Mechanical Ventilation

One of the most hotly debated aspect of inhalation injury is the best method of mechanical
ventilation. Mechanical ventilation protocols differ between both physicians and burn centers,
and multiple different strategies for mechanical ventilation are currently being used to support
the burn patient with inhalation injury. These strategies range from applying recent advances in
acute respiratory distress syndrome to conventional mechanical ventilation to the use of alternative modes of ventilation such as the volumetric diffusive respirator. The articles in this section
describe recent changes in philosophy with respect to mechanical ventilation, the various modes
of ventilation being used to support the patient with inhalation injury, and the rationale behind
each strategy. (J Burn Care Res 2009;30:172-183)

Low-Tidal-Volume Ventilation as a Strategy to

Reduce Ventilator-Associated Injury in ALI
and ARDS
Michael D. Peck, MD, ScD, Tammy Koppelman, MD

Smoke inhalation injury follows the breathing in of

toxic smoke from the incomplete combustion of
burning materials such as fabrics, plastics, synthetics,
and building materials. Acute lung injury (ALI) describes the acute onset of impaired oxygen exchange
that results from smoke inhalation, and is characterized by an alveolar-arteriolar gradient of less than
300. Severe cases of ALI are termed acute respiratory
distress syndrome (ARDS), defined by an alveolararteriolar gradient of less than 200.1 Radiographs of
the chest show the presence of bilateral alveolar or
interstitial infiltrates; yet there is no evidence of left
heart failure to account for the presence of pulmonary
edema.
When the severity of oxygen exchange becomes
more impaired, the associated risk of mortality from
ALI/ARDS rises, and has been reported as high as 40
to 50%.2 Mortality from ALI/ARDS may be due di-

From the Department of Surgery, Maricopa Integrated Health

System, Phoenix, Arizona.
This study was supported by Shriners Hospital for Children Grant
#8431.
Address correspondence to Michael D. Peck, MD, ScD, Arizona
Burn Center, Phoenix, Arizona 85008.
Copyright 2009 by the American Burn Association.
1559-047X/2009
DOI: 10.1097/BCR.0b013e3181923c32

172

rectly to respiratory failure and inability to oxygenate

sufficiently, or it may result from associated multisystem organ failure or ventilator-associated pneumonia. In addition, patients become ventilator dependent and length of stay in intensive care units is
increased.3 Reduced health care quality of life, increased disability, and cognitive impairment are
noted in long-term survivors.4
ALI and ARDS are characterized by diffuse alveolar
damage caused by increased permeability of the perialveolar capillary endothelia. Protein-rich fluid leaks
from the intravascular space into the extravascular
space, from which it diffuses into the alveoli. Similar
to the accumulation of plasma-like fluid in the alveoli that results from an elevation in hydrostatic
pressure within the pulmonary veins with left heart
failure, this noncardiogenic pulmonary edema has
its origin in systemic diseases, such as sepsis, pancreatitis, and drug toxicity, and in inflammatory
states secondary to trauma or aspiration. For example, the toxins adsorbed onto alveolar surfaces from
inhaled smoke diffuse across the alveolar-arteriolar
space and result in widening of cell-to-cell contact
in the vascular endothelium.
Cytokine release is also a feature of ALI/ARDS.
Macrophages and neutrophils accumulate in the
alveolar-arteriolar interstitium, and inflammatory cy-

Journal of Burn Care & Research

Volume 30, Number 1

tokines are released, adding to the local damage done

by toxins in the smoke. As the cytokines pour into
systemic circulation, they can contribute to multisystem organ failure, seen commonly with ARDS.5,6 Additionally, hyaline membranes form in the alveoli, and
surface tension is altered because of damages in surfactant production, leading to alveolar collapse.
Because of the severe impairment in gas exchange
(primarily oxygen exchange, but also involving carbon dioxide elimination eventually) and because of
loss of pulmonary compliance due to accumulation of
intra- and peri-alveolar fluid, endotracheal intubation
and mechanical ventilation are necessary for survival.
Twenty years ago, the goal of ventilatory support was
to normalize arterial blood gases, bringing pH as
close as possible to 7.4 and keeping oxyhemoglobin
saturation above 95%. This was accomplished using
high concentrations of inspired oxygen and high
minute ventilations delivered by volume-controlled
ventilators. Tidal volumes of 10 to 15 ml/kg were
not unusual, rationalized by the need for increased
recruitment of collapsed alveoli.

Treatment of Ventilator-Induced Lung Injury

With Low Tidal Volumes
Unfortunately, this approach may have violated the
injunctive, first do no harm (primum non nocere).
Ventilator-induced lung injury (VLI) is associated
with hyperinflation of normal regions of aerated lung
because of high tidal volumes. Alveolar rupture and
accumulation of extra-alveolar air (barotraumas) result from higher inflating pressures. Because compliance in poorly aerated regions of diseased lung is low,
the rapid cyclic inflation deflation of normal, inflated
alveoli in continuity to the collapsed alveoli creates
high shear forces. Additionally, the overexpansion of
normal alveoli leads to high transpulmonary pressures
in the aerated regions, making them susceptible to
direct physical damage, including disruption of alveolar epithelia and capillary endothelia. The flood of
cytokines both locally and systemically may also be
increased as the inflammatory response is aggravated.
Data from animal studies led to the recommendation of reduction in plateau pressures of 35 cm of
water to lessen the contribution of VLI to the altered
physiology of ALI and ARDS. This reduction in peak
transpulmonary pressures was accomplished by increasing positive end-expiratory pressure (PEEP) and
decreasing tidal volume. The consequent reduction in
minute ventilation mandated acceptance of some degree of hypercapnia, popularized as permissive hypercapnia.7 This recommendation led to a series of clinical
trials in the search for evidence to support the claim of
benefit of lung-protective ventilation strategy. How-

Peck and Koppelman

173

ever, severe hypercapnia and respiratory acidosis are not

without risk. Adverse effects include increase in
intracranial pressure, diminished myocardial contractility, pulmonary hypertension, and diminished
renal blood flow. For certain critically ill patients,
therefore, permissive hypercapnia may be relatively contraindicated. Despite this, multiple studies have shown
that modest permissive hypercapnia is safe.8,9,10
Meta-analysis of these trials was conducted recently
by the Cochrane Anesthesia Review Group.11 The
objective of this review was to study the effect of
ventilation with lower tidal volumes on morbidity
and mortality of critically ill adults with either ALI or
ARDS. Only randomized, controlled trials with guarantees of no selection bias were selected. Out of 10
studies of potential relevance, six were included for
the final analysis.1217 Mortality at day 28 in 1030
patients in three studies1214 showed a distinct protective advantage of a ventilation strategy using tidal
volume less than 7 ml/kg of measured body weight
and plateau pressure less than 31 cm water (Table 1).
Duration of mechanical ventilation was also lower in
288 patients studied in three studies.14,15,17
Reduction in mortality correlated directly with the
magnitude of difference in tidal volume between the
control and treatment groups. Studies in which differences in mean tidal volume between the two
groups were in the range of 2.9 to 3.7 ml/kg14,15,17
showed less protection of low-tidal-volume ventilatory strategy than did trials in which the differences

