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New techniques for neonatal respiratory support
Current Paediatrics (1997)7, 78 84 © 1997PearsonProfessionalLtd
Mini-symposium: Neonatology
New techniques for neonatal respiratory support
R A. J. Chetcuti
Considerable progress has been made in the management of respiratory distress in newborns since the introduction of positive pressure ventilation over 20 years ago. More recently, the introduction of surfactant and the increased use of steroids predelivery have led to a major increase iri survival in preterms with hyaline membrane disease. Conventional ventilation refers to the positive pressure respiratory support that is practised in newborn units. A wide variety of mechanical ventilators are currently in use in the UK and ventilator management policies vary widely between units with no consensus view as to the best approach. Trauma from ventilation is an important factor in the aetiology of the airway and lung damage seen in bronchopulmonary dysplasia (BPD). Asynchrony between the ventilator and the infant's respiration and the use of large tidal volumes to accomplish adequate ventilation are the major components of this trauma? In a study limiting tidal volume by constraints applied to the chest wall in an animal model the use of high airway pressures did not produce as much damage as when tidal volume was not limited) Therefore, changes in lung volume may be more important than changes in airway pressure in the production of lung injury. For this reason, the term volutrauma is preferred to barotrauma. In animals with healthy lungs 13 large tidal volume ventilation can damage the pulmonary capillary endothelium, alveolar and airway epithelium and basement membranes allowing fluid, protein and blood to leak into the airways, alveoli and lung interstitium.1 This sequence is well described in the evolution of respiratory distress syndrome to chronic lung disease in newborns. Despite the excellent achievements in neonatal respiratory care, a number of infants continue to respond
poorly to conventional ventilation and the incidence of BPD remains high affecting 20-30% of all preterms. A number of technologies have developed or have re-emerged in an attempt to influence these problems. This article will consider the major new developments in neonatal respiratory support.
TRIGGER VENTILATION Success in the application of trigger ventilation to treat preterm babies of all gestations with respiratory distress syndrome (RDS) is well documented,3,4 and trigger ventilation is now used widely. In patient triggered ventilation (PTV) the peak inspiratory pressure, positive end expiratory pressure and inspired oxygen are set by the operator but the rate is controlled by the baby's respiratory efforts. This has the potential advantage that the peak inspiratory pressure should be lower as the baby is contributing to transpulmonary pressure and situations in which the baby is actively breathing out during a period of ventilatory inflation should be eliminated. This potentially could reduce the incidence of volutrauma, air leaks and BPD. In a non-randomized study there was a shorter duration of ventilation and a decreased duration of oxygen therapy in infants on trigger ventilation compared with controls. 3 Two large studies in the UK are currently in progress to determine the effects of trigger ventilation compared to conventional ventilation on survival and the incidence of BPD. The most commonly employed available trigger ventilators in the UK are the SLE 2000 and Drager Babylog, which employ airway pressure sensors and airflow sensors respectively. The triggering devices are highly sensitive at detecting the maximum number of the infant's respiratory efforts. The trigger sensitivity may need to be decreased in a vigorous or crying baby and increased during sleep. The trigger delay for both
ConsultantPaediatrician, ClarendonWing,LeedsGeneralInfirmary,BelmontGrove,Leeds LS2 9NN, UK. Phillip A. J. Chetcuti DM MRCP,
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Neonatal respiratory support ventilators (the time from the onset of inspiration to the commencement of positive pressure inflation) is less than 0.1 s. This should be considered during the setting of the inspiratory time, and in practice the setting will vary between 0.25 and 0.35 s in the majority of preterms. A long inflation time is likely to result in inflation extending into expiration provoking active expiration. As immature infants have a tendency to apnoea, it is essential to have a minimum backup rate to ensure continuity of respiratory support and this is best set at 20 breaths per minute below that of the infant's spontaneous respiratory rate. Babies are weaned from trigger ventilation by weaning the peak inspiratory pressure to a level of 8-10 cm of water and then extubating. Success of PTV relies on careful observations of chest wall movement. This is important at all times but particularly when establishing the initial settings of inspiratory time, peak pressure and trigger sensitivity. Trigger ventilation can also provide synchronous intermittent mandatory ventilation (SIMV). In SIMV, the number of supported breaths is controlled by the SIMV rate. If an infant breathes at a rate of 60 breaths per minute and the SIMV rate is 20 breaths per minute, the ventilator will deliver 20 synchronized breaths per minute. Unlike PTV, the baby breathes spontaneously between the breaths. Improvements in blood gases on SIMV have been reported2 In units not employing PTV, there seems to be no logical reason not to use SIMV in non-paralysed infants when the ventilator rate is 30 or below. With reference to effectiveness in weaning infants from ventilators, studies comparing SIMV with PTV report no differences. 6,7
NASAL CONTINUOUS POSITIVE AIRWAYS PRESSURE Nasal administration of continuous positive airways pressure (CPAP) has been used in the management of neonatal respiratory distress for years. There are four
Fig. 1 (A) EME nasal CPAPdevice.(B) Infanton nasal CPAE
79
