Intervention Review

You have free access to this content

Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema

  1. Flávia MR Vital1,*,
  2. Magdaline T Ladeira2,
  3. Álvaro N Atallah3

Editorial Group: Cochrane Heart Group

Published Online: 31 MAY 2013

Assessed as up-to-date: 5 APR 2011

DOI: 10.1002/14651858.CD005351.pub3


How to Cite

Vital FMR, Ladeira MT, Atallah ÁN. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD005351. DOI: 10.1002/14651858.CD005351.pub3.

Author Information

  1. 1

    Muriaé Cancer Hospital, Department of Physiotherapy, Muriaé, Minas Gerais, Brazil

  2. 2

    Escola Paulista de Medicina, Universidade Federal de São Paulo, Department of Internal and Therapeutic Medicine, São Paulo, São Paulo, Brazil

  3. 3

    Centro de Estudos de Medicina Baseada em Evidências e Avaliação Tecnológica em Saúde, Brazilian Cochrane Centre, São Paulo, São Paulo, Brazil

*Flávia MR Vital, Department of Physiotherapy, Muriaé Cancer Hospital, Cristiano Ferreira Varella, 555, Muriaé, Minas Gerais, Brazil. fvital@fcv.org.br. flaviavital@bol.com.br.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 31 MAY 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Agmy 2008

MethodsSingle centre randomised controlled trial, parallel design, unblinded, using ITT approach. No patients were lost to follow up. Setting: RICU or CCU.


Participants129 participants. Causes: systolic, diastolic or valvular heart failure.


InterventionsCPAP group. N=44.
BILEVEL group. N=44.
Control group: standard medical care+O2 mask (High flow facemask - 60%). N= 41.
Co-intervention: morphine, diuretics, ACE and nitrates.


Outcomes
  1. Mortality
  2. Need for tracheal intubation
  3. Arterial blood gases (PaO2, PaCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Length of hospital stay
  6. Length of ICU stay
  7. Intrapulmonary shunt
  8. A-aoxygengradient
  9. Cardiac output
  10. Intolerance


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Bautin 2005

MethodsRandomised controlled trial, parallel design, unblinded, using ITT approach. No patients were lost to follow up. Setting: ICU.


Participants22 participants, with age 63.4±4.6 years in BILEVEL group and 64.3±5.6 in standard medical care group. All patients underwent cardiosurgery procedure (6 - CABG, 16 - valves replacement). Causes: HF, Mitral valve dysfunction and arrhythmias.


InterventionsBILEVEL group: EPAP=5.1±0.3 cm H2O; e IPAP= 9.8±1.1 cmH2O. N=11.
Control group: standard medical care + O2 mask. N= 11.
Co-intervention: not related.


Outcomes
  1. Mortality
  2. Need tracheal intubation
  3. Arterial blood gases (PaO2, PaCO2) and pH
  4. Vital signs (BR, BP, HR)
  5. Length of hospital stay
  6. Length of ICU stay
  7. Incidence of acute myocardial infarction (follow-up)
  8. Droupouts/ withdrawal
  9. Side effects
  10. Treatment failure


NotesMask: full face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Bellone 2004

MethodsSingle centre randomised controlled trial (used a computer-generated random number sequence in closed envelopes with identification numbers that were stored in emergency room), parallel design, unblinded, using ITT approach. No patients were lost to follow up. Written consent was obtained from the patients' relatives at the start of the protocol. Setting: emergency department.


Participants46 participants (23 males and 23 females), with age 77.3±7.3 years in BILEVEL group and 76.8±7 in CPAP group. Diagnosis criteria: bilateral rales , and typical findings of congestion on chest radiograph, without a history suggesting pulmonary aspiration or pneumonia, SaO2<90% with O2 mask>5l/min via reservoir face mask, dyspnoea, BR>30b/min, use accessory muscles or paradoxical abdominal motion in association with tachycardia, HR>100b/min, cardiac gallops. History: heart failure, coronary artery disease, diabetes, hypertension, COPD, chronic atrial fibrillation and chronic kidney failure. Causes: respiratory infections, hypertension, tachyarrhythmia, other. Excluded patients: patients required endotracheal intubation immediately or already intubated, presenting a respiratory or cardiac arrest, cardiogenic shock (SBP<90mmHg), or at the time of admission had an acute coronary syndrome, patients unresponsive, with diagnosis of pneumonia, agitated, and unable to cooperate or if they had any condition that precluded application of a face mask.


InterventionsCPAP group: PEEP=10 cmH2O. N=22, TIME=103±45 minutes.
BILEVEL group: EPAP=5 cm H2O; e IPAP= 15 cm H2O initially, and then adjusted to obtain a tidal volume of more than 400ml, without leakage. N=24, time= 98±39 minutes.
Co-intervention: morphine sulfate, furosemide, sodium nitroprusside, glyceryl trinitrate,digoxin, oxygen therapy to obtain SaO2>90%.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases (PaCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Incidence of acute myocardial infarction (follow-up)
  6. Droupouts/ withdrawal


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported

Adherence to the intention-to-treat principleLow risk

Bellone 2005

MethodsSingle centre randomised controlled trial (used a computer-generated random number sequence in closed envelopes with identification numbers that were stored in emergency room), parallel design, unblinded, using ITT approach. No losses to follow up. Written consent was obtained from the patients' relatives at the start of the protocol. Setting: Niguarda Hospital Emergency Department - Milan - Italy.


Participants36 participants (12 males and 24 females), with age 76.8±6.6 years in BILEVEL group and 76.8±6.9 in CPAP group. Diagnosis criteria: typical findings of congestion on chest radiograph and widespread rales without a history suggesting pulmonary aspiration or pneumonia, SaO2<90% with O2 mask >5l/min, dyspnoea, BR >30b/min, use accessory muscles or paradoxical abdominal motion in association with tachycardia, HR>100b/min, cardiac gallop. History: heart failure, acute myocardial infarction, diabetes, hypertension. Causes : respiratory infections, hypertension, tachyarrhythmia, myocardial infarction, others. Excluded patients: patients with PaCO2 <45mmHg, required endotracheal intubation or already intubated, presenting a respiratory or cardiac arrest, cardiogenic shock (SBP<90mmHg), severe renal failure, presenting clinical and history findings of chronic obstructive pulmonary disease or previously enrolled in other studies.


InterventionsCPAP group: PEEP=10 cmH2O. N=18, TIME=220±82 minutes.
BILEVEL group: EPAP=5 cm H2O; e IPAP= 15 cm H2O initially, and then adjusted to obtain a tidal volume of more than 400ml, without leakage. N=18, time= 205±68 minutes.
Co-intervention: morphine, furosemide, sodium nitroprusside, glyceryl trinitrate,digoxin, oxygen therapy to obtain SaO2>90%.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases (PCO2, pH)
  4. Vital signs (BR)
  5. Droupouts/ withdrawals


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Bersten 1991

MethodsSingle centre randomised controlled trial (random selection of a coloured cap), parallel design, unblinded, lack of intention-to-treat analysis confirmed on study assessment. Loss to follow up: no patients in standard medical care group and one patient in CPAP group. Patients or next-of-kin were aware through informed consent. Setting: emergency department or ward to the intensive care unit (ICU).


Participants40 participants (13 males and 27 females), with age 75±6 years in standard medical care group and 76±6 in CPAP group. Diagnosis criteria: dyspnoea of sudden onset with typical finds on chest radiographs and widespread rales without a history suggesting pulmonary aspiration or infection, jugular venous pressure elevated and third heart sound. Causes: acute myocardial infarction, myocardial ischaemia, congestive heart failure. Excluded patients: acute myocardial infarction with shock, SBP<90mmHg, severe stenotic valvular disease, chronic airflow obstruction with known carbon dioxide retention.


InterventionsCPAP group: PEEP= 10 cmH2O. N=19, TIME=9.3±4.9 hours.
Control group: O2 mask + standard medical care. N= 20.
Co-intervention: furosemide, morphine, diazepam, nitroglycerin.


Outcomes
  1. Mortality,
  2. Tracheal intubation rate
  3. Arterial blood gases ( PaO2, PaCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Treatment failure
  6. Side-effects
  7. Droupouts/ withdrawals
  8. Length of hospital stay
  9. Length of ICU stay


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High risk

Allocation concealment (selection bias)High risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported

Adherence to the intention-to-treat principleHigh risk

Crane 2004

MethodsMulticenter randomised controlled trial (2 university hospitals). Randomization procedure: random numbers produced by Microsoft Excel, assignments were concealed in an opaque envelope. Parallel design, unblinded, using ITT approach. No reported loss to follow up. Patients or next-of-kin were aware through informed consent, but in 17 cases, the patient gave verbal consent. Setting: emergency department.


Participants60 participants (23 males and 37 females), with age 74.6±11.1 years in standard medical care group, 74.9±12.2 in CPAP group and 76±8.4 in BILEVEL group. Diagnosis criteria: BR >23 bpm, Rx consistent with pulmonary oedema, pH <7,35, widespread pulmonary crepitations and diaphoresis. History: heart failure, ischaemic heart disease, DM, Hypertension, COPD. Excluded patients: Hypotension (SBP<90mmHg), T>38oC, patients requiring thrombolysis for myocardial infarction or dialysis for renal impairment, patients with impaired consciousness or with dementia.


InterventionsCPAP group: PEEP=10 cm H2O. N=20.
BILEVEL group: EPAP=5 cm H2O; e IPAP= 15 cmH2O. N=20.
Control group: standard medical care+O2 mask (To maintain SaO2 >90%). N= 20.
Co-intervention: furosemide, nitrates and diamorphine (without restriction)


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases ( PaO2, PCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Incidence of acute myocardial infarction (follow-up)
  6. Compliance of patient
  7. Treatment failure
  8. Side-effects


NotesMask: full face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported

Adherence to the intention-to-treat principleLow risk

Delclaux 2000

MethodsMulticenter randomised controlled trial (6 centres). Randomization procedure: randomisation computer-generated; sealed envelopes were used to randomly assign patients to their treatment group. Parallel design, using ITT approach. Blindness only of the investigators. No patient were lost to follow-up. Informed consent was obtained of the all patients. Setting: intensive care unit (ICU).