Table 1. Ventilator procedures according to ARDSNet

trial13
Volume assist-control mode with volumes based on predicted
weight*
Initial tidal volume 6 ml/kg of predicted weight
Reduced by 1 ml/kg until plateau pressure 30 cm H2O;
minimum tidal volume 4 ml/kg
If plateau pressure 25 cm H2O, increase tidal volume by
1 ml/kg until either plateau pressure 25 cm H2O or
tidal volume 6 ml/kg
Management of respiratory acidosis
If pH 7.30, increase respiratory rate to maximum 35
breaths per minute
If pH 7.30 and respiratory rate 35 breaths per minute,
consider bicarbonate infusion
If pH 7.15, increase tidal volume even if plateau
pressures exceed 30 cm H2O
Sedation strategies should be used that are recommended for all
critically ill, mechanically ventilated patients
* Predicted weight of males 50 0.91 (height in cm152.4); predicted
weight of females 45.5 0.91 (height in cm152.4).
Plateau pressure measured at 0.5 seconds after peak inspiration (inspiratory
pause).

Journal of Burn Care & Research

January/February 2009

174 Peck and Koppelman

between tidal volumes ranged from 4.9 to 5.6 ml/

kg.12,16 Moreover, the two studies showing the highest protective value of low-tidal-volume ventilation
also calculated delivered tidal volume based on predicted, rather than measured, patient weight.12,13 Because predicted weight is approximately 25% lower than
measured weight, the magnitude in difference between
control and treatment group tidal volumes would be
even greater if expressed in ml per kg measured weight.

CONCLUSIONS

Adjunctive Tactics in
Lung-Protective Strategies

REFERENCES

Because many of these studies utilized increases in PEEP

to ensure satisfactory oxygenation during reduction in tidal
volumes, subsequent studies focused on whether some
of the protective benefit was from higher levels of
PEEP. The ARDS Network performed a multicenter,
randomized, prospective clinical trial (ALVEOLI trial
assessment of low-tidal-volume and elevated endexpiratory pressure to obviate acute lung injury).18
All patients with ALI or ARDS were treated with 6
ml/kg predicted body weight tidal volumes, and randomized to either low (5 cm H2O up to 24) or high
(12 cm H2O up to 24) PEEP. On day 1, the difference in mean PEEP between the two groups was 5.8
cm H2O (8.9 3.5 vs 14.7 3.5 cm H2O). Although elevated PEEP theoretically confers the advantage of maintaining recruitment of alveoli during
end expiration of smaller tidal volumes, the ALVEOLI
trial showed no effect of higher levels of PEEP on
duration of mechanical ventilation, duration of nonpulmonary organ failure, and in-hospital mortality.
Similarly, lack of beneficial effect of high PEEP was
previously noted in smaller clinical studies.12,16
Additionally, prone positioning has been proposed to
be an adjunct in the treatment of hypoxemia associated
with ARDS. Placement of the patient with ARDS in the
prone position improves oxygenation via alveolar recruitment, redistribution of ventilation toward dorsal
areas (improving ventilation/perfusion matching),
and elimination of compression of the lungs by the
heart.19 22 However, prospective, randomized studies of prone positioning during mechanical ventilation in ARDS have shown consistently that although
oxygenation is transiently improved, there is no reduction in mortality.2325 Nonetheless, prone positioning may be valuable as rescue therapy in patients
with potentially injurious levels of inspired oxygen
content or plateau pressures.26 Prone positioning
should only be used with extreme caution because of
life-threatening complications such as endotracheal
tube dislodgement or obstruction.

Significant advances in mechanical ventilation strategies

in ARDS have been developed in the past 2 decades, the
majority of which are designed to decrease VLI. However, how these advances should be applied to patients
with inhalation injury is less clear. The challenge for the
burn professional is to determine when and how to apply these strategies to the patient with smoke inhalation
injury.

1. Bernard GR, Artigas A, Brigham KL, et al. Report of the

American-European Consensus conference on acute respiratory distress syndrome: definitions, mechanisms, relevant outcome, and clinical trial coordination. J Crit Care
1994;9:72 81.
2. Lewandowski K. Epidemiological data challenge ARDS/
ALI. Intensive Care Med 1999;25:884 6.
3. Davidson TA, Caldwell ES, Curtis JR, Hudson LD, Steinberg KP. Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control
patients. JAMA 1999;281:354 60.
4. Dowdy DW, Eid MP, Dennison CR, et al. Quality of life after
acute respiratory distress syndrome: a meta-analysis. Intensive
Care Med 2006;32:111524.
5. Slutsky AS, Tremblay LN. Multiple system organ failure: is
mechanical ventilation a contributing factor? Am J Respir Crit
Care Med 1998;157:17215.
6. Dreyfuss D, Saumon G. From ventilator-induced lung injury
to multiple organ dysfunction? Intensive Care Med 1998;24:
102 4.
7. Slutsky AS. Mechanical ventilation: American College of Chest
Physicians Consensus Conference. Chest 1993;104:183359.
8. Hickling KG, Walsh J, Henderson S, Jackson R. Low mortality rate in acute respiratory distress syndrome using lowvolume, pressure-limited ventilation with permissive
hypercapnia: a prospective study. Crit Care Med 1994;22:
1568 78.
9. Laffey JG, OCroinin D, McLoughlin P, Kavanagh BP. Permissive hypercapnia: role in protective lung ventilatory strategies. Intensive Care Med 2004;30:34756.
10. Bidani A, Tzouanakis AE, Cardenas VJ, Zwischenberger JB.
Permissive hypercapnia in acute respiratory failure. JAMA
1994;272:957 62.
11. Petrucci N, Iacovelli W. Lung protective ventilation strategy
for the acute respiratory distress syndrome. Cochrane Library
2007;3:CD003844.
12. Amato MBP, Barbas CSV, Medeiros DM, et al. Effect of a
protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338:34754.
13. ARDS Network. Ventilation with lower tidal volumes as
compared with traditional tidal volumes for acute lung injury
and the acute respiratory distress syndrome. N Engl J Med
2000;342:1301 8.
14. Brochard L, Roudot-Thoraval F, Roupie E, et al. Tidal volume reduction for prevention of ventilator-induced lung injury in the acute respiratory distress syndrome. Am J Respir
Crit Care Med 1998;158:1831 8.
15. Stewart TE, Meade MO, Cook DJ, et al. Evaluation of a
ventilation strategy to prevent barotrauma in patients at high
risk for acute respiratory distress syndrome. Pressure- and
Volume-Limited Ventilation Strategy Group. N Engl J Med
1998;338:355 61.
16. Villar J, Kacmarek RM, Perez-Mendez L, Aguirre-Jaime A. A
high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respi-

Journal of Burn Care & Research

Volume 30, Number 1

17.

