In very low birth weight infants who require support on breathing machines (ventilators), ventilator associated lung injury and the toxic effects of oxygen may be important factors in creating a chronic disturbance in lung function. Compared to routine conventional ventilators, high frequency jet ventilators (breathing machines that introduce short duration pulses of gas under pressure into the airway at a very fast rate) may reduce the severity of lung injury associated with mechanical ventilation. However, there is little evidence to support the use of rescue high frequency jet ventilation in the treatment of preterm infants with severe pulmonary problems. Only one trial is included in this review. This trial did not demonstrate any difference in infants who received high frequency jet ventilation. However, the trial had a small number of patients and did not report on long-term outcomes, therefore, it is difficult to interpret these findings.
Pulmonary disease continues to be a major cause of mortality and morbidity in very low birth weight infants despite increased use of antenatal steroids and surfactant therapy. In addition to immaturity, ventilator injury and oxygen toxicity are thought to be important factors in the pathogenesis of chronic pulmonary disease (Jobe 2000). Animal studies (Barringer 1982; Carlon 1983; Hoff 1981) and adult human studies (Carlon 1981; Turnbull 1981) provide evidence that high frequency jet ventilation may reduce the severity of lung injury associated with mechanical ventilation.
High-frequency jet ventilators (HFJV) deliver high-flow, short-duration pulses of pressurized gas directly into the upper airway through a specifically designed endotracheal lumen. The pulses are delivered to the upper airway and are superimposed on a background gas flow from a conventional ventilator that provides positive end-expiratory pressure (PEEP). In addition, conventional breaths may be delivered in conjunction with the jet ventilation. The systems operate at rates of 150 - 600 breaths per minute. Exhalation is passive. This is substantially different from high-frequency oscillators (HFOV), which use an electromagnetically driven diaphragm to generate a sinusoidal pattern of pressure within the ventilatory circuit. The oscillating movement of diaphragm causes active inspiratory and expiratory phases that drive the mixing of gas between the circuit and alveoli. The amplitude of the pressure generated by the diaphragm and the mean airway pressure can be adjusted independently. The major difference between HFJV and HFOV is the inspiratory:expiratory ratios they generate. The piston driven HFOV devices have a mandatory 1:1 ratio. The SensorMedics HFOV is capable of a range of ratios, but usually used with a ratio of 1:2. The Bunnel HFJV is usually used with a 1:6 ratio. This extremely short I:E ratio makes it potentially more effective in managing patients with interstitial emphysema or a bronchopleural fistula.
Certain interventions will have an influence on any ventilator strategy in preterm infants. Surfactant, by its surface tension reducing property, renders alveoli a stability and prevents their collapse and increases the alveolar recruitment. Thus, use of surfactant will have a beneficial effect in infants with hyaline membrane disease. The use of high lung volume strategy has been shown to be effective in reducing mortality and chronic lung disease. The adverse effect of necrotizing tracheobronchitis has been reported in some of these studies. This was thought to be due to inadequate humidification of the inspired gases. Therefore, a priori decision to do subgroup analysis based on use of surfactant or not, incorporation of ventilation strategies to maintain optimal lung volumes, gestational age and weight and with or without adequate humidification, is taken. Included in this systematic review were trials in which patients were randomized after failure to adequately ventilate on CV, or when complications of CV developed or were likely to develop. Elective use of HFJV is not included here and is assessed in another review (Bhuta 2002).
The objective of this review is to test the hypothesis that the use of high frequency jet ventilation (HFJV) compared to conventional ventilation (CV) will rescue preterm infants with severe pulmonary dysfunction and that this would not be associated with increase in adverse effects.
Subgroup analysis:
1) Trials with and without surfactant replacement therapy
2) Trials with and without strategies to maintain lung volume
3) Infants of different gestational ages and birth weights. Specific subgroups to include < 28 weeks gestation and < 1000 gms
4) Trials with and without adequate humidification of inspired gases
Randomized and quasi-randomized controlled trials.
