Noninvasive ventilation versus conventional oxygen therapy for
treatment acute cardiogenic pulmonary edema
Naser Hemmati MD .Imam Ali Heart Center, Kermanshah University of Medical Sciences, Kermanshah,
Iran ,cardiac anesthesist
Author:Dr Naser hemmati
Tel +989121014521
Fax +988318360043
Emaih;drhemati_37@yahoo.com
AbdolHamid Zokaei MD
Imam Ali Heart Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. cardiac
anesthesist
Correspondence: Dr Abdol Hamid Zokaei
Imam Ali Heart Centre, Kermanshah University of Medical Sciences, Shaheed Beheshti Ave,
Kermanshah, Iran
Tel +989188312888
Fax +988318360043
Email: omrani_47@yahoo.com
Abstract
Back ground: Recent studies suggest the use of non – invasive ventilation in patients with acute
cardiogenic pulmonary edema (ACPE). However, it remains unclear whether patients with ACPE benefit
from non – invasive ventilation. This study achieved to investigate short – term effects of non – invasive
ventilation on respiratory, homodynamic and oxygenation parameters in patients with respiratory failure
.due to ACPE and to identify need for intubation, recovery and admission
Methods and materials: In this randomized clinical trial study, 80Patients assigned conventional oxygen
therapy or non – invasive ventilation supplied by a standard ventilator through a face mask with mode of
bi-level positive airway pressure (BIPAP), in addition to standardized Pharmacological treatment
.Physiological parameters were obtained in 0, 15, 30, 60 Minutes after non – invasive ventilation . The
main end points were intubation and recorded recovery time (defined as oxygen saturation of 96% or
.more and respiratory rate less than 30 breaths / min )and ICU stay
Results: Endo tracheal intubation was required in one (2.5%) of 40 assigned non – invasive ventilation
and in seven (17.5%) of 40 assigned conventional therapy ( p= 0.001 ) recovery time was significantly
shorter in the non – invasive ventilation group mean 42 ± 9.9vs 131± 22.5 ( P= 0,0001 ) non – invasive
ventilation led to a rapid improvement in oxygenation respiratory rate, arterial PH, heart rate and blood
pressure in the first hour ( p= 0.0001 ) . there were significant differences in intensive care unit length of
stay 2.8 ± 1.2 days in non – invasive ventilation group vs. 4.8 ± 1.5 in control group. (p= 0.0001).
Hospital mortality was 4patients (10%)in conventional group and 1patients(2.5%) in NIV group(P<0.001)
Conclusions: In this study of acute cardiogenic pulmonary edema non – invasive ventilation in mode
of BIPAP was superior to conventional oxygen therapy. We suggest further studies to compare bi-level
positive airway pressure with continuous positive airway pressure non invasive ventilation on treatment in
.these patients
Keywords: Acute carcinogenic pulmonary edema – non invasive ventilation – bi-level positive airway
pressure- continuous positive airway pressure
Introduction
Acute cardiogenic pulmonary edema (ACPE) is a common medical emergency. The condition
has a poor prognosis with a reported in-hospital mortality 10- 20 %.( 1, 2)
Acute respiratory failure due to acute cardiogenic pulmonary edema (ACPE) requires rapid
assessment and treatment. Although this may be secondary to chronic heart failure, myocardial
ischemia is also common. Usually In patients with acute respiratory failure increased work of
breathing, acidosis because of both respiratory and metabolic factors (3), Diastolic dysfunction is
the major cause to raised hydrostatic pressure and pulmonary edema (4). Despite standard
medical therapy with oxygen, morphine, diuretics and nitrates, ventilatory support may be
needed.