18.

19.

20.

21.

ratory distress syndrome: a randomized, controlled trial. Crit

Care Med 2006;34:1311 8.
Brower RG, Shanholtz CB, Fessler HE, et al. Prospective
randomized, controlled clinical trial comparing traditional vs.
reduced tidal volume ventilation in ARDS patients. Crit Care
Med 1999;27:1492 8.
ARDS Network. Higher versus lower positive end-expiratory
pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004;351:32736.
Guerin C, Badet M, Rosselli S, et al. Effects of prone position
on alveolar recruitment and oxygenation in acute lung injury.
Intensive Care Med 1999;25:122230.
Mutoh T, Guest RJ, Lamm WJ, Albert RK. Prone position
alters the effect of volume overload on regional pleural pressures and improves hypoxemia in pigs in vivo. Am Rev Respir
Dis 1992;146:300 6.
Richard JC, Janier M, Lavenne F, et al. Effect of position,

Harrington

22.

23.

24.

25.

26.

175

nitric oxide, and almitrine on lung perfusion in a porcine

model of acute lung injury. J Appl Physiol 2002;93:218191.
Albert RK, Hubmayr RD. The prone position eliminates
compression of the lungs by the heart. Am J Respir Crit Care
Med 2000;161:1660 5.
Gattinoni L, Tognoni G, Pesenti A, et al. Effect of prone
positioning on the survival of patients with acute respiratory
failure. N Engl J Med 2001;345:568 73.
Guerin C, Gaillard S, Lemasson S, et al. Effects of systematic
prone positioning in hypoxemic acute respiratory failure: a
randomized controlled trial. JAMA 2004;292:2379 87.
Mancebo J, Fernandez R, Blanch L, et al. A multicenter trial
of prolonged prone ventilation in severe acute respiratory
distress syndrome. Am J Respir Crit Care Med 2006;173:
12339.
Girard TD, Bernard GR. Mechanical ventilation in ARDS: a
state-of-the-art review. Chest 2007;131:9219.

Volumetric Diffusive Ventilator

David Harrington, MD, FACS

Following an airway and parenchymal injury such as

inhalation injury, an ideal ventilator would apply low
peak airway pressures, facilitate clearance of soot,
sloughed mucosa and secretions, and recruit collapsed airways. The Volume Diffusive Respirator
(VDR), which has been utilized for the management
of burn patients with inhalation injury since the mid
1980s, has these abilities. It is a pneumatically powered, pressure limited ventilator that stacks oscillatory
breaths to a selected peak airway pressure by means of
a sliding venturi called a phasitron. After inspiration,
exhalation is passive and ends at a selected level of
oscillatory CPAP. A retrospective analysis comparing
the VDR ventilator to conventional volume ventilation, in patients with similar distribution of age and
burn sizes, revealed a decreased rate of pneumonia
and mortality in those patients ventilated with the
VDR.1 The beneficial effects of this ventilator have
been confirmed in other burn centers clinically and in
a primate model of inhalation injury.2,3 The VDR
ventilator also reestablishes normal gas exchange in
that it returns gas exchange to a predominately diffuFrom the Warren Alpert Medical School of Brown University,
Providence, Rhode Island.
This study was supported by a Grant 8431 from Shriners Hospitals
for Children.
Address correspondence to David Harrington, MD, FACS, 593
Eddy Street, APC 443, Rhode Island Hospital, Providence,
Rhode Island 02818.
Copyright 2009 by the American Burn Association.
1559-047X/2009
DOI: 10.1097/BCR.0b013e3181923c44

sive process. Standard ventilatory strategies such as

pressure-control ventilation (PCV) and volumecontrol ventilation predominately employ convective gas exchange. Reestablishing diffusive ventilation
allows for the use of lower airway pressures to ventilate patients as shown in a recent prospective, randomized comparison of the VDR with PCV in
burned children with inhalation injury.4 Similar findings of lower airway pressures and improved survival
with the VDR in comparison to PCV were found in a
7 day LD100 sheep model of smoke/burn injury.5
The adoption of VDR in many burn centers for the
treatment of inhalation injury preceded the strategy
of low-pressure, low-volume ventilation for Acute
Respiratory Distress Syndrome that received wide
publication in the New England Journal of Medicine
in 1998 and 2000.6,7 The VDR was the original lowvolume ventilatory strategy.
Despite good outcomes the VDR is not universally
adopted by burn centers. Several reasons may explain
this phenomenon. One is that the ventilator is quite
unlike other ventilators and it requires special training
and attention by both respiratory therapists and surgeons. Because of its unique phasitron delivery device
where entrained air and exhaled gas is mixed, it does not
allow for a monitoring of tidal volumes and minute volumes and therefore electronic low-volume alarms are
not possible. Due to the high flow of gas in the airways,
the ventilator needs both humidified air and nebulized
saline to prevent airway dessication. Lastly, some burn
surgeons and intensivists feel that the VDR showed an

Journal of Burn Care & Research

January/February 2009

176 Mlcak

improvement in survival when it was compared with

high-pressure, high-volume ventilatory strategies, and
that this survival benefit would not be shown in todays
burn intensive care unit if the VDR was compared with
low-volume pressure-limited ventilation.

CONCLUSION
There are two major questions that should be explored
concerning the VDR and they should be explored in a
sequential manner:
1. What are the optimal settings for the VDR ventilator? Some papers use the VDR with the oscillation set at 10 Hertz, other papers use significantly
lower oscillation of 4 to 7 Hertz.
2. Does the VDR impart a survival benefit as compared with low-volume, pressure-limited ventilation in patients with moderate size burn and
smoke inhalation injury?
The answers to these questions will only be determined by employing well-designed multicenter clinical
trials.

REFERENCES
1.

2.

3.

4.

5.

6.

7.