potential roles; in the management of respiratory distress syndrome, as a weaning tool in infants on mechanical ventilation, in the management of babies with severe apnoeas of prematurity and in infants with BPD. Continuous positive airways pressure may restore functional residual capacity (FRC) and correct hypoxia secondary to ventilation-perfusion mismatch by recruiting collapsed alveoli. Traditionally, CPAP has been delivered by cut endotracheal tubes (ET) placed in the nares, nasal prongs or face masks. Face masks are difficult to apply and maintain, particularly in small preterm infants, and cerebellar haemorrhage from over zealous strapping of the mask has been reported. With cut ET tubes and nasal prongs, CPAP is frequently not maintained because of leakage of gases through the mouth or at the nasal attachment and attempts to increase the airway pressure by increasing the flow results in wider variations in the CPAP levels as the resistance in the prongs becomes more significant with increased flow. Developing a system to minimize the resistance to flow would increase the demand on the flow dynamics of the CPAP generator making the traditional systems inadequate. Flow resistance within the prong and wide variations in CPAP levels can also increase the work of breathing. 8'9 Given the potential difficulties described above, a new technique for delivery of nasal CPAP has been developed. 1° The gases are delivered from two separated jets directed towards the nasal openings (Fig. 1). By the ejector action of the fresh gas converting kinetic energy into pressure, CPAP is generated in the immediate vicinity of the nasal airway. In laboratory experiments comparing this system to nasal prongs, CPAP is maintained throughout the respiratory cycle and the work of breathing is reduced? ° This system is now commercially available. Improved delivery of nasal CPAP raises a number of important questions. Should we be considering the use of nasal CPAP as first line respiratory support in a larger number of infants with RDS? Would this
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confer any significant advantages to infants? How would surfactant be administered? In a Danish study using nasal CPAP routinely in all preterm infants with RDS there was no recourse to mechanical ventilation in over 70% of infants from 26 to 32 weeks gestation. 11 In a further Scandinavian study of infants with RDS (25-35 weeks gestation) managed with nasal CPAP, the administration of a single dose of a natural surfactant (Curosurf 200 mg/kg) led to a 40% reduction in the requirement for mechanical ventilation compared to babies managed with nasal CPAP alone. 12 Continuous positive airways pressure levels between 6 and 10 cm of water were used in both studies. In the latter study, surfactant was administered following intravenous doses of morphine and atropine and intubation. Infants remained intubated for a maximum of 1 h until respiratory effort was satisfactory and then extubated. Despite the above studies, it is unlikely that the majority of infants of 26 weeks gestation and under would tolerate nasal CPAP as first line respiratory support in RDS. In infants of 27 weeks gestation and over nasal CPAP and intermittent administration of surfactant may be an alternative to conventional ventilation. However, the outcomes of these higher gestation infants in terms of survival and incidence of chronic lung disease are already very good. Therefore, would nasal CPAP confer any additional advantages? Possibly these infants would spend less time on intensive care, which might have financial implications. A large multicentre trial is required to answer these questions and to determine the optimal level of CPAP. A number of studies have assessed the role of nasal CPAP as a weaning tool in infants recovering from RDS with conflicting results. ~3-17 There are many reasons for these discrepant findings including the method of delivery of CPAP, the level of CPAP, extubation criteria, reintubation criteria, population characteristics and the use of theophyllines. In our practice, nasal CPAP appears to be a useful weaning tool, particularly in smaller infants.
HI GH FREQUENCY OSCILLATORY VENTILATION This form of ventilation has emerged in a number of neonatal units in the last 3 years. The concept is best understood by considering the results of a number of studies on animal models. In these, high frequency ventilation minimizes the propagation of lung injury by supporting adequate gas exchange with small tidal volumes less than the dead space volume of the respiratory system? 8 Lung volume is maintained above functional residual capacity by the use of a constant distending pressure; the mean airway pressure. Lung volume is held relatively constant and the potentially deleterious cycle of inflation and deflation associated with conventional ventilation is greatly reduced. The
avoidance of high lung volumes prevents over inflation of the more compliant lung units and the avoidance of low lung volumes prevents collapse of the less compliant lung units with potential benefits in ventilation perfusion mismatching, gas exchange and a reduction in lung damage. TM In the premature baboon model of hyaline membrane disease, the use of high frequency oscillatory ventilation (HFOV) reduces the occurrence of air leak, improves gas exchange and lung mechanics compared to conventional ventilation. 19,2°The amount of inflammatory mediators and the number of leucocytes recovered in lung lavage usually present in the evolution to chronic lung disease are reduced in the animals managed with HFOV. 2° These pathological findings are also reduced in animals treated immediately after delivery compared to the use of HFOV after 8 h of conventional ventilation. 21 Studies on preterm neonates are not as encouraging. In a study from North America, randomizing over 600 infants with RDS to receive HFOV or conventional ventilation, there were no differences in survival or incidence of chronic lung disease. = There was a small but significant increase in the occurrence of Grade III and IV intraventricular haemorrhage and periventricular leucomalacia. A further study on a smaller number of infants approached the ventilation strategy differently. They used a high volume strategy using higher mean airway pressures to recruit and maintain optimal lung inflation)3 Infants with RDS were randomized to HFOV until extubation, HFOV for 72 h followed by conventional ventilation or conventional ventilation alone. Patients treated with HFOV until extubation had a reduced incidence of chronic lung disease at 36 weeks post conceptual age compared to the other groups. There was no difference in the incidence of chronic lung disease between those treated with HFOV for 72 h followed by conventional ventilation and in patients treated with conventional ventilation. Mortality and the incidence of severe intracranial problems were similar in all groups. A study of large numbers of infants is required to confirm or refute these findings. Given uncertainties about the benefits of using HFOV from birth in infants with RDS, is there any evidence of benefits as a rescue tool in RDS? One hundred and eighty preterms with severe RDS within the first 48 h of life, as defined by the presence of pulmonary interstitial emphysema or high peak inspiratory pressures (> 25 cm water in 0.5-1 kg babies, > 28 cm water in 1-1.5 kg infants and > 30 cm in > 1.5 kg infants), were randomized to receive HFOV or conventional ventilation. 24 A high volume strategy was employed. The incidence of new air leak was reduced in infants treated with HFOV but there were no differences in the incidence of chronic lung disease or survival rates in the two groups. Patients assigned to HFOV had a higher incidence of severe intraventricular haemorrhage.
