HMD was similar and intermediate to that of both groups of babies dying from HMD. The PC fraction composition of the surfactant of the babies dying acutely from HMD contained significantly lower proportions of the disaturated fraction than those of the babies dying later from HMD, stillborn babies or mature babies.

THEOPHYLLINE, SAFELY AND EFFECTIVELY HASTENS WEANING FROM VENTILATION IN PRETERM NEWBORNS

Methylxanthines have been used for many years to treat neonatal apnoea in preterm infants. Preliminary evidence suggests they may also have a role in weaning such infants from artificial ventilation (IPPV). This was investigated in a double blind randamised trial giving thecphylline orally to preterm infants (x GA 28.5 weeks), using a loading dose of 5 mg/kg and a maintenance dose of 5 mg/kg/24 hrs in four divided doses. Control infants received a placebo solution which was indistinguishable from the active preparation. Forty infants were entered into the study and the two groups were well matched for gestational and postnatal age, sex, type and place of delivery.Administration of theophylline caused both a significant improvement in compliance (p< 0.05) six hours after commencing treatment and hastened weaning from IPPV, (p< 0.01) compared to the controls. Its use was not associated with an increased incidence of side-effects, in particular no fits, gastric irritation or fluid and electrolyte inbalance was seen.We conclude that the use of oral theophylline is a safe and effective method of hastening weaning from IPPV in preterm neonates.