Rue LW III, Cioffi WG, Mason AD, McManus WF, Pruitt BA

Jr. Improved survival of burned patients with inhalation injury. Arch Surg 1993;128:772 80.
Cioffi WG, DeLemos RA, Coalson JJ, Gerstmann DA, Pruitt
BA Jr. Decreased pulmonary damage in primates with inhalation injury treated with high-frequency ventilation. Ann
Surg 1993;218:328 35; discussion 3357.
Rodeberg DA, Housinger TA, Greenhalgh DG, Maschinot
NE, Warden GD. Improved ventilatory function in burn patients using volumetric diffusive respiration. J Am Coll Surg
1994;179:518 22.
Carman B, Cahill T, Warden G, McCall J. A prospective, randomized comparison of the volume diffusive respirator vs conventional ventilation for ventilation of burned children. 2001
ABA paper. J Burn Care Rehabil 2001;13:444 8.
Wang D, Zwischenberger JB, Savage C, et al. Highfrequency percussive ventilation with systemic heparin improves short-term survival in a LD100 sheep model of acute
respiratory distress syndrome. J Burn Care Res 2006;27:
46371.
Ventilation with Lower Tidal Volumes as Compared with
Traditional Tidal Volumes for Acute Lung Injury and the
Acute Respiratory Distress Syndrome. The Acute Respiratory
Distress Syndrome Network. N Engl J Med 2000;342:
1301 8.
Amato MB, Barbas CS, Medeiros DM, et al. Effect of a
protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998;339:198 9.

Airway Pressure Release Ventilation

Ronald P. Mlcak, PhD, RRT, FAARC

Airway pressure release ventilation (APRV) is a relatively new approach to ventilation that was first
described by Stock et al.1 APRV can be classified as
a time-triggered, pressure-limited and time-cycled
ventilation mode. Basically, APRV provides two levels of airway pressure, Pressure high (P high) and
Pressure low (P low) during two time periods, Time
high (T high) and Time low (T low). APRV usually
involves a long T high (4 7) seconds and a short T
low (0.5 0.8 seconds). Because of this APRV has
From the Respiratory Care Department, Shriners Hospital for
Children; and Department of Respiratory Care, The School of
Allied Health Science, The University Texas Medical Branch,
Galveston.
This study was supported by a Grant 8431 from Shriners Hospital
for Children.
Address correspondence to Ronald P. Mlcak, PhD, RRT, FAARC,
Respiratory Care Department, Shriners Hospital for Children,
Galveston Burns Unit, 815 Market Street, Galveston, Texas
77550.
Copyright 2009 by the American Burn Association.
1559-047X/2009
DOI: 10.1097/BCR.0b013e3181923c58

been referred to as a ventilation mode that basically

sets a continuous positive airway pressure that intermittently time-cycles to a lower airway pressure. Additionally, APRV uses an active exhalation valve that
allows spontaneous breathing during both T high
and T low. APRV generates a higher mean airway
pressure with a lower tidal volume and lower endexpiratory pressure when compared with other ventilator strategies.2 The concept of APRV is based on a
mechanical ventilator approach designed to maximize and maintain alveolar recruitment throughout
the entire ventilatory cycle.3 This is accomplished by
setting the P high well above the closing pressure of
recruitable alveoli. During the long inflation phase
alveolar recruitment is maintained, and during the
short release phase, inherent recoil properties of the
lung facilitate ventilation.4 Oxygenation is a function
of open surface area, therefore airway pressure and
PaO2 are directly related. APRV improves oxygenation with prolonged increases in inspiratory pressure
and long inspiratory times.

Journal of Burn Care & Research

Volume 30, Number 1

The theoretical advantages of APRV includes:

minimize ventilator induced lung injury, improved
hemodynamic parameters, provides benefits from
allowing spontaneous breathing, decreases the work
of breathing and decreases the need for sedation/
neuromuscular blocker.2,3 The proposed indications
for the use of APRV include: recruitable low lung
compliance disorders and inadequate oxygenation.
The advantages to APRV include; lower peak inspiratory pressures at similar mean airway pressure and it
allows for spontaneous breathing which can lead to
increased patient comfort and synchrony.
A number of clinical crossover studies have looked
at physiological end points with APRV.510 These
studies suggest that APRV required less applied endinflation pressures and less sedation. Additionally
APRV often produced better oxygenation than other
forms of mechanical ventilation. There have been two
randomized controlled trials (RCT) of APRV. One
RCT enrolled 30 mechanically ventilated trauma
patients.11 In this study, APRV was compared with
Pressure Controlled Ventilation (PCV) with sedation
and paralysis for 72 hours. After 72 hours the PCV
group was crossed over to APRV. APRV was associated with lower end inflation pressures, improved
oxygenation, decreased ventilator days, decreases in
intubation days and intensive care unit stay. However, there was no change in mortality and the PCV
group required paralysis for the first 72 hours.
In the second RCT, Varpula et al12 compared 45
patients on APRV to synchronized intermitted mandatory ventilation and pressure support. Findings included
a lower end-inflation pressure, similar gas exchange, sedation needs and ventilator free days. There was no difference in mortality or intensive care unit stay.
A possible limitation of this mode of ventilation for
patients with inhalation injury include a high level of
intrinsic positive end expiratory pressure secondary to
increased airway resistance and short expiratory times
which may result in hyperinflation of the lungs.

Mlcak

177

CONCLUSIONS
APRV provides the clinician with an additional potential ventilatory modality for the use in inhalation
injury. However, its role in mechanical ventilation of
the burn patient remains to be defined. Thus, further
study of the effects of APRV in inhalation injury is
warranted to determine how this mode of ventilation
should be applied in inhalation injury.
REFERENCES
1. Stock MC, Downs JB, Frolicher DA. Airway pressure release
ventilation. Crit Care Med 1987;15:462 6.
2. Myers TR, MacIntyre NR. Does airway pressure support ventilation offer important new advantages in mechanical ventilation support? Respir Care 2007;52:452 8.
3. Habashi NM. Other approaches to open lung ventilation:
airway pressure release ventilation. Crit Care Med 2005;
33(Suppl 3):S228 S240.
4. Haitsma JJ, Lachmann B. Lung protective ventilation in ARDS:
the open lung maneuver. Minerva Anestesiol 2006;72:11732.
5. Kaplan LJ, Bailey H, Formosa V. Airway pressure release
ventilation increases cardiac performance in patients with
acute lung injury/adult respiratory distress syndrome. Crit
Care 2001;5:221 6.
6. Rasanen J, Cane RD, Downs JB, et al. Airway pressure release
ventilation during acute lung injury: a prospective multicenter trail. Crit Care Med 1991;19:1234 41.
7. Schuttz TR, Costarino AT Jr, Durning SM, et al. Airway
pressure release ventilation in pediatric. Pediatr Crit Care
Med 2001;2:243 6.
8. Dart BW IV, Maxwell RA, Richart CM, et al. Preliminary
experience with airway pressure release ventilation in a trauma/
surgical intensive care unit. J Trauma 2005;59:71 6.
9. Sydow M, Burchardi H, Ephraim E, Zielmann S, Crozier TA.
Long-term effects of two different ventilatory modes on oxygenation in acute lung injury: comparison of airway pressure
release ventilation and volume-controlled inverse ratio ventilation. Am J Respir Crit Care Med 1994;149:1550 6.
10. Cane RD, Peruzzi WT, Shapiro BA. Airway pressure release
ventilation in severe acute respiratory failure. Chest 1991;
100:460 3.
11. Putensen C, Zech S, Wrigge H, et al. Long-term effects of
spontaneous breathing during ventilatory support in patients
with acute lung injury. Am J Respir Crit Care Med 2001;164:
439.
12. Varpula T, Jousela I, Niemi R, Takkunen O, Pettiala V. Combined effects of prone positioning and airway pressure release
ventilation on gas exchange in patients with acute lung injury.
Acta Anaesthesiol Scand 2003;47:516 24.