Neonatal respiratory support In a prospective randomized comparison of H F O V and conventional ventilation in larger infants (> 2 kg) with severe respiratory distress (FiO 2 > 50%, PIP (peak inspiratory pressure) > 30) H F O V was a more effective rescue tool than conventional ventilation. 25 Sixty-three percent not responding to conventional ventilation responded to HFOV whereas 23% not responding to HFOV responded to conventional ventilation. There were no differences with respect to the need for extra corporeal membrane oxygenation (ECMO). The numbers are too small to make inferences about the incidence o f chronic lung disease or survival. In our practice, employing H F O V in preterms and older infants as a rescue tool, with infants fulfilling similar criteria to those described in the studies above, we have seen a small but impressive number of responses which justifies its value to us. Early experience of HFOV in the United Kingdom has been with the SensorMedics model 3100A (Fig. 2). This is an electronically controlled piston diaphragm oscillator. Pressure oscillations are generated by the excursions of a plate diaphragm and are superimposed on the mean airways pressure. A standard endotracheal tube is used to deliver HFOV. Exhalation is active because of the biphasic pressure waveform. The adjustable parameters are mean airway pressure (MAP), ventilatory frequency, pressure amplitude and percentage of inspiratory time. Recently, SLE and Drager have added an oscillator mode to their conventional ventilators. The adjustable parameters on these ventilators are similar to those described above, with the exclusion of percentage of inspiratory time. The value of this parameter in relation to HFOV is not clearly understood. The effectiveness of these ventilators as oscillators requires further evaluation. In respiratory distress syndrome a relatively high mean airway pressure is used to recruit lung volume. This is usually 2 cm of H20 greater than the mean airway pressure on conventional ventilation. In the first few hours of administration of HFOV every attempt should be made to achieve the optimal lung volume. Mean airway pressure must be increased cautiously so as not to result in lung overdistension, air leak and a decrease in cardiac output. The assessment of lungdistension is difficult, and, in theory, measures of FRC would be valuable. Frequent chest radiographs are taken to assess the degree of lung distension. The optimal diaphragmatic position is between the 8th and 9th posterior ribs. It is not unusual for an infant to have up to six chest radiographs in the first 24 h on HFOV. This high volume strategy is usually accompanied by a significant reduction in FiO 2. When F i O 2 falls below 30%, judicious weaning of the MAP is possible. Ventilatory frequency is set at 10-15 Hz and inspiratory time at 30%. These variables are not altered throughout the course of oscillation. We have found that larger infants (> 3 kg) sometimes require a slightly lower frequency (8-9 Hz). The pressure amplitude is set to a level at which good chest wall movement is observed. The use
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Fig. 2 Infant on HFOV (SensorMedics 3100A).
of a transcutaneous CO 2 monitor may be helpful in establishing the optimal pressure amplitude. The pressure amplitude is then increased or decreased depending on arterial CO 2 concentrations. The baby should not be disconnected from the ventilator if at all possible, as this might result in collapse of alveoli and loss of lung volume. If reintubation is required it is important to remember that changes in endotracheal tube size can affect arterial CO 2 tension more significantly than with conventional ventilation. It is our practice to paralyse and sedate all infants on HFOV, and when the MAP is 8-9 cm of H 2 0 , transfer to conventional ventilation. However, a well described strategy is to wake the infant, reduce the M A P to 4-5 cm of H20, reduce the pressure amplitude to zero and extubate directly. There is no time limit on HFOV. Occasionally, infants are placed on conventional ventilation because of problems with secretions and airways collapse. In contrast to the management of RDS, the management of infants with air leak and meconium aspiration syndrome conditions associated with lung overdistension are managed with a low volume and consequently low M A P strategy. The MAP is set at the same level or slightly lower (1-2 cm of H 2 0 ) than the M A P on conventional ventilation. Dramatic initial improvements in oxygenation, sometimes seen in RDS, are less commonly seen in these conditions. Settings for other ventilator parameters are similar to those described above. A similar approach is used in persistent foetal circulation. The use of exogenous surfactant in infants receiving high frequency oscillation needs further evaluation. With HFOV as a rescue tool, infants have usually received at least one dose of surfactant during treatment with conventional ventilation. In animal studies, the combination of the two improves gas exchange and pulmonary mechanics. 26 Like surfactant, high frequency ventilation can cause rapid increases in lung volume and the combination of the two could be potentially deleterious with lung overdistension, air leak, hypotension and possibly intracranial haemorrhage. If they are to be combined, judicious monitoring is essential.
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HIGH FREQUENCY JET VENTILATION A special endotracheal tube and pinch valve are required to deliver inspiratory pulses of gases into the trachea. The adjustable variables are peak inspiratory pressure, frequency and inspiratory time. The range of frequencies are lower than that of HFOV, in the range of 4-10 Hz. Exhalation is passive, and is promoted by short inspiratory times (2~34 ms) and long expiratory times. The latter is provided by convention/d ventilation connected in tandem at the endotracheal tube. The conventional ventilator also provides end expiratory pressure and intermittent breaths (maximum 10 per min) which interrupt the jet pulses when the peak pressure set on the conventional ventilator is higher than that set on the high frequency jet ventilation (HFJV). During HFJV pressure is delivered to and monitored in the trachea. A multicentre study of 144 infants with pulmonary interstitial enphysema showed that they were more likely to respond to HFJV than to conventional ventilation. There was improved gas exchange at lower peak and mean airway pressures and a more rapid resolution of the pulmonary interstitial emphysema (PIE)?7 Infants treated with HFJV had a better survival rate (65% vs 47%). Early reports suggested that HFJV was associated with a high incidence of necrotizing tracheobronchitis. Improvements in humidification appear to have minimized this problem. At the present time, HFJV is rarely used in the UK and comparative studies with HFOV as a rescue tool have not been done.
CONTINUOUS NEGATIVE EXTRATHORACIC PRESSURE Prior to the introduction, over 20 years ago, of positive pressure ventilation in the management of newborns with RDS negative pressure respiratory support was used with some success. Enthusiasm for the technique was rekindled in the search for a relatively non-invasive type of ventilation in the management of difficult infants with BPD?8 Initially, there were technical problems with temperature control of small infants, accessibility and trauma to the neck and upper airways secondary to obstruction from the tight neck seal. However, extensive design modifications have been made29 with the development of a temperature controlled infant incubator capable of delivering constant or intermittent negative pressure (Fig. 3). The device includes a perspex chamber into which the infant is placed. The infant's head passes through a thin latex membrane which separates the interior of the chamber from the atmosphere. The chamber is heated with a servo-controlled incubator heater, and an electric suction device provides regulated negative pressure. Access to the infant is accomplished through portholes equipped with packed cell foam gaskets to maintain negative pressure. This equipment permits the use of
Fig. 3 Infant on CNEP Tank (reproduced by kind permission of Dr Martin Samuels,University of Keele).
radiant heat sources. The only other commercially available system for delivering negative pressure is a jacket (Hyek) which has not been evaluated in preterms. Negative pressure respiratory support may have a number of advantages over positive pressure ventilation. Continuous negative extrathoracie pressure (CNEP) may result in a more uniform distribution of ventilation, less ventilation perfusion mismatching and therefore improved oxygenation. Comparisons of CNEP and positive end-expiratory pressure (PEEP) in animal studies suggest the former may have beneficial effects on pulmonary vascular resistance and cardiac output. 3°,~1Anecdotal success with CNEP in the management of infants with BPD prompted an interest in the use of CNEP to treat RDS. Preliminary results on a large randomized trial of CNEP at 4-6 cm of H 2 0 compared to conventional ventilation in preterms with early respiratory distress syndrome (4 h), showed a 10% reduction in the incidence of chronic lung disease.32The full study results are awaited. Comparative studies of CNEP and nasal CPAP in early RDS would be of some interest. Given the relative difficulties of applying this technique, it is unlikely to gain popular support unless such a comparative study showed that CNEP had significant advantages.
