Biomedical subjects
Publications and source records attributed to C J Morley.
Among 320 low birthweight infants seen at nine months post term those using a soft object, thumb, or fingers as comforter were significantly less likely to wake at night (9/96, 9%) than those with no comforter or using a dummy (66/224, 29%). Dummy users were as likely to wake (27/93, 29%) as those without a comforter (39/131, 30%).
Artificial surfactant (ALEC) made from DPPC and uPG 7:3 w/w has been given at birth to babies under 30 weeks of gestation in three trials. The first trial enrolled 62 resuscitated babies: 28 treated with 25 mg ALEC powder and 34 controls. The mortality fell from 41 to 7% (p = 0.0005). In the second trial babies were randomized to receive 1 ml of 100 mg ALEC suspension into the pharynx at birth and up to 3 more endotracheal doses in 24 h. Controls received 1 ml of saline. There were 69 ALEC-treated babies and 67 controls. The mortality due to complications of respiratory distress syndrome (RDS) fell from 31 to 9% (p less than 0.01); periventricular haemorrhage was reduced from 40 to 19% (p less than 0.01). The third trial involved 328 babies randomized in 10 centres. ALEC treatment reduced the neonatal mortality from 27 to 14% (p less than 0.002); intracerebral haemorrhages fell from 24 to 16% (p = 0.06) and severe RDS by 27% (p less than 0.03). Regression analysis showed a significant reduction in hours receiving ventilation and greater than 30% oxygen during the first 10 days.
Artificial surfactant (ALEC), when used in a crystalline state, has physical properties similar to natural surfactant. It is composed of two phospholipids with no protein. When placed in the trachea of ventilated premature rabbits it significantly increased the lung compliance. In three prophylactic clinical trials with babies under 30 weeks gestation this surfactant has been shown to reduce the neonatal mortality by about half and to significantly decrease the incidence of intraventricular haemorrhage and bronchopulmonary dysplasia without any increase in the incidence of subsequent handicap.
A technique for recording activity in the external abdominal oblique muscles of the human newborn is described. It uses simple, self-adhesive, surface electrodes arranged to reduce electrocardiographic interference. This method is applicable to studies of the respiratory patterns of very pre-term babies undergoing intensive medical care.
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.
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.
Artificial surfactant (ALEC) composed of dipalmitoylphosphatidylcholine and unsaturated phosphatidylglycerol in a ratio of 7:3 (w/w) and a dose of 50-100 mg was suspended in 1 ml of cold saline and used at birth as a prophylaxis against the respiratory distress syndrome and its complications in a two centre randomized prospective trial involving 341 babies from 23 to 34 weeks gestation regardless of their antenatal problems. The surfactant had little effect in babies above 29 weeks gestation and was most beneficial in babies under 30 weeks gestation (67 controls and 69 surfactant treated babies). In this subgroup the artificial surfactant significantly reduced the inspired oxygen and peak ventilator pressure requirements during the first 96 h, the incidence of intraventricular haemorrhages from 40% to 19% (P less than 0.01), the overall mortality from 36% to 17% (P less than 0.02), the mortality due to RDS from 31% to 9% (P less than 0.01), the need for more than 28 days oxygen from 37% to 21% (P = 0.05) and the use of pancuronium in ventilated babies from 52% to 27% (P less than 0.01). There were no apparent side effects. This protein free, artificial surfactant should be a useful addition to the therapy of babies under 30 weeks gestation to reduce the severity of their RDS and the incidence of serious complications.
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Twenty preterm infants ventilated for the respiratory distress syndrome were studied on 44 occasions to identify the pattern of interaction between their spontaneous respiratory efforts and the ventilator, using three techniques: (1) an oesophageal balloon and pneumotachograph, (2) impedance respirography and (3) clinical scoring. The information was in agreement on 23 of the occasions. In 7 infants the balloon and pneumotachograph showed active expiration which was not detected by the other methods. Four of these infants sustained a pneumothorax, one after paralysis with pancuronium. This study shows that only a system incorporating an accurate assessment of the baby's own respiratory pattern is able to detect different patterns of interaction. Impedance respirography and clinical observation appear to be unsatisfactory in this context.
