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Early High-Frequency Oscillatory Ventilation Versus Synchronized Intermittent Mandatory Ventilation in Very Low Birth Weight Infants: A Pilot Study of Two Ventilation Protocols

Abstract

OBJECTIVE:To evaluate the feasibility of conducting a prospective, randomized trial comparing early high-frequency oscillatory ventilation (HFOV) to synchronized intermittent mandatory ventilation (SIMV) in very low birth weight (VLBW) premature infants. This pilot study evaluated two ventilator management protocols to determine how well they could be implemented in a multicenter clinical trial. Although this pilot study was not powered to detect differences in outcome, we also collected outcome data.

DESIGN:Prospective, multicenter, randomized pilot study.

SETTING:Seven tertiary-level intensive care nurseries with previous experience with both HFOV and flow-triggered SIMV.

PATIENTS:Fifty infants weighing 501 to 1200 g, less than 4 hours of age, who had received one dose of surfactant and required ventilation with mean airway pressure ≥6 cm H 2O and F IO 2 ≥0.25, and had an anticipated duration of ventilation greater than 24 hours.

INTERVENTIONS:Patients were stratified by birth weight and prenatal steroid status, then randomized to either HFOV or SIMV with tidal volume monitoring. Ventilator management for patients in both study arms was strictly governed by protocols that included optimizing lung inflation and blood gases, weaning strategies, and extubation criteria.

MEASUREMENTS:Data were collected using the tools planned for the larger collaborative study. Protocol compliance was closely monitored, with successive changes in the protocol made as necessary to improve clarity and increase compliance. The incidence of major neonatal adverse outcomes was recorded.

MAIN RESULTS:Data are presented for 24 HFOV and 24 SIMV infants (two infants, twins, were withdrawn from the study at parent's request). Nineteen of the 24 HFOV infants and 20 of the 24 SIMV infants survived to 36 weeks corrected age. Age at final extubation for survivors was 16±16 (mean±SD) days for HFOV infants and 24±24 days for SIMV infants. At 36 weeks corrected age, 14 of the 19 HFOV survivors were extubated and in room air, whereas 5 required supplemental oxygen. In comparison, 6 of the 20 SIMV survivors were extubated and in room air, whereas 14 required supplemental oxygen. Grade III/IV IVH and/or periventricular leukomalacia occurred in 2 HFOV and 2 SIMV patients.

Overall compliance with the ventilator protocols was 82% for the SIMV protocol, and 88% for the HFOV protocol.

CONCLUSIONS:The preliminary outcome data supports conducting the large randomized trial, which began in July of 1998. The protocols for the ventilator management of VLBW infants, both with HFOV and with SIMV were easily implemented and consistently followed, and are presented here.

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Acknowledgements

This pilot study could not have been completed without the help of many individuals. The Steering Committee included David J. Durand, MD, Jeanette M. Asselin, RRT MS, Sherry E. Courtney, MD MS, Mark L. Hudak, MD, Thomas E. Wiswell, MD, Craig T. Shoemaker, MD, and Judy L. Aschner, MD. The study sites included: Children's Hospital Oakland, Oakland CA; Wolfson Children's Hospital, University of Florida, Jacksonville, FL; Wake Forest University School of Medicine, Winston-Salem, NC; New Hanover Regional Medical Center, Wilmington, NC; Children's Hospital Orange County, Orange, CA; Lucille Packard Children's Hospital at Stanford, Palo Alto, CA; Kosair Children's Hospital, University of Louisville, Louisville, KY; MeritCare Medical Center, Fargo, ND; Cooper Hospital/University Medical Center, Camden, NJ. The masked ultrasound reviewers included Daniel A. Merton, RDMS and Larry Needleman, MD from Thomas Jefferson University Medical Center, Philadelphia, PA.

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Additional information

This study was presented in part at the Society for Pediatric Research in May 1998 in New Orleans, LA. This study was supported in part by Abbott Laboratories/Ross Products Division, Hamilton Medical, Ballard Medical Products, SensorMedics, the Society for Pediatric Research, the East Bay Neonatology Foundation, and Cooper Hospital/UMC.

APPENDIX

APPENDIX

The underlying philosophy of the following protocols includes optimizing lung inflation, avoiding both atelectasis and overdistension, tolerating moderate hypercapnia, maintaining oxygen saturation within a narrow range, and aggressively weaning toward extubation. The frequency and magnitude of ventilator changes outlined in the protocol are initial guidelines; larger or more frequent ventilatory changes may be required to maintain infants in the target ranges. It is essential that every effort be made to rapidly return infants to the target ranges if they have “drifted” outside these ranges.

Target Ranges for Blood Gas Values

Because the target ranges are fairly broad, weaning of ventilator settings is strongly encouraged for patients who have P aCO 2 values in the lower end of the target ranges. Likewise, weaning of patients with stable oxygenation is strongly encouraged.

The target ranges for blood gases are as follows:

  • Pulse oximeter saturation 88% to 96%;

  • pH≥7.25.

