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Neonatal ventilation
Early Human Development, 13 (1986) 121- 136
127
Elsevier
EHD 00736
Review article
Neonatal ventilation Anne Greenough “(Children
’
Narionwide) Research Fund, Dept. of Child Health, King’s College Hospital, London SE 5. h Depi. of Paediatrics, New Addenbrooke’s Hospital, Cambridge, U.K. Accepted
newborns;
a and N.R.C. Roberton
artificial
ventilation;
for publication
respiratory
26 October
1985
failure
Artificial ventilation is now an established therapy for all forms of respiratory failure in the newborn, particularly in infants with the respiratory distress syndrome (RDS) in whom apnoea supervenes or when hypoxaemia with concurrent respiratory acidosis develops [44]. Initially, however, mechanical ventilation was used only as a last resort in critically ill patients, for example following cardiac arrest or infants severely bradycardic with profound hypoxaemia and hypoventilation [18] but even then it was found to improve survival. Delivoria-Papadopoulos et al. [18] reported a survival rate of 7 out of 20 ventilated neonates (mean gestational age 34.1 weeks and mean postnatal age 29.1 h) and Adamson et al. [l] had 12 survivors out of 40 ventilated infants. Increased experience in using this technique led to an encouraging trend in survival figures; with Roberton [46] reporting 38% surviving, Lindroth et al. [33] 41% and the Cambridge neonatal intensive care unit for 1980-1983 reporting a survival of 78% [25]. This reduction in mortality represents a much larger increase in the actual numbers of infants surviving as many more infants are now ventilated, but this improvement in survival has not been achieved without a considerable incidence of complications. An increased incidence of all forms of air leak has been reported [34] and the emergence of chronic respiratory insufficiency following prolonged artificial ventilation, particularly bronchopulmonary dysplasia (BPD) [39] is an increasing problem. A variety of techniques and manipulations of mechanical ventilation by conventional ventilators have been studied in infants suffering from RDS in an attempt to improve its efficacy and reduce these complications.
Address /or correspondence: Dr. A. Greenough, (Children Nationwide), Senior Lecturer in Neonatology. Department of Child Health, King’s College Hospital, Denmark Hill, London SE 5. U.K.
0378-3782/86/$03.50
0 1986 Elsevier Science Publishers
B.V. (Biomedical
Division)
128
1. Volume-cycled
Initially volume cycled ventilators were used in the treatment of hyaline membrane disease. Their design allowed delivery of small volumes at high frequencies, matching the typical tidal volume and respiratory rates of the preterm infant with RDS. The ventilator “adjusted” the pressures to achieve the preset rate and tidal volumes. Short Inspiratory : Expiratory (I : E) ratios were used, with high flow rates generating the high inflating pressures which were often necessary to overcome the stiffness of the lungs in RDS. This use of fast rates with a short inspiratory phase copied adult ventilation techniques and, by mimicking the infant’s frequency of breathing (up to 80 breaths/mm), it was thought that fighting the ventilator and subsequent barotrauma would be less likely to occur [l]. However, at such frequencies, although PaCO, could be kept reasonably normal, adequate oxygenation could only be achieved with the use of very high peak pressures. The survival rate of infants ventilated in that way was low and many died from BPD [56]. Although certain authors [2,33] had incriminated oxygen toxicity as the cause for BPD, Taghizadeh and Reynolds [56] were able to demonstrate that the presence of lesions in this condition strongly correlated with the use of high peak pressures but not with the inspired oxygen concentrations.
2. Slow rate ventilation In view of the correlation of chronic lung disease with high pressures, studies were performed to determine if methods of ventilation could be developed to allow the successful use of lower inflating pressures and slower frequencies [28&l]. In RDS the compliance is low and alveoli show a high tendency to collapse, therefore to inflate the maximum number of alveoli to a normal volume as early as possible in inspiration it was suggested that the inspiratory wave form generated by the ventilator which would achieve this best would be a modified square wave. Using this wave form four variables of ventilator settings were studied; peak inflating pressure, positive expiratory end pressure (PEEP), I : E ratio and ventilator rate. It was found that more effective oxygenation could be achieved at a slower respiratory frequency (30 breaths/min) [28,44,49,50]. Oxygenation could also be improved by increasing the relative duration of inspiration (increasing the I : E ratio), applying PEEP and increasing the peak airway pressure. Keeping the peak pressure and rate constant and increasing mean airway pressure (MAP) by altering the I : E ratio was found to provide a more effective method of improving oxygenation than by increasing PEEP. Increasing PEEP could actually decrease oxygenation by decreasing tidal volume and alveolar ventilation. From these results guidelines about appropriate initial ventilator settings were laid down; peak inflating pressures of 20-25 cm H,O, PEEP of 3 cm H,O, and I : E ratio of 1: 1 and a rate of 30 breaths/mm. If on such settings oxygenation was a problem then the I : E ratio was increased and later if necessary PEEP or peak inflating pressures were also increased.
129
This method of ventilation as advocated by Reynolds et al [28,44] was associated with a reduction in the incidence of BPD [56]. Using such an approach to mechanical ventilation most centres reported a reduction in the incidence of all forms of chronic lung disease [35]. Observations in animals with RDS confirmed that slow rates and long inspiratory times gave fewer histological changes of the type seen in early BPD and better lung compliance [31,38].
3. The effect of I : E ratio Spahr et al. [53] randomly assigned infants to receive an I : E ratio of either 1 : 2 or 2 : 1. Their results confirmed the value of lengthened I : E ratios, in that infants in the “2 : 1” group required less inspired oxygen and a lower end expiratory pressure However, there was no difference in the to achieve satisfactory oxygenation. mortality or morbidity between the two groups. Muller and Schober [37] also advocated use of this prolonged inspiratory time (1.5 set), but felt that a prolonged expiratory time was necessary to allow for adequate pulmonary perfusion. To achieve this they used low frequency ventilation (rates of lO/min) with an I : E ratio of less than 1 : 2. Satisfactory oxygenation and control of PaCO, was achieved and although there was only a 59% survival, none of the infants studied had radiological evidence of BPD. Interestingly the infants were allowed to breathe spontaneously during the expiratory phase of artificial ventilation and this may have made a significant contribution to gas exchange. Their lowered incidence of pneumothoraces (6.8%) compared to 14% in an earlier series [56] was attributed to the short expiratory time in the latter series causing air-trapping and alveolar distension.