Cerebral blood flow velocity was measured using Doppler ultrasonography in 20 babies who weighed less than 2500 g at birth and who were receiving assisted ventilation; their patterns of spontaneous respiration were recorded simultaneously. The babies were induced to breathe synchronously or asynchronously with the ventilator by manipulating the inspiratory and expiratory time settings. The variability of cerebral blood flow velocity (coefficient of variation) was calculated from the area of the maximum Doppler frequency shift envelope for 10 cardiac cycles from 211 recordings made on 42 occasions, and was greatest within 12 hours of birth after which it fell progressively over the next 48 hours. Variability of cerebral blood flow velocity was significantly greater when the infants were breathing out of synchrony with the ventilator (median 11%, interquartile range 8-14%) than when they were either apnoeic (median 5%, 3-7%), or breathing synchronously with the ventilator (median 5%, 3-6%).
The activity of the right external abdominal oblique muscle, in relation to respiration, in newborn babies from 25 to 34 weeks' gestation was studied, using surface electrodes. Babies without respiratory difficulties showed no activity associated with respiration in these muscles. Grunting babies with respiratory disease showed pronounced activity during expiration. This activity continued when the babies were endotracheally intubated; if the babies were ventilated it sometimes disturbed the tidal ventilation delivered by the machines. When the baby expired during a ventilator inflation, so that gas came up the endotracheal tube against the inflating pressure, the abdominal oblique muscles contracted in 98% of the breaths.
A protein-free artificial surfactant (ALEC) composed of two phospholipids when given as a prophylactic treatment at birth to very premature babies in randomized controlled trials. It was shown to reduce the severity of RDS, the ventilator pressure, the inspired oxygen requirements, the compliance of the respiratory system, the neonatal mortality and the incidence of ventricular hemorrhage. There are no apparent side effects from this treatment.
The composition of surfactant from the lungs of neonatal puppies dying from 'fadding puppy complex' differs from that of neonates dying from other causes. Surfactant from 'fading puppies' contained significantly less phosphatidylcholine than did the surfactant from other puppies, and therefore abnormal surfactant may be implicated in fading puppy complex. Abnormal surfactant has been implicated in the pathogenesis of sudden infant death syndrome in human infants.
Surface and electrokinetic properties of purified calf lung surfactant in various electrolyte solutions were determined. Surface properties were pH dependent in distilled water and the surfactant performed as a good lung surfactant only below pH 4. In more physiological media it was pH insensitive over the range 2-8.5. In distilled water at pH 6 its surface properties improved when NaCl was added up to 20 mM; above this concentration it had the surface properties required to stabilise alveoli. The surface properties of surfactant in distilled water were also restored by certain cations (Ca2+, Mg2+, Mn2+, Cd2+ and Ni2+) but not others (Na+, K+, La3+ and Fe3+) when added to an ionic strength of 5.6 mM. Cations that restored its surface activity also reduced the surface charge density on the surfactant particles. Aggregation of surfactant by various metal chlorides was studied by light scattering measurements and bore no relation to surface activity or the charge on the particles. Aggregation of surfactant particles by Ca2+, Cd2+ and Mn2+ was instantly reversed by addition of excess EGTA. The influence of electrolytes on the surface properties of lung surfactant is explained in terms of the electrostatic forces operating in the system.
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 infant's 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.
We describe a simple technique of neonatal ventilation that induces the neonate to breathe in synchrony with the ventilator. This preserves the beneficial effects of spontaneous respiration (unlike therapeutic paralysis) and reduces potentially harmful interactions between baby and ventilator. The technique uses measurements of the neonate's own respiratory timing.
A technique for monitoring the ventilated neonate's own respiratory efforts using a pneumatic capsule apnoea alarm is described.
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.