Preterm infants less than 35 weeks of gestational age or birth weight less than 2000 grams with severe pulmonary dysfunction, including pulmonary interstitial emphysema and an unsatisfactory response to conventional ventilation.
Included in the systematic review were trials in which patients were randomized after failure to adequately ventilate on conventional ventilation (CV) or when complications of CV developed or were likely to develop. "Rescue" high frequency jet ventilation (HFJV) (for severe disease unresponsive to CV) is compared with continued CV. Elective use of HFJV is not included here and is assessed in another review (Bhuta 2002). Conventional ventilation (CV) implies time-cycled, pressure limited ventilation with respiratory rates of approximately 30 - 80/min, and HFJV implies high-flow, short-duration pulses of pressurised gas directly into the upper airway through a specifically designed endotracheal lumen, at rates of 150 - 600 breaths per minute.
The following are the main outcomes compared in this review:
1) Mortality at 28 - 30 days
2) Chronic lung disease
i) at 28 days
ii) at 36 weeks postconceptional age
3) Pulmonary air leak syndromes
4) Intraventricular haemorrhages
i) all grades
ii) grades 3 and 4
5) Periventricular leukomalacia
i) cystic
ii) haemorrhagic
6) Periventricular echodensities
7) Necrotising tracheobronchitis
8) Long term pulmonary and neurodevelopmental outcomes
We included airway obstruction as an outcome, post-hoc.
Methods used to collect the data from included trials:
The two authors extracted data separately, then compared and resolved
the differences. Additional data were requested from one author regarding
22 babies who were excluded post-randomization. The outcomes on these babies
could not be obtained from the author.
Methods used to synthesize data:
The standard method of the Neonatal Review Group was used, including
for categorical data, use of relative risk (RR) and risk difference (RD).
Heterogeneity was evaluated using the I2 statistic.
The included study (Keszler 1991) was conducted from January 1987 to March 1989. 166 infants were enrolled. The birth weights of enrolled infants were equal to or more than 750 grams and less than 2000 grams and they developed pulmonary interstitial emphysema within the first seven days of age while receiving conventional ventilation. Infants were randomized to receive treatment with high frequency jet ventilation or rapid rate conventional mechanical ventilation (CV) with short inspiratory time. 144 infants were included in the analysis. Infants who did not respond to the initial mode of ventilation and met the specific criteria for treatment failure, were permitted to cross over to other ventilation therapy.
Criteria for treatment failure were:
(1) worsening pulmonary interstitial emphysema (PIE), as demonstrated by significant radiographic worsening of PIE or development of intractable air leaks, accompanied by deteriorating gas exchange requiring increasing ventilator support to maintain target blood gas values
(2) lack of improvement, defined as no improvement of PIE after 96 hours, accompanied by deteriorating gas exchange
(3) inadequate gas exchange during maximal support, including arterial oxygen tension < 40 mmHg, or arterial carbon dioxide tension > 65 mmHg on mean airway pressure > 15 cm of H2O and fraction of inspired oxygen equal to one
(4) acute deterioration, demonstrated by sudden worsening of the patient's status, so that continued participation in the study would be contrary to his or her best interest. The 39% of babies from HFJV group were crossed over to CV and 63% of babies from CV group crossed over to HFJV, when criteria for treatment failure were met. The infants were analyzed in this review in the groups to which they were originally randomized. None of the infants in the study received surfactant. See table Characteristics of Included Studies for more details.
1) Overall mortality
There was no statistically significant difference in the overall mortality
between the HFJV and CV groups [RR 1.07 (0.67, 1.72)], [RD 0.02 (-0.13, 0.18)].