PARTIAL LIQUID VENTILATION Considerable interest has emerged in the potential for this kind of ventilation employing perfluorochemical liquids; chemicals with a low surface tension and high solubility. Partial liquid ventilation employs a conventional ventilator to deliver gas tidal volumes into a lung with a liquid functional residual capacity. More recently, a medical grade perfluorochemical liquid perflubron has become available with high spreading properties and low vapour pressure. In a study on premature lambs with RDS/5 pre-oxygenated perflubron pre-warmed to 39°C was instilled into the trachea
Neonatal respiratory support
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complications. Despite this, each technique may have a role in specific clinical settings. Traditionally, our knowledge of what is best in newborn ventilation has not been driven by well designed large randomized trials. At present a number of trials are underway or in development which will help to determine the precise roles for these new techniques in the respiratory care of newborn infants. REFERENCES
Fig. 4 Chest radiograph of infant on partial liquid ventilation (reproduced by kind permission of Professor Alan Spitzer, The Jefferson School of Medicine, Philadelphia, USA).
until a meniscus of fluid was consistently visible in the endotracheal tube on expiration without PEER 33 Perflubron was replaced at a rate of 2.5 ml/kg/h to compensate for evaporative loss and to maintain a constant FRC. There was a dramatic improvement in lung mechanics and gas exchange in lambs receiving partial liquid ventilation. Preliminary reports are emerging on the use of partial liquid ventilation in humans. A chest radiograph of an infant receiving partial liquid ventilation is shown in Figure 4. In a recent report this technique was used to treat 19 patients (adults, children and neonates) with respiratory failure on extracorporeal life support and 1 1 patients survived. 34This exciting new form of ventilation requires further evaluation and, in particular, safety data is required.
CONCLUSIONS
Major technological developments in respiratory support have taken place in the last few years. The challenges are twofold. Tfie first is finding an effective technique when conventional ventilation fails. There is good evidence that high frequency ventilation has a role in this situation with impressive responses in a number of infants. The second challenge is to employ a technique that will reduce the incidence of chronic lung disease. Although there are theoretical reasons why a number of these techniques might be helpful in this role, there is, as yet, no convincing evidence that any of these techniques are superior to conventional support in the routine management of infants with RDS. There may be increased risks with these new techniques, for example HFOV may increase the incidence of intracranial
1. Parker J, Hernandez L, Peevy K. Mechanisms of ventilator induced lung injury. Crit Care Med 1993; 21: 131-143. 2. Drefus D, Saumon G. Role of tidal volume FRC and endinspiratory volumes in development of pulmonary edema following mechanical ventilation. Am Rev Respir Dis 1993; 148: 1194-1203. 3. Visveshwara N, Freeman B, Peck M e t al. Patient triggered synchronized assisted ventilation of newborns. Report of a preliminary study and 3-years experience. J Perinatol 1991; 11: 347-354. 4. de Boer R, Jones A, Ward et al. Long-term trigger ventilation in neonatal respiratory distress syndrome. Arch Dis Child 1993; 68:308 311. 5. Cleary J, Bernstein (3, Mannino F et al. Improved oxygenation during synchronized intermittent mandatory ventilation in neonates with respiratory distress syndrome: a randomized, crossover study. J Pediatr 1995; 126:407411. 6. Chan V, Greenough A. Comparison of weaning by patient triggered ventilation or synchronous mandatory intermittent ventilation. Acta Paediatr 1994; 83: 335-337. 7. Dimitriou G, Greenough A, Giffin F et al. Synchronous intermittent mandatory ventilation modes compared with patient triggered ventilation during weaning. Arch Dis Child 1995; 72: F188-F190. 8. Goldman S, Brady J, Dumpit E Increased work of breathing associated with nasal prongs. Pediatrics 1979; 64: 160-164. 9. Henry W, West G, Wilson R. A comparison of the oxygen cost of breathing between a continuous flow CPAP system and a demand flow CPAP system. Respir Care 1983; 28:1273 1278. 10. Moa G, Nilsson K, Zetterstrom H e t al. A new device for administration of nasal continuous positive airway pressure in the newborn: an experimental study. Crit Care Med 1988; 16: 1238 1242. 11. Kamper J, Wnlff K, Larsen C et al. Early treatment with nasal continuous positive airway pressure in very low birth weight infants. Acta Paediatr 1993; 82:193 197. 12. Verder H, Robertson B, Greison G e t al. Surfactant therapy and nasal continous positive airway pressure for newborns with respiratory distress syndrome. N Engl J Med 1994; 331: 1051 1055. 13. Engelke S, Rotoff D, Kuhns L. Postextubation nasal continous positive airway pressure. Arch Dis Child 1982; 136:35~361. 14. Higgins R, Richter S, David J. Nasal continuous positive airway pressure facilitates extubation of very low birth weight neonates. Pediatrics 1991; 88: 99%1003. 15. Chart V, Greenough A. Randomized trial of methods of extubation in acute and chronic respiratory distress. Arch Dis Child 1993; 68" 57G572. 16. Annibale D, Hulsey T, Engstrom P e t al. Randomized controlled trial of nasopharyngeal continuous positive airway pressure in the extubation of very low birth weight infants. J Pediatr 1994; 124: 455~460. 17. Horng So B, Tamura M, Mishina J e t al. Application of nasal continuous positive airway pressure to early extubation in very low birth weight infants. Arch Dis Child 1995; 72: F188-F190. 18. Gerstmann D, Clark R, de Lemos R. High Frequency Ventilation: issues of strategy. Clin Perinatol 1991; 18: 563-580. 19. de Lemos R, Coalson J, Gerstmann D et al. Ventilatory management of infant baboons with hyaline membrane disease: the use of high frequency ventilation. Pediatr Res 1987; 21:594 602. 20. Meredith K, de Lemos R, Coalson J e t al. Role of lung injury in the pathogenesis of hyaline membrane disease in premature baboons. J Appl Physiol 1989; 66: 2150-2158.