Pulmonary edema refers to the accumulation of fluid into the alveolar spaces throughout the
lungs resulting from disruption of the normal fluid flux with in the lungs. 4,
If hydrostatic pressure increased in the pulmonary capillaries, due to elevated pulmonary venous
pressure from increased left ventricular end-diastolic pressure and left atrial pressure then
leading to increased transvascular fluid filtration. Elevations of left atrial pressure between 18 to
25mmHg cause only edema in the interstitial space. When the atrial pressure rises over
25mmHg, edema fluid breaks through the lung epithelium, flooding the alveoli with protein-poor
fluid.5
After the onset of pulmonary edema process due to increases pulmonary congestion, oxygen
saturation decreases, resulting in decreased myocardial oxygen supply. This leads to ischemia in
regions with already borderline blood supply, further impairing cardiopulmonary system6,7
The immediate treatment of acute ACPE are to improve systemic oxygen saturation by giving
oxygen with a high flow facemask ( Venturi mask), reduction of preload and afterload of
both the ventricles by a combination of morphine, diuretics, and nitrates.8 An important point
to consider that respiratory failure and dyspnea are not directly related to hypoxemia, and
thus cannot be reversed with oxygen administration alone.
Traditionally Patients who do not have a response to initial therapy often require tracheal
intubation and ventilation, with the associated potential for complications.9
Endotracheal intubation has some well-known risks of complications. These complications are
related directly to intubation (injury of the vocal cord or trachea), to aspiration of gastric content,
irritation or injury due to the endotracheal tubes, edema, nosocomial infection, inflammation and
increased mucus production. Furthermore patients need more sedatives and analgesics.9
Non-invasive positive pressure ventilation ventilation (NIPPV) delivered via a tight-fitting mask
without need an endotracheal tube or tracheostomy and it is one of the most important advances
in the management of acute respiratory failure in the past 2 decades. It is now recommended as
the first choice for ventilatory support in selected patients, such as cardiogenic pulmonary
edema.10–12 Using masks as interfaces is the most important advantage of non-invasive positive
pressure ventilation (NPPV). NPPV preserves normal swallowing, speaking, cough, air warming,
and humification, and complications associated with endotracheal intubation, such as nosocomial
pneumonia and upper airway trauma, are avoided . (13,14).
The respiratory failure of ACPE can be managed with conventional oxygen therapy , noninvasive positive pressure ventilation (NIPPV) include, continuous positive airways pressure
(CPAP) and bi-level positive airways pressure (BiPAP) and Invasive techniques include
endotracheal intubation and mechanical ventilation.15.
The effectiveness of the use of bilevel-PAP in the treatment of acute cardiogenic pulmonary
edema has been studied in some clinical trials, with different results. Noninvasive bi-level
positive airway pressure (BiPAP) ventilation delivers positive airway pressure at two different
levels during inspiration and expiration can decrease inspiratory work of breathing, and improve
gas exchange [16)and reduces the need for invasive ventilation in patients with hypercapnic
respiratory failure compared with conventional medical therapy 17.Comparing bilevel-PAP with
oxygen, Park et al(18,19) and Crane et al(20)have shown physiological improvement and
reduction in endotracheal intubation rates..
Nava et al(17) in a multicenter European trial, enrolled 130 patients, 65 to oxygen support
treatment and 65 to bilevel-PAP. In this trial, normocapnic (PaCO2 35-45 mmHg) patients using
bilevel-PAP showed no improvement in endotracheal intubation and mortality rates, whereas,
hypercapnic (PaCO2 > 45 mm Hg) patients had a reduction in endotracheal intubation rates (P =
0.015). This finding was similar to that of Masip et al(16) where hypercapnic patients had a
substantial physiological and probably clinical improvement when compared to normocapnic
patients using similar airway pressures to those used by Nava et al.8
There is no conclusion about the mortality rate in acute cardiogenic pulmonary edema patients
treated with bilevel-PAP when compared to conventional treatment. In fact, only 1 study,
performed by Park et al(9) has shown a reduction of mortality associated with bilevel-PAP at the
15-day follow-up. Other studies, such as those of Masip et al16 Nava et al(17) and Crane et al(20)
did not find a reduction in mortality rates, although there were different strategies in the
respiratory support of patients.