4. The effect of PEEP The value of PEEP was confirmed [16]. The improvement in oxygenation caused by the addition of PEEP could have been due both to the resultant increase in MAP or surfactant conservation [60]. Although the addition of PEEP was usually beneficial, its use was associated with various complications. It can cause hypercapnia [17] and was associated with an increased incidence of pneumothoraces [3], although this latter study reported a comparison of the two types of ventilation used at two separate time periods.
5. The importance of mean airway pressure More recent studies demonstrated that mean airway pressure was an important determinant of oxygenation and the form of application of the airway pressure appeared to be less important. In animal studies Boros et al. [7] showed that both optimum ventilation and oxygenation were related to MAP but not to I : E ratio or peak inflatin,g pressure. However, over a certain level of MAP (> 14 cm H,O) there
130
was a progressive deterioration in blood gas values, which was attributed to alveolar distension. This study was followed up in neonates suffering from severe HMD [8], again in all patients oxygenation was directly related to the level of MAP. Optimal oxygenation and ventilation occurred with the I : E ratio and pressure wave form combination that produced the highest MAP. Boros and Campbell [9] compared the effectiveness of slow ventilator rates in combination with high tidal volumes against rapid rates and low tidal volumes (minute ventilation, inspired oxygen, PEEP and I : E ratio were held constant). Once again they were able to demonstrate that the best arterial oxygenation occurred at the combination of settings that produced the highest MAP. As the highest MAP was always found at the slowest rates and highest tidal volumes, these settings, not surprisingly, gave the best arterial oxygenation (P < 0.001). However, the differences found at the two ventilator rates may not only have been due to differences in MAP, since deadspace ventilation is proportional to respiratory frequency, at the same minute volume, the effective alveolar ventilation would be reduced during fast frequency ventilation [48]. Cizek et al. [13] confirmed that MAP is an important determinant of oxygenation, but also demonstrated that significant changes in PaCO, could be affected by altering PIP and PEEP despite a constant MAP.
6. Fast rate ventilation Recently fast rate ventilation has again found favour. As the use of excessive airway pressure was incriminated as a cause of the high incidence of extrapulmonary air leaks and severe forms of chronic lung disease [40], Bland et al. [4] attempted an alternative approach, that of high frequency, low volume ventilation. Bland et al. [4] demonstrated that small preterm infants (750-1750 g) could be effectively ventilated with rapid respiratory rates (60-llO/min) and low end tidal pressures (4-9 cm H,O) with a peak pressure less than 35 cm H,O. 92% of their patients survived and only 2 of the 24 infants sustained pneumothoraces; however, there were no “control” infants ventilated at slower rates with which to make a comparison. Boros and Campbell [9] suggested this apparent success may have been due to the type of ventilator used in the study of Bland et al. Increasing ventilator rates on certain ventilators resulted in a decreased MAP (Bennett PR2 pressure preset) while in others (Bourns LS104 volume preset) MAP increased with increasing ventilator rates. However, other studies have also claimed advantages for fast rate ventilation; Heicher et al. [26] demonstrated that rapid rates (60/min) with an inspiratory time of 0.5 set were as effective a means of ventilation as the use of slower rates (20-40/min) with a longer inspiratory time of 1 sec. Interestingly, they were able to demonstrate a lower incidence of pneumothoraces in the fast rate group, but unfortunately their study was of an alternate allocation design and could therefore have been exposed to bias. In a further, non-randomised study [24] we also demonstrated a reduction in the incidence of airleaks amongst infants ventilated at fast rates who were suffering from the pulmonary interstitial emphysema (PIE), but
131
there was no difference in the mortality and the PIE actually worsened presumably due to lack of decompression. The results of Ratner and Hernandez [43] suggest a possible mechanism for the beneficial effects of fast rates as using Baby Bird ventilators they were able to successfully ventilate preterm infants (26-36 weeks) at lower peak pressures by increasing ventilator rate to keep MAP constant. Interestingly in that study all the patients included were unparalysed and the faster ventilator rates more closely mimicked the infant’s respiratory frequency. The earlier lack of success and high morbidity at such fast rates may have been due either to the lack of PEEP or that mechanical ventilation was given by relatively unsophisticated ventilators which were only used much later in the disease course; that is to treat severe hypoxia despite breathing 95% oxygen or incipient collapse [28]. The difference in results may also have been due to the nature of the patient studied [28], that is more mature infants with very severe RDS. Before we become too enthusiastic about fast rate ventilation, it must be noted Robinson et al. [47], having performed detailed follow-up lung function tests 22-67 weeks following mechanical ventilation on a series of preterm infants, demonstrated that the degree of impairment of lung function of the ventilated infants could be significantly related to the length of time spent on high frequency ventilation (> 30/min), however only 14 babies were included and rates varied from 30 to 180/min.
7. The importance of the infant’s spontaneous
respiration during ventilation
Although the manipulations described above (in Sections 2-4) improved the effectiveness of mechanical ventilation and resulted in a decrease in the incidence of BPD, the incidence of air leaks remained high (range 25540%) [34]. Few preterm infants were paralysed during ventilation, therefore it seemed possible that their spontaneous respiratory efforts during ventilation could be an important influence on its effectiveness and even be incriminated as a factor in the causation of air leaks and BPD, Pollitzer et al. [42] postulated that damage to the lungs could be caused by the infant taking a spontaneous breath simultaneously with the ventilator’s inspiratory cycle, this combination could generate large transpulmonary pressure swings resulting in ruptured or damaged airways and alveoli. It was also recognised that asynchronous ventilation could have a deleterious effect on oxygenation [30], and in such circumstances paralysis has since been shown to improve oxygenation [15;27]. However trials of paralysis to prevent pneumothoraces, although demonstrating a number of beneficial effects of pancuronium (improved oxygenation and survival and a reduction in chronic lung disease) did not result in a significant reduction in the incidence of air leaks. This lack of success may be explained by inclusion of all ventilated infants with RDS in these studies, since certainly there are infants in whom paralysis has been shown to result in hypoxaemia and the compensatory increased peak pressures may actually result in increased barotrauma and possible air leaks. Interestingly, the only study which aimed to paralyse infants fighting the ventilator did claim to show a reduction in pneumothoraces, but was not significant [55]. Recently we have shown that by detailed respiratory monitor-
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ing, it can be detected that the infant’s spontaneous respiration interacts in different ways during mechanical ventilation at conventional rates [22]. Only one such was consistently demonstrated as occurring before interaction “active expiration” the development of an air leak. Amongst this select group of infants paralysis with pancuronium significantly reduced the incidence of airleaks [23]. This successful, selective use of pancuronium to reduce the occurrence of pneumothoraces has also been confirmed by Cooke et al. [14], using clinical findings to detect infants fighting the ventilator.