Participants123 participants, but only a subgroup with 42 participants had CPO. Diagnosis criteria: acute respiratory insufficiency (PaO2/FiO2<300 with O2 =10l/min, bilateral lung infiltrates on a posteroanterior chest radiograph, randomisation within 3 hours after the criteria were first fulfilled. Because a cardiogenic mechanism contributing to the pulmonary oedema might have had a substantial influence on the study results, the randomisation was stratified based on whether there was an underlying cardiac disease. Causes: ischaemia, arrhythmias, fluid overload, hypertension, valvular disease, pneumonia, aspiration, systemic inflammatory response syndrome (SIRS), shock, other. Excluded patients: younger than 18 years, intubation was refused or contraindicated, history of COPD, acute respiratory acidosis (defined as a pH<7,30 and PaCO2 > 50 mmHg, systolic blood pressure less than 90 mmHg under optimal therapy (fluid repletion), ventricular arrhythmias, coma or seizures, life-threatening hypoxaemia, use of epinephrine or norepinephrine, and the inability to clear copious airway secretions.


InterventionsCPAP group: PEEP= 7,5 cmH2O with increase or decrease 2,5 cmH2O. N=22, TIME=6 hours or more.
Control group: standard medical care+O2 mask. N= 20.
Co-intervention: diuretics, antibiotics.


Outcomes
  1. Mortality
  2. Tracheal intubation rate


NotesMask: full face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasLow risk

Adherence to the intention-to-treat principleLow risk

Ferrari 2007

MethodsSingle centre randomised controlled trial (according to a random sequence previously generated from a table of random numbers, the assignments were placed in closed boxes, with identification numbers, stored in the HDU), parallel design, unblinded, lack of intention-to-treat analysis. Two patients were lost (Two patients refused) to follow up. Written consent was obtained from the patients. Setting: High Dependency Unit (HDU) of the Emergency Department.


Participants52 participants (23 males and 29 females), with age 74.2±9.7 years in BILEVEL group and 76.7±9.2 in CPAP group. Diagnosis criteria: rapid onset of symptoms,severe dyspnoea at rest, respiratory rate 30 breaths/min, use of accessory respiratory muscles, oxygen saturation by pulse oximetry (Spo2) 90% with a fraction of inspired oxygen (Fio2) of 60% via a Venturi mask, radiologic findings of ACPE. Causes : hypertensive crisis, tachyarrhythmia, chronic Ischaemic cardiomyopathy, dilated cardiomyopathy and valvular heart disease. Excluded patients: acute coronary syndrome on hospital admission,18 haemodynamic instability (systolic BP 90 mm Hg with dopamine or dobutamine infusion 5 g/kg/min) or life-threatening arrhythmias, need for immediate endotracheal intubation (respiratory arrest, bradypnoea, or gasping for air), inability to protect the airways, impaired sensorium (unconsciousness or agitation), inability to clear secretions, respiratory tract infection, recent oesophageal/gastric surgery, GI bleeding, facial deformities, hematologic malignancy or cancer with an Eastern Cooperative Oncology Group performance status 2, chronic respiratory failure necessitating long-term oxygen therapy, diagnosis of myocardial infarction, pulmonary embolism, pneumonia, exacerbation of COPD, pneumothorax in the previous 3 months, and denial or refusal of intubation.


InterventionsCPAP group: PEEP = 8.8±1.9 cmH2O. N = 27, TIME= 8.1±8.3 hours.
BILEVEL group: EPAP = 7±1.2 cm H2O e IPAP= 15±3.1 cmH2O . N=25, TIME= 6.0±4.7 hours.
Co-intervention:


Outcomes
  1. Rate of acute myocardial infarction
  2. Mortality
  3. ETI
  4. Duration of ventilatory assistance
  5. HDU length of stay
  6. Hospital length of stay
  7. Arterial blood gases (PaCO2, pH, PaO2/FiO2, SaO2)
  8. Vital signs (BR, HR)


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported

Adherence to the intention-to-treat principleHigh risk

Ferrari 2010

MethodsMulticenter (3 - Italy) randomised controlled trial (according to a random sequence previously generated from a table of random numbers, the assignments were placed in closed boxes, each with an identification number and were stored in the ED), parallel design, unblinded, using intention-to-treat analysis. Written consent was obtained from patients’ next of kin if patients were unable to give informed consent due to the severity of their disease. Setting: Emergency Department.


Participants80 adults participants with age 76.55±9.48 years in BILEVEL group and 77.25±9,17 in CPAP group, with acute respiratory failure due to severe ACPE. Diagnosis criteria: severe dyspnoea at rest, respiratory rate > 30 breaths/min, use of accessory respiratory muscles, PaO2/FiO2 < 200 despite oxygen via Venturi mask with a FiO2 of 60%, radiologic findings of ACPE. Causes : hypertensive crisis, dysrhythmias, UA/NSTEMI, respiratory infections. Exclusion criteria: STEMI (patients with unstable angina/Non-ST elevation MI were included in the study protocol),haemodynamic instability (systolic arterial pressure 90 mmHg), need for immediate ETI (respiratory arrest, bradypnoea), Inability to protect the airways, impaired sensorium (severe agitation or unconsciousness), COPD, exacerbation, pulmonary embolism, pneumonia, recent oesophageal-gastric surgery, gastrointestinal bleeding, facial deformities, hematological malignancy or cancer with ECOG performance status > 2.


InterventionsCPAP group: PEEP = 8.88±1.77 cmH2O. N = 40, TIME = 8.46±7.14 hours.
BILEVEL group: EPAP = 6.75±1.44 cmH2O e IPAP= 14±3.11 cmH2O . N=40, TIME = 5.91±4.01 hours.
Co-intervention: furosemide, glycerol trinitrate, sodium nitroprusside, morphine hydrochloride.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Duration of ventilatory assistance
  4. Hospital length of stay
  5. Arterial blood gases (PaCO2, PaO2/FiO2, SaO2) and pH
  6. Vital signs (BP, BR, HR)


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot reported if there were drop-outs over the monitoring of patients.

Selective reporting (reporting bias)High risk

Detection biasUnclear riskNot reported

Adherence to the intention-to-treat principleLow risk

Ferrer 2003

MethodsMulticenter (3 - Spain), prospective, randomised (randomly allocated within 24-hours, using a computer-generated table for each centre), controlled trial, parallel-group, using intention-to-treat analysis. No patient were lost to follow-up. Informed consent was obtained in all cases. Setting: ICU.


ParticipantsGroup of patients with acute hypoxaemic respiratory failure whose sub-group contained 30 patients with pulmonary oedema cardiogenic (10 males and 20 females), with age 76±9 years in standard medical care group and 71±13 in BILEVEL group. Diagnosis criteria: dyspnoea of sudden onset with physical findings consistent with pulmonary oedema, such as widespread rales with or without third heart sound, and typical findings of congestion on a chest x-ray. Exclusion criteria: hypercapnia (PaCO2 of more than 45 mm Hg) on admission; need for emergency intubation; recent oesophageal, facial, or cranial trauma or surgery; severely decreased consciousness (a Glasgow coma score of 11 or less); severe haemodynamic instability despite fluid repletion and use of vasoactive agents; a lack of cooperation; tracheotomy or other upper airway disorders; severe ventricular arrhythmia or myocardial ischaemia; active upper gastrointestinal bleeding; an inability to clear respiratory secretions; and more than one severe organ dysfunction in addition to respiratory failure.


InterventionsBILEVEL group. N=15.
Control group: standard medical care + O2 mask (To maintain SaO2 >92%). N= 15.


Outcomes
  1. Tracheal intubation rate
  2. Mortality
  3. ICU length of stay
  4. Hospital length of stay
  5. Droupouts/ withdrawals
  6. Side-effects
  7. Treatment failure
  8. Arterial blood gases (PaCO2, pH, PaO2/FiO2, SaO2)
  9. Vital signs (BR, BP, HR)


NotesMask: face mask or nasal mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskNot submitted multiple planning outcomes reported on results.

Detection biasUnclear riskNot reported

Adherence to the intention-to-treat principleLow risk

Fontanella 2010

MethodsRandomised controlled trial. Losses to follow up not reported. Informed consent not described. Setting: Cardiac Care Unit (CCU).


Participants40 participants with age 80±7 in CPAP group and 76±9 in BILEVEL group.Diagnosis criteria: patients with acute cardiogenic pulmonary oedema.


InterventionsCPAP group: PEEP = 8±2 cmH2O. N = 21.
BILEVEL group: EPAP = 10±2 cmH2O e IPAP= 18±3 cmH2O . N=19.
Co-intervention: ?


Outcomes
  1. Tracheal intubation rate
  2. Mortality
  3. ICU length of stay
  4. Arterial blood gases (PaO2, pH, PaO2/FiO2, SaO2)
  5. Vital signs (BR, BP, HR)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot reported if there were drop-outs over the monitoring of patients.

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Frontin 2010

MethodsSingle centre (France) randomised controlled trial (by balanced blocks of random numbers was provided by telephone using sealed opaque envelopes), parallel design, unblinded, not using ITT approach by Cochrane - All patients after randomisation. Two patients (in the CPAP group) refused the ongoing use of their data once their condition stabilised and were not analysed. Informed consent was obtained from patients or their surrogates. Setting: out-of-hospital medical emergencies is the responsibility of the "Service d'Aide Médicale Urgente" (SAMU) and continued on ICU.


Participants124 participants randomised, 122 analysed (52 males and 70 females), with age 79.3±10.5 years in standard medical care group and 79.4±10.7 in CPAP group. Inclusion criteria: 18 years or older with clinical symptoms of ACPE such as orthopnoea, diffuse crackles without evidence of pulmonary aspiration or infection, pulse oximetry (SpO2) less than 90% and a respiratory rate greater than 25 breaths per minute. Excluded patients: cardiovascular collapse or an impaired level of consciousness, acute myocardial infarction, or if they had an immediate need for intubation. Patient with a history of gastric surgery (b8 days) and patients vomiting were also excluded


InterventionsCPAP group: PEEP= 10 cmH2O. N=60.
Control group: standard medical care+O2 mask. N= 62.
Co-intervention: furosemide - 1mg/Kg, morphine pre-hospital, isosorbide dinitrate injections was 4 (range, 3-5) in both groups.