Furthermore, the results of one of the earlier studies suggested that BiPAP compared with CPAP
found physiological improvement but with increase the risk for new onset acute myocardial
infarction in patients with acute cardiogenic pulmonary edema (21)
In the present study we assessed the potential beneficial and harmful effects of BiPAP compared
with conventional oxygen therapy in a clinical trial study in patients with acute cardiogenic
pulmonary oedema. We assessed the need for intubation, length of CCU and hospital stay
hemodynamic and respiratory parameters.
Material and method: The study was approved by the ethics committee of the medical
university of Kermanshah, and all patients or their family gave written informed consent. The
study was performed in all patients with ACPE and age more than 20years.
Inclusion criteria:(1) Diagnosed Cardiogenic pulmonary edema on the basis of clinical ,bilateral
crackles on auscultation , elevated jugular venous pressure and cardiac gallop with radiological
findings of congestion (bilateral alveolar and/or interstitial opacities on chest X-ray) by
cardiologist;(2)consciousness patients;(3)cooperation patients and ;(4) hemodynamic stability
Exclusion criteria: were (1) ) severely decreased consciousness (a Glasgow coma score of 11 or
less) (2 ) severe hemodynamic instability systolic blood pressure< 80 mmhg ; (3) recent
esophageal, facial, or cranial trauma or surgery(4); severe ventricular arrhythmia , bradycardia
HR< 45/ min or tachycardia HR>120/min;(5)nausea and vomiting despite of use antiemetic
drugs; (6) myocardial ischemia need to thrombolytic agents a lack of cooperation; (7) an
inability to clear respiratory secretions; (8) tracheotomy or other upper airway disorders; (9)
active upper gastrointestinal bleeding; (10) need for emergency intubation and (11)more than one
severe
organ
dysfunction
in
addition
to
respiratory
failure;(12)respiratory
rate>35/min;(13)PaO2<50 mmhg;(14)PaCo2>50 mmhg.
After confirmation of the diagnosis in the Emergency ward immediate treatment include oxygen
therapy and sublingual nitroglycerin (0.8 mg) if systolic blood pressure was above 120 mm Hg
was performed. Patients were transported to the CCU.
After admition to the coronary care unit (CCU). The patients with inclusion criteria were
randomly assigned to receive either conventional Oxygen therapy with Venturi mask (controlled
group ) or noninvasive ventilation through a face mask (NIV group).
The head of the bed was kept elevated at a 45-degree angle. Heart rate (electrocardiography) and
respiratory rate were monitored continuously, Arterial blood gas sampling was obtained through
a 18-gauge plastic cannula placed in the radial artery and blood pressure was measured
invasively. pulsoximeter was used to control arterial oxygen(by Space Labe monitor).
Respiratory rate, heart rate, blood pressure, and arterial blood gases were recorded at baseline
(before randomization) (T0), and after 15 min (T15) and 30 min (T30) and 60 min (T60) of
ventilation support and then every 30 min if patients need at entry into the study.
patients were given standardized pharmacological treatment include intravenous furosemide 40320 mg to achieve sufficient urinary output, continuous intravenous nitroglycerin (0.1-0.8 mg/h)
if systolic blood pressure was above 100 mm Hg, morphine sulphate 5-10 mg and weightadjusted doses of subcutaneous or intravenous heparin and aspirin if the ECG was suggestive of
ischemia. Secondary medical treatment was given on an 'as needed' basis including continuous
infusions of catecholamines (dopamine, dobutamine and adrenaline) if mean blood pressure was
below 60 mm Hg and/or urinary output decreased below 20 ml/h. Digitoxin and/or calcium
channel blockers were given in case of atrial tachyarrhythmia.
Ventilation support based on randomization include: Patients assigned to the conventional
Oxygen therapy group received oxygen by a Venturi mask 10 lit/min (controlled group).