8. High frequency jet and high frequency oscillatory ventilation The apparent success using high frequency positive pressure ventilation encouraged the development of methods of ventilation using even faster frequencies-high frequency jet ventilation (HFJV), using compressed gas delivered through a small bore cannula at frequencies up to 400/min and high frequency oscillation (HFO), using frequencies up to 40 Hz and quasi-sinusoidal volume excursions. Very limited date has so far accumulated as to the effectiveness of HFJV. Pokora et al. [41] used this technique in 10 infants, 9 of whom had progressive air leaks. Following HFJV, the pulmonary air leaks decreased radiologically in 7 and oxygenation improved in 8 of 10 patients. However only 5 of the infants survived and 3 of the 6 infants exposed to HFJV for longer than 20 h developed significant tracheal obstruction, possibly due to poor humidification of the inspired gas. Spitzer et al. [54] described improvements in gas exchange at lower pressures during HFJV and suggested that the addition of IMV could be of benefit, but only studied 6 infants. Carlo et al. [12] recently reported a well designed cross over study comparing conventional ventilation with HFJV and demonstrated a significant reduction in the average peak pressure without impairment of oxygenation during the period of HFJV, but this study only included 12 infants for up to periods of 3 h. On a note of caution, as with conventional ventilators, Lewallen [32] pointed out that different jet ventilators perform differently and the results of the study of one system can not be applied to another. The most recent report of 34 infants from a 4-year period by Boros et al. [ll] demonstrated significant improvements in pH, PaCO, and PaO, with 74% of the infants showing radiological evidence of a decrease in air leak. Unfortunately, only 32% of infants survived, but again only severely ill infants were included in the study-intractable air leaks, severe congenital diaphragmatic hernia (CDH) and end stage respiratory failure. The effect of HFJV on the trachea remains a most worrying effect although the exact nature of the problem and its causation remain somewhat controversial. Smith [51] and Carlo et al. [12] reported that using “appropriate” humidification no changes in mucociliary transport occurred. However the most recent study by Boros et al. [ll] described tracheal lesions in many of the infants studied and in 83% dying following 8 h or more of HFJV-lesions included inflammation, necrosis and at times erosion always occurring in the region of the endotracheal tube tip. They suggested that the earlier explanation of poor humidity may have been too simplistic as in
133
animal models, comparing different humidity systems with conventional and HFJV. the latter always resulted in more tracheal damage regardless of humidity. However. this effect may not be a specific effect of HFJV as Fox et al. [19] describe similar lesions in infants ventilated by other means and again stressed the need for adequate humidification. Tolkin et al. [57] stressed a mixed aetiology as they reported tracheal lesions following the use of dry gas, conventional rates and HFJV. HFO was first successfully used in animal studies, Bohn et al. [5] demonstrated that gas exchange could be supported for many hours by applying small volume, high frequency oscillations in the airway. A frequency of 15 Hz was used with input volumes of less than half the subject’s dead space volume. Frantz et al. [20] later reported the effectiveness of this technique in 5 premature infants, oxygenation and CO, elimination being optimal at about 20 Hz. Marchak et al. [36] reported improvements in oxygenation in changing from conventional slow rate ventilation to HFO at frequencies ranging from 8 to 20 Hz with a mean airway pressure of 9-20 cm H,O, subsequent improvements in oxygenation during HFO could be related to changes in MAP. However this study only included 9 infants for a mean time of 147 min, therefore no comment on long term complications could be made. Frantz et al. [21] demonstrated that HFO might provide a means of ventilating infants at significantly lower pressures than conventional ventilation and in certain cases this was associated with improvement in severe PIE. However although one infant was ventilated for 26 days this was unusual and again only small numbers of infants were included in the study. Recently, this technique has been used in other severely compromised infants-CDH. Karl et al. [29] were able to demonstrate a reversal of acidosis using HFO in these infants when conventional ventilation had failed, unfortunately all 4 infants died within 13-80 h of commencing HFO. Bohn et al. [6] did find improvement in PaO, in 23 infants with CDH unresponsive to other treatment, unfortunately the response was only temporary and no long term outcome is given. Conflicting evidence has been given regarding possible side-effects of this technique, particularly regarding phospholipids. Truog et al. [59] found no difference in lung and lavage phospholipid composition in animal studies between conventional and HFO ventilation, however, Solimano et al. [52] demonstrated a possible disruption in surfactant turnover in lambs ventilated by HFO.
9. Conclusion Artificial ventilation by conventional ventilators is a successful method of respiratory support for infants suffering from RDS. Only preliminary evidence exists regarding the efficacy of high frequency ventilation either by jet ventilator or oscillation, both methods have only been studied in a small number of infants. Although this preliminary evidence suggests a useful role in very compromised infants unresponsive to other treatments, no long term studies have been done or any assessment made in the preterm neonate suffering from uncomplicated RDS and the side-effects of HFJV remain worrying. Until such information is available we must continue to use conventional ventilators in the most effective way. The
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change in the nature of patients at present being ventilated on our neonatal intensive care units, means that policies derived from more mature infants with more severe RDS can not be applied without question. Preliminary evidence suggests that fast rate ventilation (60-120/min) may confer advantages in such a population, however no large long-term randomised study exists to accurately test this hypothesis and we must be aware of the different performances of different ventilators at higher rates [lo]. Evidence also exists that a greater understanding and monitoring of the infant’s spontaneous respiration is important and that by using such tools paralysis can be effectively used to reduce to incidence of certain of the complications of ventilation, but again there is a necessity for long term studies to assess the value of this approach.