  • P aCO 2 40 to 55 Torr in patients without PIE, gross air leak, hyperinflation, chronic changes on chest X-ray (CXR);

  • P aCO 2 45 to 65 Torr in patients with PIE, gross air leak, hyperinflation, or chronic changes on CXR;

Target Ranges for Lung Inflation

“Ideal” lung inflation is defined as the top margin of the dome of the right hemidiaphragm located between the bottom of the eighth rib and no more than midway between the ninth and tenth ribs. The major focus will be avoidance of atelectasis and hyperinflation. In addition to overexpansion, small heart and flat diaphragms may also indicate hyperinflation. Patients with PIE or AL will be managed with a low-lung-volume strategy, defined as diaphragm level between the seventh and eighth ribs.

Nontidal Volume Ventilation Strategy (HFOV)

Initial HFOV settings

Initiate HFOV at these settings:

  • Inspiratory time ( Tinsp) 33%;

  • Mean airway pressure ( Paw) at least 2 cm H 2O greater than patient was receiving on conventional ventilation. This apparent increase is because HFOV causes a pressure measurement artifact that results in a Paw reading that is 2 cm H 2O higher at the proximal tip of the ETT than the actual distal Paw;

  • Frequency 10 to 15 Hz;

  • Amplitude (Δ P) adjusted based on physical examination and/or transcutaneous monitoring.

Adjusting HFOV settings to optimize lung inflation

The initial goal on HFOV is to optimize lung inflation. The optimal position of the right hemidiaphragm is between 8 and 9.5 ribs. Diaphragm position is primarily determined by Paw. If top dome of right diaphragm is:

  • Below the 11th rib, decrease Paw by 2 cm H 2O;

  • Between the 10th and 11th rib, decrease Paw by 1 cm H 2O;

  • Between 8 and 9.5 ribs, no change;

  • Above the eighth rib, increase Paw by 1 cm H 2O;

  • Above the seventh rib, increase Paw by 2 cm H 2O;

  • Above the eighth rib, but infant in room air, increasing Paw is optional.

Adjusting HFOV settings based on F I O 2

Assuming acceptable lung inflation, adjust Paw based on F IO 2

  • F IO 2 ≥0.40, increase Paw 1 to 2 cm H 2O;

  • F IO 2 0.30 to 0.39, may increase Paw or make no change, depending on CXR;

  • F IO 2 <0.30, decrease Paw 1 to 2 cm H 2O;

  • If F IO 2 changes by 0.2 within a 6-hour period, repeat a CXR to evaluate lung inflation.

Adjusting HFOV settings based on P a CO 2

Assuming a constant HFOV frequency, P aCO 2 is primarily determined by HFOV amplitude, measured as Δ P.

  • P aCO 2 <30 Torr, decrease Δ P by 20%;

  • P aCO 2 30 to 39 Torr, decrease Δ P by 10%;

  • P aCO 2 40 to 55 Torr, no change in Δ P is necessary unless P aCO 2 has been in this range for >12 hours (see HFOV Weaning);

  • P aCO 2 56 to 65, increase Δ P by 10%;

  • P aCO 2 >65, increase Δ P by 20%;

  • During initial stabilization, repeat arterial blood gas every 20 to 30 minutes until the P aCO 2 is within the target range.

HFOV management of PIE and/or gross air leak with low-lung-volume strategy

  • If the infant has PIE or gross air leak such as pneumothorax or pneumomediastinum, change to a low-lung-volume strategy (diaphragm level between seventh and eighth ribs) accepting whatever F IO 2 is necessary to maintain target blood gases, until the air leak has resolved for ≥24 hours.

  • If the infant has unilateral PIE, he/she should be positioned with affected side down (at 90-degree angle to bed). Attempt to keep the infant primarily in this position until PIE is resolved.

  • Once PIE or AL has resolved for ≥24 hours, return to optimal lung volume strategy.

  • Patients with PIE and/or gross air leak should be managed with a higher target P aCO 2 range (e.g., 45 to 65 Torr).

HFOV management of patients with hyperinflation and/or CLD

  • Some patients with early CLD have relative hyperinflation. This should be treated by aggressive weaning of Paw and amplitude, as well as by accepting a higher target P aCO 2 range (e.g., 45 to 65 Torr);

  • Hyperinflation may decrease with a lower ventilator frequency;

  • Patients with obvious CLD changes on chest radiograph should also be treated by accepting a higher target P aCO 2 range (e.g., 45 to 65 Torr).

  • If hyperinflation persists, decrease ventilator frequency and simultaneously decrease amplitude to prevent hypocarbia.

Weaning HFOV

The goal is to aggressively wean infants toward extubation;

  • If P aCO 2 remains in target range for >12 hours and patient is stable, wean Δ P by 10%. However, if P aCO 2 is >50 cm H 2O (with normal inflation on CXR) or >60 cm H 20 (with hyperinflation on CXR), weaning is optional;

  • If saturation and lung inflation remain in target range >12 hours, wean Paw by 0.5 to 1.0 cm H 2O, unless this results in an increase in F IO 2 of more than 0.05;

  • Avoid weaning Paw too rapidly, particularly if weaning Paw is associated with increasing F IO 2.