Outcomes
  1. Mortality 30 days
  2. Tracheal intubation rate
  3. Arterial blood gases (PaO2, PaCO2)
  4. Vital signs (BR, BP, HR)
  5. Side-effects
  6. Intensive care unit (ICU) length of stay
  7. Length of hospital stay


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleHigh risk

Gray 2008

MethodsMulticenter, open, prospective, randomised, controlled trial, parallel-group trial with three treatment groups:
standard oxygen therapy, CPAP, and bilevel NIPPV. Patients were randomly assigned to one of the three treatments at a 1:1:1 ratio with the use of a 24 hour telephone randomisation service. The randomisation sequence was stratified according to centre, with variable block length. Lack of intention-to-treat analysis. Eighty-seven patients were excluded after randomisation because of ineligibility or previous recruitment into the trial. Informed written or witnessed oral consent from the patient or relative was obtained. Setting: emergency department.


Participants1156 participants, 56.9% were women, with age 79±9 years in standard medical care group and 78±10 in CPAP group and 77±10 in BILEVEL group. Diagnosis criteria: age of more than 16 years, a clinical diagnosis of acute cardiogenic pulmonary oedema, pulmonary oedema shown by a chest radiograph, a respiratory rate of more than 20 breaths per minute, and an arterial hydrogen ion concentration of greater than 45 nmol per litre (pH <7.35). Excluded patients: patients requirement for a lifesaving or emergency intervention, such as primary percutaneous coronary intervention; inability to give consent; or previous recruitment into the trial.


InterventionsCPAP group: PEEP= 10±4 cmH2O. N=346. Time = 2.2±1.5hours.
Bilevel NPPV group: EPAP= 7±3 cm H2O e IPAP= 14±5 cmH2O. N=356. Time= 2.0±1.3 hours.
Control group: standard medical care + O2 mask with a reservoir. N= 367.
Co-intervention: nitrates, diuretics and opioids.


Outcomes
  1. 7-day mortality
  2. 7-day tracheal intubation rate
  3. 30-day mortality
  4. Admission to the critical care unit
  5. Arterial blood gases ( PaO2, PaCO2, pH)
  6. Vital signs (BR, BP, HR)
  7. Incidence of acute myocardial infarction
  8. Compliance of patients with NPPV
  9. Side-effects and complications
  10. Length of hospital stay
  11. PEEP levels, PS levels and bilevel NPPV vs CPAP.
  12. Duration of therapy.


NotesAlthough the study reports that held ITT, analyses submitted have not included all randomised patients (follow-up bias), as well as, it was not described as the total distribution of randomisation by group. Results were presented in the format completely different from other studies included, making impossible their inclusion in meta-analyses (variables dicotômicas acute myocardial infarction and Intolerance to the allocated treatment not possessed N total to perform ITT or were analysed in times different from those envisaged in this review - mortality and intubation in 7 or 30 days). Continuous variables were presented just as mean value of the difference between 0 and 1 hour after the intervention and not as mean and standard deviation. However the author, although asked, did not send the data in the format required to include in Meta-analysis.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasLow risk

Adherence to the intention-to-treat principleHigh risk

Kelly 2002

MethodsSingle centre randomised controlled trial (by balanced blocks using sealed envelopes), parallel design, unblinded, using ITT approach. No patients were lost to follow up. Informed consent was obtained of the patients. Setting: emergency department and continued in the high dependency unit.


Participants58 participants (26 males and 32 females), with age 78±2 years in standard medical care group and 77±2 in CPAP group. Diagnosis criteria: acute onset of breathlessness, BR>20bpm, bilateral basal crackles or chest auscultation, Rx typical of pulmonary oedema. Causes: left ventricular systolic dysfunction and hypertensive crisis; the CPAP group had more severe disease with a slightly greater acidosis and hypercapnia. Excluded patients: patients with radiograph consistent with pneumonia or pneumothorax, or if they had received pre-hospital treatment with intervention other than oxygen, diuretics or opiates.


InterventionsCPAP group: PEEP= 7.5 cmH2O. N=27, TIME= minimum of 6 hours.
Control group: standard medical care+O2 mask. N= 31. (FiO2=60%).
Co-intervention: furosemide, morphine sulfate, nitrate.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases ( PaO2, PaCO2)
  4. Vital signs (BR, BP, HR)
  5. Incidence of acute myocardial infarction (follow-up)
  6. Treatment failure
  7. Side-effects
  8. Droupouts/ withdrawals
  9. Length of hospital stay


NotesMask: full face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported

Adherence to the intention-to-treat principleLow risk

L'Her 2004

MethodsMulticenter randomised controlled trial, in three teaching hospitals in France. The randomisation protocol was computer generated and equalised in groups of 10 patients, parallel design, unblinded, using ITT approach. No patients were lost to follow up. Patients or their next of kin gave written informed consent. Setting: emergency department.


Participants89 participants (37 males and 51 females), with age 84±6 years in standard medical care group and 84±6 in CPAP group. Diagnosis criteria: Age similar or more than 75 year, acute hypoxaemic respiratory failure (PaO2/ FiO2<300 despite O2> 8l/min for 15 minutes), BR> 25bpm, contraction of accessory muscles, clinical examination: systolic and/or diastolic hypertension, widespread crackles or wheezing; medical record : previous cardiomyopathy, and/or acute dyspnoea with progressive orthopnoea; electrocardiographic tracing (Q waves and/or abnormalities in the T wave and ST segment; left ventricular hypertrophy, bundle branch block, atrial fibrillation); and chest radiography ( cardiac enlargement with a cardiothoracic ratio>50%, and/or pulmonary congestion with Kerley B lines, alveolar filing, pleural effusions) compatible with a diagnosis of cardiogenic pulmonary oedema. Causes: Tachyarrythymia, acute Ischaemic heart disease, hypertensive crises, respiratory tract infection, undiagnosed. Exclusion criteria: Glasgow Coma Scale less or similar 7, SpO2 similar or less 85% despite oxygen, haemodynamic instability, chronic respiratory insufficiency.


InterventionsCPAP group: PEEP= 7.5 cmH2O. N=43, TIME=8±6 hours.
Control group: standard medical care+O2 mask. N= 46.
Co-intervention: furosemide, nitroglycerin, glyceryl-trinitrate, morphine, isosorbide dinitrate.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases ( PCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Treatment failure
  6. Side-effects
  7. Droupouts/ withdrawals
  8. Length of hospital stay
  9. Compliance of patient


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)High risk

Detection biasUnclear riskNot reported

Adherence to the intention-to-treat principleLow risk

Levitt 2001

MethodsSingle centre randomised controlled trial (from a previously computer-generated list), parallel design, unblinded, lack of intention-to-treat analysis confirmed on study assessment. Four patients were lost to follow up. Informed consent was obtained of the patients. Setting: emergency department.


Participants42 patients were randomised, but 4 patients did not meet inclusion criteria following randomisation. Therefore, study entry 38 participants (13 males and 25 females), with age 68.5±15 years in standard medical care group and 67.4±15 in BILEVEL group. Diagnosis criteria: tachypnoea, BR>30bpm, diaphoresis or accessory muscle use, pulmonary rales, distended neck veins, peripheral oedema, history CHF (congestive heart failure) and radiograph findings of the pulmonary oedema. Causes: acute congestive heart failure. Excluded patients: patients with radiograph were found not to have CHF or required immediate intubation.


InterventionsBILEVEL group: EPAP= cm H2O e IPAP= cmH2O. N=21, time= 2 hours.
Control group: standard medical care+O2 mask. N= 17.
Co-intervention: morphine,furosemide, nitroglycerin.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Treatment failure
  4. Incidence of acute myocardial infarction (follow-up)
  5. Length of hospital stay


NotesMask:nasal or face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasHigh risk

Adherence to the intention-to-treat principleHigh risk

Liesching 2003

MethodsSingle centre randomised controlled trial, parallel design, unblinded, using ITT approach. Losses to follow up not reported. Informed consent not described.


Participants27 participants. Diagnosis criteria: patients with acute cardiogenic pulmonary oedema. Patients with myocardial infarction at presentation were excluded.


InterventionsCPAP group: PEEP=10 cmH2O. N=14.
BILEVEL group: EPAP=4 cm H2O e IPAP= 12cmH2O. N=13.
Co-intervention: medical treatment..


Outcomes
  1. Tracheal intubation rate
  2. Incidence of acute myocardial infarction (follow-up)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot reported if there were drop-outs over the monitoring of patients.

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Lin 1991

MethodsSingle centre randomised controlled trial, parallel design, unblinded, lack of intention-to-treat analysis confirmed on study assessment. 15 patients in CPAP group and 10 patients in O2 group were lost to follow up. Infomed consent was obtained of the patients. Setting: intensive care unit. Wash out of 30 minutes.


Participants80 patients were randomised, but 25 patients did not meet inclusion criteria following randomisation. Therefore, study entry 55 patients (50 males and 5 females), with age 74.1±8.8 years in standard medical care group and 73.4±8.2 in CPAP group. Diagnosis criteria: Radiologic evidence of acute interstitial or alveolar oedema of cardiac origin, tachypnoea, BR>22bpm, intercostal or suprasternal retractions, PaO2/FiO2 > 200, P(A-a)O2>200. Causes: CHF, dilated cardiomyopathy, Ischaemic heart disease, hypertensive cardiovascular disease, acute myocardial infarction. Excluded patients: patients unresponsive to speech or unable to maintain a patent airway and who had cardiogenic shock, signs of lung infection, evidence pulmonary embolism, chronic lung disease with CO2 retention at rest.


InterventionsCPAP group: PEEP=3.75±1.76 cmH2O in first hour (pressure was applied by connecting a serial CPAP valve -2,5 cm, 5 cm, 7,5 cm, 10 cm, 12,5 cm - to the face mask at each 30 min interval. N=25, TIME=6 hours.
Control group: standard medical care+O2 mask. N= 30.
Co-intervention: medical treatment of pulmonary oedema was not restricted.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases ( PaO2, PCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Droupouts/ withdrawals
  6. Treatment failure


NotesMask: face mask.
FiO2=100% full time.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
High risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleHigh risk

Lin 1995

MethodsSingle centre randomised controlled trial, parallel design, unblinded, using ITT approach. No losses to follow up were reported. Informed consent not reported. Setting: emergency department or the patient was recruited during hospitalisation. Wash out of 30 minutes.


