Emerg Med Clin N Am

26 (2008) 835–847

Noninvasive Positive Pressure

Ventilation in the Emergency
Department
Mei-Ean Yeow, MDa, Jairo I. Santanilla, MDa,b,*
a
Division of Critical Care Medicine, University of California San Francisco,
505 Parnassus Avenue, M-917 San Francisco, CA 94143-0624, USA
b
Alameda County Medical Center, Highland Hospital, 1411 East 31st Street,
Oakland, CA 94602-1018, USA

Noninvasive ventilation is defined as the provision of ventilatory assis-

tance to the respiratory system without an invasive artificial airway. Nonin-
vasive ventilators consist of both negative and positive pressure ventilators.
Because negative pressure ventilation is so rarely used today, discussion is
limited here to positive pressure ventilation.
One of the earliest descriptions of a ‘‘pulmonary plus pressure machine’’
was in 1936 when Poulton described using an Electrolux or Hoover vacuum
cleaner to supply air at positive pressure to treat patients with ‘‘cardiac and
bronchial asthma’’. He also wisely cautioned that: ‘‘the machine should be
run for some minutes first of all to get rid of the dust’’ [1].
Before the 1960s, the use of negative pressure ventilation in the form of
the tank ventilator or the ‘‘iron lung’’ was the most common form of
mechanical ventilation outside of the anesthesia suite. It was not until the
1952 polio epidemic in Copenhagen that anesthesiologist Bjorn Ibsen
showed that he could improve the survival of patients who had respiratory
paralysis by using invasive positive pressure ventilation.
Despite this, negative pressure or iron lungs were the mainstay of venti-
latory support for patients who had chronic respiratory failure until as late
as the mid-1980s. In the early 1980s, nasal continuous positive airway pres-
sure (CPAP) was introduced to treat obstructive sleep apnea. These tight-
fitting masks proved to be an effective means of assisting ventilation and
noninvasive positive pressure ventilation (NPPV) quickly displaced

* Corresponding author.
E-mail address: [email protected] (J.I. Santanilla).

0733-8627/08/$ - see front matter ! 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.emc.2008.04.005 emed.theclinics.com
836 YEOW & SANTANILLA

traditional negative pressure ventilation as the treatment of choice for

chronic respiratory failure in patients with neuromuscular and chest wall
deformities. Current NPPV devices are able to provide a set respiratory
rate, set tidal volume, and set amount of inspiratory oxygen. The use of
NPPV has also been integrated into the acute inpatient setting where it is
now used to treat acute respiratory failure [2].
This article reviews the indications for NPPV in the treatment of acute
respiratory failure, the evidence for its application in the emergency depart-
ment (ED), and some relative and absolute contraindications for NPPV.
The use of high flow nasal cannulae and their potential treatment benefit
in patients with respiratory distress is also discussed.

Definitions
The current literature uses different definitions for NPPV. Although some
authors use NPPV as umbrella terms that include CPAP and bilevel positive
airway pressure, more recently other authors have used the term NPPV as
synonymous with bilevel and consider CPAP a separate entity. The terms
NPPV and noninvasive intermittent positive pressure ventilation (NIPPV)
are often used interchangeably with bilevel.
As its name suggests, CPAP supplies continuous positive pressure via
a tight-fitting facemask. NPPV or bilevel provides an inspiratory pressure
(set as IPAP or inspiratory positive airway pressure) in addition to end-
expiratory positive pressure (set as EPAP or expiratory positive airway pres-
sure) and breaths are usually triggered by the patient. On many such devices,
backup rates may be set, that deliver bilevel pressures even if patients fail to
initiate a breath.

