Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs.

The reason why some infants with respiratory distress syndrome fail to respond to surfactant, or respond only transiently, is incompletely understood. We hypothesized that resuscitation with large breaths at birth might damage the lungs and blunt the effect of surfactant. Five pairs of lamb siblings were delivered by cesarean section at 127-128 d of gestation. One lamb in each pair was randomly selected to receive six manual inflations of 35-40 mL/kg ("bagging") before the start of mechanical ventilation, a volume roughly corresponding to the inspiratory capacity of lamb lungs after prophylactic surfactant supplementation. Both siblings were given rescue porcine surfactant, 200 mg/kg, at 30 min of age. Blood gases and deflation pressure-volume (P-V) curves of the respiratory system were recorded until the lambs were killed at 4 h. The P-V curves became steeper after surfactant in the control group, but no such effect was seen in those subjected to bagging. At 4 h, inspiratory capacity and maximal deflation compliance were almost three times higher (p < 0.01) in the controls than in the bagged lambs. The latter were also more difficult to ventilate and tended to have less well expanded alveoli and more widespread lung injury in histologic sections. We conclude that a few inflations with volumes that are probably harmless in other circumstances might, when forced into the surfactant-deficient lung immediately at birth, compromise the effect of subsequent surfactant rescue treatment. Our findings challenge current neonatal resuscitation practice of rapidly establishing a normal lung volume by vigorous manual ventilation.

Changes in lung volume and static expiratory pressure-volume diagram after surfactant rescue treatment of neonates with established respiratory distress syndrome.

The effect of natural surfactant on respiratory system mechanics in infants with respiratory distress syndrome (RDS) is incompletely understood, possibly because the analysis has usually been confined to the tidal breath. We studied 11 paralyzed neonates weighing 540 to 1,850 g before and approximately 30 min after surfactant, which was instilled at 4 to 41 h of age. Diagrams relating airway pressure to expired volume were obtained by having the infant exhale passively through a flowmeter, starting at 30 and ending at 0 cm H20 of pressure. An interrupter intermittently stopped the flow so that pressure could be recorded under static conditions. FRC was measured by sulfur hexafluoride washout, and TLC was calculated from FRC and the pressure-volume (P-V) curve. Ventilation homogeneity was assessed from the washout curve as pulmonary clearance delay (PCD). TLC increased by 10% or more in five infants, but it remained unchanged in the others. Median TLC was 19 ml/kg before and 21.5 ml/kg after surfactant (p = 0.39). The P-V curve became markedly steeper at low pressures after surfactant in most infants, the slope of the steepest segment, i.e., maximal compliance, increasing from 0.65 to 1.22 ml/cm H20/kg (medians, p = 0.008). Dynamic compliance (Cdyn) was unchanged at 0.28 ml/cm H20/kg, whereas specific dynamic compliance (Cdyn/FRC) decreased (p = 0.04). There was no significant immediate change in PCD. The findings imply that during the first 30 min surfactant acted mainly by stabilizing already ventilated air spaces.

Lung volumes and pressure-volume relations of the respiratory system in small ventilated neonates with severe respiratory distress syndrome.

Total lung capacity (TLC), inspiratory capacity (IC), functional residual capacity (FRC), and deflation pressure-volume (P-V) curves were studied in 16 intubated neonates (540-3300 g), 10 with severe respiratory distress syndrome (RDS) and 6 air-ventilated with normal chest radiograms. FRC was measured using washout of a tracer gas (sulfur hexafluoride), and TLC and IC were calculated after inflating the lungs to 30 cm H2O. P-V curves were obtained during expiration from TLC using an interrupter technique, and the steepest slope of the curve, i.e. the maximum compliance (Crs-max), was calculated. In addition, an index of ventilation inhomogeneity (pulmonary clearance delay, PCD) was computed from the shape of the SF6 washout curve. TLC/body weight was less in the RDS group than in the air-ventilated group (median 19 and range 16-43 mL/kg versus 48 and 43-52 mL/kg, respectively; p < 0.01), mainly because of a marked reduction in IC (median 11 and range 8-24 mL/kg versus 29 and 28-40 mL/kg; p < 0.01). The flatter P-V curve in the RDS group was reflected also in a lower Crs-max (median 0.7 and range 0.4-1.7 cm H2O-1 kg-1) than in the air-ventilated group (2.3 and 2.0-3.1 mL cm H2O-1 kg-1, respectively; p < 0.01). Thus, there was no overlap in IC or Crs-max between the groups, suggesting that reductions in these measures may be main characteristics of RDS. On the other hand, no difference in PCD was found, indicating that, in infants with RDS, the tidal volume is distributed fairly homogeneously to the ventilated parts of the lungs.

Exogenous surfactant therapy increases static lung compliance, and cannot be assessed by measurements of dynamic compliance alone.