Journal of Burn Care & Research

January/February 2009

178 Cartotto

Use of High Frequency Oscillatory Ventilation in

Inhalation Injury
Robert Cartotto, MD, FRCS(C)

High frequency oscillatory ventilation (HFOV) is an

unconventional form of mechanical ventilation which
has been used for the past two decades in the neonatal
intensive care unit for respiratory distress syndrome.
Recognition of HFOVs lung protective properties
combined with sound physiologic evidence of its ability to open and recruit the lung, have led to translation of HFOV to the adult ICU, for patients with the
Acute Respiratory Distress Syndrome (ARDS). Initially HFOV was employed as a rescue therapy for
severe ARDS cases with end-stage oxygenation failure. More recently, however, HFOV has been successfully employed as a ventilation approach earlier
and earlier in the course of ARDS among diverse
patient populations including burn patients.
Currently, very little has been reported on the use
of HFOV after inhalation injury, aside from one animal experiment,1 a pediatric case report,2 and data
(unpublished) from 19 adult burn and inhalation injury patients treated with HFOV at our institution.3
Therefore, at the present time (and for the purposes
of this discussion), HFOV must primarily be viewed
within the context of its use as a rescue ventilation
strategy in ARDS, to which smoke inhalation injury
patients are obviously prone. Consideration of HFOV
after smoke inhalation outside the scenario of severe
ARDS, for example, as a mode of ventilation for early
acute lung injury (ALI), or immediately after injury,
may be somewhat premature. Nevertheless, there are
distinct and potentially fruitful research questions
surrounding HFOV and its role among thermally injured patients with smoke inhalation, which will be
explored in this section.

From the Department of Surgery, The Ross Tilley Burn Centre at

Sunnybrook Health Sciences Centre, Toronto, Canada.
This study was supported by a Grant 8431 from Shriners Hospitals
for Children.
Address correspondence to Robert Cartotto, MD, FRCS(C), The
Ross Tilley Burn Centre at the Sunnybrook Health Sciences
Centre, Toronto, Ontario, Canada.
Copyright 2009 by the American Burn Association.
1559-047X/2009
DOI: 10.1097/BCR.0b013e3181923c6a

What is HFOV?
HFOV uses extremely small Vts (12 ml/kg), at
high frequencies (315 Hz), combined with application
of a relatively high sustained mean airway pressure
(mPaw) (30 40 cm H2O). The key difference between
CMV and HFOV is demonstrated in Figure 1.4
Primarily oxygenation is achieved by using the elevated and sustained mPaw to achieve highly effective recruitment of the available lung (ie, increased
total lung volume).4 7 Alveolar ventilation is mainly related to the frequency of ventilation which is inversely
related to tidal volume, (ie, higher frequency lower
Vt, lower frequency larger Vt), and is relatively independent of total lung volume.4,5 Hence, oxygenation
and ventilation are essentially uncoupled and can each
be controlled independent of the other.4,5 HFOV is
currently delivered using the SensorMedics 3100B high
frequency oscillatory ventilator (the adult oscillator).

How is HFOV a Lung Protective

Ventilation Strategy?
Numerous animal studies have found HFOV to produce less VILI than CMV.8 12 HFOVs ability to limit
VILI is best understood by examining Figure 2.13
HFOV ventilates the lung in a relatively restricted safe
window, avoiding excursion into the zone of alveolar
overdistention (volutrauma) at high Vts and high inflation pressures, and the zone of alveolar derecruitment
(atelectrauma) at insufficient pressures.13 The very small
Vts during HFOV limit alveolar stretch even at higher
airway pressures because the incremental expansion of

Figure 1. Airway pressure Vs. time during conventional

mechanical ventilation (CMV) and high frequency oscillatory ventilation (HFOV). Adapted from Ferguson et al.4

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Cartotto

179

RCTs of HFOV in Adult ARDS

Figure 2. A hypothetical pressure volume curve during conventional mechanical ventilation (CMV) showing excursion
(grey shaded area) into zones of injury at high pressure and
volume and again at low end expiratory pressures during deflation, compared to high frequency oscillatory ventilation
(HFOV) which ventilates the lung in a safe zone (white
area). Reprinted with permission from Froese AB. Highfrequency oscillatory ventilation for adult respiratory syndrome: lets get it right this time. Crit Care Med 1997; 25:
906 8. Copyright 1997, Lippincott Williams & Wilkins.

the alveolus with each inspiration is still quite small. The

use of such small Vts then allows application of a higher
sustained mPaw which opens and recruits the lung to
prevent atelectrauma in many groups of alveoli that
would otherwise be subject to repetitive collapse and
re-opening. The lung recruitment directly improves oxygenation, allowing use of a lower FiO2, thus limiting
oxygen toxicity.