Tidal Ventilation Strategy (SIMV)

Initial SIMV settings

Peak end expiratory pressure (PEEP) 4 to 6 cm H 2O;

  • Tinsp 0.25 to 0.35 second;

  • PIP adequate to give exhaled tidal volume 4 to 7 ml/kg;

  • Rate adjusted to give P aCO 2 in target range, but not to exceed 60 breaths per minute;

  • Flow adequate to deliver PIP.

Adjusting SIMV settings to achieve optimal lung inflation

All of the following changes assume that the exhaled tidal volume is in the target range of 4 to 7 ml/kg. If the dome of the right diaphragm is:

  • Below the 11th rib, decrease PEEP by 2 cm H 2O;

  • Between the 10th and 11th rib, decrease PEEP by 1 cm H 2O;

  • Between 8 and 9.5 ribs, no change in PEEP;

  • Above the eighth rib, increase PEEP by 1 cm H 2O;

  • Above the seventh rib, increase PEEP by 2 cm H 2O;

  • Above the eighth rib, but infant in room air, increasing PEEP is optional;

  • If F IO 2 increases by 0.2 within a 6-hour period, repeat a CXR to evaluate lung inflation.

Adjusting SIMV settings based on P a CO 2

  • P aCO 2 <30 Torr, decrease rate by 20%;

  • P aCO 2 30 to 39 Torr, decrease rate by 10%;

  • P aCO 2 40 to 55 Torr, no change in rate is necessary unless P aCO 2 has been in this range for >12 hours (see SIMV Weaning);

  • P aCO 2 56 to 65 Torr, increase rate by 10%;

  • P aCO 2 >65 Torr, increase rate by 20%;

  • During initial stabilization, repeat arterial blood gas every 20 to 30 minutes until the P aCO 2 is within the target range.

SIMV management of PIE and/or gross air leak with low-lung-volume strategy

  • If the infant has PIE or gross air leak such as pneumothorax or pneumomediastinum, change to a low-lung-volume strategy (diaphragm level between seventh and eighth ribs) accepting whatever F IO 2 is necessary to maintain target blood gases, until the air leak has resolved for ≥24 hours.

  • If the infant has unilateral PIE, he/she should be positioned with affected side down (at 90-degree angle to bed). Attempt to keep the infant primarily in this position until PIE is resolved.

  • Once PIE and/or gross air leak has resolved, return to optimal lung volume strategy. Patients with PIE and/or gross air leak should be managed with a higher target P aCO 2 range (e.g., 45 to 65 Torr).

SIMV management of patient with hyperinflation and/or CLD

  • Some patients with early CLD have relative hyperinflation. This should be treated by aggressive weaning of PEEP and/or PIP, as well as by accepting a higher target P aCO 2 range (e.g., 45 to 65 Torr).

  • If infant is hyperinflated with a tidal volume of 4 ml/kg and high respiratory rate (>40 breaths/min), consider decreasing Tinsp by 0.05 second;

  • Patients with obvious CLD changes on chest radiograph should also be treated by accepting a higher target P aCO 2 range (e.g., 45 to 65 Torr).

Weaning SIMV

The goal is to aggressively wean infants toward extubation.

  • If P aCO 2 remains in target range for >12 hours and patient is stable, wean rate and/or PIP by 10%. However, if P aCO 2 is >50 cm H 2O (with normal inflation on CXR) or >60 cm H 20 (with hyperinflation on CXR), weaning is optional;

  • Weaning may be attempted more frequently than every 12 hours.

Extubation and Reintubation

Extubation will be attempted as soon as the patient is stable on minimal ventilator settings without excess work of breathing.

Extubation will be attempted when patient meets both the following criteria:

  • Paw ≤5 cm H 20 (SIMV) or Paw ≤7 cm H 20 (HFOV);

  • F IO 2 ≤0.25.

Patients who remain stable on these minimal ventilator settings for 6 to 12 hours should be extubated.

Before extubation, infants will be treated with caffeine or theophylline, as prophylaxis for apnea and bradycardia. Infants will be extubated to nasal CPAP (NCPAP) of 4 to 6 cm H 2O (using the Aladdin or Infant-Flow NCPAP system).

  • Initiate NCPAP before extubating the infant;

  • Wean NCPAP by 1 cm H 20 every 24 hours, until infant is on 4 cm H 20 NCPAP;

  • Infant should remain on 4 cm H 20 NCPAP and an F I0 2 of # 0.30 for at least 24 hours, before attempting to discontinue NCPAP and placing infant on nasal cannula or room air.

Patients with the following should be reintubated:

  • Need for more than 8 cm H 2O of nasal CPAP and F IO 2 >0.50 to maintain pulse oximeter saturation in the target range of 88% to 96%;

  • P aCO 2 >65 and pH <7.25;

  • Recurrent apnea and/or bradycardia resulting in oxygen saturation <85%;

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Durand, D., Asselin, J., Hudak, M. et al. Early High-Frequency Oscillatory Ventilation Versus Synchronized Intermittent Mandatory Ventilation in Very Low Birth Weight Infants: A Pilot Study of Two Ventilation Protocols. J Perinatol 21, 221–229 (2001). https://doi.org/10.1038/sj.jp.7210527

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