2) Chronic lung disease
i) at 28 days
No statistically significant differences were found in the incidence
of CLD in survivors [RR 0.77 (0.54, 1.07)], [RD -0.16 (-0.35, 0.04)].
ii) at 36 weeks postconceptional age - not reported
3) Mortality excluding the survival after cross-over
Mortality in the HFJV group was significantly lower compared to the CV group [RR 0.66 (0.45, 0.97)], [RD -0.18 (-0.34, -0.02)]
4) Pulmonary air leak syndromes
There were no statistically significant differences in the incidence
of new air leaks [RR 0.76 (0.46,1.23)], [RD -0.09 (-0.24, 0.06)]
5) Intraventricular haemorrhages
i) all grades - not reported
ii) grades 3 and 4
There was no statistically significant difference in the incidence of
total IVH (grades 3,4) [RR 0.74 (0.42,1.28)], [RD- 0.09 (-0.26, 0.07)]. The
incidence of new IVH in infants assessed was lower in the rescue HFJV group,
but this was not statistically significant [RR 0.49 (0.19,1.24)].
6) Periventricular leukomalacia (cystic or haemorrhagic) was not reported
7) Periventricular echodensities were not reported
8) Necrotising tracheobronchitis
There was no statistically significant difference in the incidence of
necrotizing tracheobronchitis at autopsy in 17 infants [RR 1.33 (0.29, 6.06)],
[RD 0.08 (-0.35, 0.51)].
9) Long term pulmonary and neurodevelopmental outcomes were not reported
10) Airway obstruction was included as an outcome, post-hoc. There was no statistically significant difference between the two groups [RR 3.78 (0.43,33.03)], [RD 0.04 (-0.02, 0.10)].
The overall mortality (including survival after cross-over) was not statistically different in infants treated with high frequency jet ventilation versus conventional ventilation [RR 1.07 (0.67, 1.72)]. The survival by original assignment did not differ between the two groups. Mortality up until the point of cross-over, was lower in the HFJV group [RR 0.66, (0.45, 0.97)] compared with infants who received conventional ventilation. Because of the cross-over design of the trial and high cross-over rate, it is difficult to interpret data on these important outcomes. Although the reduction of the incidence of bronchopulmonary dysplasia [RR 0.77, (0.54, 1.07)] was a potential benefit, this was not statistically significant. At the same time, the intervention in these infants with severe respiratory failure and established barotrauma may have come too late to have an impact on the incidence of bronchopulmonary dysplasia. The incidence of airway obstruction and necrotizing tracheobronchitis did not differ significantly between the groups suggesting that HFJV does not cause a disproportionate amount of airway damage.
Neurological injury, both acute and chronic, was always a major concern since the advent of high frequency ventilation. This is usually measured in the neonatal period by assessing the rates of intraventricular haemorrhage and periventricular leukomalacia and more accurately at neurodevelopmental follow up within the first three years of life. There was no increase in the incidence of complications such as IVH (all grades) in HFJV group. However, there was a lack of information on PVL and long term neurodevelopmental outcome, which is of concern.
The one included study showed improved survival in the group receiving rescue HFJV (excluding survival after cross-over) without any significant increase in adverse effects (IVH, new air leaks, airway obstruction and necrotizing tracheobronchitis), but the overall survival was not different between the two groups. There were no data on other important long term neurodevelopmental outcomes. Thus, there is not enough evidence to support the use of high frequency jet ventilation as a rescue therapy in preterm infants.
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Keszler 1991 | Multicentre trial, enrolment between Jan 1987-Mar 1989. Concealment at randomization - Yes. Randomization performed centrally by calling 24 hour hotline. Blinding of intervention - No Complete follow up - No. 22 of 166 infants were excluded after initial randomisation. Blinding of outcome assessment - No | 166 preterm infants less than 7 days of age and weighing less than or equal to 750gm at birth, with pulmonary interstitial emphysema. Eligible infants were stratified by birthweight and severity of illness. Of 144 infants analysed, mean birthweight was 1340gm and mean gestational age at study entry was 29.3 weeks. | HFJV with 400-450 cycles/min (treatment group), CV with
rates of 60-100 breaths/min, with short inspiratory time (control group).