Experience With HFOV in Adult ARDS

HFOV has now been widely reported as a rescue
strategy for oxygenation crisis in adults with ARDS,
arising from critical illness,14 17 trauma,18,19 and
burn injury.20 The main combined findings from
these studies can be summarized as follows:
HFOV appears to be safe with relatively low
rates of barotrauma.
HFOV produces rapid and sustained correction
of oxygenation failure, when used as a rescue
strategy.
The improved oxygenation is usually achieved at
a lower mean airway pressure cost, as measured by the oxygenation index (OI).
Improved oxygenation is not related to improved
survival, and no conclusions on HFOVs effect on
mortality can be reached from these studies.
Optimal application of HFOV likely requires use
of periodic Lung Recruitment Maneuvers
(LRM)21 (similar to that which has been previously shown in animal models).22,23

Two Randomized Controlled Trials (RCT) (N 14824

and N 6125) have compared HFOV with CMV in
adults with ARDS. Neither of these studies raised any
important safety concerns, but importantly neither
showed any definitive advantage of HFOV over CMV.
However, interpretation of these findings must take
into account certain limitations, specifically13,22:
a. HFOV may not have been optimally utilized (lack of
LRMs, lower frequencies, premature weaning of
mean Paw, and too early conversion to CMV).
b. The control arms CMV strategy may not have
been optimally lung protective (high or unlimited plateau pressures [PPLAT], absence of initial
LRMs, relatively low PEEP).
In summary, the existing RCTs of adult HFOV are inconclusive. The need for a larger RCT of optimum
HFOV against the best protective CMV strategy of
the day is being addressed by the multi-center OSCILLATE Trial (Ferguson and Meade) which is based in
Toronto and which is now entering patients into its
pilot phase. This study will compare HFOV (utilizing
LRMs, relatively higher frequencies, and less aggressive
weaning/conversion to CMV), with protective CMV
(utilizing LRMs, Vt 6 8 mL/kg, PPLAT 35 cm
H2O, and relatively higher PEEP settings). This study is
extremely important because it will likely set the best acceptable standard for any subsequent trials where HFOV is
studied (eg, application of HFOV in specialized patient
subsets such as smoke inhalation injury).

Important Considerations for Research of

HFOV After Smoke Inhalation
Although smoke inhalation injury predisposes burn
patients to ALI and ARDS, it does not necessarily
follow that HFOV may be a rational or effective ventilatory modality for smoke inhalation patients despite the promising early experience with HFOV in
adult ALI and ARDS. This is due to the unique clinical and pathophysiologic features of smoke inhalation which may pose limitations to the application of
HFOV, including:
1. Small airway obstruction (edema, bronchospasm,
sloughing mucosa and carbonaceous debris) may
limit the ability of HFOV to recruit alveoli distally.
2. Gas trapping and related hypercapnia in inhalation injury may be difficult to control during
HFOV. During HFOV measures to increase
CO2 removal are slow-working and potentially
compromise HFOVs protective effects.
3. Copious secretions after inhalation injury are
difficult to manage during HFOV.

Journal of Burn Care & Research

January/February 2009

180 Cartotto

4. ARDS is recognized as a heterogeneous disease

process whereby different etiologies can potentially produce important variations in pathology.
For example, it is conceivable, (but unknown at
present), whether ARDS after smoke inhalation
may feature a predominance of sticky non-recruitable alveoli, rather than loose more recruitable alveoli. This fundamental difference in
pathology could affect HFOVs ability to effectively open and recruit the lung.26,27
5. HFOV complicates delivery of adjunctive therapies
in inhalation injury (nebulized heparin, mucomyst,
bronchodilators, therapeutic bronchoscopy).
Because of these considerations, research into HFOVs
role should follow a logical sequence which proceeds from
use of HFOV as a rescue therapy in ARDS in smoke inhalation patients, to earlier application as a protective strategy
in ALI or early phase ARDS, and ultimately to consider it
as an initial ventilatory strategy immediately after smoke
inhalation injury.

findings is needed because of the small number of subjects studied (N 3),and the absence of reported data
on the mean Paw in the HFOV treated cases, and the
likelihood that optimal HFOV, based on todays standards, was not employed.
A key question regarding HFOV is whether it is
suitable as an immediate ventilation modality after
smoke inhalation injury. Gas trapping, small airway
obstruction, and copious respiratory secretions are
classic features after smoke inhalation, and would
likely prove to be problematic during HFOV. Furthermore, HFPV has proven benefits as an immediate
ventilation strategy immediately after smoke inhalation.28 30 However, one important advantage of
HFOV might be the reduced nosocomial infection
risks from respiratory droplet dissemination, compared with HFPV, which is an open system with a
deflated endotracheal balloon cuff.

Is HFOV Effective as Rescue Strategy

in ARDS Among Burn Patients With
Smoke Inhalation?

Although HFOV is a promising mode of ventilation

for ARDs, at present the data do not clearly indicate
how or whether it should be used following inhalation injury. Further investigation is needed to determine the optimal use of HFOV as well as its efficacy in
comparison with other modes of ventilation.

Among human adults with ARDS after smoke inhalation, our group has found that patients with burns and
smoke inhalation do not respond as vigorously to
HFOV as those with a burn injury alone, when HFOV
was used as a rescue strategy for ARDS- related oxygenation failure. Those with inhalation injury failed to
achieve significant improvement in PaO2/FiO2 ratio or
OI compared with baseline on CMV before HFOV,
until after 72 hours of HFOV therapy, and never obtained a significant reduction in OI. This contrasted
sharply with non-inhalation cases where there was a significant improvement in oxygenation within 8 hours of
HFOV. There were no differences between those with
inhalation injury and those without with respect to CO2
levels, duration of ventilation, or mortality. However,
this was a retrospective study that did not use a fixed
HFOV strategy, and there were significant baseline differences between the groups in timing of HFOV initiation (earlier in inhalation group), and pre-HFOV
PEEP level on CMV (lower in inhalation group).3 Is
HFOV a beneficial (and protective) early interventional
strategy in ALI or early ARDS after smoke inhalation?
No studies to date have attempted to answer this question. Conceptually, the use of a protective ventilation
strategy earlier in the course of lung injury in an effort to
prevent deterioration is appealing. One animal study1
found that HFOV actually produced more histologic
evidence of lung injury than CMV or high frequency
percussive ventilation, in a primate model of smoke inhalation. However, cautious interpretation of these

CONCLUSION

REFERENCES
1. Cioffi WG, deLemos RA, Coalson JJ, Gerstmann DA, Pruitt
BA. Decreased pulmonary damage in primates with inhalation injury treated with high frequency ventilation. Ann Surg
1993;218:328 37.
2. Jackson MP, Philip B, Murdoch LJ, Powell BWEM. High
frequency oscillatory ventilation successfully used to treat a
severe pediatric inhalation injury. Burns 2002;28:509 11.
3. Cartotto R, Walia G, Ellis S, Gomez M, Fowler R. HFOV for
the burn patient with ARDS: does inhalation injury affect the
response? (abstract) J Burn Care Res 2007;28:S56.
4. Ferguson ND, Stewart TE. New therapies for adults with
acute lung injury: high frequency oscillatory ventilation. Crit
Care Clin 2002;18:113.
5. Derdak S. High-frequency oscillatory ventilation for acute
respiratory distress syndrome in adult patients. Crit Care Med
2003;31:S31723.
6. Suzuki H, Papazoglou K, Bryan AC. Relationship between
PaO2 and lung volume during high frequency oscillatory ventilation. Acta Paediatr Jpn 1992;34:494 500.
7. Kolton M, Cattran CB, Kent G, Volgyesi G, Froese AB,
Bryan AC. Oxygenation during high-frequency ventilation
compared with conventional mechanical ventilation in two
models of lung injury. Anesth Analg 1982;61:32332.
8. Hamilton PP, Onayemi A, Smyth JA, et al. Comparison of conventional and high-frequency oscillatory ventilation: oxygenation and lung pathology. J Appl Physiol 1983;55:131 8.
9. McCulloch PR, Forkert PG, Froese AB. Lung volume maintenance prevents lung injury during high frequency oscillatory ventilation in surfactant-deficient rabbits. Am Rev Respir
Dis 1988;137:118592.
10. Bond DM, Froese AB. Volume recruitment maneuvers are
less deleterious than persistent low lung volumes in the

Journal of Burn Care & Research

Volume 30, Number 1

11.