In the noninvasive ventilation group, patients were ventilated using the bilevel positive airway
pressure mode (BiPAP Vision; Respironics Inc., Murrysville, PA). A face mask was used as the
first choice, but the nasal mask was optionally used if patients did not tolerate face mask.
NIPSV was initiated after starting standardized drug therapy on admission to the CCU. Pressure
support was started at an inspiratory positive airway pressure (PAP) of 10 cm H2O and an
expiratory PAP of 4 cm H2O in a spontaneous/timed mode. Pressure support ventilation can
supply up to 20 cm H2O inspiratory and up to 12 cm H2O expiratory pressure. Inspiratory
pressures were increased for each patient in increments of 2-3 cm H2O to obtain an respiratory
rate<20/min and resting of respiratory muscles. Slight expiratory PAP (4-7 cm H2O) was used to
increase PaO2, O2sat and to prevent atelectasis [14, 15]. All patients were given NIPSV for at
least 1 hour. Clinical stability was defined as an improvement in oxygenation (paO2 >60 mm Hg
or oxygen saturation >90% SaO2) with an oxygen flow rate <3 liters O2/min, a respiratory rate
<25 breaths/min or a reduction of at least 25% of baseline combined with the presence of a
normal breathing pattern and a heart rate <110 beats/min [22]. NIPSV was considered successful
when patients remained clinically stable after discontinuation of ventilation for more than 2
hours.
Intubation: intubation was performed if respiratory rate after 1 h of NPPV was >30 breaths/min,
persistent hypoxemia, in hemodynamic instability (systolic blood pressure <70 mmHg), in
agitation or worsened neurological status, inability to tolerate the mask or aspiration of gastric
content.
Statistic:\
All parameters are presented as means ± SD. after initiation of treatment, changes in
physiological variables, and arterial blood gas values were compared with the use of Leven and
Student's t-test. The primary analysis compared the rates of 7-day mortality in each group with
the need of tracheal intubation In two groups were matched in terms of Some qualitative factors
of the chi-square test and Fisher exact test was used. Due to the non-homogeneous distribution of
the outlined parameters, a non-parametric test (Mann-Whitney test) was used to assess the effect
of NIPSV on physiological parameters for the overall study P value of less than 0.05 was
considered to indicate statistical significance Software SPSS version 12 was used.
RESULTS:
During the 12-month study period89 consecutive patients with acute cardiogenic pulmonary
edema were admitted to the coronary care unit (CCU) of the Imam Ali Hospital of Kermanshah.
All patients were transported to the CCU ,emergency treatment included oxygen therapy (2-10
l/min) and sublingual nitroglycerin (0.8 mg) if systolic blood pressure was above 120 mm
Hg.However, 9 patients were excluded due to exacerbation COPD (n = 3), pneumonia (n = 2)
cardiogenic shock(3) and immediate need for intubation (n = 1). Therefore, the data reported are
based on the remaining 80 patients. The patients with inclusion criteria were randomly assigned to
receive either conventional Oxygen therapy 40 patients with Venturi mask (controlled group)or
noninvasive ventilation through a face mask 40 patients (NIV group).
Non-invasive ventilation was generally well tolerated. Only few side effects were observed, such
as skin erosions, claustrophobia and conjunctivitis. However, none of the subjects had to
discontinue NIPSV because of these side effects.
No significant differences between the two groups were shown in age, sex, presence of and
underlying diseases (P>0.05) ( table 1).
variable
Mean age
Female
Male
Heart failure
Diabetes mellitus
Hypertension
Old myocardial infarction
Controlled group
78.5
16
24
25%,
N=10
20%
N=8
27.5% N=11
27.5% N=11
NIV group
75.5
22
18
22.5% N=9
25% N=10
30% N=12
22.5% N=9
P Value
P>0.05
P>0.05
P>0.05
P>0.05
P>0.05
P>0.05
P>0.05
Table 1. Patient characteristics and underlying diseases etiology of ACPE
Fifteen patients (18.75%) had an acute MI and 5 patients (6.25%) had ischemic heart disease
(Unstable Angina) without a recent MI Other reasons for ACPE were Congestive heart
failure(25%) Tachyarrhythmia 3 patients (3.75%)and hypertension in 39 (48.25)%( table 2).