Participants100 participants (90 males and 10 females), with age 73±9 years in standard medical care group and 72±8 in CPAP group. Diagnosis criteria: dyspnoea and tachypnoea, BR>22bpm, use of accessory respiratory muscles, PaO2/FiO2 between 200 and 400, P(A-a)O2< 250. Rx bilateral diffuse interstitial or alveolar oedema and most rales, and without history aspiration or infection. Causes: CHF, dilated cardiomyopathy, Ischaemic heart disease, hypertensive crisis, acute myocardial infarction. Excluded patients: patients unresponsive, unable to maintain a patent airway and who had cardiogenic shock, ventricular septal rupture, any severe stenotic valvular disease or chronic lung disease.


InterventionsCPAP group: PEEP=3.75±1.7 cmH2O in first hour (pressure was applied by connecting a serial CPAP valve -2,5 cm, 5 cm, 7,5 cm, 10 cm, 12,5 cm - to the face mask at each 30 min interval. N=41, TIME=6 hours.
Control group: standard medical care+O2 mask. N= 33.
Co-intervention: Isosorbide dinitrate, morphine, furosemide, nitroprusside, nitroglycerin, dopamine.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases (PaO2, PCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Droupouts/ withdrawals
  6. Length of hospital stay
  7. Length of ICU stay
  8. Treatment failure


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskNot submitted multiple planning outcomes reported on results.

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Martin-Bermudez 2002

MethodsRandomised controlled trial. Losses to follow up not reported. Informed consent not described.


Participants84 consecutive patients with respiratory failure due to severe cardiogenic pulmonary oedema were randomly assigned to receive either pressure support ventilation plus positive end expiratory pressure or continuous positive airway pressure. Lack of intention-to-treat analysis confirmed on study assessment. 3 patients in CPAP group and 1 patients in BILEVEL group were lost after randomisation (a case of respiratory failure by aspiration pneumonia, a re-acute CPE and two declined to continue participating in the study).


InterventionsCPAP group: time= 107±57 min. N=42.
BILEVEL group: time= 76±50 min . N=42.
Co-intervention: ?


Outcomes
  1. Mortality
  2. Length of hospital stay
  3. Length of ICU stay
  4. Arterial blood gases (pH, PaCO2, PaO2/FiO2,)
  5. Vital signs (BR, BP, HR)
  6. Incidence of acute myocardial infarction (follow-up)
  7. Dyspnea score
  8. Tidal volume


NotesMask: face mask


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskNot submitted multiple planning outcomes reported on results.

Detection biasLow risk

Adherence to the intention-to-treat principleHigh risk

Masip 2000

MethodsSingle centre randomised controlled trial (the randomisation sequence was generated by a table of random numbers, the assignments were placed in closed envelopes with identification numbers that were stored in the intensive-care unit), parallel design, unblinded, lack of intention-to-treat analysis confirmed on study assessment. Two patients in standard medical care group and one patient in BILEVEL group were lost to follow up. Patients or next-of-kin were aware through informed consent. Setting: emergency department or ward to the intensive care unit (ICU).


Participants40 participants went randomised, but 3 patients were excluded from the analysis. Therefore, study entry 37 patients (19 males and 18 females), with age 78.5±5 years in standard medical care group, 75.3±11 in BILEVEL group. Diagnosis criteria: dyspnoea of sudden onset with physical findings consistent with pulmonary oedema (widespread rales with or without third heart sound) and typical findings of congestion on a chest radiograph. History: heart failure, acute myocardial infarction, Hypertension, diabetes mellitus, chronic obstructive pulmonary disease. Causes: acute myocardial infarction, hypertensive crisis, hypervolaemia,unstable angina, tachyarrhythmia, respiratory-tract infection, treatment non-compliance. Excluded patients: cardiogenic shock (SBP < 90mmHg), severe acute or chronic airflow obstruction without evidence of cardiogenic pulmonary oedema, severe chronic renal failure, neurological impairment, acute myocardial infarction necessitating thrombolysis, evidence of pneumonia, immediate need for intubation, and absence of pulmonary oedema on a first chest radiograph.


InterventionsBILEVEL group: EPAP= 5 cm H2O e IPAP= 15.2±2.4 cmH2O. N=19, time= 254±90 min.
Control group: standard medical care+O2 mask (FiO2 > or = 50%). N= 26
Co-intervention: morphine, furosemide, glyceryl trinitrate, digoxin.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases (pH)
  4. Vital signs (BR, BP, HR)
  5. Incidence of acute myocardial infarction (follow-up)
  6. Dropouts/ withdrawals
  7. Side-effects
  8. Length of hospital


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskNot reported.

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleHigh risk

Mehta 1997

MethodsSingle centre randomised controlled trial (computer random number sequence), parallel design, double-blind, lack of intention-to-treat analysis confirmed on study assessment. 4 patients in CPAP group and 5 patients in BILEVEL group were lost to follow up. Patients or next-of-kin were aware through informed consent. Single blind. Setting: emergency department and ICU.


Participants36 participants (11 males and 25 females), with age 76±7 years in CPAP group and 77±12 in BILEVEL group. Diagnosis criteria: moderate-to-severe dyspnoea, BR>30bpm, use of accessory respiratory muscles or paradoxical abdominal motion in combination with tachycardia (heart rate of >100 bpm), cardiac gallops, bilateral rales, and typical findings of congestion on a chest radiograph, without a history suggesting pulmonary aspiration or infection. Causes: acute myocardial infarction, left bundle-branch block, coronary artery disease. Excluded patients: already intubated, suffering a respiratory or cardiac arrest, had an unstable cardiac rhythm, or a systolic blood pressure (BP)<90mmHg, patients unresponsive, agitated, and unable to cooperate, or if they had any condition that precluded application of a face mask.


InterventionsCPAP group: PEEP=10 cmH2O. N=13, TIME= 6.4±5.8 hours.
BILEVEL group: EPAP=5 cm H2O and IPAP= 15cmH2O. N=14, TIME = 7.1±4.7 hours.
Co-intervention: morphine, furosemide, isosorbide dinitrate.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Incidence of acute myocardial infarction (follow-up)
  4. Dropouts/ withdrawals
  5. Side-effects
  6. Length of hospital stay
  7. Length of ICU stay


NotesMask: nasal mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
High risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleHigh risk

Moritz 2007

MethodsMulticenter randomised controlled trial (3 centres), randomisation procedure: allocation to treatment was stratified for centre and based on block randomisation of 10 consecutive study numbers. Parallel design, single blind. Lack of intention-to-treat analysis confirmed on study assessment, eleven patients were withdrawn because no informed consent was obtained (n7) or because they were lost to follow-up. Patients or next-of-kin gave written informed consent. Setting: emergency department.


Participants109 participants (57 males and 52 females), with age 77.6±9.4 years in CPAP group and 77.7±9.2 in BILEVEL group. Diagnosis criteria: association of sudden onset of dyspnoea; presence of bilateral rales on auscultation, with no medical history suggesting pulmonary aspiration or infection; or congestion found on chest radiograph. Furthermore, patients had to present 2 of the following severity criteria of respiratory failure: respiratory frequency greater than 30 breaths/min; pulse oxymetry saturation (SpO2) below 90%, with oxygen at greater than 5 L per minute through reservoir facemask; and use of accessory muscles (Patrick scale 3). Causes: acute myocardial infarction, treatment noncompliance, respiratory tract infection, myocardial ischaemia, hypertensive emergency, previous pulmonary oedema. Excluded patients: out-of-hospital use CPAP or BILEVEL, temperature above 39°C, altered mental state, severe acute or chronic airflow obstruction, with no evidence of pulmonary oedema, chronic renal failure, evidence of pneumonia, acute myocardial infarction necessitating thrombolysis or primary angioplasty, immediate indication for tracheal intubation, respiratory or cardiac arrest, SpO2 < 85% with 100% FiO2, decreased alertness or major agitation requiring sedation, clinical signs of exhaustion: active contraction of the respiratory accessory muscles, with paradoxic abdominal or thoracic motion.


InterventionsCPAP group: PEEP=7.7±2.1 cmH2O. N=59, TIME= 2.3 hours.
BILEVEL group: EPAP=4.9±0.9 cm H2O and IPAP= 12±3.2cmH2O. N=50, time= 2.8 hours.
Co-intervention: morphine sulfate, furosemide, nitroprusside, sublingual or topical or intravenous nitroglycerin.


Outcomes
  1. Hospital mortality
  2. ETI
  3. Incidence of acute myocardial infarction
  4. Vital signs (pulse rate, systolic and diastolic blood pressure, BR)
  5. Arterial blood gases (PaO2, PCO2, pH)
  6. Acessory muscle use evaluated with Patrick Scale
  7. SpO2
  8. Duration of the ventilation period
  9. Length of hospital stay


NotesMask: full face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasLow risk

Adherence to the intention-to-treat principleHigh risk

Nava 2003

MethodsMulticenter randomised controlled trial (5 centres), randomisation procedure: the randomisation schedule had a block design for each centre and was generated by an independent statistician who used random numbers (because the level of PaCO2 might have a substantial influence on the study results, the randomisation was balanced according to whether the patients had an admission PaCO2< or >45mmHg), parallel design, unblinded, using ITT approach. No patients were lost to follow up. Patients or next-of-kin were aware through informed consent. Setting: emergency department.


Participants130 participants (101 males and 29 females), with age 73.1±8.3 years in standard medical care group and 72.1±9.1 in BILEVEL group. Diagnosis criteria: dyspnoea of sudden onset with BR>30bpm, PaO2/FiO2<250, typical finds on chest radiographs (congestion) and physical signs of pulmonary oedema (widespread rales) without a history suggesting pulmonary aspiration or infection. Causes: acute acute myocardial infarction, hypertension, hyperthermia (but not showing any signs of pulmonary infection), arrhythmia, aortic stenosis, mitral regurgitation. Excluded patients: immediate need for endotracheal intubation, severe sensorial impairment, shock, ventricular arrhythmias, life threatening hypoxia (SaO2<80%), acute myocardial infarction necessitating thrombolysis, severe chronic renal failure and pneumothorax.