References 1 Adamson, T.M., Collins, L.M., Dehan, M. et al. (1968): Mechanical ventilation in newborn infants with respiratory failure. Lancet, 2, 227-231. 2 Banerjee, C.K., Girling, D.G. and Wigglesworth, J.S. (1972): Pulmonary fibroplasia in newborn infants treated with oxygen and artificial ventilation. Arch. Dis. Child., 47, 509-515. 3 Berg, T.J., Pagtakhan, R.D., Langston, C. et al. (1976): Bronchopulmonary dysplasia and lung rupture in HMD: Influence of continuous distending pressure. Pediatrics, 55, 51-53. 4 Bland, R.D., Kim, M.H., Light, M.J. et al. (1980): High frequency mechanical ventilation in severe hyaline membrane disease: An alternative therapy? Crit. Care Med., 8, 275-280. 5 Bohn, D.J., Miyasaka, K., Marchak, B.E. et al. (1980): Ventilation by high frequency oscillation. J. Appl. Physiol., 48, 710-716. 6 Bohn, D.J., Tamura, M. and Bryan, C. (1984): Respiratory failure in congenital diaphragmatic hernia: ventilation by high frequency oscillation. Pediat. Res., 18, 387A. 7 Boros, S.J., Matalon, S.V., Ewald, R. et al. (1977): The effect of independent variations in inspiratory-expiratory ratio and expiratory pressure during mechanical ventilation in hyaline membrane disease. J. Pediatr., 91, 794-798. 8 Boros, S.J. (1979): Variations in inspiratory : expiratory ratio and airway pressure waveform during mechanical ventilation: The significance of mean airway pressure. J. Pediatr., 94, 114-117. 9 Boros, S.J., and Campbell, K. (1980): A comparison of the effects of high frequency-low tidal volume and low frequency-high tidal volume mechanical ventilation. J. Pediatr., 97, 108-112. 10 Boros, S.J., Bing, D.R., Mammel, M.C. et al. (1984): Using conventional infant ventilators at unconventional rates. Pediatrics, 74, 487-492. 11 Boros, J., Mammel, M.C., Coleman, J.M. et al. (1985): Neonatal high frequency jet ventilation: four years experience. Pediatrics, 75, 657-663. 12 Carlo, W.A., Chatburn, R.L. and Martin, R.J. (1984): Decrease in airway pressure during high frequency jet ventilation in infants with respiratory distress syndrome. J. Pediatr., 104, 101-107. 13 Ciszek, T.A., Modanlou, H.D., Owings, D. et al. (1981): Mean airway pressure-significance during mechanical ventilation of neonates. J. Pediatr., 99, 121-126. 14 Cooke, R.W.I. and Rennie, J.M. (1984): Pancuronium and pneumothorax. Lancet i, 286-287. 15 Crone, R.K. and Favorito, J. (1980): The effect of pancuronium bromide on infants with hyaline membrane disease. J. Pediatr., 97, 991-993. 16 Cumarasamy, N., Nussli, R., Vischer, D. et al. (1973): Artificial ventilation in hyaline membrane disease. The role of positive end expiratory pressure and continuous positive airway pressure. Pediatrics, 51, 629-635. 17 DeLemos, R.A., McLaughlin, G.W. and Robinson, E.J., (1973): Continuous positive pressure as an adjunct to mechanical ventilation in the newborn with respiratory distress. Arch. Dis. Child., 40, 474-479.
135 18 Delivoria-Papadopoulos, M., Levison, H. and Swyer, P.R. (1965): Intermittent positive pressure respiration as a treatment in severe respiratory distress. Arch. Dis. Child., 40, 474-479. 19 Fox, W.W., Spitzer, A.R., Musci, M. et al. (1984): Tracheal secretion impaction during hyperventilation for persistent pulmonary hypertension of the neonate. Pediatr. Res., 18, 323A. 20 Frantz, I.D., Stark, A.R. and Dorkin, H.L. (1980): Ventilation of infants up to 18OO/min. Pediatr. Res., 14, 642. 21 Frantz, I.D., Werthammer, J. and Stark, A.R. (1983): High frequency ventilation in premature infants with lung disease: Adequate gas exchange at low tracheal pressures. Pediatrics, 71, 483-488. 22 Greenough, A., Morley, C.J. and Davis, J.A. (1983): The interaction of the infant’s spontaneous respiration with artificial ventilation. J. Pediatr., 103, 769-773. 23 Greenough, A., Wood, S., Morley, C.J. and Davis, J.A. (1984): Pancuronium prevents pneumothoraces in ventilated premature babies who actively expire against positive pressure ventilation. Lancet, i, l-4. 24 Greenough, A., Dixon, A.D. and Roberton, N.R.C. (1984): Pulmonary interstitial emphysema: Arch. Dis. Child., 59, 1046-1051. A. and Roberton, N.R.C. (1985): Morbidity and survival in neonates ventilated for the 25 Greenough, respiratory distress syndrome. Br. Med. J., 290, 597-600. 26 Heicher, D.A., Kasting, D.S. and Richards, J.R. (1981): Prospective clinical comparison of two methods for mechanical ventilation of neonates: Rapid rate and short inspiratory time versus slow rate and long inspiratory time. J. Pediatr., 98, 957-961. 27 Henry, W.H., Stevens, D.C., Schreiner, R.L. et al. (1979): Respiratory paralysis to improve oxygenation and mortality in large newborn infants with respiratory distress. J. Pediatr. Surg., 14. 761-767. 28 Herman, S. and Reynolds, E.O.R. (1973): Methods of improving oxygenation in infants mechanically ventilated for severe hyaline membrane disease. Arch. Dis. Child., 48, 612-616. 29 Karl, S.R., Ballantine, T.V.N. and Schnider, M.T. (1983): High frequency ventilation at rates of 375 to 1800 cycles/minute in 4 neonates with congenital diaphragmatic hernia. J. Pediatr. Surg., 18. 