Variable
Hypertension
Tachyarrhythmia
Myocardial infarction
Congestive heart failure
Unstable Angina
Total
Controlled group
NIV group
18
21
2
1
9
6
9
11
2
3
40
40
Table 2. Causes of ACPE
P Value
P>0.05
P>0.05
P>0.05
P>0.05
P>0.05
Patients showed an initial and sustained improvement of the mean PaO2 and in both

groups NIPSV initiation significantly increased paO2 from a baseline level of 57 ± 5.7,
T0 to 66.6 ± 12, T15 .77± 12.8T30, and 87.4±15,8 T60 , and in controlled groups paO2
from a baseline level of 59±4,8 T0,60±5.3 T15, 62± 6.9 T30 and 64± 7,7 T60with
significant differences between two group (P<0.001).
O2sat at baseline in noninvasive group was 85± 5 and in controlled group was 87±3.9 in NIV
group increased O2sat inT15,T30 andT60 there was significant differences between two group.
Non – invasive ventilation led to a rapid improvement in oxygenation saturation in the first hour
( p= 0. 001 ) .
There was a significant increase of pH in both groups during the first 60minute the differences
between two groups was significant in NIV group (p<0.001).
Mean paCO2 at the time of hospital admission was 43.9 ± 7.6 mm Hg in niv group and43.7± 6.6
in controlled group. Of the 80 patients investigated, 30 were hypercapnic (paCO2 >45 mm Hg),
42 hypomanic (paCO2 <35 mm Hg) and 18 normocapnic (paCO2 35- 45 mm Hg).
The effects of NIV on arterial paCO2 levels in these two patient groups are shown in figure 2. In
patients with hypercapnic ACPE, paCO2 levels fell from54 .2 ± 8.6 mm Hg after NIV to 42.6 ±
7.6 mm Hg (p = 0.0025). There were no significant paCO2 changes in PaCo2 in two groups
(p=0.064).
variable
PH.O2
PH .NIV
O2Sat. O2
O2Sat. NIV
PaO2. O2
PaO2 NIV
PaCo2. O2
PaCo2. NIV
0 min
4.34±0.03
4.33±0.02
87±3.9
85±5
59± 5.7
57± 5.7
43.7 ±6.6
43.9± 7.6
15 min
4.35±0.03
4.35±0.01
87±4.4
89.8±4.9
60± 5.3
66.6± 12
43.2± 5.3
43.1± 5.2
30 min
4.37±0.02
4.35±0.02
90±3.2
92±4.6
62 ±6.9
77±12.8
43.2± 3.7
43.3± 3.5
60 min
4.37±0.03
4.37±0.04
91±3.8
96±3.6
64± 7.7
78.4 ±15.8
42.2 ±3.2
42.4± 3.1
P value
≤0.001
≤0.0001
≤0.001
0.064
Table 3. Arterial blood gas variables in patients before (T0) and after 15,30 and 60 min of
NIPSV therapy (mean ± SD)
Significant improvements were also noted for heart rate, at baseline heart rate in NIV group
was123± 8 vs 120± 8.4 in controlled ±group p=0.95, at 15 minutes (114± 11 in NIV group and
117± 13 in controlled group p=0.37), at 30 minutes (104± 11.8 in NIV group and 112± 13 in
controlled group p=0.008) and at 60 minutes (99± 14 in NIV group and109± 13 in controlled
group( p=0.001)
Decreased respiratory rate (RR) from 35 ± 2.9 to 24 ± 4.5 breaths/min at T60 in NIV group and
34± 3 to33± 4 in controlled group there was significant difference between two groups
(p=0.0001 fig. 1)
In NIV group systolic blood pressure at baseline was 154± 15 and in controlled group was154±
15(P=0.25), diastolic blood pressure was 87± 7.5 and in controlled group was 86± 8(P=0.4), at
60 minutes systolic blood pressure was122± 15 in NIV group and130± 15 in controlled group
(P=0.015), and diastolic blood pressure was 76± 6.6 in NIV group and79.5± 7.7 in controlled
group(P=0.048).Therefor there was not significant difference between two groups.