Rationale for using noninvasive positive pressure ventilation

The most important advantage of NPPV is avoiding the complications
associated with invasive mechanical ventilation. It has been well docu-
mented that invasive mechanical ventilation increases the incidence of air-
way and lung injury, and it augments the risk of nosocomial pneumonia.
NPPV avoids these complications by keeping the upper airway defense
mechanisms intact and allows the patient to retain the ability to eat, clear
secretions, and communicate normally when NPPV is used intermittently
[2]. NPPV has the potential to reduce the mortality of a selected group of
patients with acute respiratory failure and may shorten hospital stay,
thereby reducing costs. Specific to the ED, appropriate initiation of
NPPV may avoid unnecessary intubation of selected patients, hence avoid-
ing ICU admissions, reducing costs, decreasing complications, and improv-
ing mortality.
 NONINVASIVE POSITIVE PRESSURE VENTILATION 837

Pathophysiological effects of noninvasive positive pressure ventilation

CPAP increases alveolar recruitment and size, enhancing the area avail-
able for gas exchange, and improves ventilation-perfusion relationship,
thus improving hypoxemia. The term CPAP is synonymous with extrinsic
PEEP (PEEPe) and the bilevel expiratory positive airway pressure
(EPAP). It can also negate the effects of intrinsic positive end expiratory
pressure (PEEPi) also referred to as auto-PEEP or dynamic hyperinflation.
In patients with dynamic hyperinflation (asthma or chronic obstructive pul-
monary disease [COPD]), an increased PEEPi increases the magnitude of
the drop in airway pressure that the patient must generate to trigger a breath.
This causes an increase in the work of breathing for the patient. Careful
application PEEPe can reduce this gradient and decrease the patient’s
work of breathing. Positive pressure ventilation creates an increase in intra-
thoracic pressure. This causes preload to decrease due to diminished venous
return and also decreases transmural pressures and afterload [1].
In NPPV or bilevel, the inspiratory positive airway pressure (IPAP) is
similar to pressure support and, when combined with expiratory positive
airway pressure (EPAP), further augments alveolar ventilation and allows
some respiratory muscle rest during the inspiratory phase.

Indications for initiating noninvasive position ventilation

Acute exacerbation of chronic obstructive pulmonary disease
Numerous studies have shown that NPPV can reduce the need for intuba-
tion, length of the hospital stay, and also in-hospital mortality rate in patients
presenting with acute exacerbations of COPD. One of the earliest, prospective,
randomized studies was done by Bott and colleagues [3] in 1993 where they
reported a reduction in mortality with the use of nasal NPPV in patients
who had COPD. This study was followed by a large multi-center, prospective,
randomized trial by Brochard and colleagues [4], which confirmed selected
patients who had acute COPD exacerbations did benefit from NPPV, com-
pared with standard medical care alone. In this study, NPPV decreased intu-
bation rates compared with standard medical treatment (11/43 [26%] versus
31/42 [74%]); hospital mortality was 9% in the NPPV group compared with
29% in the standard medical therapy group. Since then, several systematic
reviews have confirmed that NPPV reduces in-hospital mortality and
decreases the need for endotracheal intubation in patients who have acute,
severe COPD exacerbations. A systematic review by Keenan suggested that
the patients who benefited most from NPPV treatment were those with severe
exacerbations as manifested by a pH of ! 7.3 [5]. This finding, however, has
not been borne out in other reviews [6].
Interestingly, Conti and colleagues [7] showed that if NPPV is started
later, after the failure of medical treatment, the benefits conferred by
838 YEOW & SANTANILLA

NPPV (hospital mortality, length of ICU stay, number of days on the ven-
tilator, overall complications) are eliminated. This emphasizes the impor-
tance of initiating NPPV early, alongside standard medical therapy.
It is reasonable to consider early implementation NPPV in patients who
present to the ED with an acute exacerbation of COPD.

Asthma
In many ways, an acute asthmatic attack is similar to a COPD exacerba-
tion. There is pronounced airway obstruction, significant dynamic hyperin-
flation and, increases in PEEPi. CPAP has been reported to have
a bronchodilatory effect in asthma, unloading fatigued muscles, and im-
proving gas exchange. The PEEPe from NPPV can also offset the PEEPi
that occurs during an asthmatic attack as mentioned earlier [8].
Soroksky conducted a prospective, randomized, placebo-controlled study
in 30 patients who presented to the ED with a severe asthma attack (exclud-
ing patients with signs of concurrent pneumonia). Half the patients were
assigned to NPPV (for 3 hours) and conventional therapy, while the other
half received conventional therapy and subtherapeutic pressures via
a sham device.
He found that patients who received NPPV had significantly improved
lung function test results. There was also a significant reduction in the
need for hospitalization in the treatment group (17.6% versus 62.5%, P ¼
.0134). Therefore in selected patients who have severe asthmatic attacks,
the use of NPPV may be a useful adjuvant, which potentially alleviates
the attacks faster and decreases the need for hospitalization [8].

