Randomised controlled trial of respiratory system compliance measurements in mechanically ventilated neonates.

AIM: To determine whether outcomes of neonatal mechanical ventilation could be improved by regular pulmonary function testing. METHODS: Two hundred and forty five neonates, without immediately life threatening congenital malformations, were mechanically ventilated in the newborn period. Infants were randomly allocated to conventional clinical management (control group) or conventional management supplemented by regular measurements of static respiratory system compliance, using the single breath technique, with standardised management advice based on the results. RESULTS: Fifty five (45%) infants in each group experienced one or more adverse outcomes. The median (quartile) durations of ventilation and oxygen supplementation were 5 (2-12) and 6 (2-34) days for the control group, and 4 (2-9) and 6 (3-36) days for the experimental group (not significant). On post-hoc secondary analysis, control group survivors were ventilated for 1269 days with a median (quartile) of 5 (2-13) days, and experimental group survivors were ventilated for 775 days with a median (quartile) duration of 3 (2-8) days (p = 0.03). CONCLUSIONS: Although primary analysis did not show any substantial benefit associated with regular measurement of static respiratory system compliance, this may reflect a type II error, and a moderate benefit has not been excluded. Larger studies are required to establish the value of on-line monitoring techniques now available with neonatal ventilators.

Life-threatening inadvertent positive end-expiratory pressure.

Inadvertent positive end-expiratory pressure (PEEP) is a potential cause of lung overdistension and impaired gas exchange in ventilated infants. It can be extremely difficult to diagnose clinically and if unrecognized can be life-threatening. Measurement of lung function can lead to the recognition of inadvertent PEEP, allowing appropriate ventilator adjustment with immediate substantial improvement in clinical state. Lung function measurements can help to optimize ventilation and may improve clinical outcome.

Reliability of clinical assessments of respiratory system compliance (Crs) made by junior doctors.

OBJECTIVE: To assess the reliability of estimates of static respiratory system compliance (Crs) made by junior hospital doctors caring for ventilated newborn infants. DESIGN: A prospective comparison of junior doctors' estimates of Crs to the Crs measured immediately afterwards. SETTING: A regional neonatal intensive care nursery in Edinburgh, Scotland. PATIENTS: 46 ventilated newborn infants. MEASUREMENTS AND RESULTS: Crs was estimated by three grades of junior doctor (Senior House Officer, Registrar and Research Fellow) using two different methods, (i) based on visual assessment of tidal volume in relation to inflation pressure (optical Crs) and (ii) directly using a visual analogue scale (analogue Crs). The Crs was then measured immediately afterwards using the single breath passive expiratory flow technique. The differences between the estimates and the measurements were calculated for each grade of observer and plotted against the corresponding measurements. The relationship between estimates and measurements was also expressed in terms of the coefficients of determination r2 calculated by least squares regression. With both methods of estimation observers tended to overestimate the Crs of infants with lower measured Crs and underestimate that of infants with higher measured Crs with many estimates differing from the measurements by more than 50%. Values of r2 ranged from 0.086 to 0.481 indicating a weak relationship between the estimates and the measurements. CONCLUSIONS: Junior doctors' estimates of Crs were unreliable and did not represent a useful method of assessing respiratory function. The clinical use of compliance measurements merits wider evaluation.

Static respiratory compliance in the newborn. I: A clinical and prognostic index for mechanically ventilated infants.

Accurate measures of the severity of respiratory disease are important, both clinically and epidemiologically. The apparent prognostic value of static respiratory system compliance (Crs) on the first day and mean appropriate fractional inspired oxygen (FIO2) in the first 12 hours of life were compared in 48 infants who received mechanical ventilation in a regional neonatal unit. Their median (range) gestation was 30 (25-41) weeks and they were representative of all 140 newborn infants born to residents of a geographically defined area who received mechanical ventilation over a 30 month period. Using the best cut off value (< or = 0.6 ml/cm H2O/m corrected for body length), static Crs predicted hospital death with 98% accuracy, 80% sensitivity, and 100% specificity. Using the best cut off value (> 0.60), mean FIO2 in the first 12 hours predicted hospital death with 81% accuracy, 80% sensitivity, and 81% specificity. Static Crs appeared to be a more accurate measure of respiratory function and disease severity than mean FIO2, perhaps because static Crs is less dependent on ventilator management than routine indices based on blood gases. Static Crs now merits wider evaluation, both as an aid to routine clinical management and as a prognostic index in comparative studies.