Variable
HR 02
HR NIV
RR 02
RR NIV
Sys BP 02
Sys BP NIV
Dias BP 02
Dias BP NIV
0Min
120±8.4
123± 8
34± 3
35 ±2.9
150 ±17
154 ±15
86± 8
87 ±7
60Min
109±13
99 ±14
33 ±4
24 ±4.5
130± 15
122 ±15
79 ±7
76± 6
P Value
0.001
0.0001
0.015
0.048
Table 4. Physiological variables in patients before (T 0) and after 60 and 60 min of NIPSV therapy (mean ± SD)
Length of CCU stay 2.8± 1.2 days in NIV group and 4.8± 1.5 days in controlled group there was
.) significant differences between two group (P<0.001
Recovery time was significantly shorter in the non – invasive ventilation group mean 42 ± 9.9vs
.) 131± 22.5 in controlled group (P= 0, 0001
Intubation: intubation was performed if respiratory rate after 1 h of NPPV was >35 breaths/min
persistent hypoxemia, in hemodynamic instability (systolic blood pressure <70 mmHg), in
Worsened neurological status, inability to tolerate the mask or aspiration of gastric agitation
content.
Endotracheal intubation was required due to persistently high or increasing respiratory rate
and/or progressive hypoxemia in 2 of the 40 patients (5%) treated in NIV group and 7of the 40
patients (17.5%) treated in controlled group. patients who required intubation had lower paCO2,
lower serum bicarbonate levels and a lower BPsys than patients who were not intubated (table 3)..
The in-hospital mortality was 6.25 %( n =5) 4 patients in controlled group and one patient in
NIV group. Death occurred in 4 of the 5 patients (80%) who were intubated and in 1 other
patient. Four of the 5 patients (80%) who died in hospital had a paCO2 <35 mm Hg at the time of
admission.Causes of death were cardiogenic shock in (n = 2), nosocomial infections (n = 1),
multiorgan failure (n = 1) and fatal stroke (n = 1). However, there was significant difference
between the mortality rate in two groups P<0.001
variable
CCU stay (day)
Recovery time (min)
Intubation
Hospital mortality
4.8± 1.5
131± 22.5
17.5% N=7
10%
N=4
NIV group
2.8± 1.2
42± 9.9
5% N=2
2.5% N=1
P Value
P<0.001
P<0.0001
P<0.001
P<0.001
Table 5. CCU stay, Recovery time , number of Intubation and Hospital mortality in two groups
In this study , Noninvasive pressure support ventilation( NIPSV) by Bi-Positive Airway Pressure
mode( BIPAP) rapidly increased PaO2, pH and O2Saturation in patients with respiratory failure
due to ACPE, while respiratory rate, blood pressure, and heart rate significantly decreased.
The mean age of our study was 75 years which is consistent with those described in other studies
with a range of 69-80 years, implying that the elderly are commonly affected.23,24
According to pre-determined intubation criteria, only 11.25% of the patients with acute
respiratory failure due to ACPE required endotracheal intubation and invasive mechanical
ventilation. All those patients who required intubation were hypocapnic with evidence of acute
respiratory alkalosis at the time of presentation. In contrast, none of the patients with
hypercapnic ACPE and severe respiratory acidosis required intubation. Therefor patients who
were intubated had a lower systolic blood pressure than those who were not. Similar findings
were observed with respect to in-hospital mortality.
This study confirms previous reports using NIPSV in the treatment of ACPE [16, 24, 25, 26, 27,
28].
In agreement with this study, Noninvasive pressure support ventilation( NIPSV) effectively
improved alveolar ventilation and gas exchange and decreased respiratory failure. Wigder et al.