Acute cardiogenic pulmonary edema

The great majority of patients who have acute cardiogenic pulmonary
edema (ACPE) present to the ED. When these patients do not respond to
conventional medical treatment, ventilator assistance becomes necessary.
CPAP ventilation has been shown to be efficacious in ACPE. An early sys-
tematic review by Pang and colleagues [9] revealed that CPAP could reduce
the rate of intubation and led to a trend toward decreasing mortality. A
later, pooled analysis by Collins and colleagues [10] suggested that CPAP
and NPPV both reduced the risk of subsequent intubation in the ED, al-
though the mortality benefits were less convincing.
The data for NPPV or bilevel has been mixed, with an early article by
Mehta and colleagues [11] describing an increase rate of acute myocardial
infarction in patients who have ACPE treated with NPPV. Since this study,
there have been several trials that have refuted this increased risk of myocar-
dial infarction. Most of these have been small studies, the largest being
a multicenter trial randomizing 130 patients who have ACPE to either
NPPV or conventional therapy. This study found that the patients treated
 NONINVASIVE POSITIVE PRESSURE VENTILATION 839

with NPPV had faster improvements in oxygenation, respiratory rates, and

sensation of dyspnea. No difference was noted between the two groups with
regard to rates of intubation, hospital mortality, length of stay, or myocar-
dial infarction [12]. More recently, Ferrari and colleagues [13] compared
CPAP and NPPV head-to-head in 52 patients with ACPE. They found no
significant difference in the rates of intubation and hospital stay. Both tech-
niques were found to be effective in improving gas exchange and vital signs
in patients who have ACPE. More importantly, no significant difference was
observed in the rate of acute myocardial infarction in the two groups.
In the largest study of patients presenting with ACPE in the ED, author
Newby has reported in Chest Physician (October 2007) that in his study of
1,069 UK patients, both CPAP and NPPV were effective in resolving pa-
tient’s symptoms (eg, dyspnea), but the mortality rate at 7 and 30 days after
treatment was similar in the three groups (CPAP, NPPV and passive oxygen
therapy).
It seems that it is safe to use either CPAP or NPPV for patients who pres-
ent with ACPE. Although it seems that neither therapy improves mortality,
it does seem to improve symptoms and may decrease intubation rates in the
ED, thus avoiding the associated complications of intubation and poten-
tially avoiding an ICU admission.

Hypoxemic respiratory failure

The data for NPPV in patients with acute hypoxemic respiratory failure
is mixed. The largest study examined 105 patients who had acute hypoxemic
respiratory failure (PaO2 ! 60 mmHg, SpO2 ! 90% on oxygen by facemask).
Patients who had hypercapnia were excluded. These 105 patients were as-
signed randomly to NPPV or oxygen therapy. The authors reported marked
reductions in rates of endotracheal intubation, septic shock, ICU and cumu-
lative 90-day mortality in the patients who were treated with NPPV [14]. This
group also included patients who had cardiogenic pulmonary edema.
Antonelli and colleagues [15] looked at whether NPPV could be beneficial
in patients who had acute hypoxemic respiratory failure and who would
otherwise need intubation. They studied 64 patients who presented with
acute hypoxemic respiratory failure and excluded patients who had
COPD. The authors found that NPPV was as effective as conventional ven-
tilation in improving gas exchange, and NPPV was associated with fewer
serious complications (particularly pneumonia and sinusitis) and resulted
in shorter stays in the ICU. The etiology for the respiratory failure in this
cohort of patients was variable, and included patients who had cardiogenic
pulmonary edema.
For patients who have pneumonia causing acute respiratory failure, the
evidence is even more controversial, with some papers suggesting a decrease
in intubation rates, while others have found no difference in intubation rates
or in-hospital mortality [16,17].
840 YEOW & SANTANILLA

In summary, although some of the literature suggests that NPPV may be

beneficial in the setting of acute hypoxemic respiratory failure, doubts still
exist, in part due to the heterogeneity of patients included in previous stud-
ies. A large multicenter trial of NPPV in patients who have acute hypoxemic
respiratory failure that excludes patients who have cardiogenic pulmonary
edema and COPD may help to clarify the use of NPPV in this setting.

