Noninvasive Ventilation Versus Conventional Oxygen Therapy for Treatment Acute Cardiogenic

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

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Emaih;[email protected]

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

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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 40- 320 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 weight- adjusted 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 [1 4, 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 Controlled group NIV group P Value Mean age 78.5 75.5 P>0.05 Female 16 22 P>0.05 Male 24 18 P>0.05 Heart failure N=10 ,25% N=9 22.5% P>0.05 Diabetes mellitus N=8 20% N=10 25% P>0.05 Hypertension N=11 27.5% N=12 30% P>0.05 Old myocardial infarction N=11 27.5% N=9 22.5% 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

P Value NIV group Controlled group Variable P>0.05 21 18 Hypertension P>0.05 1 2 Tachyarrhythmia P>0.05 6 9 Myocardial infarction P>0.05 11 9 Congestive heart failure P>0.05 3 2 Unstable Angina 40 40 Total Table 2. Causes of ACPE

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 P value min 60 min 30 min 15 min 0 variable 4.37±0. 4.37±0. 4.35±0. 4.34±0. PH.O2 0.001≥ 03 02 03 03 4.37±0. 4.35±0. 4.35±0. 4.33±0. PH .NIV 04 02 01 02 91±3.8 90±3.2 87±4.4 87±3.9 O2Sat. O2 ≥ 96±3.6 92±4.6 89.8±4. 85±5 O2Sat. NIV 0.0001 9 7.7 64± ±6.9 62 5.3 60± 5.7 59± PaO2. O2 0.001≥ 78.4 77±12. 66.6± 5.7 57± PaO2 NIV ±15.8 8 12 42.2 43.2± 43.2± 43.7 PaCo2. O2 0.064 ±3.2 3.7 5.3 ±6.6 42.4± 43.3± 43.1± 43.9± PaCo2. NIV 3.1 3.5 5.2 7.6

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

in controlled group p=0.37), at 30 minutes (104± 11.8 in NIV group and 112± 13 in 13 117±

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

P Value 60Min 0Min Variable 109±13 120±8.4 HR 02 0.001 ±14 99 8 123± HR NIV ±4 33 3 34± RR 02 0.0001 ±4.5 24 ±2.9 35 RR NIV 15 130± ±17 150 Sys BP 02 0.015 ±15 122 ±15 154 Sys BP NIV ±7 79 8 86± Dias BP 02 0.048 6 76± ±7 87 Dias BP NIV

(Table 4. Physiological variables in patients before (T0) 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 agitation Worsened neurological status, inability to tolerate the mask or aspiration of gastric .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 NIV group P Value (CCU stay (day 1.5 4.8± 1.2 2.8± P<0.001 (Recovery time (min 22.5 131± 9.9 42± P<0.0001 Intubation N=7 17.5% N=2 5% P<0.001 Hospital mortality N=4 10% N=1 2.5% 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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