Static respiratory compliance in the newborn. II: Its potential for improving the selection of infants for early surfactant treatment.

Static respiratory system compliance (Crs) and lecithin/sphingomyelin (L/S) ratios in tracheal aspirates were estimated in two independent groups of mechanically ventilated infants. Crs was measured rapidly at the cotside using a passive expiratory flow technique and L/S ratios were estimated in the laboratory by high performance liquid chromatography. In the reference group of 22 infants, Crs < 1.8 ml/cm H2O/m predicted surfactant deficiency with a positive predictive value of 100% and a negative predictive value of 92%. In the validation group of 23 infants, Crs < 1.8 ml/cm H2O/m predicted surfactant deficiency with a positive predictive value of 94% and a negative predictive value of 83%. Measurement of static Crs is a rapid, non-invasive technique which may usefully supplement current methods of selecting infants at high risk of respiratory distress syndrome.

Static respiratory compliance in the newborn. III: Early changes after exogenous surfactant treatment.

Static respiratory system compliance (Crs) was measured by a single breath passive expiratory flow technique in 73 newborn infants treated with exogenous surfactant. The first 39 received Curosurf, a natural porcine surfactant. The other 34 received Exosurf Neonatal, a synthetic surfactant. All had a diagnosis of respiratory distress syndrome with an arterial/alveolar oxygen ratio < 0.22. Static Crs and arterial blood gases were measured shortly before, and at three and 12 hours after the first dose of surfactant. In 32 infants treated with Curosurf with initial static Crs < 1.8 ml/cm H2O/m body length, which is consistent with surfactant deficiency, static Crs improved by 18% at three hours and by 39% at 12 hours along with a median reduction in fractional inspired oxygen (FIO2) at three hours by 0.32. In 26 infants treated with Exosurf with initial Crs < 1.8 ml/cm H2O/m, Crs did not improve three and 12 hours after treatment and oxygenation improved less than after Curosurf, with a median reduction in FIO2 at three hours of 0.11. Fifteen of the 73 (21%) infants had initial static Crs of > or = 1.8 ml/cm H2O/m, not consistent with surfactant deficiency. Thirteen of these 15 infants showed a fall in static Crs after surfactant treatment, raising the question whether exogenous surfactant did them more harm than good. Initial static Crs and surfactant type both appear to determine the early response to the first dose of surfactant. Only a considerably larger, randomised study can show which surfactant is more effective in reducing adverse clinical outcome.

Comparison of methods of measurement of compliance of the respiratory system in children.

Compliance of the respiratory system (Crs) was compared using 2 previously described methods, namely, the passive expiratory flow and multiple occlusion techniques. These 2 methods have the advantage of being totally noninvasive, but both have limitations precluding their use in some circumstances. The results of this study of 10 intubated patients, who varied widely in age (premature newborn to adolescence) and diseases, showed no significant difference between the Crs obtained by the 2 methods. The Crs measurements can therefore be used interchangeably, the choice of technique being dependent on the subjects' clinical state.

Effect of bronchodilators on airway resistance in ventilator-dependent neonates with chronic lung disease.

Using a noninvasive passive flow volume technique to measure respiratory system resistance (Rrs) and compliance (Crs), the effects of two inhaled bronchodilators, salbutamol (beta 2-agonist) and ipratropium bromide (muscarinic blocker), were studied in 17 premature infants ranging in age from 19 to 103 days. All were ventilator dependent with chronic lung disease. The pretreatment Rrs was high (range 0.15 to 0.27 cm H2O X ml-1 X sec). After administration of salbutamol, the mean group Rrs decreased 24% +/- 11% (mean +/- SD), and Crs increased significantly, 17% +/- 21%. The response to ipratropium bromide in five infants did not differ significantly from their responses to salbutamol. Nebulized saline solution had no bronchodilator effect in five infants. These results suggest that in infants with early and late chronic lung disease, bronchospasm can be partially alleviated by inhaled bronchodilators.

Wiedemann-Beckwith syndrome in one of monozygotic twins.

A pair of monozygotic twins discordant for Wiedemann-Beckwith syndrome is described. The probability of monozygosity is 0.995. This observation suggests that the syndrome is unlikely to be under single gene control and genetic counselling should be based on multifactorial inheritance.