822-828. 30 Krauss. A.N. (1980): Assisted ventilation: A critical review. Clin. Perinatol., 7, 61-74. 31 Lachmann, B., Grossman, G., Freyse, J. et al. (1981): Lung thorax compliance in the artificially ventilated premature rabbit neonate in relation to variation in inspiration-expiration ratio. Pediatr. Res., 15, 833-838. 32 Lewallen, P.K., Mammel, M.C., Gordon, M.J. et al. (1984): The effect of changing rate and I : E ratio using different high frequency jet ventilators. Pediatr. Res., 18. 396A. 33 Lindroth, M., Svenningsen, N.W., Ahlstrom, H. et al. (1980): Evaluation of mechanical ventilation in newborn infants. Acta Pediatr. Stand., 69, 143-158. D.L., Lawson, E.E., Cherniack, V. et al. (1979): Pneumothorax and other forms of air 34 Madansky, leak. Am. Rev. Respir. Dis., 120, 729-737. F.P., Grassi, A.E., Schnecher, S. et al. (1978): Evaluation of methods of assisted 35 Manginello, ventilation in HMD. Arch. Dis. Child., 53, 878-881. B.E., Thompson, W.K., Duffty, P. et al. (1981): Treatment of RDS by high frequency 36 Marchak, oscillatory ventilator: A preliminary report. J. Pediatr., 99, 287-292. plateau 37 Muller. W.D. and Schober, P. (1980): Artificial ventilation in severe IRDS using inspiratory prolonged expiratory time and low frequency. Helv. Pediatr. Acta. 35, 449-458. G. and Robertson, B. (1978): Lung surfactant and the pathogenesis of 38 Nilsson, R., Grossman, neonatal bronchiolar lesions induced by artificial ventilation. Pediatr. Res., 12, 249-254. 39 Northway. W.H., Rosan, R.C. and Porter, D.Y. (1967): Pulmonary disease following respiratory therapy of hyaline membrane disease. N. Engl. J. Med., 276, 357-358. 40 Phillips. J.P., Setzer, E.S., Drummond, W.H. et al. (1979): Hypoxaemia in ventilated neonates after pancuronium paralysis. Lancet, i, 877-879. 41 Pokora. T.. Bing, D., Mammel, M. et al. (1983): Neonatal high frequency jet ventilation. Pediatrics, 72, 27-32. 42 Pollitzer, M.J.. Reynolds, E.O.R., Shaw, D.J. et al. (1981): Pancuronium speeds recovery of lungs of infants with hyaline membrane disease. Lancet, i, 346-348. J. and Accuroso, F. (1982): Low peak pressure inspiratory pressures for 43 Ratner. I., Hernandez, ventilation of infants with hyaline membrane disease. J. Pediatr., 100, 802-804.
136 44 Reynolds, E.O.R. (1971): Effects of alterations in mechanical ventilator settings on pulmonary gas exchange in hyaline membrane disease, Arch. Dis. Child., 46, 152-159. of hyahne membrane disease. Br. Med. Bull., 31, 18-24. 45 Reynolds, E.O.R. (1975): Management of neonatal respiratory failure. J. R. Coll. Phys., 11, 389-400. 46 Roberton, N.R.C. (1977): Management 47 Robinson, M.J., Maayan, C., Eyal, F.G. et al. (1982): Does the pattern of ventilation determine the degree of lung damage following intensive care of the newborn. Israel J. Med., Sci., 18, 835-839. versus low frequency mechanical ventilation. J. 48 Silverman, M. (1981): High frequency ventilation Pediatr., 98, 1032. 49 Smith, P.C., Daily, W.J.R., Fletcher, G. et al. (1969): Mechanical ventilation of newborn infants. 1. The effect of rate and pressure on arterial oxygenation of infants with respiratory distress syndrome. Pediatr. Res., 3, 498-502. 50 Smith, P.C., Schach, E. and Daily, W.J.R. (1972): Mechanical ventilation of newborn infants. 2. Effects of independent variation of rate and pressure on arterial oxygenation of infants with respiratory distress syndrome. Anaesthesiology, 37, 498-502. during high frequency ventilation. Respir. Care, 27, 1371. 51 Smith, R.B. (1982): Humidification 32 Solimano, A.J., Bryan, A.C., Jobe, A.H. et al. (1984): High frequency oscillation versus conventional mechanical ventilation: Barotrauma, surfactant pools and surface tensions in premature lambs. Pediatr. Res., 348. 53 Spahr, R.C., Klein, A.M., Brown, D.R. et al. (1980): Hyahne membrane disease. A controlled study of inspiratory to expiratory ratio. Am. J. Dis. Child., 134, 373-376. 54 Spitzer, A.R., Bunnell, B. and Fox, W.W. (1984): High frequency jet ventilation with intermittent mandatory jet. ventilation: An alternative approach to severe neonatal respiratory distress. Pediatr. Res., 18, 348. 55 Stark, A.R., Bascom, R. and Frantz, I.D. (1979): Muscle relaxation in mechanically ventilated infants. J. Pediatr., 94, 439-444. 56 Taghizadeh, A., Reynolds, E.O.R. (1976): Pathogenesis of bronchopulmonary dysplasia following hyahne membrane disease. Am. J. Pathol., 82, 241-246. 57 Tolkin, J. Kirpalani, H, Fitzhardinge, P et al. (1984): Necrotizing tracheobronchitis: A new complication of neonatal mechanical ventilation. Pediatr. Res., 18, 391A. 58 Tooley, W.H. (1979): Epidemiology of bronchopulmonary dysplasia. J. Pediatr., 95, 851-860. 59 Troug, W.E., Standaert, T.A., Murphy, J. et al. (1982): Effect of high frequency oscillation on gas exchange and pulmonary phospholipids in experimental hyaline membrane disease. Am. Rev. Respir. Dis., 127, 585-589. 60 Wyszogrodski, I., Kyer-Aboagye, K. and Taeusch, H.W. (1975): Surfactant conservation by hyperventilation, conservation at end-expiratory pressure. J. Appl. Physiol., 38, 461-464.