Immunosuppressed patients
NPPV can also be useful in patients who are profoundly immunosup-
pressed, either due to solid organ transplantation or from hematological
conditions. In these patients, mortality after endotracheal intubation is par-
ticularly high, therefore any attempts to avoid this procedure may result in
improved survival.
One study randomized 40 patients with acute hypoxemic respiratory fail-
ure after solid organ transplant to conventional treatment, including oxygen
via facemask or NPPV. The patients assigned to NPPV had a lower rate of
endotracheal intubation, shorter ICU stays, and lower ICU mortality. In-
house mortality did not differ significantly between the two groups [18].
Another study included immunosuppressed patients who had pulmonary
infiltrates, fever, and acute respiratory failure. This study also included pa-
tients who were immunosuppressed from: chemotherapy; bone marrow
transplantation for hematologic cancers; corticosteroid or cytotoxic therapy
for a nonmalignant disease; or, AIDS. They found that in these patients,
early initiation of NPPV was associated with significant reductions in the
rates of endotracheal intubation and serious complications, with lower rates
of death in the ICU and in the hospital [19]. Of note, all of the patients who
developed ventilator-associated pneumonia died in the ICU, in both afore-
mentioned studies (2/26 in the NPPV group; 6/26 in the standard treatment
group in Hilbert’s study). This emphasizes the potential dangers of intuba-
tion in this group of patients.
When faced with a severely immunosuppressed patient with acute hypox-
emic respiratory failure in the ED, early initiation of NPPV may be benefi-
cial in avoiding the serious complications of endotracheal intubation.

Do not intubate patients

Although most studies of NPPV have focused on patients with acute re-
spiratory failure who desire maximum life-prolonging treatment, there is an
emerging interest in using NPPV for patients who have made the decision to
forego endotracheal intubation (DNI). A recent review article on this topic
suggests that with good patient–family–physician communication, NPPV
can successfully be used in these patients on a trial basis [20].
In DNI patients willing to undergo NPPV, success would be measured by
improved ventilation or oxygenation. NPPV can provide support for the
 NONINVASIVE POSITIVE PRESSURE VENTILATION 841

patient while the underlying cause of the respiratory failure is treated. NPPV
should be discontinued if it is not producing the desired response or if the
patient is unable to tolerate it. In these circumstances, a decision should
be made by the health care team, the patient, and their family to discontinue
NPPV and make the transition toward comfort measures.
The authors suggest that in patients who have chosen to forego any life-
prolonging therapy and are receiving comfort care measures only, NPPV
might be used as a form of palliative care, in an attempt to reduce associated
dyspnea. In this circumstance, the use of NPPV is considered successful if it
alleviates the patient’s symptoms. If it causes any discomfort to the patient,
it should be discontinued because the primary goal is patient comfort. This
use of NPPV is controversial and there are no studies that have assessed the
benefits of NPPV in this group of patients [20]. Another use of NPPV in
patients who have chosen comfort care measures is a time-limited trial of
NPPV to achieve the goal of survival until the arrival of family and friends.
In this situation, NPPV would be used to provide life support until friends
and family can achieve closure.
Even if a patient with a known DNI advanced directive presents to the ED
with acute respiratory failure of reversible etiology, it still can be beneficial dis-
cussing the use of NPPV with the patient and their family. In this situation,
communication about expectations and goals of care is of utmost importance.

Facilitation of weaning and extubation

Recent studies have shown that NPPV can potentially be useful in the
discontinuation of mechanical ventilation in patients when respiratory fail-
ure is due to COPD. A recent meta-analysis found that in those patients
who have COPD who failed a spontaneous breathing trial, extubating to
NPPV decreased mortality, hospital length of stay, incidence of ventila-
tor-associated pneumonia, and total duration of mechanical ventilation
[21]. Although it is rare to extubate a patient in the ED, one does sometimes
encounter patients with exacerbations of their COPD who were prematurely
intubated in the field, or who have improved remarkably since arrival to the
ED. These patients can be considered for extubation to NPPV on a case-
by-case basis if there are no contraindications to extubation, and only if
the clinician is confident that the patient can be re-intubated if necessary.