12.

13.
14.
15.

16.

17.
18.

19.
20.

atelectasis-prone rabbit lung during high-frequency oscillation. Crit Care Med 1993;21:40212.
Rotta AT, Gunnarsson B, Fuhrman BP, Hernan LJ, Steinhorn DM. Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury. Crit Care Med
2001;29:2176 84.
Imai Y, Nakagawa S, Ito Y, Kawano T, Slutsky AS, Miyasaka
K. Comparison of lung protection strategies using conventional and high-frequency oscillatory ventilation. J Appl
Physiol 2001;91:1836 44.
Froese AB. High-frequency oscillatory ventilation for adult
respiratory distress syndrome: lets get it right this time. Crit
Care Med 1997;25:906 8.
Fort P, Farmer C, Westerman J, et al. High-frequency oscillatory ventilation for adult respiratory distress syndromea
pilot study. Crit Care Med 1997;25:937 47.
Mehta S, Lapinsky SE, Hallett DC, et al. A prospective trial of
high frequency oscillatory ventilation in adults with acute
respiratory distress syndrome. Crit Care Med 2001;29:
1360 9.
Andersen FA, Guttormsen AB, Flaatten HK. High frequency
oscillatory ventilation in adult patients with acute respiratory
distress syndromea retrospective study. Acta Anaesthesiol
Scand 2002;46:1082 8.
Mehta S, Granton J, MacDonald RJ, et al. High-frequency
oscillatory ventilation in adults: the Toronto experience.
Chest 2004;126:518 27.
Claridge JA, Hostetter RG, Lowson SM, Young JS. Highfrequency oscillatory ventilation can be effective as rescue
therapy for refractory acute lung dysfunction. Am Surg 1999;
65:1092 6.
David M, Weiler N, Heinrichs W, et al. High-frequency oscillatory ventilation in adult acute respiratory distress syndrome. Intensive Care Med 2003;29:1656 65.
Cartotto R, Ellis S, Gomez M, Cooper A, Smith T. High frequency oscillatory ventilation in burn patients with the acute
respiratory distress syndrome. Burns 2004;30:453 63.

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21. Ferguson ND, Chiche JD, Kacmarek RM, et al. Combining

high-frequency oscillatory ventilation and recruitment maneuvers in adults with early acute respiratory distress
syndrome: the Treatment with Oscillation and an Open Lung
Strategy (TOOLS) Trial pilot study. Crit Care Med 2005;33:
479 86.
22. Froese AB. The incremental application of lung-protective
high-frequency oscillatory ventilation. Am J Respir Crit Care
Med 2002;166:786 7.
23. Froese AB. Role of lung volume in lung injury: HFO in the
atelectasis-prone lung. Acta Anaesthesiol Scand Suppl 1989;
90:126 30.
24. Derdak S, Mehta S, Stewart TE, et al. High frequency oscillatory ventilation for acute respiratory distress syndrome: a
randomized controlled trial. Am J Respir Crit Care Med
2002;166:801 8.
25. Bollen CW, van Well GT, Sherry T, et al. High frequency
oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial. Crit Care 2005;9:R430 9.
26. Crotti S, Mascheroni D, Caironi P, et al. Recruitment and
derecruitment during acute respiratory failure: a clinical
study. Am J Respir Crit Care Med 2001;164:131 40.
27. Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment
in patients with the acute respiratory distress syndrome.
N Engl J Med 2006;354:1775 86.
28. Cioffi WG, Loring WR, Graves TA, McManus WF, Mason
AD, Pruitt BA. Prophylactic use of high frequency percussive
ventilation in patients with inhalation injury. Ann Surg 1991;
213:575 82.
29. Reper P, Wibaux O, VanLaeka P, Vandeenan D, Duinslager
L, Vanderkelen A. High frequency percussive ventilation and
conventional ventilation after smoke inhalation: a randomized study. Burns 2002;28:503 8.
30. Hall JJ, Hunt JL, Arnoldo BD, Purdue GF. Use of high
frequency percussive ventilation in inhalation injuries. J Burn
Care Res 2007;28:396 400.

Potential Studies of Mode of Ventilation in

Inhalation Injury
Michael D. Peck, MD,* David Harrington, MD, Ronald P. Mlcak, PhD,
Robert Cartotto, MD, FRCS(C)

Future studies of modes of ventilation after inhalation

injury fall into two categories: 1) optimizing a specific
ventilator modes use in inhalation injury followed by 2)
comparison of the different ventilator modes in inhala-

From the *Arizona Burn Center, Phoenix; Department of

Surgery, Brown University Medical School, Providence, Rhode
Island; Shriners Hospital for Children, Galveston, Texas; and
The Ross Tilley Burn Centre at the Sunnybrook Health Sciences
Centre, Toronto, Canada.
Address correspondence to Michael D. Peck, MD, 2601 East
Roosevelt Street, Phoenix, Arizona 85008.
Copyright 2009 by the American Burn Association.
1559-047X/2009
DOI: 10.1097/BCR.0b013e3181923c7a

tion injury. The key to determining optimal ventilator

strategies is the use of well-defined hypotheses in conjunction with meticulous study design. Studies assessing
modes of ventilation after smoke inhalation injury
should include attention to several issues that arose during the trials of low tidal volume therapy. Ventilatory
goals need to be clarified, and protocols for ventilator
adjustments need to be developed. For example, during
permissive hypercapnia, how low can the pH descend
without needing treatment, and when respiratory acidosis does need treatment, should it be done with sodium bicarbonate, increased ventilation rate, or larger
tidal volumes need to be clarified prior to study initiation. When tidal volumes are calculated should they be

Journal of Burn Care & Research

January/February 2009

182 Peck et al

reported as related to predicted or measured body

weight? Should the interventions be based on tidal volume or plateau pressure? What levels of positive end
expiratory pressure should be used? Should chest wall
compliance and intraabdominal pressures be measured?
Dependent variables should be expanded beyond mortality to include:
Development of multisystem organ failure
Duration of mechanical ventilation
Length of intensive care unit and hospital stay
Long-term mortality
Long-term health-related quality of life
Long-term cognitive outcome
Costs/charges.
The first phase of the study of ventilator modes is
the determination of the ideal parameters after
inhalation injury. This could entail an initial retrospective comparison of ventilator parameters and
outcomes followed by a prospective observational
data collection of outcomes utilizing the goals and
parameters developed in the retrospective cohort.
An example of such a proposal appears below.

