Jonas Ingimarsson

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.

Lung recruitment at birth does not improve lung function in immature lambs receiving surfactant

Background: In mature animals with surfactant deficiency induced by lung lavage, the therapeutic effect of exogenous surfactant is enhanced by a lung recruitment maneuver. We then tested whether a lung recruitment maneuver at birth immediately before surfactant treatment would improve lung function also in preterm lambs with surfactant deficiency due to immaturity.

The pressure at the lower inflexion point has no relation to airway collapse in surfactant-treated premature lambs.

Background: The lower inflexion point (LIP) on the inspiratory part of the pressure–volume (PV) loop has been suggested to be related to the pressure at which air spaces collapse. Our hypothesis is that airway collapse might instead be assessed from the upper inflexion point on the expiratory part of the PV‐loop (UIPexp), where lung volume starts to decrease significantly. We therefore examined whether there was a relation between LIP and UIPexp in premature surfactant‐treated lambs.

Coronary flow reserve in the newborn lamb: An intracoronary Doppler guide wire study

Recent studies indicate a severely reduced coronary flow reserve (CFR) in neonates with congenital heart disease. The significance of these studies remains debatable, as the ability of the anatomically normal neonatal heart to increase coronary flow is currently unknown. This study was designed to establish normal values for CFR in newborns after administration of adenosine [pharmacologic CFR (pCFR)] and as induced by acute hypoxemia (reactive CFR). Thirteen mechanically ventilated newborn lambs were studied. Coronary flow velocities were measured in the proximal left anterior descending coronary artery before and after adenosine injection (140 and 280 μg/kg i.v.) using an intracoronary 0.014-in Doppler flow-wire. Measurements were made at normal oxygen saturation (Sao2) and during progressive hypoxemia induced by lowering the fraction of inspired oxygen. CFR was defined as the ratio of hyperemic to basal average peak flow velocity. In a hemodynamically stable situation with normal Sao2, pCFR was 3.0 ± 0.5. pCFR decreased with increasing hypoxemia. Regression analysis showed a linear relation between Sao2 and pCFR (R = 0.86, p < 0.0001). Reactive CFR obtained at severe hypoxemia (Sao2 <30%) was 4.2 ± 0.8, and no significant further increase in coronary flow velocity occurred by administration of adenosine. Newborn lambs have a similar capacity to increase coronary flow in response to both pharmacologic and reactive stimuli as older subjects. Administration of adenosine does not reveal the full capacity of the newborn coronary circulation to increase flow, however, as the flow increase caused by severe hypoxemia is significantly more pronounced.

A lung recruitment maneuver immediately before rescue surfactant therapy does not affect the lung mechanical response in immature lambs with respiratory distress syndrome.

Background:  In animals with acquired surfactant‐deficiency, a recruitment maneuver by increased tidal volumes enhances the effect of exogenous surfactant. In contrast, in the preterm lamb model, hyperinflation early after birth impairs the effect of surfactant prophylaxis. Here we examined whether a lung recruitment maneuver just before surfactant would affect the response to rescue treatment in immature lambs with established respiratory distress syndrome (RDS).

Preceding surfactant treatment does not protect against lung volutrauma at birth |[dagger]| 1518

Manual ventilation with a few large breaths at birth may cause lung injury in immature lambs. The severity of injury was related to the size of lung inflations (8-32 ml/kg), but even modest inflations before surfactant (S) caused a significant lung function impairment (Pediatr Res 1996;39:326A). We now studied if preceding S treatment would protect the lungs against this injury, and if not, for how long after S the lungs would be sensitive to deep inflations. Twelve lambs of gestational age 127 days were randomized to four different treatments: 1) Five inflations of 16 ml/kg at birth immediately followed by S, 2) S at birth immediately followed by inflations, 3) S at birth, inflations at 10 min, 4) S at birth, inflations at 60 min. Lung mechanics was repeatedly measured during 4 hours of pressure limited mechanical ventilation. Significantly higher airway pressures were generated by inflations at birth (groups 1 and 2) than when inflations were postponed(groups 3 and 4). Static compliance (see figure) and inspiratory capacity remained low throughout the study in groups 1 and 2. We conclude that deep inflations at birth caused lung function impairment whether they were preceded by S or not, but already at 10 min inflations of the same size caused no apparent harm. Ventilation of preterm infants may need to be very tender during the first few minutes of life.

Lung Trauma From Five Moderately Large Manual Inflations Immediately After Surfactant Instillation in Newborn Immature Lambs † 1678

Lung Trauma From Five Moderately Large Manual Inflations Immediately After Surfactant Instillation in Newborn Immature Lambs † 1678

LUNG INJURY CAUSED BY NEONATAL RESUSCITATION OF IMMATURE LAMBS - RELATION TO VOLUME OF LUNG INFLATIONS. |[dagger]| 1942

We have previously shown that manual ventilation with a few large breaths(35-40 ml/kg) at birth compromises the effect of subsequent surfactant treatment in immature lambs [Acta Anaesthesiol Scand 1995;39(suppl 105):153]. We now studied if also smaller lung inflations would damage the surfactant-deficient lung. Lambs with gestational age 126-128 days were randomized to five different treatment schedules with Curosurf (C) 200 mg/kg: 1) C mixed with lung liquid before birth, 2) C after birth, but before the first breath. and 3-5) five sustained lung inflations (8, 16 and 32 ml/kg, respectively) at birth, immediately followed by C. The lambs were then mechanically ventilated, and blood gases, lung volumes and deflation pressure-volume curves of the respiratory system were recorded regularly during 4 h. There was no significant difference in oxygenation between the groups, but the other lung function parameters indicated an increase in lung injury in relation to the volume of early lung inflations. The lambs given the smallest lung inflations (group 3), still had a 38% reduction of static compliance at 4 h as compared to lambs in group 1. We conclude that even modest inflations of surfactant-deficient lungs during resuscitation may cause significant lung injury. Figure