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21. de Lemos R, Coalson J, de Lemos J et al. Rescue ventilation with high frequency oscillation in premature baboons with hyaline membrane disease. Pediatr Putmonol 1992; 12: 11 16. 22. The HIFI Study Group. High frequency oscillatory ventilation compared with conventional mechanical ventilation in the treatment of respiratory failure in preterm infants. N Engl J Med 1989; 320: 88-93. 23. Clark R, Gerstmann D, Null D et al. Prospective randomized comparison of high frequency oscillatory and conventional ventilation in respiratory distress syndrome. Pediatrics 1992; 89:5 12. 24. HIFO Study Group. Randomized study of high frequency oscillatory ventilation in infants with severe respiratory distress syndrome. J Pediatr 1993; 122:609 619. 25. Clark R, Yoder B, Seel M. Prospective, randomized comparison of high frequency oscillation and conventional ventilation in candidates for extracorporeal membrane oxygenation. J Pediatr 1994; 124: 447454. 26. Froese A, McCulloch P, Sugiura M e t al. Optimizing alveolar expansion prolongs the effectiveness of exogenous surfactant therapy in the adult rabbit. Am Rev Respir Dis 1993; 148: 569-577. 27. Keszler M, Donn S, Bucciarelli R. Multicentre controlled trial comparing high frequency jet ventilation and conventional
28. 29. 30.
31.
32.
33.
34.
mechanical ventilation in newborn infants with pulmonary interstitial emphysema. J Pediatr 1991; 119: 85-93. Samuels M. Personal communication. Samuels M, Southall D. Negative extrathoracic pressure in treatment of respiratory failure in infants and young children. BMJ 1989; 229: 1253-1257. Adams J, Suguihara C, Osiovich H et al. Haemodynamic effects of continuous negative extrathoracic pressure (CNEP) and continuous positive airway pressure (CPAP) in piglets with normal lungs. Ped Res 1989; 25: 1784A. Skaburskis M, Helal R, Zidulka A. Haemodynamic effects of external continuous negative pressure ventilation compared with those of continuous positive pressure ventilation in dogs with acute lung injury. Am Rev Respir Dis 1987; 136:886 891. Samuels M, Southall D, Raine R et al. A randomized controlled trial of continuous negative extrathoracic pressure in neonatal respiratory failure. Proceedings of British Paediatric Association Annual Meeting 1995; 67:53 (Abstract). Leach C, Holm B, Morin III E Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant. J Pediatr 1995; 126: 412420. Hirschl R, Pranikoff T, Gauger P e t al. Liquid ventilation in adults, children and full term neonates: Lancet 1995; 346: 1201-1202.
Mini-symposium: Neonatology
New techniques for neonatal respiratory support
R A. J. Chetcuti
Considerable progress has been made in the management of respiratory distress in newborns since the introduction of positive pressure ventilation over 20 years ago. More recently, the introduction of surfactant and the increased use of steroids predelivery have led to a major increase iri survival in preterms with hyaline membrane disease. Conventional ventilation refers to the positive pressure respiratory support that is practised in newborn units. A wide variety of mechanical ventilators are currently in use in the UK and ventilator management policies vary widely between units with no consensus view as to the best approach. Trauma from ventilation is an important factor in the aetiology of the airway and lung damage seen in bronchopulmonary dysplasia (BPD). Asynchrony between the ventilator and the infant's respiration and the use of large tidal volumes to accomplish adequate ventilation are the major components of this trauma? In a study limiting tidal volume by constraints applied to the chest wall in an animal model the use of high airway pressures did not produce as much damage as when tidal volume was not limited) Therefore, changes in lung volume may be more important than changes in airway pressure in the production of lung injury. For this reason, the term volutrauma is preferred to barotrauma. In animals with healthy lungs 13 large tidal volume ventilation can damage the pulmonary capillary endothelium, alveolar and airway epithelium and basement membranes allowing fluid, protein and blood to leak into the airways, alveoli and lung interstitium.1 This sequence is well described in the evolution of respiratory distress syndrome to chronic lung disease in newborns. Despite the excellent achievements in neonatal respiratory care, a number of infants continue to respond
poorly to conventional ventilation and the incidence of BPD remains high affecting 20-30% of all preterms. A number of technologies have developed or have re-emerged in an attempt to influence these problems. This article will consider the major new developments in neonatal respiratory support.
TRIGGER VENTILATION Success in the application of trigger ventilation to treat preterm babies of all gestations with respiratory distress syndrome (RDS) is well documented,3,4 and trigger ventilation is now used widely. In patient triggered ventilation (PTV) the peak inspiratory pressure, positive end expiratory pressure and inspired oxygen are set by the operator but the rate is controlled by the baby's respiratory efforts. This has the potential advantage that the peak inspiratory pressure should be lower as the baby is contributing to transpulmonary pressure and situations in which the baby is actively breathing out during a period of ventilatory inflation should be eliminated. This potentially could reduce the incidence of volutrauma, air leaks and BPD. In a non-randomized study there was a shorter duration of ventilation and a decreased duration of oxygen therapy in infants on trigger ventilation compared with controls. 3 Two large studies in the UK are currently in progress to determine the effects of trigger ventilation compared to conventional ventilation on survival and the incidence of BPD. The most commonly employed available trigger ventilators in the UK are the SLE 2000 and Drager Babylog, which employ airway pressure sensors and airflow sensors respectively. The triggering devices are highly sensitive at detecting the maximum number of the infant's respiratory efforts. The trigger sensitivity may need to be decreased in a vigorous or crying baby and increased during sleep. The trigger delay for both
ConsultantPaediatrician, ClarendonWing,LeedsGeneralInfirmary,BelmontGrove,Leeds LS2 9NN, UK. Phillip A. J. Chetcuti DM MRCP,
78
Neonatal respiratory support ventilators (the time from the onset of inspiration to the commencement of positive pressure inflation) is less than 0.1 s. This should be considered during the setting of the inspiratory time, and in practice the setting will vary between 0.25 and 0.35 s in the majority of preterms. A long inflation time is likely to result in inflation extending into expiration provoking active expiration. As immature infants have a tendency to apnoea, it is essential to have a minimum backup rate to ensure continuity of respiratory support and this is best set at 20 breaths per minute below that of the infant's spontaneous respiratory rate. Babies are weaned from trigger ventilation by weaning the peak inspiratory pressure to a level of 8-10 cm of water and then extubating. Success of PTV relies on careful observations of chest wall movement. This is important at all times but particularly when establishing the initial settings of inspiratory time, peak pressure and trigger sensitivity. Trigger ventilation can also provide synchronous intermittent mandatory ventilation (SIMV). In SIMV, the number of supported breaths is controlled by the SIMV rate. If an infant breathes at a rate of 60 breaths per minute and the SIMV rate is 20 breaths per minute, the ventilator will deliver 20 synchronized breaths per minute. Unlike PTV, the baby breathes spontaneously between the breaths. Improvements in blood gases on SIMV have been reported2 In units not employing PTV, there seems to be no logical reason not to use SIMV in non-paralysed infants when the ventilator rate is 30 or below. With reference to effectiveness in weaning infants from ventilators, studies comparing SIMV with PTV report no differences. 6,7