127
Elsevier
EHD 00736
Review article
Neonatal ventilation Anne Greenough “(Children
’
Narionwide) Research Fund, Dept. of Child Health, King’s College Hospital, London SE 5. h Depi. of Paediatrics, New Addenbrooke’s Hospital, Cambridge, U.K. Accepted
newborns;
a and N.R.C. Roberton
artificial
ventilation;
for publication
respiratory
26 October
1985
failure
Artificial ventilation is now an established therapy for all forms of respiratory failure in the newborn, particularly in infants with the respiratory distress syndrome (RDS) in whom apnoea supervenes or when hypoxaemia with concurrent respiratory acidosis develops [44]. Initially, however, mechanical ventilation was used only as a last resort in critically ill patients, for example following cardiac arrest or infants severely bradycardic with profound hypoxaemia and hypoventilation [18] but even then it was found to improve survival. Delivoria-Papadopoulos et al. [18] reported a survival rate of 7 out of 20 ventilated neonates (mean gestational age 34.1 weeks and mean postnatal age 29.1 h) and Adamson et al. [l] had 12 survivors out of 40 ventilated infants. Increased experience in using this technique led to an encouraging trend in survival figures; with Roberton [46] reporting 38% surviving, Lindroth et al. [33] 41% and the Cambridge neonatal intensive care unit for 1980-1983 reporting a survival of 78% [25]. This reduction in mortality represents a much larger increase in the actual numbers of infants surviving as many more infants are now ventilated, but this improvement in survival has not been achieved without a considerable incidence of complications. An increased incidence of all forms of air leak has been reported [34] and the emergence of chronic respiratory insufficiency following prolonged artificial ventilation, particularly bronchopulmonary dysplasia (BPD) [39] is an increasing problem. A variety of techniques and manipulations of mechanical ventilation by conventional ventilators have been studied in infants suffering from RDS in an attempt to improve its efficacy and reduce these complications.
Address /or correspondence: Dr. A. Greenough, (Children Nationwide), Senior Lecturer in Neonatology. Department of Child Health, King’s College Hospital, Denmark Hill, London SE 5. U.K.
0378-3782/86/$03.50
0 1986 Elsevier Science Publishers
B.V. (Biomedical
Division)
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1. Volume-cycled
Initially volume cycled ventilators were used in the treatment of hyaline membrane disease. Their design allowed delivery of small volumes at high frequencies, matching the typical tidal volume and respiratory rates of the preterm infant with RDS. The ventilator “adjusted” the pressures to achieve the preset rate and tidal volumes. Short Inspiratory : Expiratory (I : E) ratios were used, with high flow rates generating the high inflating pressures which were often necessary to overcome the stiffness of the lungs in RDS. This use of fast rates with a short inspiratory phase copied adult ventilation techniques and, by mimicking the infant’s frequency of breathing (up to 80 breaths/mm), it was thought that fighting the ventilator and subsequent barotrauma would be less likely to occur [l]. However, at such frequencies, although PaCO, could be kept reasonably normal, adequate oxygenation could only be achieved with the use of very high peak pressures. The survival rate of infants ventilated in that way was low and many died from BPD [56]. Although certain authors [2,33] had incriminated oxygen toxicity as the cause for BPD, Taghizadeh and Reynolds [56] were able to demonstrate that the presence of lesions in this condition strongly correlated with the use of high peak pressures but not with the inspired oxygen concentrations.
2. Slow rate ventilation In view of the correlation of chronic lung disease with high pressures, studies were performed to determine if methods of ventilation could be developed to allow the successful use of lower inflating pressures and slower frequencies [28&l]. In RDS the compliance is low and alveoli show a high tendency to collapse, therefore to inflate the maximum number of alveoli to a normal volume as early as possible in inspiration it was suggested that the inspiratory wave form generated by the ventilator which would achieve this best would be a modified square wave. Using this wave form four variables of ventilator settings were studied; peak inflating pressure, positive expiratory end pressure (PEEP), I : E ratio and ventilator rate. It was found that more effective oxygenation could be achieved at a slower respiratory frequency (30 breaths/min) [28,44,49,50]. Oxygenation could also be improved by increasing the relative duration of inspiration (increasing the I : E ratio), applying PEEP and increasing the peak airway pressure. Keeping the peak pressure and rate constant and increasing mean airway pressure (MAP) by altering the I : E ratio was found to provide a more effective method of improving oxygenation than by increasing PEEP. Increasing PEEP could actually decrease oxygenation by decreasing tidal volume and alveolar ventilation. From these results guidelines about appropriate initial ventilator settings were laid down; peak inflating pressures of 20-25 cm H,O, PEEP of 3 cm H,O, and I : E ratio of 1: 1 and a rate of 30 breaths/mm. If on such settings oxygenation was a problem then the I : E ratio was increased and later if necessary PEEP or peak inflating pressures were also increased.
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This method of ventilation as advocated by Reynolds et al [28,44] was associated with a reduction in the incidence of BPD [56]. Using such an approach to mechanical ventilation most centres reported a reduction in the incidence of all forms of chronic lung disease [35]. Observations in animals with RDS confirmed that slow rates and long inspiratory times gave fewer histological changes of the type seen in early BPD and better lung compliance [31,38].
3. The effect of I : E ratio Spahr et al. [53] randomly assigned infants to receive an I : E ratio of either 1 : 2 or 2 : 1. Their results confirmed the value of lengthened I : E ratios, in that infants in the “2 : 1” group required less inspired oxygen and a lower end expiratory pressure However, there was no difference in the to achieve satisfactory oxygenation. mortality or morbidity between the two groups. Muller and Schober [37] also advocated use of this prolonged inspiratory time (1.5 set), but felt that a prolonged expiratory time was necessary to allow for adequate pulmonary perfusion. To achieve this they used low frequency ventilation (rates of lO/min) with an I : E ratio of less than 1 : 2. Satisfactory oxygenation and control of PaCO, was achieved and although there was only a 59% survival, none of the infants studied had radiological evidence of BPD. Interestingly the infants were allowed to breathe spontaneously during the expiratory phase of artificial ventilation and this may have made a significant contribution to gas exchange. Their lowered incidence of pneumothoraces (6.8%) compared to 14% in an earlier series [56] was attributed to the short expiratory time in the latter series causing air-trapping and alveolar distension.
