C.J. Morley

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.

PROLONGED EXPIRATORY APNOEA: A DISORDER RESULTING IN EPISODES OF SEVERE ARTERIAL HYPOXAEMIA IN INFANTS AND YOUNG CHILDREN

Ten infants with rapidly developing and severe episodes of hypoxaemia (15-120 s duration) were studied. In infants over 2 months old most episodes occurred when awake, after a sudden noxious stimulus. In younger infants frequent yet undetected episodes occurred during sleep and feeding. Arterial PO2 fell below 20 mm Hg within 20 s, and loss of consciousness, sometimes with convulsions, occurred after 30 s. Clinical observations, measurements of respiratory movements, air flow, oesophageal pressure, external oblique surface electromyogram, and, in two cases, chest fluoroscopy and microlaryngoscopy documented episodes of no inspiratory flow but continued expiratory activity at low lung volume with partial or complete glottic closure. In five infants, episodes continued despite tracheostomy or an indwelling nasotracheal tube. No intracardiac shunt could be demonstrated and the rapid fall in arterial PO2 was attributed to lack of ventilation at a maximum expiratory position in the presence of a rapid recirculation time. In five infants tested there was a low proportion of phosphatidylcholine in the tracheal aspirate. In one infant audible expiratory braking (grunting) was present for most of the awake time. This previously unrecognised mechanism for severe hypoxaemia may be one cause of neurodevelopmental damage and sudden death in infants and young children.

Fighting the ventilator — are fast rates an effective alternative to paralysis?

We investigated the effect of increased ventilator rates on the respiratory activity of 17 infants, all actively expiring against the ventilator at conventional rates. Fast rate ventilation was rarely associated with apnoea (3 babies only) and the infants respiratory efforts even at rates of 120/min had an important effect on tidal exchange. Seven infants altered their respiratory response to breathe in synchrony with the ventilator at 60 breaths/min and 5 maintained this at 120 breaths/min. Nine of the 17 infants continued to actively expire against positive pressure inflation at 60 breaths/min and in two this persisted at 120/min, the remaining 7 infants showed incoordinated breathing at that rate. We conclude that fast rate ventilation appears to have only limited success in suppressing respiratory activity in infants actively expiring against the ventilator.

Comparison of Different Rates of Artificial Ventilation in Preterm Neonates with Respiratory Distress Syndrome

The effectiveness of three different ventilator rates of artificial ventilation (30, 60 and 120/min) was studied in 32 preterm infants, all of whom were suffering from the Respiratory Distress Syndrome (16 were paralysed). Ventilator pressures, I: E ratio and MAP were kept constant at each rate. Increase in rate from 30 to 60 and to 120/min was well tolerated and not associated with episodes of hypotension. The only significant improvement in oxygenation was amongst the non‐paralysed infants and at a rate of 120/min (p<0.01) this was associated with synchronous respiration. Two different ventilators were used in the study and a significant change in Paco2, (reduction) occurred only in non‐paralysed infants ventilated at a rate of 120/min by Sechrist ventilators (p<0.05). This difference may be a direct reflection of differences in ventilator performance at fast rates.

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.

Introductory remarks about artificial lung expanding compounds (ALEC)

Abstract A dry protein-free powder consisting of a 7:3 mole/mole mixture of dipalmitoylphosphatidylcholine/phosphatidylglycerol seems to function as a reasonably good substitute for natural lung surfactant in very premature babies. It has the following necessary properties: (1) It spreads rapidly and spontaneously at an air/water interface at 37°C, reducing the surface tension of water by about 2/3. (2) The unsaturated phosphatidylglycerol (PG) moiety can be squeezed out of the mixed monolayer by rapid overcompression (equivalent to exhalation) and is irreversibly lost to the surface system by reassembly into liposomes. (3) The residual dipalmitoylphosphatidylcholine (DPPC) becomes progressively enriched to the point that, at 37°C, it condenses out as a solid phase so rigid that it prevents the alveoli from collapsing. (4) The preparation is protein-free. It is suggested that this simple mixture of two phospholipids exhibits both thermodynamic (equilibrium) and kinetic forces during the course of a compression/decompression cycle on a trough. Likewise, during a respiratory cycle, the alveoli might be kept open (or more precisely, the liquid lining the alveoli is prevented from filling them up) at full expiration by the presence of a permanent residue of almost pure DPPC which, being condensed (solid), is incompressible. The work of extending the uncovered air/water interface, upon inspiration, is reduced by replenishment from the stockpile of dry surfactant as though from a lamellar body. The respiratory cycle is thus seen as a dynamic sequence of ablution and replenishment of phospholipid molecules. The material has been used cautiously in a clinical trial involving some 100 or more at-risk babies and the encouraging results so far will be reported.

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.