I don’t post much about animal studies, but there are some things which are extremely difficult to study in human babies and at least for preliminary studies they may be essential and very informative. That great Melbourne group has been looking at the effects of prolonged inflation time on response to resuscitation. Both in preterm animal models, and in asphyxiated near-term models.
They have shown that in rabbit cage experiments, preterm rabbits using a sustained inflation, of for example 20 seconds achieves an FRC much faster. The publications from 2009 show a fascinating series of images from phase-contrast x-rays showing the difference in lung volumes: I reproduce one here
Phase contrast x-ray images from prematurely delivery newborn rabbit pups ventilated from birth. Top panel are the images from the group with no SI (1 s in duration; images A, B, C, and D). Bottom panel are the images from the group with SI of 20 s (images E, F, G, and H). Images were acquired at 1 (A and E), 5 (B and F), 10 (C and G), and 20 (D and H) s after birth. The double asterisks (**) indicate images acquired at the end of the first inflation. Images acquired after the first inflation were acquired at end inspiration.
One could reasonably ask if that is a good thing? Does achieving a good FRC faster really help? Well a new study from the group, this time in asphyxiated near-term lambs, would certainly suggest that a clinical benefit is very much a possibility (Klingenberg C, Sobotka KS, Ong T, Allison BJ, Schmölzer GM, Moss TJM, Polglase GR, Dawson JA, Davis PG, Hooper SB: Effect of sustained inflation duration; resuscitation of near-term asphyxiated lambs. Archives of Disease in Childhood – Fetal and Neonatal Edition 2012.) In this study lambs ventilated with a single ventilation of 30 seconds had a much more rapid recovery of their heart rate and blood pressure than did those with 5 x 3 second inflations with 1 sec expiratory time, or those ventilated at a rate of 60 per min with 0.5 sec inflations. So as well as increasing FRC cardiovascular recovery is faster with sustained inflations.
I must admit, that despite the lack of RCT evidence I have been doing this for many years, often I will take over ventilation when a baby is not responding immediately to the initial attempts (by a resident or someone following NRP guidelines) I will give a long inflation of 20 to 30 seconds (which is very long during a resuscitation) with a gradually increasing pressure. I have been doing this following the research from many years ago of Vyas and Milner. They showed that the apparent opening pressure of the lungs could be eliminated by such an inflation, and the lungs developed an FRC as a result of this maneuver. There has never been any poof that this improves outcomes of resuscitation, but given this physiologic evidence I have tried it many times, and very often a baby who was difficult to ventilate and bradycardic has responded with good chest movements (which I now know are probably excessive tidal volumes!) and improvements in circulation.
The next stage should surely be to examine the use of prolonged inflations in human resuscitation.
But please see Carlos Blanco’s comment on this post.
It is very interesting to follow the literature on sustained inflations of the lung for recruiting FRC. Many years ago (see abstracts below) one of my PhD student went through a lot of premature lambs trying to evaluate the effects of SI, at that time it was 5 seconds, now SI are 20 seconds. We did not find any benefit of SI on lung function during the first hour of life. What worried us at the time was the influence of SI on blood pressure, which could increase the risk of bleeding in the very immature infants. It would be very interesting to see new data on the impact of 20 sec SI on cardiovascular parameters.
ABSTRACTS
1. Acta Paediatr. 1994 Oct;83(10):1017-21.
Effect of sustained inflations applied directly after cord clamping on lung
function in premature newborn lambs.
Klopping-Ketelaars WA, Maertzdorf WJ, Blanco CE.
Department of Neonatology, University of Limburg, Maastricht, The Netherlands.
We studied the possibility of improving lung volume and therefore clinical
outcome in premature newborn lambs by increasing the inspiratory volumes during the first minute after birth. Sixteen lambs from eight were delivered byhysterotomy after 130-131 days’ gestation. In eight lambs the lungs were inflate with a bag with a sustained inspiratory inflation (SI) of 5 s and expiratory time of 5 s during the first four inflations after cord clamping and then mechanically ventilated. Their siblings did not receive SI and served as a control group. At 8h postnatally, the SI and control groups showed the following results (mean +/-SEM): mean airway pressure 14.8 +/- 1.8 cmH2O versus 11.9 +/- 1.1 cmH2O, PaO2 41.5 +/- 7.3 kPa versus 31.3 +/- 7.7 kPa, alveolar-arterial oxygen gradient 359+/- 55 mmHg versus 437 +/- 58 mmHg. Clinical course, incidence of pneumothorax,oxygenation index, total static compliance, parenchymal-alveolar air area ratio or mortality rate were not different. There was no significant difference between the two groups at this time or at any other time during the experiments.
PMID: 7841694 [PubMed – indexed for MEDLINE]
2. Acta Paediatr. 1994 Sep;83(9):897-902.
Cardiovascular changes during sustained lung inflations in premature newborn
lambs.
Klopping-Ketelaars WA, Maertzdorf WJ, Blanco CE.
Department of Neonatology, University of Limburg, Maastricht, The Netherlands.
We studied the effect of sustained inspiratory inflations (SI) on the
cardiovascular system by measuring mean central venous pressure (MCVP), mean arterial blood pressure (MABP) and heart rate (HR), before and during sustained lung inflations in premature lambs (128-133 days’ gestation). SI consisted of four inflations of 5 s at a peak inspiratory pressure of 35 cmH2O, with a mixture of 5% carbon dioxide and 95% oxygen. Each inflation was followed by a positive end-expiratory pressure of 5 cmH2O for 5 s. Percentage change from baseline was -3.88% for MABP and -2.55% for HR during the first inflation. The changes in MCVP fluctuated with each inflation (mean 9.61%; p < 0.01 versus baseline) and deflation (mean -3.87%; p < 0.05 versus baseline). These changes were dependent on the time after birth and the pressure used for SI. The observed cardiovascular changes produced by this procedure are considered clinically relevant when managing premature infants with a high risk of intraventricular haemorrhage.
PMID: 7819682 [PubMed – indexed for MEDLINE]