PHASE 1 PROPOSAL EXAMPLE:

OPTIMIZATION OF VENTILATOR
MODE: THE VOLUMETRIC DIFFUSIVE
VENTILATOR (VDR)
The settings on the VDR ventilator can be set in
many ways. The sinusoidal rate (essentially the respiratory rate on standard ventilation), inspiratory
time, ratio of inspiratory to expiratory time (i/e
ratio), oscillatory continuous positive airway pressure (CPAP), peak inspiratory pressure, oscillatory
rate and i/e ratio of the oscillatory component can
all be titrated to desired effect. In the published
literature, there are two basic methods the VDR is
used. The groups in Cincinnati and Galveston used
the VDR with an oscillatory rate of 4 to 7 Hertz.
This method improves the ventilatory component
of the ventilator at the expense of oxygenation. The
Institute of Surgical Research in San Antonio uses a
standard oscillatory rate of 10 Hertz. These settings will improve oxygenation at the expense of
ventilation. Each group then uses the oscillatory
CPAP and FiO2 to attain a desired systemic oxygen
saturation and titrates sinusoidal rate and positive
inspiratory pressure (PIP) to attain CO2 clearance.
Both groups reported improved outcomes in their
experience utilizing the VDR, though their study
groups where different with one group studying
the pediatric population and the other an adult
population. An optimal method for using the VDR
should be found so that experience with the venti-

lator and improvements in outcome can be standardized.

Study Hypothesis
Oscillatory rates of 10 Hertz with a standard inspiratory time of 2 seconds will attain better outcomes
than oscillatory rates of either 4 or 7 Hertz.

Methods and Materials

Patients of all ages with bronchoscopic evidence of inhalation injury and burn size greater than 20% will be
randomized to different standard settings on the VDR
ventilator. Group 1 will have an oscillatory rate of 10
Hertz, an i/e ratio of 1 and an inspiratory time of 2
seconds. Group 2 will have an oscillatory rate of 7 Hz,
an i/e ratio of 1 and an inspiratory time of 2 seconds.
Group 3 will have an oscillatory rate of 4 Hz, an i/e
ratio of 1 and an inspiratory time of 2 seconds. Each
group will titrate PIP, SR to a PaCO2 between 35 and
45 and will titrate oscillatory CPAP, FiO2 to keep O2
saturation 90%. The primary outcome measures will
be best double product (sinusoidal rate PIP) on postburn day 5, 10, and 15. The secondary outcome measure will be best P/F ratio on postburn day 5, 10, and
15. Performing a power analysis is difficult because
the PIP from the Institute of Surgical Research were
not reported from the adult survival studies. Assuming a 5 cm H2O (30 cm H2O 5 SD and 25 cm
H2O 5, 20 cm H2O 5 SD) difference between
the groups and a power of 0.9, an @ error of 0.05, and
2 planned, nonindependent, pairwise comparisons, 27
patients will be needed for each group to detect a statistically significant difference.

Comments
Optimizing and standardizing the use of any mode of
mechanical ventilation is a necessary first step before
embarking on a multicenter trial comparing different
modes of ventilation. The study cited above needs to
be applied to each of the newer modes of mechanical
ventilation (airway pressure release ventilation [APRV],
oscillatory ventilator, etc) prior to beginning phase 2,
the comparison of different modes of ventilation. Phase
1 will likely require multiple centers to establish population generalizability. Due to its observational nature, it would be less likely to interfere with other
studies in progress, but will be subject to vagaries in
patient treatment.
Phase 2 would involve a multicenter comparative
trial of different modes of ventilation on inhalation
injury and would ideally occur only after phase 1 has
been completed. This study will require a significantly
larger number of patients, multiple centers, and be of
much longer duration to have sufficient power to

Journal of Burn Care & Research

Volume 30, Number 1

detect a difference in groups. Comparing more than

two modes of mechanical ventilation in a single study
is not likely to be feasible. This phase will need to
prioritized with other studies of burn and inhalation
injury to maximize research productivity in burns. An
example of such a trial is described below.

PHASE 2 PROPOSAL EXAMPLE:

DETERMINING THE BEST MODE OF
VENTILATION: APRV VS VDR
Proposed Study
Whether APRV ventilation will be of value to patients
with inhalation injury is yet to be determined. A randomized clinical trial for patients with inhalation injury is necessary to answer the question.
Hypothesis. This proposed project will test the
central hypothesis that APRV ventilation will decrease mortality, improve oxygenation, decrease ventilator days and length of intubation and decrease the
incidence of pneumonia/atelectasis when compared
to High Frequency Percussive Ventilation in patients
with inhalation injury.
Endpoints. The primary endpoint will be survival
and the secondary endpoints will include: improved
oxygenation, decreased ventilator days, decreased intubation time, decreased incidence of pneumonia/
atelectasis, decreased end-inflation pressures and improved pulmonary function studies.
Feasibility. Primary endpoint, survival, based on
the Varpula et al1 study, the number of patients
needed to show a significant difference in mortality is

Peck et al

183

497 per group. Secondary endpoints based on published clinical trials of APRV, the number of patients
needed to show a significant difference in secondary
endpoints is 30 to 40 patients per group.
Cost. To be determined based upon the following
major factors:
1. Finalizing endpoints.
2. Total no. of patients required.
3. Centers needing ventilators with the APRV
mode and high frequency percussive ventilation.
4. Training of all centers to follow specific protocols for initial set-up, ventilator usage and weaning
patients.
5. A point person for design, coordination and execution of study protocols.

Clinical Relevance of Study

Reduced mortality.
Reduction in ventilator days and length of intubation:
1. Reduce the incidence of ventilator-associated
pneumonia.
2. Reduce cost.
Determination of the best mode of mechanical ventilation is likely to remain a challenge to clinicians for
decades to come.
REFERENCE
1. Varpula T, Jousela I, Niemi R, et al. Combined effects of
prone positioning and airway pressure release ventilation on
gas exchange in patients with acute lung injury. Acta Anaesthesiol 2003;47:516 524.