InterventionsBILEVEL group: EPAP=6.1±3.2 cm H2O e IPAP= 14.5±21,1cmH2O. N=65, time= 11.4±3.6 hours.
Control group: standard medical care+O2 mask (to maintain an SpO2>90%). N= 65
Co-intervention: morphine sulfate, furosemide, glyceryl trinitrate.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases (PaO2, PCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Incidence of acute myocardial infarction (follow-up)
  6. Compliance of patient
  7. Side-effects
  8. Length of hospital stay


NotesMask: full face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Park 2001

MethodsSingle centre randomised controlled trial (computer random number sequence in closed envelopes), parallel design, unblinded, not using ITT approach. Loss to follow up not reported. Patients or guardians were aware through informed consent. Setting: in hospital.


Participants26 participants (10 males and 16 females), with mean age 69±7 years. Diagnosis criteria: dyspnoea of acute onset or worsening, respiration rate more or similar 25 bpm, Rx compatible with pulmonary congestion. Causes: acute myocardial infarction, hypertensive emergencies, acute ischaemic heart disease, infectious endocarditis or undetermined. Excluded patients: SBP less than 90mmHg, arrhythmias requiring electric cardioversion, decreased consciousness level, bradypnoea, lack of cooperation or agitation, repetitive vomiting, upper digestive haemorrhage, facial deformities or any other decompensated respiratory disease.


InterventionsCPAP group: PEEP= 7.5 cmH2O. N=9, TIME=170±90min.
BILEVEL group: EPAP=4 cm H2O e IPAP= 12cmH2O. N=7, time= 155±38min.
Control group: standard medical care+O2 mask (15l/min). N= 10.
Co-intervention: Isosorbide dinitrate (5mg) + standard medication


Outcomes
  1. Mortality,
  2. Traqueal intubation rate,
  3. Arterial blood gases ( PaO2, PaCO2, pH),
  4. Vital signs (BR, BP, HR),
  5. Incidence of acute myocardial infarction (follow-up),
  6. Compliance of patient,
  7. Dropouts/ withdrawals.


NotesOutcome 6 was poorly reported as a brief comment: BILEVEL group more cooperated and related less dyspnoea.
Mask: CPAP: closed face mask, BILEVEL: nasal mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot reported.

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleHigh risk

Park 2004

MethodsSingle centre randomised controlled trial (the patients were randomised with sealed envelopes - nine per envelope - using a 3:3:3 assignment scheme), parallel design, lack of intention-to-treat analysis confirmed on study assessment. Two patients in BILEVEL group and one patients in O2 group were lost to follow up. Patients or guardians were aware through informed consent. Setting: in emergency department. Wash out of 6 minutes.


Participants83 participants went randomised, but 3 patients did not meet inclusion criteria for study entry. Therefore, study entry 80 patients (34 males and 46 females), with age 65±15 years in standard medical care group, 61±17 in CPAP group and 66+/-14 in BILEVEL group. Diagnosis criteria: More than 16 years, acute onset of severe respiratory distress (BR>25rpm), associated tachycardia and diaphoresis and findings of pulmonary congestion on physical examination and chest Rx 2 hours after randomisation. Causes: acute myocardial infarction, myocardial ischaemia, crisis hypertensive, progressive heart failure, hypervolaemia (20%with CPO severe). Excluded patients: SBP < 90mmHg, decrease consciousness level, intractable vomiting, acute myocardial infarction with persistent ST segment elevation, pulmonary embolism, COPD, pneumonia or pneumothorax .


InterventionsCPAP group: PEEP=11±2 cmH2O. N=27, TIME=102±41min.
BILEVEL group: EPAP=11±2 cm H2O e IPAP= 17±2cmH2O. N=7, time= 124±62min.
Control group: standard medical care+O2 mask (FiO2 > or = 50%). N=26
Co-intervention: Isosorbide dinitrate, morphine, furosemide, nitroprusside, nitroglycerin


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Incidence of acute myocardial infarction (follow-up)
  4. Compliance of patient
  5. Dropouts/ withdrawals
  6. Treatment failure
  7. Side-effects
  8. Length of hospital stay


NotesMask: face mask. CPAP or BILEVEL with FiO2=50%.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleHigh risk

Räsänen 1985

MethodsSingle centre randomised controlled trial. The patients were randomly assigned to 1 of 2 group by opening 1 of 40 sealed envelopes. Parallel design, unblinded, using ITT approach. Loss to follow up not reported. Informed consent not described. Wash out of 10 minutes. Setting: intensive care unit (ICU).


Participants40 participants (13 males and 17 females), with age 73±9 years in standard medical care group and 74±9 in CPAP group. Diagnosis criteria: respiratory failure and clinical and radiologic evidence of acute alveolar pulmonary oedema of cardiac origin, dyspnoea, signs increase respiratory work (intercostal and suprasternal retractions or use of accessory respiration muscles), respiratory rate of more than 25 bpm. PaO2/FiO2<200. Causes: severe heart failure primarily after acute myocardial infarction, acute exacerbation of chronic left ventricular dysfunction, ventricular arrhythmia or acute valve incompetence. Excluded patients: patients unresponsive to speech or unable to maintain patent airway, with lung infection, pulmonary embolism, chronic lung disease with CO2 retention at rest or after treatment PaO2<50mmHg, PaCO2>55mmHg, BR>35bpm.


InterventionsCPAP group: PEEP= 10 cmH2O. N=20, TIME=180min.
Control group: standard medical care+O2 mask (FiO2=28-30%). N= 20.
Co-intervention: furosemide, morphine, diazepam, chlorpromazine, nitroglycerin, nitroprusside, digitalis, dopamine and dobutamine.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Arterial blood gases ( PaO2, PCO2, pH)
  4. Vital signs (BR, BP, HR)
  5. Incidence of acute myocardial infarction (follow-up)
  6. Treatment failure
  7. Side-effects


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskNot submitted multiple planning outcomes reported on results.

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Sharon 2000

MethodsSingle centre randomised controlled trial (according to their numerical order on list that had been predetermined by lot), parallel design, unblinded, using ITT approach. No losses to follow up. Informed consent was obtained. Setting: mobile intensive care unit teams in the patient's home or during delivery to the emergency department.


Participants40 patients went randomised (19 males and 21 females), with age 73±7 years in standard medical care group and 72+/-6 in BILEVEL group. Diagnosis criteria: symptoms and signs of pulmonary oedema accompanied by oxygen saturation of < 90% measured by pulse oximetry, prior to oxygen administration. Echocardiographics findings: moderate aortic stenosis, moderate mitral regurgitation, ejection fraction. Excluded patients: previous treatment with nitrates above 40 mg/d, or mononitrate or long-acting trinitrates administered more than twice daily or short acting trinitrates administered more than three times a day; previous treatment with furosemide> 80 mg/d; hypotension (blood pressure <110/70 mmHg); previous adverse effect of nitrates; ST elevations consistent with acute myocardial infarction on baseline ECG; and absence of pulmonary oedema on chest radiograph obtained on arrival to the emergency department.


InterventionsBILEVEL group: EPAP= 4.2±3,.cm H2O, e IPAP=9.3±2.3 cmH2O + ISDN = 3.5±2.5mg. N=20, time=at least 50 minutes.
Control group: O2 mask + high dose IV ISDN =10.8±5.7mg . N= 20.
Co-intervention: IV ISDN (Isorsobide-dinitrate), furosemide and morphine


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Incidence of acute myocardial infarction (follow-up)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Takeda 1997

MethodsSingle centre randomised controlled trial, parallel design, unblinded, using ITT approach. Loss to follow up not reported. Patients or guardians were aware through informed consent. Setting: intensive care unit (ICU).


Participants30 participants (22 males and 8 females), with age 64±9 years in standard medical care group and 69+/-10 in CPAP group. Diagnosis criteria: dyspnoea of sudden onset, PaO2<80mmHg with FiO2>ou= 50%, typical finds on chest radiographs, and widespread rales without a history suggesting pulmonary aspiration or infection. Causes: acute myocardial infarction, prior myocardial infarction, cardiomyopathy, mitral valve regurgitation. Exclusion criteria: complicated with aspiration and/or pneumonia, immediate need for endotracheal intubation, shock, and life-threatening hypoxia at study entry.


InterventionsCPAP group: PEEP= 7±3 cmH2O. N=15, TIME=11.9±8.4hours.
Control group: standard medical care+O2 mask. N=15.
Co-intervention: furosemide, morphine, nitroglycerin, digitalis, dopamine, dobutamine, norepinephrine.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Length of ICU stay


NotesMask: nasal mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Unclear riskThe method used was not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskNot submitted multiple planning outcomes reported on results.

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Takeda 1998

MethodsSingle centre randomised controlled trial (by envelope method), parallel design, unblinded, using ITT approach. No patients were lost after randomisation. Patient's next of kin were aware through informed consent. Setting: coronary care unit (CCU).


Participants22 participants (17 males and 5 females), with age 75±10 years in standard medical care group and 74±11 in CPAP group. Diagnosis criteria: dyspnoea of sudden onset, PaO2<80mmHg with FiO2= 50%, typical finds on chest radiographs and widespread rales without a history suggesting pulmonary aspiration or infection, typical chest pain 30 minutes creatine kinase twice a least the normal, ECG changes consistent with acute myocardial infarction. Causes: Acute myocardial infarction. Exclusion criteria: complicated with aspiration and/or pneumonia, immediate need for endotracheal intubation, shock, and life-threatening hypoxia at study entry.


InterventionsCPAP group: PEEP= 7±3 cmH2O. N=11, TIME=48hours.
Control group: standard medical care+O2 mask. N= 11.
Co-intervention: furosemide, morphine, nitroglycerin, dopamine, dobutamine, norepinephrine, epinephrine.