Feasibility of using noninvasive positive pressure ventilation in the

emergency department
Most of the earlier NPPV studies were performed in the ICU. With the
growing clinical and fiscal pressures to avoid endotracheal intubation when-
ever feasible, there has been an increasing interest in using this technology in
the ED. Pollock showed in his study that the use of NPPV was feasible and
had the potential utility in the management of patients with respiratory
842 YEOW & SANTANILLA

distress [22]. This early intervention had the potential to avoid the risks and
complications of endotracheal intubation and shorten or possibly eliminate
intensive care admissions. There is very little literature on the safety of using
NPPV in the ED, how to identify patients who would benefit from this treat-
ment or how long these patients should be treated with NPPV in the ED.
There is also controversy over which type of mask should be used.
Nasal masks had been traditionally used in the setting of chronic home
therapy and they were initially the masks of choice in the acute setting. Be-
cause dyspneic patients tend to be mouth breathers, it is thought that face-
masks are preferable for the treatment of acute respiratory failure in the ED
[1]. Poponick and colleagues, as well as Merlani and colleagues, have sought
to define and identify those patients who might benefit from NPPV and con-
versely, identify what factors would predict failure of NPPV in the ED. Po-
ponick and colleagues [23] investigated factors associated with NPPV failure
in the emergency setting in 58 patients receiving a 30 minute trial of bilevel.
Lack of improvement of pH and PaCO2 level were identified as indicators
for endotracheal intubation. Merlani and colleagues [24] retrospectively an-
alyzed a total of 104 patients admitted to the ED and found that factors as-
sociated with failure of NPPV in the univariate analysis included Glasgow
Coma Scale ! 13 at ED admission, or a RR O 20/min, or a pH ! 7.35
after one hour of NPPV. In the multivariate analysis, pH ! 7.35 and RR
O 20/min after one hour of NPPV were independently associated with
NPPV failure and subsequent intubation of these patients. Both these stud-
ies looked at patients who had acute respiratory failure and the studies in-
cluded predominantly patients who had COPD and congestive heart failure.
These two studies emphasize the importance of close follow-up of pa-
tients who are started on NPPV in the ED. It is important to serially assess
patient response as soon as 30 minutes after the initiation of NPPV. Those
who are persistently tachypneic and acidemic should be considered for intu-
bation sooner rather than later.

Initiation of noninvasive positive pressure ventilation

There is no standard approach to the initiation of NPPV. Different
methods have been used in clinical trials, yet these methods have never
been compared. There are two main strategies: a high-low approach and
a low-high approach.
In the high-low approach, one initially starts with a high IPAP (20–25
cmH2O) and then lowers this if the patient is unable to tolerate such high
pressures. In the low-high approach, one starts with a lower IPAP (8–10
cmH2O). This is gradually increased as tolerated to achieve alleviation of
dyspnea, decreased respiratory rate, increased tidal volume, and patient–
ventilator synchrony. The EPAP is usually set at 3–4 cmH2O, unless the pa-
tient has a significant amount of autopeep or PEEPi. In these patients, one
would start with an EPAP between 4–8 cmH2O. The FiO2 is titrated to keep
 NONINVASIVE POSITIVE PRESSURE VENTILATION 843

the pulse oximetry R 90%. Much like conventional ventilation, the EPAP
can be adjusted to improve oxygenation and the D IPAP-EPAP can be ad-
justed to create a higher minute ventilation and thus mitigate hypercapnia.
As mentioned in the previous section, it is imperative to closely observe
the patient for deterioration. Blood gases should be checked within 1 to
2 hours after initiation of NPPV to assess treatment success or failure.
Patients who do not improve clinically should be considered for intubation.