NASAL CONTINUOUS POSITIVE AIRWAYS PRESSURE Nasal administration of continuous positive airways pressure (CPAP) has been used in the management of neonatal respiratory distress for years. There are four
Fig. 1 (A) EME nasal CPAPdevice.(B) Infanton nasal CPAE
79
potential roles; in the management of respiratory distress syndrome, as a weaning tool in infants on mechanical ventilation, in the management of babies with severe apnoeas of prematurity and in infants with BPD. Continuous positive airways pressure may restore functional residual capacity (FRC) and correct hypoxia secondary to ventilation-perfusion mismatch by recruiting collapsed alveoli. Traditionally, CPAP has been delivered by cut endotracheal tubes (ET) placed in the nares, nasal prongs or face masks. Face masks are difficult to apply and maintain, particularly in small preterm infants, and cerebellar haemorrhage from over zealous strapping of the mask has been reported. With cut ET tubes and nasal prongs, CPAP is frequently not maintained because of leakage of gases through the mouth or at the nasal attachment and attempts to increase the airway pressure by increasing the flow results in wider variations in the CPAP levels as the resistance in the prongs becomes more significant with increased flow. Developing a system to minimize the resistance to flow would increase the demand on the flow dynamics of the CPAP generator making the traditional systems inadequate. Flow resistance within the prong and wide variations in CPAP levels can also increase the work of breathing. 8'9 Given the potential difficulties described above, a new technique for delivery of nasal CPAP has been developed. 1° The gases are delivered from two separated jets directed towards the nasal openings (Fig. 1). By the ejector action of the fresh gas converting kinetic energy into pressure, CPAP is generated in the immediate vicinity of the nasal airway. In laboratory experiments comparing this system to nasal prongs, CPAP is maintained throughout the respiratory cycle and the work of breathing is reduced? ° This system is now commercially available. Improved delivery of nasal CPAP raises a number of important questions. Should we be considering the use of nasal CPAP as first line respiratory support in a larger number of infants with RDS? Would this
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confer any significant advantages to infants? How would surfactant be administered? In a Danish study using nasal CPAP routinely in all preterm infants with RDS there was no recourse to mechanical ventilation in over 70% of infants from 26 to 32 weeks gestation. 11 In a further Scandinavian study of infants with RDS (25-35 weeks gestation) managed with nasal CPAP, the administration of a single dose of a natural surfactant (Curosurf 200 mg/kg) led to a 40% reduction in the requirement for mechanical ventilation compared to babies managed with nasal CPAP alone. 12 Continuous positive airways pressure levels between 6 and 10 cm of water were used in both studies. In the latter study, surfactant was administered following intravenous doses of morphine and atropine and intubation. Infants remained intubated for a maximum of 1 h until respiratory effort was satisfactory and then extubated. Despite the above studies, it is unlikely that the majority of infants of 26 weeks gestation and under would tolerate nasal CPAP as first line respiratory support in RDS. In infants of 27 weeks gestation and over nasal CPAP and intermittent administration of surfactant may be an alternative to conventional ventilation. However, the outcomes of these higher gestation infants in terms of survival and incidence of chronic lung disease are already very good. Therefore, would nasal CPAP confer any additional advantages? Possibly these infants would spend less time on intensive care, which might have financial implications. A large multicentre trial is required to answer these questions and to determine the optimal level of CPAP. A number of studies have assessed the role of nasal CPAP as a weaning tool in infants recovering from RDS with conflicting results. ~3-17 There are many reasons for these discrepant findings including the method of delivery of CPAP, the level of CPAP, extubation criteria, reintubation criteria, population characteristics and the use of theophyllines. In our practice, nasal CPAP appears to be a useful weaning tool, particularly in smaller infants.
HI GH FREQUENCY OSCILLATORY VENTILATION This form of ventilation has emerged in a number of neonatal units in the last 3 years. The concept is best understood by considering the results of a number of studies on animal models. In these, high frequency ventilation minimizes the propagation of lung injury by supporting adequate gas exchange with small tidal volumes less than the dead space volume of the respiratory system? 8 Lung volume is maintained above functional residual capacity by the use of a constant distending pressure; the mean airway pressure. Lung volume is held relatively constant and the potentially deleterious cycle of inflation and deflation associated with conventional ventilation is greatly reduced. The
avoidance of high lung volumes prevents over inflation of the more compliant lung units and the avoidance of low lung volumes prevents collapse of the less compliant lung units with potential benefits in ventilation perfusion mismatching, gas exchange and a reduction in lung damage. TM In the premature baboon model of hyaline membrane disease, the use of high frequency oscillatory ventilation (HFOV) reduces the occurrence of air leak, improves gas exchange and lung mechanics compared to conventional ventilation. 19,2°The amount of inflammatory mediators and the number of leucocytes recovered in lung lavage usually present in the evolution to chronic lung disease are reduced in the animals managed with HFOV. 2° These pathological findings are also reduced in animals treated immediately after delivery compared to the use of HFOV after 8 h of conventional ventilation. 21 Studies on preterm neonates are not as encouraging. In a study from North America, randomizing over 600 infants with RDS to receive HFOV or conventional ventilation, there were no differences in survival or incidence of chronic lung disease. = There was a small but significant increase in the occurrence of Grade III and IV intraventricular haemorrhage and periventricular leucomalacia. A further study on a smaller number of infants approached the ventilation strategy differently. They used a high volume strategy using higher mean airway pressures to recruit and maintain optimal lung inflation)3 Infants with RDS were randomized to HFOV until extubation, HFOV for 72 h followed by conventional ventilation or conventional ventilation alone. Patients treated with HFOV until extubation had a reduced incidence of chronic lung disease at 36 weeks post conceptual age compared to the other groups. There was no difference in the incidence of chronic lung disease between those treated with HFOV for 72 h followed by conventional ventilation and in patients treated with conventional ventilation. Mortality and the incidence of severe intracranial problems were similar in all groups. A study of large numbers of infants is required to confirm or refute these findings. Given uncertainties about the benefits of using HFOV from birth in infants with RDS, is there any evidence of benefits as a rescue tool in RDS? One hundred and eighty preterms with severe RDS within the first 48 h of life, as defined by the presence of pulmonary interstitial emphysema or high peak inspiratory pressures (> 25 cm water in 0.5-1 kg babies, > 28 cm water in 1-1.5 kg infants and > 30 cm in > 1.5 kg infants), were randomized to receive HFOV or conventional ventilation. 24 A high volume strategy was employed. The incidence of new air leak was reduced in infants treated with HFOV but there were no differences in the incidence of chronic lung disease or survival rates in the two groups. Patients assigned to HFOV had a higher incidence of severe intraventricular haemorrhage.