Outcomes
  1. Mortality
  2. Tracheal intubation rate


NotesMask: nasal mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Thys 2002

MethodsSingle centre randomised controlled trial (through opaque and sealed envelopes by batches of 20 envelopes), parallel design with placebo, single blind, using ITT approach. None patient went lost. Informed consent was obtained of the patients. Setting: emergency department and intensive care unit (ICU).


Participants8 participants (5 males and 3 females), with age 77.5±8.38 years. Diagnosis criteria: orthopnoea, bibasilar crackles, bilateral perihilar infiltrates on chest radiograph with cardiomegaly and a compatible clinical history; age more than 18 years, acute onset of moderate-to-severe dyspnoea, BR>30 or < 10bpm, hypoxaemia (PaO2 <55mmHg) or need for O2 supplementation, pH<7,33. Excluded patients: immediate indication for endotracheal intubation, major unrest, haemodynamic instability, facial or thoracic trauma, lack of cooperation, difficult adaptation of a facial mask, pulmonary embolism, retrosternal pain suggestive of a acute myocardial infarction.


InterventionsBILEVEL group: EPAP= 6.1±1.5 cmH2O e IPAP= 16.5±1.5 cmH2O. N=3, time= 77.33±16.25 minutes.
Control group: standard medical care+O2 with similar mask (placebo). N= 5.
Co-intervention: furosemide, isosorbide dinitrate.


Outcomes
  1. Mortality
  2. Tracheal intubation rate
  3. Incidence of acute myocardial infarction (follow-up)
  4. Side-effects
  5. Length of hospital stay
  6. Length of ICU stay


NotesMask: face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method used was not reported.

Allocation concealment (selection bias)Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low risk

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleLow risk

Weitz 2007

MethodsSingle centre randomised controlled trial, parallel design, unblinded, not using ITT approach. Three patients allocated to the standard group were not followed up because it was obvious on admission that these patients did not suffer from an acute cardiogenic pulmonary oedema. Informed consent was obtained. Setting: mobile intensive care unit teams in the patient's home or during delivery to the emergency department.


Participants23 participants (12 males and 11 females), with age 72-92 years in standard medical care group and 54-86 in BILEVEL group. Diagnosis criteria: severe dyspnoea and consecutively showed additional clinical signs of ACPE (SaO2< 90% and basal rales). Excluded patients: severe uncontrolled agitation, angina, obvious ST elevation in the ECG, emesis and aspiration, cardiogenic shock, life threatening arrhythmias, coma or any obvious need for intubation.


InterventionsBILEVEL group: EPAP= 5 cm H2O e IPAP= 12.5±1.2 cmH2O. N=10.
Control group: standard medical care+O2 with similar mask (placebo). N= 5.
Co-intervention: furosemide, isosorbide dinitrate.


Outcomes
  1. SaO2 at the time of the hospital admission
  2. Measure the brain natriuretic peptide (BNP)
  3. Mortality
  4. Length of hospital stay
  5. Length of ICU stay
  6. Vital signs (BR, BP, HR)
  7. Dyspnea scale
  8. Tracheal intubation rate
  9. Incidence of acute myocardial infarction (follow-up)
  10. Side-effects


NotesMask: Face mask.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High risk

Allocation concealment (selection bias)High riskInadequate

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskNot submitted multiple planning outcomes reported on results.

Detection biasUnclear riskNot reported.

Adherence to the intention-to-treat principleHigh risk

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Acosta 2000The clinical situation is different.

Albert 2000The clinical situation is different.

Alper 2007It is not a RCT or QRCT.

Alper 2008It is not a RCT or QRCT.

Andrade 1998The clinical situation is different.

Antonelli 2001It is not a RCT or QRCT.

Aronow 2007It is not a RCT or QRCT.

Barach 1938It is not a RCT or QRCT.

Baratz 1992It is not a RCT or QRCT.

Bavry 2008It is not a RCT or QRCT.

Bellone 2002The outcomes did not meet the inclusion criteria.

Blomqvist 1991Study with dogs.

Bollaert 2002Study involve other kind of ventilatory support (PAV)

Bouquin 1998It is not a RCT or QRCT.

Bradley 2000The clinical situation is different.

Brezins 1993Study involve other kind of ventilatory support (invasive mechanical ventilation).

Brijker 1999It is not a RCT or QRCT.

Brochard 1998It is a letter commenting the L'Her's article.

Chadda 2002The outcomes did not meet the inclusion criteria.

Chen 2008Compare NPPV vs. mechanical ventilation.

Crane 2002It is not a RCT or QRCT.

Craven 2000It is not a RCT or QRCT.

Cross 2000It is not a RCT or QRCT.

Cross 2003This is study is in patients with acute respiratory failure and include a subgroup with pulmonary edema (inclusion criteria not clear for cardiogenic pulmonary edema). However, although the author have been contected, he is not replay.

Cydulka 2005It is a letter commenting the Nava's article.

Domenighetti 2002It is not a RCT or QRCT.

Du Cailar 1975It is not a RCT or QRCT.

Eaton 2002The clinical situation is different.

Evans 2001It is not a RCT or QRCT.

Fromm 1995It is not a RCT or QRCT.

Giacomini 2003It is not a RCT or QRCT.

Girou 2003The clinical situation is different.

Gorbunova 2005The end point doesn't similar commended in protocol.

Gray 2009It is the same study published in New England in 2008 by Gray et al.

Guerra 2005It is not a RCT or QRCT.

Guntupalli 1984It is not a RCT or QRCT.

Gust 1998It is a letter to the editor.

Hao 2002It is not a RCT or QRCT.

Hess 2004It is not a RCT or QRCT.

Hilberg 1997It is not a RCT or QRCT.

Hipona 1996It is a letter to the editor.

Hoffman B 1999It is not a RCT or QRCT.

Hoffmann 1999It is not a RCT or QRCT.

Holt 1994It is not a RCT or QRCT.

Hotchkiss 1998It is not a RCT or QRCT.

Hubble 2006It is not a RCT or QRCT.

Hughes 1999It is a letter to the editor.

Iapichino 2004It is not a RCT or QRCT.

Jackson 2000It is not a RCT or QRCT.

Jackson 2001It is not a RCT or QRCT.

Jackson R 2001It is not a RCT or QRCT.

Kallio 2003It is not a RCT or QRCT.

Keenan 2004It is not a RCT or QRCT.

Kelly 2001It is a letter to the editor.

Kiely 1998The outcomes did not meet the inclusion criteria.

Kindgen-Milles 2000It is not a RCT or QRCT.

Kosowsky 2000It is not a RCT or QRCT.

Kosowsky 2001It is not a RCT or QRCT.

Kramer 1995This is study is in acute respiratory failure and include only two patients with cardiogenic pulmonary edema that received NPPV and nobody received CPAP or SMC.

L'Her 1998It is not a RCT or QRCT.

L'Her E 1998It is not a RCT or QRCT.

Lal 1969The study test only different oxygen masks.

Lapinsky 1994It is not a RCT or QRCT.

Leman 2005It is a RCT, but only compared two different brands of CPAP equipment.

Lenique 1997It is not a RCT or QRCT.

Li 2004It is a RCT, it is Chinese paper  whose data was translated by Cochrane, but dichotomous variables advocated not were analyzed and the continuous variables analysis happened in different period of advocated - 2hs and 24hs after the start of the intervention.

Liesching T 2003It is not a RCT or QRCT.

Lo Coco 1997It is not a RCT or QRCT.

Mackay CA 2000It is a Poster of Congress. Did not assess relevant outcomes.

Masip 2008It is not a RCT or QRCT.

Massaria 1976It is not a RCT or QRCT.

Meduri 1991The clinical situation is different. It was conducted in patients with COPD or asthma.

Mehta 2000The outcomes did not meet the inclusion criteria.

Mehta 2004It is not a RCT or QRCT.

Mehta 2005It is not a RCT or QRCT.

Minuto 2003It is not a RCT or QRCT.

Mollica 2001It is not a RCT or QRCT.

Moritz 2003The outcomes did not meet the inclusion criteria.

Murray 2002It is not a RCT or QRCT.

Murray 2003It is not a RCT or QRCT.

Nadar 2005It is not a RCT or QRCT.

Nava 2002It is not a RCT or QRCT.

Newberry 1995It is not a RCT or QRCT.

Newby 2007It is a brief presentation of RCT published in The New England in 2008 by Gray et al.

Nikki 1982The study compares CPAP vs. mechanical ventilation.

Niranjan 1998It is a letter to the editor with comment about noninvasive ventilation.

Panacek 2002It is not a RCT or QRCT.

Pang 1998It is not a RCT or QRCT.

Park 2005It is not a RCT or QRCT.

Park 2006It is an article of review.

Perel 1983It is not a RCT or QRCT.

Perkins 2006It is not a RCT or QRCT.

Philip-joet 1999The clinical situation is different.

Plaisance 2007It is a RCT, but this study cross-over, the groups were compared in different times were different from those described in this review.

Pollack 1996It is not a RCT or QRCT.

Poponick 1999It is not a RCT or QRCT.

Popova 2010The outcomes did not meet the inclusion criteria.

Poulton 1936It is not a RCT or QRCT.

Rabatin 1999It is not a RCT or QRCT.

Rasanen J 1985It is not a RCT or QRCT.

Rizk 1982It is not a RCT or QRCT.

Roche 2003The clinical situation is different.

Rusterholtz 1999It is not a RCT or QRCT.

Rutherholtz 2008It is a RCT, but compared CPAP vs.PAV.

Sacchetti 2001It is a letter to the editor .

Sachetti 1995It is not a RCT or QRCT.

Salvucci A 2001It is not a RCT or QRCT.

Sarullo 2004It is not a RCT or QRCT.

Schettino 2008It is not a RCT or QRCT.

Severinghaus 2002It is not a RCT or QRCT.

Simonds 2000It is not a RCT or QRCT.

Sinuff 2000It is not a RCT or QRCT.

Somauroo 2000The clinical situation is different. It was conducted in patients with chronic congestive heart failure.

Sutton 2002It is a letter to the editor.

Trevisan 2008It is a RCT, but compared It is a RCT, but compared NPPV as a method of weaning.

Uy 2003The study compares CPAP vs. mechanical ventilation.