4. The effect of PEEP The value of PEEP was confirmed [16]. The improvement in oxygenation caused by the addition of PEEP could have been due both to the resultant increase in MAP or surfactant conservation [60]. Although the addition of PEEP was usually beneficial, its use was associated with various complications. It can cause hypercapnia [17] and was associated with an increased incidence of pneumothoraces [3], although this latter study reported a comparison of the two types of ventilation used at two separate time periods.
5. The importance of mean airway pressure More recent studies demonstrated that mean airway pressure was an important determinant of oxygenation and the form of application of the airway pressure appeared to be less important. In animal studies Boros et al. [7] showed that both optimum ventilation and oxygenation were related to MAP but not to I : E ratio or peak inflatin,g pressure. However, over a certain level of MAP (> 14 cm H,O) there
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was a progressive deterioration in blood gas values, which was attributed to alveolar distension. This study was followed up in neonates suffering from severe HMD [8], again in all patients oxygenation was directly related to the level of MAP. Optimal oxygenation and ventilation occurred with the I : E ratio and pressure wave form combination that produced the highest MAP. Boros and Campbell [9] compared the effectiveness of slow ventilator rates in combination with high tidal volumes against rapid rates and low tidal volumes (minute ventilation, inspired oxygen, PEEP and I : E ratio were held constant). Once again they were able to demonstrate that the best arterial oxygenation occurred at the combination of settings that produced the highest MAP. As the highest MAP was always found at the slowest rates and highest tidal volumes, these settings, not surprisingly, gave the best arterial oxygenation (P < 0.001). However, the differences found at the two ventilator rates may not only have been due to differences in MAP, since deadspace ventilation is proportional to respiratory frequency, at the same minute volume, the effective alveolar ventilation would be reduced during fast frequency ventilation [48]. Cizek et al. [13] confirmed that MAP is an important determinant of oxygenation, but also demonstrated that significant changes in PaCO, could be affected by altering PIP and PEEP despite a constant MAP.
6. Fast rate ventilation Recently fast rate ventilation has again found favour. As the use of excessive airway pressure was incriminated as a cause of the high incidence of extrapulmonary air leaks and severe forms of chronic lung disease [40], Bland et al. [4] attempted an alternative approach, that of high frequency, low volume ventilation. Bland et al. [4] demonstrated that small preterm infants (750-1750 g) could be effectively ventilated with rapid respiratory rates (60-llO/min) and low end tidal pressures (4-9 cm H,O) with a peak pressure less than 35 cm H,O. 92% of their patients survived and only 2 of the 24 infants sustained pneumothoraces; however, there were no “control” infants ventilated at slower rates with which to make a comparison. Boros and Campbell [9] suggested this apparent success may have been due to the type of ventilator used in the study of Bland et al. Increasing ventilator rates on certain ventilators resulted in a decreased MAP (Bennett PR2 pressure preset) while in others (Bourns LS104 volume preset) MAP increased with increasing ventilator rates. However, other studies have also claimed advantages for fast rate ventilation; Heicher et al. [26] demonstrated that rapid rates (60/min) with an inspiratory time of 0.5 set were as effective a means of ventilation as the use of slower rates (20-40/min) with a longer inspiratory time of 1 sec. Interestingly, they were able to demonstrate a lower incidence of pneumothoraces in the fast rate group, but unfortunately their study was of an alternate allocation design and could therefore have been exposed to bias. In a further, non-randomised study [24] we also demonstrated a reduction in the incidence of airleaks amongst infants ventilated at fast rates who were suffering from the pulmonary interstitial emphysema (PIE), but
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there was no difference in the mortality and the PIE actually worsened presumably due to lack of decompression. The results of Ratner and Hernandez [43] suggest a possible mechanism for the beneficial effects of fast rates as using Baby Bird ventilators they were able to successfully ventilate preterm infants (26-36 weeks) at lower peak pressures by increasing ventilator rate to keep MAP constant. Interestingly in that study all the patients included were unparalysed and the faster ventilator rates more closely mimicked the infant’s respiratory frequency. The earlier lack of success and high morbidity at such fast rates may have been due either to the lack of PEEP or that mechanical ventilation was given by relatively unsophisticated ventilators which were only used much later in the disease course; that is to treat severe hypoxia despite breathing 95% oxygen or incipient collapse [28]. The difference in results may also have been due to the nature of the patient studied [28], that is more mature infants with very severe RDS. Before we become too enthusiastic about fast rate ventilation, it must be noted Robinson et al. [47], having performed detailed follow-up lung function tests 22-67 weeks following mechanical ventilation on a series of preterm infants, demonstrated that the degree of impairment of lung function of the ventilated infants could be significantly related to the length of time spent on high frequency ventilation (> 30/min), however only 14 babies were included and rates varied from 30 to 180/min.
7. The importance of the infant’s spontaneous
respiration during ventilation
Although the manipulations described above (in Sections 2-4) improved the effectiveness of mechanical ventilation and resulted in a decrease in the incidence of BPD, the incidence of air leaks remained high (range 25540%) [34]. Few preterm infants were paralysed during ventilation, therefore it seemed possible that their spontaneous respiratory efforts during ventilation could be an important influence on its effectiveness and even be incriminated as a factor in the causation of air leaks and BPD, Pollitzer et al. [42] postulated that damage to the lungs could be caused by the infant taking a spontaneous breath simultaneously with the ventilator’s inspiratory cycle, this combination could generate large transpulmonary pressure swings resulting in ruptured or damaged airways and alveoli. It was also recognised that asynchronous ventilation could have a deleterious effect on oxygenation [30], and in such circumstances paralysis has since been shown to improve oxygenation [15;27]. However trials of paralysis to prevent pneumothoraces, although demonstrating a number of beneficial effects of pancuronium (improved oxygenation and survival and a reduction in chronic lung disease) did not result in a significant reduction in the incidence of air leaks. This lack of success may be explained by inclusion of all ventilated infants with RDS in these studies, since certainly there are infants in whom paralysis has been shown to result in hypoxaemia and the compensatory increased peak pressures may actually result in increased barotrauma and possible air leaks. Interestingly, the only study which aimed to paralyse infants fighting the ventilator did claim to show a reduction in pneumothoraces, but was not significant [55]. Recently we have shown that by detailed respiratory monitor-
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ing, it can be detected that the infant’s spontaneous respiration interacts in different ways during mechanical ventilation at conventional rates [22]. Only one such was consistently demonstrated as occurring before interaction “active expiration” the development of an air leak. Amongst this select group of infants paralysis with pancuronium significantly reduced the incidence of airleaks [23]. This successful, selective use of pancuronium to reduce the occurrence of pneumothoraces has also been confirmed by Cooke et al. [14], using clinical findings to detect infants fighting the ventilator.