Neonatal respiratory support In a prospective randomized comparison of H F O V and conventional ventilation in larger infants (> 2 kg) with severe respiratory distress (FiO 2 > 50%, PIP (peak inspiratory pressure) > 30) H F O V was a more effective rescue tool than conventional ventilation. 25 Sixty-three percent not responding to conventional ventilation responded to HFOV whereas 23% not responding to HFOV responded to conventional ventilation. There were no differences with respect to the need for extra corporeal membrane oxygenation (ECMO). The numbers are too small to make inferences about the incidence o f chronic lung disease or survival. In our practice, employing H F O V in preterms and older infants as a rescue tool, with infants fulfilling similar criteria to those described in the studies above, we have seen a small but impressive number of responses which justifies its value to us. Early experience of HFOV in the United Kingdom has been with the SensorMedics model 3100A (Fig. 2). This is an electronically controlled piston diaphragm oscillator. Pressure oscillations are generated by the excursions of a plate diaphragm and are superimposed on the mean airways pressure. A standard endotracheal tube is used to deliver HFOV. Exhalation is active because of the biphasic pressure waveform. The adjustable parameters are mean airway pressure (MAP), ventilatory frequency, pressure amplitude and percentage of inspiratory time. Recently, SLE and Drager have added an oscillator mode to their conventional ventilators. The adjustable parameters on these ventilators are similar to those described above, with the exclusion of percentage of inspiratory time. The value of this parameter in relation to HFOV is not clearly understood. The effectiveness of these ventilators as oscillators requires further evaluation. In respiratory distress syndrome a relatively high mean airway pressure is used to recruit lung volume. This is usually 2 cm of H20 greater than the mean airway pressure on conventional ventilation. In the first few hours of administration of HFOV every attempt should be made to achieve the optimal lung volume. Mean airway pressure must be increased cautiously so as not to result in lung overdistension, air leak and a decrease in cardiac output. The assessment of lungdistension is difficult, and, in theory, measures of FRC would be valuable. Frequent chest radiographs are taken to assess the degree of lung distension. The optimal diaphragmatic position is between the 8th and 9th posterior ribs. It is not unusual for an infant to have up to six chest radiographs in the first 24 h on HFOV. This high volume strategy is usually accompanied by a significant reduction in FiO 2. When F i O 2 falls below 30%, judicious weaning of the MAP is possible. Ventilatory frequency is set at 10-15 Hz and inspiratory time at 30%. These variables are not altered throughout the course of oscillation. We have found that larger infants (> 3 kg) sometimes require a slightly lower frequency (8-9 Hz). The pressure amplitude is set to a level at which good chest wall movement is observed. The use
81
Fig. 2 Infant on HFOV (SensorMedics 3100A).
of a transcutaneous CO 2 monitor may be helpful in establishing the optimal pressure amplitude. The pressure amplitude is then increased or decreased depending on arterial CO 2 concentrations. The baby should not be disconnected from the ventilator if at all possible, as this might result in collapse of alveoli and loss of lung volume. If reintubation is required it is important to remember that changes in endotracheal tube size can affect arterial CO 2 tension more significantly than with conventional ventilation. It is our practice to paralyse and sedate all infants on HFOV, and when the MAP is 8-9 cm of H 2 0 , transfer to conventional ventilation. However, a well described strategy is to wake the infant, reduce the M A P to 4-5 cm of H20, reduce the pressure amplitude to zero and extubate directly. There is no time limit on HFOV. Occasionally, infants are placed on conventional ventilation because of problems with secretions and airways collapse. In contrast to the management of RDS, the management of infants with air leak and meconium aspiration syndrome conditions associated with lung overdistension are managed with a low volume and consequently low M A P strategy. The MAP is set at the same level or slightly lower (1-2 cm of H 2 0 ) than the M A P on conventional ventilation. Dramatic initial improvements in oxygenation, sometimes seen in RDS, are less commonly seen in these conditions. Settings for other ventilator parameters are similar to those described above. A similar approach is used in persistent foetal circulation. The use of exogenous surfactant in infants receiving high frequency oscillation needs further evaluation. With HFOV as a rescue tool, infants have usually received at least one dose of surfactant during treatment with conventional ventilation. In animal studies, the combination of the two improves gas exchange and pulmonary mechanics. 26 Like surfactant, high frequency ventilation can cause rapid increases in lung volume and the combination of the two could be potentially deleterious with lung overdistension, air leak, hypotension and possibly intracranial haemorrhage. If they are to be combined, judicious monitoring is essential.
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HIGH FREQUENCY JET VENTILATION A special endotracheal tube and pinch valve are required to deliver inspiratory pulses of gases into the trachea. The adjustable variables are peak inspiratory pressure, frequency and inspiratory time. The range of frequencies are lower than that of HFOV, in the range of 4-10 Hz. Exhalation is passive, and is promoted by short inspiratory times (2~34 ms) and long expiratory times. The latter is provided by convention/d ventilation connected in tandem at the endotracheal tube. The conventional ventilator also provides end expiratory pressure and intermittent breaths (maximum 10 per min) which interrupt the jet pulses when the peak pressure set on the conventional ventilator is higher than that set on the high frequency jet ventilation (HFJV). During HFJV pressure is delivered to and monitored in the trachea. A multicentre study of 144 infants with pulmonary interstitial enphysema showed that they were more likely to respond to HFJV than to conventional ventilation. There was improved gas exchange at lower peak and mean airway pressures and a more rapid resolution of the pulmonary interstitial emphysema (PIE)?7 Infants treated with HFJV had a better survival rate (65% vs 47%). Early reports suggested that HFJV was associated with a high incidence of necrotizing tracheobronchitis. Improvements in humidification appear to have minimized this problem. At the present time, HFJV is rarely used in the UK and comparative studies with HFOV as a rescue tool have not been done.