(29) studied patients with ACPE who were offered NIPSV at the emergency department as a
first-line treatment in addition to maximum conventional treatment . They reported a success rate
of 90%, with rapid improvement in hemodynamic and oxygenation parameters after 60 min.
In another report, Masip et al. [16] tested NIPSV versus conventional oxygen treatment in
ACPE and observed a rapid improvement in arterial oxygenation with NIPSV compared to
oxygen therapy alone. In accordance with our findings, they observed a very good response in
patients presenting with hypercapnia on admission.
There are of some clinical evidence, since respiratory failure in ACPE is not directly related to
hypoxemia and cannot be reversed with oxygen therapy alone. Therefor primary goal of NIPSV
in ACPE is support the respiratory muscle activity and decrease respiratory rate that will improve
the efficacy of the patient's effort and allows a reduction in the respiratory work [30,31,32,33],
resulting increased spontaneous tidal volume and reduced respiratory rate. Based on these
mechanisms, NIPSV therapy does offer great advantages in patients with cardiogenic pulmonary
edema and acute respiratory acidosis.
The only other study on patients with hypocapnia in ACPE was performed by Rusterholtz et al.
[26]. In support of our findings, the authors found an association between low paCO2 levels and
NIPSV failure resulting in higher intubation rates.
In the present report, we have searched the need for intubation and in-hospital mortality. Need
for intubation were associated with hypocapnia and low BPsys
There are several factors that need to be considered when interpreting these findings. A low
paCO2 might be secondary to an underlying metabolic acidosis, which was supported by blood
gas analyses in our patients. Hypocapnia might also reflect discomfort of the patient resulting in
hyperventilation and respiratory muscle fatigue, but the respiratory rate at presentation was not
different between patients who were intubated and those who were not. Furthermore, a low
paCO2 might represent subjects who were able to ventilate adequately, and the action of NIPSV
to increase ventilation did not provide further advantage. Although hypocapnia induced by
hyperventilation may increase alveolar oxygen tension, some important pulmonary effects of
hypocapnic alkalosis such as bronchoconstriction [34] and attenuation of hypoxic pulmonary
vasoconstriction [35] result in a net decrease of arterial oxygenation.
In addition, hypocapnia decreases myocardial oxygen delivery during increasing oxygen demand
[29] and increased systemic vascular resistance [36, 37]. Based on these mechanisms,
myocardial function might have been impaired due to hypocapnia, but hypocapnia might also
have been an indicator of a worse cardiac function per se [38]. This link between ventilatory
parameters and hemodynamic variables suggests that any changes in paCO2 might reflect
.changes in myocardial function and vice versa
However, the severity of respiratory distress in our patients at the time of presentation might
have been an indication for intubation itself [26]. Consequently, intubation and subsequent
complications of invasive ventilation might have been avoided in 24 of 28 patients treated with
NIPSV.
We didn’t observed any new Myocardial infarction in two groups.
In contrast to Mehta et al. [25] we found no association between the occurrence of MI and the
use of NIPSV. The authors reported a higher incidence of MI among patients treated with NIPSV
(71%) in contrast to those receiving continuous PAP ventilation (31%). They suggested that a
rapid decrease in BPsys, probably due to NIPSV, might have extended the areas of myocardial
ischemia in progress. In contrast to that report, Masip et al. [16] observed no increased incidence
of myocardial ischemia with the use of non-invasive ventilation, confirming our data.
However, we have found that patients with a lower BPsys were more likely to require intubation. .
During mechanical ventilation, increases in intrathoracic pressure are known to have differential
effects on cardiac output, depending on the initial preload and contractile state of the
myocardium [33]. Therefore, we cannot reject the possibility that lowered cardiac output due to
raised intrathoracic pressure caused by NIPSV resulted in a relative decrease of myocardial
perfusion and contributed to the bad outcome observed in patients with hypocapnia.