Uy 2004It is a RCT, but compared It is a RCT, but compared CPAP vs.invasive mechanical ventilation

Vaisanen 1987The outcomes did not meet the inclusion criteria.

Valipour 2004It is not a RCT or QRCT.

Werdan 1999It is not a RCT or QRCT.

Widger 2001It is not a RCT or QRCT.

Wood 1998This is study is in acute respiratory failure and include a subgroup with cardiogenic pulmonary oedema. However, although the author have been contected, he is not replay.

Wright 2001It is a letter to the editor.

Wysocki 1995This is study is in acute respiratory failure and include a subgroup with cardiogenic pulmonary oedema. However, although the author have been contected, he is not replay.

Wysocki 1999It is not a RCT or QRCT.

Zhang 2008The end point doesn’t similar commended in protocol.

 
Characteristics of ongoing studies [ordered by study ID]
NCT00554580

Trial name or titleEffect of Continuous Positive Airway Pressure on Short Term Inhospital Prognosis for Acute Pulmonary Edema

MethodsAllocation: Randomised
Endpoint classification: Efficacy Study
Intervention model: Parallel Assignment
Masking: Open label
Primary purpose: Treatment

ParticipantsAdults with acute cardiogenic pulmonary oedema

Interventions
  • A: Active comparator
    • usual care of pulmonary acute oedema
    • Intervention: usual care of acute pulmonary oedema
  • B: Experimental
    • CPAP + usual care of pulmonary acute oedema
    • Intervention: continuous positive airway pressure (CPAP)

OutcomesDeath, tracheal intubation and mechanical ventilation rates, persistence of inclusion criteria for respiratory distress and shock until H2, reappearance of inclusion criteria after H2. [ Time Frame: 48 hours ]

Brain natriuretic factor value curves from H0, H6 and H24; composite criteria without intubation rate; clinical and biological parameters evolution during the first 48 hours, myocardial infarction rate, CPAP non tol [ Time Frame: H0, H6, H24, H48 ]

Starting dateNovember 6, 2007

Contact information

Noteshttp://clinicaltrials.gov/ct2/show/NCT00554580

NCT00912158

Trial name or titleNoninvasive Mechanical Ventilation in Acute Cardiogenic Pulmonary Edema

MethodsAllocation: Randomised
Endpoint classification: Safety/efficacy study
Intervention model: Parallel assignment
Masking: Open label
Primary purpose: Treatment

ParticipantsAdults with acute cardiogenic pulmonary oedema

InterventionsOther: standard therapy (ST)
Device: CPAP and BIPAP

OutcomesNumber of patients who were intubated, arterial blood gases, respiratory rate, blood pressure, cardiac output, intrapulmonary shunt, A-a oxygen gradient, heart rate, and dyspnoea duration of hospital and ICU stay and mortality [ Time Frame: Hospital stay ]

Starting dateApril 8, 2009

Contact informationmahaghanem@hotmail.com

Noteshttp://clinicaltrials.gov/ct2/show/NCT00912158

 
Comparison 1. Hospital mortality

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) x SMC201107Risk Ratio (M-H, Random, 95% CI)0.66 [0.48, 0.89]

 2 NPPV (CPAP and BILEVEL) X SMC - sensitivity analysis181023Risk Ratio (M-H, Random, 95% CI)0.65 [0.46, 0.91]

 3 NPPV (CPAP and BILEVEL) X SMC- ED place9717Risk Ratio (M-H, Random, 95% CI)0.55 [0.36, 0.86]

 4 NPPV (CPAP and BILEVEL) X SMC - ICU place7365Risk Ratio (M-H, Random, 95% CI)0.48 [0.28, 0.83]

 5 NPPV (CPAP and BILEVEL) X SMC - in patients hypercanics - baseline9603Risk Ratio (M-H, Random, 95% CI)0.60 [0.40, 0.88]

 6 CPAP x SMC13699Risk Ratio (M-H, Random, 95% CI)0.60 [0.39, 0.94]

 7 CPAP X SMC - sensitivity analysis12659Risk Difference (M-H, Random, 95% CI)-0.12 [-0.19, -0.04]

 8 BILEVEL X SMC11506Risk Ratio (M-H, Random, 95% CI)0.65 [0.39, 1.09]

 9 BILEVEL X SMC - sensitivity analysis9458Risk Ratio (M-H, Random, 95% CI)0.63 [0.37, 1.09]

 10 BILEVEL X SMC - in patients hypercanics - baseline7401Risk Ratio (M-H, Random, 95% CI)0.59 [0.34, 1.02]

 11 BILEVEL X SMC - in patients hypercanics2104Risk Ratio (M-H, Random, 95% CI)0.20 [0.04, 0.86]

 12 CPAP X BILEVEL12694Risk Ratio (M-H, Random, 95% CI)1.10 [0.61, 1.97]

 13 CPAP X BILEVEL - in patients hypercanics - baseline9518Risk Ratio (M-H, Random, 95% CI)0.98 [0.45, 2.14]

 14 CPAP X BILEVEL - in patients hypercanics298Risk Ratio (M-H, Random, 95% CI)1.06 [0.33, 3.37]

 
Comparison 2. EETI rate

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC221261Risk Ratio (M-H, Random, 95% CI)0.52 [0.36, 0.75]

 2 NPPV (CPAP and BILEVEL) X SMC - sensitivity analysis201195Risk Ratio (M-H, Random, 95% CI)0.53 [0.37, 0.78]

 3 NPPV (CPAP and BILEVEL) X SMC - in patients hypercapnics - baseline9621Risk Ratio (M-H, Random, 95% CI)0.44 [0.25, 0.77]

 4 CPAP X SMC14825Risk Ratio (M-H, Random, 95% CI)0.47 [0.33, 0.67]

 5 CPAP X SMC - sensitivity analysis13785Risk Ratio (M-H, Random, 95% CI)0.48 [0.34, 0.67]

 6 BILEVEL X SMC12536Risk Ratio (M-H, Random, 95% CI)0.55 [0.26, 1.17]

 7 BILEVEL X SMC - sensitivity analysis10470Risk Ratio (M-H, Random, 95% CI)0.45 [0.26, 0.80]

 8 BILEVEL X SMC - in patients hypercapnics - baseline7401Risk Ratio (M-H, Random, 95% CI)0.47 [0.22, 0.97]

 9 BILEVEL X SMC - in patients hypercapnics3120Risk Ratio (M-H, Random, 95% CI)0.28 [0.12, 0.69]

 10 CPAP X BILEVEL13721Risk Ratio (M-H, Random, 95% CI)1.04 [0.55, 1.97]

 11 CPAP X BILEVEL - in patients hypercapnics - baseline9518Risk Ratio (M-H, Random, 95% CI)1.17 [0.58, 2.33]

 12 CPAP X BILEVEL - in patients hypercapnics298Risk Ratio (M-H, Random, 95% CI)0.92 [0.26, 3.21]

 
Comparison 3. Incidence of acute myocardial infarction (during intervention)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC8461Risk Ratio (M-H, Random, 95% CI)1.24 [0.79, 1.95]

 2 CPAP X SMC3152Risk Ratio (M-H, Random, 95% CI)0.91 [0.37, 2.24]

 3 BILEVEL X SMC7356Risk Ratio (M-H, Random, 95% CI)1.40 [0.78, 2.49]

 4 CPAP X BILEVEL7409Risk Ratio (M-H, Random, 95% CI)0.66 [0.39, 1.10]

 5 BILEVEL X SMC - heterogeneity analysis6316Risk Ratio (M-H, Random, 95% CI)1.14 [0.69, 1.88]

 
Comparison 4. Incidence of acute myocardial infarction (after intervention)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC4154Risk Ratio (M-H, Random, 95% CI)0.70 [0.11, 4.26]

 2 CPAP X SMC299Risk Ratio (M-H, Random, 95% CI)1.08 [0.11, 10.23]

 3 BILEVEL X SMC365Risk Ratio (M-H, Random, 95% CI)0.52 [0.02, 11.54]

 4 CPAP X BILEVEL268Risk Ratio (M-H, Random, 95% CI)1.57 [0.57, 4.32]

 
Comparison 5. Intolerance to allocated treatment

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC131848Risk Ratio (M-H, Random, 95% CI)0.47 [0.29, 0.77]

 2 NPPV (CPAP and BILEVEL) X SMC - heterogeneity analysis12692Risk Ratio (M-H, Random, 95% CI)0.42 [0.30, 0.58]

 3 CPAP X SMC91304Risk Ratio (M-H, Random, 95% CI)0.55 [0.36, 0.85]

 4 BILEVEL X SMC7995Risk Ratio (M-H, Random, 95% CI)0.58 [0.24, 1.42]

 5 CPAP X BILEVEL3894Risk Ratio (M-H, Random, 95% CI)0.94 [0.35, 2.53]

 
Comparison 6. Hospital length of stay

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC10542Mean Difference (IV, Random, 95% CI)-0.80 [-2.10, 0.51]

 2 NPPV (CPAP and BILEVEL) X SMC - heterogeneity analysis9519Mean Difference (IV, Random, 95% CI)-0.38 [-1.35, 0.58]

 3 CPAP X SMC5337Mean Difference (IV, Random, 95% CI)-0.51 [-1.69, 0.67]

 4 BILEVEL X SMC7311Mean Difference (IV, Random, 95% CI)-1.38 [-3.38, 0.62]

 5 CPAP X BILEVEL6402Mean Difference (IV, Random, 95% CI)-0.46 [-1.99, 1.07]

 
Comparison 7. ICU length of stay

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC6222Mean Difference (IV, Random, 95% CI)-0.89 [-1.33, -0.45]

 2 CPAP X SMC3169Mean Difference (IV, Random, 95% CI)-1.09 [-1.63, -0.56]

 3 BILEVEL X SMC353Std. Mean Difference (IV, Random, 95% CI)-0.65 [-1.37, 0.06]

 4 CPAP X BILEVEL3159Mean Difference (IV, Random, 95% CI)0.31 [-0.78, 1.40]

 
Comparison 8. Breath rate after one hour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC9438Mean Difference (IV, Random, 95% CI)-2.86 [-3.85, -1.87]