8. High frequency jet and high frequency oscillatory ventilation The apparent success using high frequency positive pressure ventilation encouraged the development of methods of ventilation using even faster frequencies-high frequency jet ventilation (HFJV), using compressed gas delivered through a small bore cannula at frequencies up to 400/min and high frequency oscillation (HFO), using frequencies up to 40 Hz and quasi-sinusoidal volume excursions. Very limited date has so far accumulated as to the effectiveness of HFJV. Pokora et al. [41] used this technique in 10 infants, 9 of whom had progressive air leaks. Following HFJV, the pulmonary air leaks decreased radiologically in 7 and oxygenation improved in 8 of 10 patients. However only 5 of the infants survived and 3 of the 6 infants exposed to HFJV for longer than 20 h developed significant tracheal obstruction, possibly due to poor humidification of the inspired gas. Spitzer et al. [54] described improvements in gas exchange at lower pressures during HFJV and suggested that the addition of IMV could be of benefit, but only studied 6 infants. Carlo et al. [12] recently reported a well designed cross over study comparing conventional ventilation with HFJV and demonstrated a significant reduction in the average peak pressure without impairment of oxygenation during the period of HFJV, but this study only included 12 infants for up to periods of 3 h. On a note of caution, as with conventional ventilators, Lewallen [32] pointed out that different jet ventilators perform differently and the results of the study of one system can not be applied to another. The most recent report of 34 infants from a 4-year period by Boros et al. [ll] demonstrated significant improvements in pH, PaCO, and PaO, with 74% of the infants showing radiological evidence of a decrease in air leak. Unfortunately, only 32% of infants survived, but again only severely ill infants were included in the study-intractable air leaks, severe congenital diaphragmatic hernia (CDH) and end stage respiratory failure. The effect of HFJV on the trachea remains a most worrying effect although the exact nature of the problem and its causation remain somewhat controversial. Smith [51] and Carlo et al. [12] reported that using “appropriate” humidification no changes in mucociliary transport occurred. However the most recent study by Boros et al. [ll] described tracheal lesions in many of the infants studied and in 83% dying following 8 h or more of HFJV-lesions included inflammation, necrosis and at times erosion always occurring in the region of the endotracheal tube tip. They suggested that the earlier explanation of poor humidity may have been too simplistic as in
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animal models, comparing different humidity systems with conventional and HFJV. the latter always resulted in more tracheal damage regardless of humidity. However. this effect may not be a specific effect of HFJV as Fox et al. [19] describe similar lesions in infants ventilated by other means and again stressed the need for adequate humidification. Tolkin et al. [57] stressed a mixed aetiology as they reported tracheal lesions following the use of dry gas, conventional rates and HFJV. HFO was first successfully used in animal studies, Bohn et al. [5] demonstrated that gas exchange could be supported for many hours by applying small volume, high frequency oscillations in the airway. A frequency of 15 Hz was used with input volumes of less than half the subject’s dead space volume. Frantz et al. [20] later reported the effectiveness of this technique in 5 premature infants, oxygenation and CO, elimination being optimal at about 20 Hz. Marchak et al. [36] reported improvements in oxygenation in changing from conventional slow rate ventilation to HFO at frequencies ranging from 8 to 20 Hz with a mean airway pressure of 9-20 cm H,O, subsequent improvements in oxygenation during HFO could be related to changes in MAP. However this study only included 9 infants for a mean time of 147 min, therefore no comment on long term complications could be made. Frantz et al. [21] demonstrated that HFO might provide a means of ventilating infants at significantly lower pressures than conventional ventilation and in certain cases this was associated with improvement in severe PIE. However although one infant was ventilated for 26 days this was unusual and again only small numbers of infants were included in the study. Recently, this technique has been used in other severely compromised infants-CDH. Karl et al. [29] were able to demonstrate a reversal of acidosis using HFO in these infants when conventional ventilation had failed, unfortunately all 4 infants died within 13-80 h of commencing HFO. Bohn et al. [6] did find improvement in PaO, in 23 infants with CDH unresponsive to other treatment, unfortunately the response was only temporary and no long term outcome is given. Conflicting evidence has been given regarding possible side-effects of this technique, particularly regarding phospholipids. Truog et al. [59] found no difference in lung and lavage phospholipid composition in animal studies between conventional and HFO ventilation, however, Solimano et al. [52] demonstrated a possible disruption in surfactant turnover in lambs ventilated by HFO.
9. Conclusion Artificial ventilation by conventional ventilators is a successful method of respiratory support for infants suffering from RDS. Only preliminary evidence exists regarding the efficacy of high frequency ventilation either by jet ventilator or oscillation, both methods have only been studied in a small number of infants. Although this preliminary evidence suggests a useful role in very compromised infants unresponsive to other treatments, no long term studies have been done or any assessment made in the preterm neonate suffering from uncomplicated RDS and the side-effects of HFJV remain worrying. Until such information is available we must continue to use conventional ventilators in the most effective way. The
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change in the nature of patients at present being ventilated on our neonatal intensive care units, means that policies derived from more mature infants with more severe RDS can not be applied without question. Preliminary evidence suggests that fast rate ventilation (60-120/min) may confer advantages in such a population, however no large long-term randomised study exists to accurately test this hypothesis and we must be aware of the different performances of different ventilators at higher rates [lo]. Evidence also exists that a greater understanding and monitoring of the infant’s spontaneous respiration is important and that by using such tools paralysis can be effectively used to reduce to incidence of certain of the complications of ventilation, but again there is a necessity for long term studies to assess the value of this approach.
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