On the contrary, Nava et al (17) in a multicenter study randomized 130 patients to medical
therapy or BIPAP. BiPAP improved hypoxemia, respiratory rate, and dyspnea significantly faster
than conventional treatment by oxygen therapy but the intubation rate, hospital mortality, and the
duration of hospital stay were similar in the two groups. However, in the subgroup of
hypercapnic patients, intubation rates were lower in the BiPAP group than oxygen therapy.
However, we have found that patients with a lower BPsys were more likely to require intubation.
During mechanical ventilation, increases in intrathoracic pressure are known to have differential
effects on cardiac output, depending on the initial preload and contractile state of the
myocardium [39]. Therefore, we cannot reject the possibility that lowered cardiac output due to
raised intrathoracic pressure caused by NIPSV resulted in a relative decrease of myocardial
perfusion and contributed to the bad outcome observed in patients with hypocapnia.
On the contrary, Nava et al (40) in a multicentre study randomised 130 patients to medical
therapy or BIPAP. BiPAP improved hypoxaemia, respiratory rate, and dyspnea significantly
faster than did oxygen therapy but the intubation rate, hospital mortality, and the duration of
hospital stay were similar in the two groups. However, in the subgroup of hypercapnic patients,
intubation rates were lower in the BiPAP group than oxygen therapy.
The results of this study show that the use of NIV in patients with severe acpe decreased the need
for intubation, endotracheal intubation was required in 2 (5%) of 40 patients assigned NIPSV
and in seven (17.5%) of 40 assigned conventional oxygen therapy (p=0.001).
In a systematic Review and Meta-analysis by Masip et al (40) NIV and Conventional Oxygen
Therapy. Pooled data included 727 patients. Overall, immediate treatment with noninvasive
ventilation in patients with acute cardiogenic pulmonary edema have reported a 47% reduction in
mortality (40). (P<0.001)15
In summary, our study shows that the application of NIPSV was successful in improving
oxygenation and respiratory distress in patients with ACPE. With respect to outcome
measurements, e.g. intubation rate and in-hospital mortality, patients with hypercapnia and
respiratory acidosis seem to benefit most. Hypocapnia and low BPsys, however, might be
associated with higher intubation and in-hospital mortality rates. Based on our and previously
published findings, we conclude that NIPSV should be considered especially in patients with
hypercapnic respiratory failure due to ACPE, and paCO2 levels should be monitored closely in
order to assess the response to treatment.
Non-invasive ventilation (NIV) has been shown to be effective in acute respiratory failure of
various etiologies’ in different health care systems and ward settings. It should be seen as
complementary to invasive ventilation and primarily a means of preventing some patients from
deteriorating to the point at which intubation is needed.
Generally avoidance of intubation and complications associated with invasive mechanical
ventilation appear to be the main reasons of improved survival. Our data provide strong evidence
for the use of NIV as a first-line intervention in patients with severe ACPE in the absence of
contraindications for using this technique it is best initiated early before assisted ventilation is
mandatory, although it has been shown to be effective even in very sick patients. Important
benefits include the avoidance of endotracheal tube associated infections, which carry an
important morbidity and mortality, and a reduction in hospital stay.
The most important ingredient for an acute NIV service is a well-trained enthusiastic ward team.
In addition to an appropriate selection of patients and the experience of the attending clinicians
and nurses in the use of NIV, the type of ventilator used may be one of the possible reasons to
explain the efficacy of NIV. In this study, we used a ventilator specifically designed for NIV,
able to provide high levels of oxygen, a proper maintenance of the positive pressure levels by
leak control.
Summary
 Noninvasive ventilation is well suited for patients with cardiogenic pulmonary edema.
 The greatest benefits are realized in relief of symptoms and dyspnea.
 A decrease in intubation and mortality rates are the advantages of NIV.
 Patients with hypercapnic respiratory acidosis may derive the greatest benefit from
noninvasive ventilation.
 Importantly, adjust to standard therapy, including diuretic and nitroglycerin.
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