Cautions for use of noninvasive positive pressure ventilation

Most studies involving NPPV have excluded patients who were hemody-
namically unstable, had an altered level of consciousness, or were unable to
protect their airway. This was based on the concern that a depressed senso-
rium would predispose the patient to aspiration. The International Consen-
sus Conference in Intensive Care Medicine on Noninvasive Positive Pressure
Ventilation in Acute Respiratory Failure held in April 2000 considered the
presence of severe encephalopathy, as manifested by a GCS ! 10 to be
a contraindication for NPPV [25].
Other accepted contraindications to NPPV are listed below: (Box 1).
Recently there have been studies looking specifically at the use of NPPV
in patients presenting with hypercapnic coma secondary to acute respiratory
failure. This was based on the observation that some DNI patients who
declined intubation had successful outcomes using NPPV therapy despite
their initial comatose presentation. Diaz and colleagues [26] conducted an
observational study and found that success rates were comparable between
the comatose and noncomatose group. Scala and colleagues [27,28] per-
formed two studies, both showing that NPPV could be used successfully
in treating patients with COPD exacerbations with hypercapnic encephalop-
athy. Their 2007 study showed that the use of NPPV performed by an expe-
rienced team led to similar short-term and long-term survivals, fewer
nosocomial infections, and shorter durations of hospitalization compared
with patients who were placed on mechanical ventilation. Of note, the above

Box 1. Contraindications to the use of noninvasive ventilation

Impending cardiovascular collapse or respiratory arrest
Severe upper gastrointestinal bleeding
Facial surgery, trauma or deformity, limiting placement of the
NPPV mask
Upper airway obstruction
Inability to cooperate/protect the airway, altered mental status
Inability to clear respiratory secretions
High risk for aspiration
844 YEOW & SANTANILLA

studies were conducted in the ICU [26] or specialized respiratory care units
[28], with a nursing ratio of at least 1:3. The patients were also very closely
monitored by staff while they received NPPV. This high level of nursing to
patient ratio may not be feasible in a busy ED.
The other key point in these studies was the rapid improvement in neu-
rologic status that occurred 1–2 hrs after the initiation of NPPV. The impor-
tance of close monitoring of patients started on NPPV is crucial in
identifying those who will fail this therapy.

High flow nasal cannula

The high flow nasal cannula (HFNC) is a relatively new oxygen delivery
system. Conventional nasal cannula uses a low flow system; at higher flows
(O6 L/min), it can cause nasal dryness, epistaxis and patient discomfort.
The HFNC system (Fig. 1) is a novel device, combining oxygen, pressurized
air, and warm humidification to deliver tolerable flows of up to 40 L/min
through a nasal cannula. The FiO2 and flow rates can be adjusted. With
higher flows, less air entrapment occurs and the higher flow rates match
the dyspneic patient’s increased minute ventilation.
Use of the HFNC has been more extensively studied in neonatal respi-
ratory care where ongoing studies suggest that HFNC may be as effective
as nasal CPAP in the preterm neonate [29]. One study looked at the effect

Fig. 1. High flow nasal cannula system. A) High flow flowmeter, B) oxygen blender, C) low
flow flowmeter, D) nasal cannula, E) low compliance, heated-wire circuit, F) high flow humid-
ifier, G) water reservoir, H) air/O2 supply.
 NONINVASIVE POSITIVE PRESSURE VENTILATION 845

of HFNC on exercise performance in adults with COPD [30]. Currently,

there are no published studies investigating the use of HFNC in patients
who have acute respiratory failure. Anecdotally, this system has been
used with some success in adults in the ICU, targeting immunosuppressed
patients in hopes of avoiding intubation. It seems to be better tolerated
than NPPV and, at higher flows, it is believed to provide a certain amount
of continuous positive pressure. More studies will have to be performed
before this technology becomes a mainstay treatment of patients with
acute respiratory failure.

Summary
NPPV has been shown to work well in patients with reversible conditions
and acts as a bridge while allowing medical therapy (eg, bronchodilators,
steroids, diuretics) to take effect, thus potentially avoiding the need for
endotracheal intubation. Those with less reversible causes of their acute
respiratory failure (ARDS, pneumonia) may be less likely to respond.
With careful patient selection, NPPV can be safely initiated in the ED, giv-
ing time for the medical treatment to work, and potentially avoiding an ICU
admission. Patients who are being considered for intubation should be eval-
uated for the potential use of NPPV.
Close monitoring and follow-up of patients placed on NPPV is crucial in
determining whether the therapy has been successful or if further interven-
tion is needed. Therefore, in EDs where the staff have been adequately
trained, selected patients, even those who present in a hypercapnic coma
can be considered for a short trial of NPPV, with the caveat that extreme
diligence in monitoring these patients must be employed and if improvement
is not seen in 1–2 hours, intubation should not be delayed.

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