CONTINUOUS NEGATIVE EXTRATHORACIC PRESSURE Prior to the introduction, over 20 years ago, of positive pressure ventilation in the management of newborns with RDS negative pressure respiratory support was used with some success. Enthusiasm for the technique was rekindled in the search for a relatively non-invasive type of ventilation in the management of difficult infants with BPD?8 Initially, there were technical problems with temperature control of small infants, accessibility and trauma to the neck and upper airways secondary to obstruction from the tight neck seal. However, extensive design modifications have been made29 with the development of a temperature controlled infant incubator capable of delivering constant or intermittent negative pressure (Fig. 3). The device includes a perspex chamber into which the infant is placed. The infant's head passes through a thin latex membrane which separates the interior of the chamber from the atmosphere. The chamber is heated with a servo-controlled incubator heater, and an electric suction device provides regulated negative pressure. Access to the infant is accomplished through portholes equipped with packed cell foam gaskets to maintain negative pressure. This equipment permits the use of
Fig. 3 Infant on CNEP Tank (reproduced by kind permission of Dr Martin Samuels,University of Keele).
radiant heat sources. The only other commercially available system for delivering negative pressure is a jacket (Hyek) which has not been evaluated in preterms. Negative pressure respiratory support may have a number of advantages over positive pressure ventilation. Continuous negative extrathoracie pressure (CNEP) may result in a more uniform distribution of ventilation, less ventilation perfusion mismatching and therefore improved oxygenation. Comparisons of CNEP and positive end-expiratory pressure (PEEP) in animal studies suggest the former may have beneficial effects on pulmonary vascular resistance and cardiac output. 3°,~1Anecdotal success with CNEP in the management of infants with BPD prompted an interest in the use of CNEP to treat RDS. Preliminary results on a large randomized trial of CNEP at 4-6 cm of H 2 0 compared to conventional ventilation in preterms with early respiratory distress syndrome (4 h), showed a 10% reduction in the incidence of chronic lung disease.32The full study results are awaited. Comparative studies of CNEP and nasal CPAP in early RDS would be of some interest. Given the relative difficulties of applying this technique, it is unlikely to gain popular support unless such a comparative study showed that CNEP had significant advantages.
PARTIAL LIQUID VENTILATION Considerable interest has emerged in the potential for this kind of ventilation employing perfluorochemical liquids; chemicals with a low surface tension and high solubility. Partial liquid ventilation employs a conventional ventilator to deliver gas tidal volumes into a lung with a liquid functional residual capacity. More recently, a medical grade perfluorochemical liquid perflubron has become available with high spreading properties and low vapour pressure. In a study on premature lambs with RDS/5 pre-oxygenated perflubron pre-warmed to 39°C was instilled into the trachea
Neonatal respiratory support
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complications. Despite this, each technique may have a role in specific clinical settings. Traditionally, our knowledge of what is best in newborn ventilation has not been driven by well designed large randomized trials. At present a number of trials are underway or in development which will help to determine the precise roles for these new techniques in the respiratory care of newborn infants. REFERENCES
Fig. 4 Chest radiograph of infant on partial liquid ventilation (reproduced by kind permission of Professor Alan Spitzer, The Jefferson School of Medicine, Philadelphia, USA).
until a meniscus of fluid was consistently visible in the endotracheal tube on expiration without PEER 33 Perflubron was replaced at a rate of 2.5 ml/kg/h to compensate for evaporative loss and to maintain a constant FRC. There was a dramatic improvement in lung mechanics and gas exchange in lambs receiving partial liquid ventilation. Preliminary reports are emerging on the use of partial liquid ventilation in humans. A chest radiograph of an infant receiving partial liquid ventilation is shown in Figure 4. In a recent report this technique was used to treat 19 patients (adults, children and neonates) with respiratory failure on extracorporeal life support and 1 1 patients survived. 34This exciting new form of ventilation requires further evaluation and, in particular, safety data is required.
CONCLUSIONS
Major technological developments in respiratory support have taken place in the last few years. The challenges are twofold. Tfie first is finding an effective technique when conventional ventilation fails. There is good evidence that high frequency ventilation has a role in this situation with impressive responses in a number of infants. The second challenge is to employ a technique that will reduce the incidence of chronic lung disease. Although there are theoretical reasons why a number of these techniques might be helpful in this role, there is, as yet, no convincing evidence that any of these techniques are superior to conventional support in the routine management of infants with RDS. There may be increased risks with these new techniques, for example HFOV may increase the incidence of intracranial
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21. de Lemos R, Coalson J, de Lemos J et al. Rescue ventilation with high frequency oscillation in premature baboons with hyaline membrane disease. Pediatr Putmonol 1992; 12: 11 16. 22. The HIFI Study Group. High frequency oscillatory ventilation compared with conventional mechanical ventilation in the treatment of respiratory failure in preterm infants. N Engl J Med 1989; 320: 88-93. 23. Clark R, Gerstmann D, Null D et al. Prospective randomized comparison of high frequency oscillatory and conventional ventilation in respiratory distress syndrome. Pediatrics 1992; 89:5 12. 24. HIFO Study Group. Randomized study of high frequency oscillatory ventilation in infants with severe respiratory distress syndrome. J Pediatr 1993; 122:609 619. 25. Clark R, Yoder B, Seel M. Prospective, randomized comparison of high frequency oscillation and conventional ventilation in candidates for extracorporeal membrane oxygenation. J Pediatr 1994; 124: 447454. 26. Froese A, McCulloch P, Sugiura M e t al. Optimizing alveolar expansion prolongs the effectiveness of exogenous surfactant therapy in the adult rabbit. Am Rev Respir Dis 1993; 148: 569-577. 27. Keszler M, Donn S, Bucciarelli R. Multicentre controlled trial comparing high frequency jet ventilation and conventional
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