70 infants were assigned to CV and 74 infants were assigned to HFJV. Crossover
to alternate therapy was allowed if infants failed with allocated ventilator
therapy. (Treatment failure defined as: worsening PIE, lack of improvement,
inadequate gas exchange during maximal support, or acute deterioration.) Effective gas heating and humidification system. | Mortality at 28-30 days, success in the original assignment, CLD at 28-30 days, IVH ( grade III & IV), new air leak, necrotising tracheobronchitis, airway obstruction, CLD in survivors. | Prenatal steroids were not reported. None of the babies received exogenous surfactant. Study supported by Bunnell Inc. | A |
| Study | Reason for exclusion |
| Davis 1992 | Non-randomized trial |
| Engle 1997 | The study population restricted to term and near-term neonates |
Keszler M, Donn SM, Bucciarelli RL, Alverson DC, Hart M, Lunyong V et al. Multicenter controlled trial comparing high-frequency jet ventilation and conventional mechanical ventilation in newborn infants with pulmonary interstial emphysema. Journal of Pediatrics 1990;119:85-93.
Davis JM, Richter SE, Kending JW, Notter RH. High-frequency jet ventilation and surfactant treatment of newborns with severe respiratory failure. Pediatric Pulmonology 1992;13:108-12.
Engle 1997 {published data only}
Engle WA, Yoder MC, Andreoli SP, Darragh RK, Langefeld CD, Hui SL. Controlled prospective randomized comparison of high-frequency jet ventilation and conventional ventilation in neonates with respiratory failure and persistent pulmonary hypertension. Journal of Perinatology 1997;17:3-9.
* indicates the primary reference for the study
Barringer M, Meredith J, Prough D, Gibson R, Blinkhorn R. Effectiveness of high-frequency jet ventilation in management of experimental bronchopleural fistula. American Surgeon 1982;48:610-3.
Bhuta T, Henderson-Smart DJ. Elective high frequency jet ventilation versus conventional ventilation for respiratory distress syndrome in preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 2, 2002.
Carlon GC, Kahn RC, Howland WS, Ray C Jr, Turnbull AD. Clinical experience with high frequency jet ventilation. Critical Care Medicine 1981;9:1-6.
Carlon GC, Griffin J, Ray C Jr, Groeger JS, Patrick K. High frequency jet ventilation in experimental airway disruption. Critical Care Medicine 1983;11:353-5.
Smith RB, Cutaia F, Hoff BH, Babinski M, Gelineau J. Long-term transtracheal high frequency ventilation in dogs. Critical Care Medicine 1981;9:311-4.
Jobe AH, Ikegami M. Lung development and function in preterm infants in the surfactant era. Annual Review of Physiology 2000;62:825-46.
Turnbull AD, Carlon G, Howland WS, Beattie EJ Jr. High-frequency jet ventilation in major airway or pulmonary disruption. Annals of Thoracic Surgery 1981;32:468-74.
| Comparison or outcome | Studies | Participants | Statistical method | Effect size |
|---|---|---|---|---|
| 01 Rescue HFJV vs CV in preterm infants | ||||
| 01 Overall mortality | 1 | 144 | RR (fixed), 95% CI | 1.07 [0.67, 1.72] |
| 02 CLD at 28-30 days in survivors | 1 | 97 | RR (fixed), 95% CI | 0.77 [0.54, 1.07] |
| 03 Mortality excluding survival after cross-over | 1 | 144 | RR (fixed), 95% CI | 0.66 [0.45, 0.97] |
| 04 New air leak | 1 | 144 | RR (fixed), 95% CI | 0.76 [0.46, 1.23] |
| 05 Total IVH (grade 3 & 4) | 1 | 118 | RR (fixed), 95% CI | 0.74 [0.42, 1.28] |
| 06 Necrotising tracheobronchitis at autopsy | 1 | 17 | RR (fixed), 95% CI | 1.33 [0.29, 6.06] |
| 07 Airway obstruction | 1 | 144 | RR (fixed), 95% CI | 3.78 [0.43, 33.03] |
| The review is published as a Cochrane review in The
Cochrane Library, Issue 1, 2006 (see http://www.thecochranelibrary.com for
information). Cochrane reviews are reguarly updated as new evidence emerges
and in response to comments and criticisms, and The Cochrane Library should
be consulted for the most recent version of the Review. |