OBJECTIVE: To study the immediate effects of exogenous surfactant therapy on blood gases, lung volumes, and lung mechanics in adult rabbits with experimentally induced respiratory distress syndrome. DESIGN: Prospective randomized, controlled study. SETTING: Laboratory and animal facility of a large university. SUBJECTS: Twelve adult New Zealand white rabbits. INTERVENTIONS: Respiratory failure was induced by repeated bilateral whole-lung lavage with saline (30 mL/kg body weight). After the last lavage, the animals were randomly assigned to two groups. Group 1 received surfactant (120 mg/kg body weight) that was suspended in a 0.6% sodium chloride solution. Group 2 received comparable volumes of the same hypotonic solution and served as controls. MEASUREMENTS AND MAIN RESULTS: Before and after endotracheal surfactant instillation, blood gases and functional residual capacity were measured, and lung mechanics from tidal volumes and pressure-volume curves were calculated. Functional residual capacity was measured by a computerized, multiple-breath, washin-washout method using sulfur hexafluoride (SF6) as tracer gas. The pressure-volume curves were obtained by an occlusion technique originally described for measuring static breath-by-breath compliance. The technique was modified for present use and fully computerized. Within 60 mins after surfactant instillation, there were marked improvements in Pao2 (61 +/- 7 torr [8.2 +/- 0.9 kPa] to 470 +/- 47 torr [62.6 +/- 6.2 kPa]) and in functional residual capacity (7.6 +/- 1.4 to 17.7 +/- 1.6 mL/kg body weight) at unchanged ventilatory settings. The pressure-volume curves became steeper over time and the pressure-volume curves for total lung volume were restored to an almost normal state. Maximum compliance calculated from the pressure-volume curves increased by 92% but there was no significant change in dynamic compliance. In the control group, no improvements in any measured or calculated lung parameters were seen. CONCLUSIONS: The findings indicate that during mechanical ventilation, the effects of surfactant therapy on lung mechanics are best characterized by changes in functional residual capacity and maximum compliance obtained from static pressure-volume curves and not by dynamic compliance.

Natural surfactant instilled in premature lambs increases lung volume and improves ventilation homogeneity within five minutes.

The immediate effects on lung volume, ventilation homogeneity, and lung mechanics of tracheal instillation of surfactant were studied in premature lambs, gestational age 120-122 d, with respiratory distress syndrome. Six lambs received surfactant by tracheal instillation 25 min after delivery by cesarean section; five received only vehicle and served as controls. The lambs were studied for 60 min thereafter. Functional residual capacity was measured with a computerized tracer gas washin-washout technique using sulfur hexafluoride as tracer gas. A measure of ventilation inhomogeneity (pulmonary clearance delay) was also calculated from the washout curves. Pressure-volume curves were studied with an interrupter technique during deflation of the lungs from an airway pressure of 30 cm H2O. In the surfactant group, arterial oxygenation and ventilation homogeneity improved within 5 min of giving surfactant; major increases in functional residual capacity, vital capacity, and compliance occurred within 5 to 20 min and were followed by gradual further improvements. The pressure-volume curve thus increased in amplitude and became steeper, but the lung volumes at various inflation pressures, and compliance, remained constant when expressed as fractions of total lung capacity volume. It is concluded that an improvement in lung volume, respiratory mechanics, and ventilation homogeneity occurs very soon after surfactant instillation and that there is a phase of successive further improvement over the next hour. Although the amplitude of the pressure-volume curve varied considerably, its basic shape varied little. This suggests that opening of new distal airways by surfactant predominated over changes in the mechanics of already aerated lung regions.

Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates.

A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas.

Lung mechanics (FRC and static pressure-volume diagram) after endotracheal surfactant instillation: preliminary observations.

Preliminary measurements of functional residual capacity (FRC) with the sulphurhexafluoride technique and static pressure volume diagrams were performed in newborn infants with respiratory distress syndrome receiving endotracheal instillation of natural porcine surfactant (Curosurf, 100 or 200 mg/kg). Within the first hour after surfactant treatment there was an increase in FRC and distensibility of the lungs persisting for 24-48 h.

Functional residual capacity in anesthetized children: normal values and values in children with cardiac anomalies.

To assess the increase in functional residual capacity (FRC) with growth, FRC was measured after induction of anesthesia in two groups of children. One group consisted of 74 children, 0.1-11.2 yr of age, without signs of cardiorespiratory disease (referred to here as "normal" children), and the other of 21 children, 0.2-6.9 yr of age, with cardiac malformations. Anesthesia was maintained with halothane in the normal children and with fentanyl, droperidol, and nitrous oxide in the children with cardiac anomalies. All patients were paralyzed, their tracheas intubated, and their lungs mechanically ventilated. FRC was measured with an automated tracer gas washout technique. In 70 patients the measurements were performed in duplicate with a mean coefficient of variation of 2.0%. FRC correlated significantly with height, weight, and age in both groups. Multiple regression analysis for both groups considered together indicated no significant improvement when factors for the sex of the child or for the presence of cardiac anomalies were incorporated into the model. In normal children the simple linear and nonlinear regression equations for FRC (in milliliters) versus height (in centimeters) were: FRC = -529 + 9.48 x height, r = 0.96; and FRC = 0.00175 x height2.66, r = 0.97, respectively. The corresponding equations for FRC (in milliliters) versus weight (in kilograms) were: FRC = -92 + 29.9 x weight, r = 0.93; and FRC = 9.51 x weight1.31, r = 0.95.(ABSTRACT TRUNCATED AT 250 WORDS)