 2 CPAP X SMC7300Mean Difference (IV, Random, 95% CI)-2.39 [-3.70, -1.07]

 3 BILEVEL X SMC6254Mean Difference (IV, Random, 95% CI)-3.52 [-4.80, -2.23]

 4 CPAP X BILEVEL5218Mean Difference (IV, Random, 95% CI)0.57 [1.00, 2.13]

 
Comparison 9. Heart rate after one hour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC9438Mean Difference (IV, Random, 95% CI)-4.01 [-8.16, 0.15]

 2 NPPV (CPAP and BILEVEL) X SMC - heterogeneity analysis7329Mean Difference (IV, Random, 95% CI)-3.79 [-6.88, -0.70]

 3 CPAP X SMC7300Mean Difference (IV, Random, 95% CI)-4.45 [-10.81, 1.92]

 4 CPAP X SMC - heterogeneity analysis5191Mean Difference (IV, Random, 95% CI)-4.10 [-8.93, 0.72]

 5 BILEVEL X SMC6254Mean Difference (IV, Random, 95% CI)-4.21 [-7.77, -0.65]

 6 CPAP X BILEVEL4182Mean Difference (IV, Random, 95% CI)-0.56 [-5.22, 4.11]

 
Comparison 10. Sistolic blood pressure after one hour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC6182Mean Difference (IV, Random, 95% CI)-1.64 [-7.83, 4.56]

 2 CPAP X SMC6211Mean Difference (IV, Random, 95% CI)0.12 [-6.56, 6.81]

 3 BILEVEL X SMC487Mean Difference (IV, Random, 95% CI)1.93 [-7.94, 11.80]

 4 CPAP X BILEVEL4182Mean Difference (IV, Random, 95% CI)-1.17 [-10.79, 8.44]

 5 CPAP X BILEVEL - heterogeneity analysis3136Mean Difference (IV, Random, 95% CI)2.57 [-4.30, 9.44]

 
Comparison 11. Diastolic blood pressure after one hour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC5138Mean Difference (IV, Random, 95% CI)-1.49 [-6.43, 3.45]

 2 CPAP X SMC5167Mean Difference (IV, Random, 95% CI)-0.92 [-9.10, 7.27]

 3 CPAP X SMC - heterogeneity analysis3107Mean Difference (IV, Random, 95% CI)-7.32 [-12.79, -1.86]

 4 BILEVEL X SMC487Mean Difference (IV, Random, 95% CI)-0.96 [-6.09, 4.16]

 5 CPAP X BILEVEL4182Mean Difference (IV, Random, 95% CI)-2.60 [-9.58, 4.37]

 6 CPAP X BILEVEL - heterogeneity analysis262Mean Difference (IV, Random, 95% CI)-7.86 [-13.03, -2.70]

 
Comparison 12. Mean blood pressure after one hour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC3256Mean Difference (IV, Random, 95% CI)-2.41 [-8.27, 3.45]

 2 CPAP X SMC189Mean Difference (IV, Random, 95% CI)3.00 [-5.31, 11.31]

 3 BILEVEL X SMC2167Mean Difference (IV, Random, 95% CI)-5.42 [-11.60, 0.76]

 4 CPAP X BILEVEL180Mean Difference (IV, Random, 95% CI)-4.40 [-13.25, 4.45]

 
Comparison 13. PaO2 (mmHg) after one hour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC4140Mean Difference (IV, Random, 95% CI)10.04 [1.09, 19.00]

 2 CPAP X SMC5177Mean Difference (IV, Random, 95% CI)-2.64 [-25.87, 20.59]

 3 CPAP X SMC - heterogeneity analysis3117Mean Difference (IV, Random, 95% CI)-22.09 [-34.35, -9.83]

 4 BILEVEL X SMC379Mean Difference (IV, Random, 95% CI)4.79 [-11.11, 20.69]

 5 CPAP X BILEVEL3136Mean Difference (IV, Random, 95% CI)-27.00 [-44.75, -9.25]

 
Comparison 14. Adverse events

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC1511329Risk Ratio (M-H, Random, 95% CI)0.85 [0.63, 1.16]

    1.1 Skin damage
11594Risk Ratio (M-H, Random, 95% CI)6.62 [1.20, 36.55]

    1.2 Pneumonia
3232Risk Ratio (M-H, Random, 95% CI)0.35 [0.05, 2.20]

    1.3 Pulmonary aspiration
51255Risk Ratio (M-H, Random, 95% CI)1.58 [0.06, 38.61]

    1.4 Gastrointestinal Bleeding
3192Risk Ratio (M-H, Random, 95% CI)1.37 [0.27, 6.89]

    1.5 Gastric distention
8484Risk Ratio (M-H, Random, 95% CI)13.26 [0.82, 215.12]

    1.6 Vomiting
51229Risk Ratio (M-H, Random, 95% CI)1.06 [0.46, 2.47]

    1.7 Asphyxia
2170Risk Ratio (M-H, Random, 95% CI)3.0 [0.12, 72.31]

    1.8 Pneumothorax
61474Risk Ratio (M-H, Random, 95% CI)0.72 [0.08, 6.89]

    1.9 Conjunctivitis
2147Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    1.10 Sinusitis
2219Risk Ratio (M-H, Random, 95% CI)3.0 [0.12, 72.31]

    1.11 Disconfort with mask
7512Risk Ratio (M-H, Random, 95% CI)5.39 [0.97, 30.09]

    1.12 Hypotension
11030Risk Ratio (M-H, Random, 95% CI)0.82 [0.58, 1.16]

    1.13 Arrhythmia
11027Risk Ratio (M-H, Random, 95% CI)0.83 [0.50, 1.38]

    1.14 Progressive respiratory distress
21122Risk Ratio (M-H, Random, 95% CI)0.58 [0.37, 0.89]

    1.15 Cardiorespiratory arrest
31252Risk Ratio (M-H, Random, 95% CI)0.60 [0.29, 1.26]

    1.16 Neurological failure (coma)
190Risk Ratio (M-H, Random, 95% CI)0.10 [0.01, 0.71]

    1.17 Eye irritation
140Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    1.18 Stroke
1130Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    1.19 Seizures
1130Risk Ratio (M-H, Random, 95% CI)0.33 [0.01, 8.03]

 2 NPPV (CPAP and BILEVEL) X SMC - AFTER 20001110703Risk Ratio (M-H, Random, 95% CI)0.87 [0.63, 1.19]

    2.1 Skin damage
8492Risk Ratio (M-H, Random, 95% CI)6.62 [1.20, 36.55]

    2.2 Pneumonia
2152Risk Ratio (M-H, Random, 95% CI)0.35 [0.05, 2.20]

    2.3 Pulmonary aspiration
21095Risk Ratio (M-H, Random, 95% CI)1.58 [0.06, 38.61]

    2.4 Gastrointestinal Bleeding
2170Risk Ratio (M-H, Random, 95% CI)2.32 [0.35, 15.42]

    2.5 Gastric distention
4302Risk Ratio (M-H, Random, 95% CI)13.26 [0.82, 215.12]

    2.6 Vomiting
51229Risk Ratio (M-H, Random, 95% CI)1.06 [0.46, 2.47]

    2.7 Asphyxia
1130Risk Ratio (M-H, Random, 95% CI)3.0 [0.12, 72.31]

    2.8 Pneumothorax
51434Risk Ratio (M-H, Random, 95% CI)0.72 [0.08, 6.89]

    2.9 Conjunctivitis
2147Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    2.10 Sinusitis
2219Risk Ratio (M-H, Random, 95% CI)3.0 [0.12, 72.31]

    2.11 Disconfort with mask
7512Risk Ratio (M-H, Random, 95% CI)5.39 [0.97, 30.09]

    2.12 Hypotension
11030Risk Ratio (M-H, Random, 95% CI)0.82 [0.58, 1.16]

    2.13 Arrhythmia
11027Risk Ratio (M-H, Random, 95% CI)0.83 [0.50, 1.38]

    2.14 Progressive respiratory distress
21122Risk Ratio (M-H, Random, 95% CI)0.58 [0.37, 0.89]

    2.15 Cardiorespiratory arrest
31252Risk Ratio (M-H, Random, 95% CI)0.60 [0.29, 1.26]

    2.16 Neurological failure (coma)
190Risk Ratio (M-H, Random, 95% CI)0.10 [0.01, 0.71]

    2.17 Eye irritation
140Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    2.18 Stroke
1130Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    2.19 Seizures
1130Risk Ratio (M-H, Random, 95% CI)0.33 [0.01, 8.03]

 3 CPAP X SMC107133Risk Ratio (M-H, Random, 95% CI)0.63 [0.45, 0.87]

    3.1 Skin damage
7343Risk Ratio (M-H, Random, 95% CI)3.0 [0.13, 69.52]

    3.2 Pneumonia
180Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    3.3 Pulmonary aspiration
5908Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    3.4 Gastrointestinal Bleeding
122Risk Ratio (M-H, Random, 95% CI)0.33 [0.02, 7.39]

    3.5 Gastric distention
7447Risk Ratio (M-H, Random, 95% CI)11.00 [0.64, 189.65]

    3.6 Vomiting
3785Risk Ratio (M-H, Random, 95% CI)0.93 [0.34, 2.54]

    3.7 Asphyxia
140Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    3.8 Pneumothorax
5998Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    3.9 Conjunctivitis
2147Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    3.10 Sinusitis
189Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    3.11 Disconfort with mask
3265Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    3.12 Hypotension
1684Risk Ratio (M-H, Random, 95% CI)0.83 [0.55, 1.25]

    3.13 Arrhythmia
1682Risk Ratio (M-H, Random, 95% CI)0.55 [0.28, 1.09]

    3.14 Progressive respiratory distress
2776Risk Ratio (M-H, Random, 95% CI)0.53 [0.31, 0.92]

    3.15 Cardiorespiratory arrest
2777Risk Ratio (M-H, Random, 95% CI)0.41 [0.18, 0.91]

    3.16 Neurological failure (coma)
190Risk Ratio (M-H, Random, 95% CI)0.10 [0.01, 0.71]

 4 BILEVEL X SMC86823Risk Ratio (M-H, Random, 95% CI)1.05 [0.76, 1.46]

    4.1 Skin damage
6296Risk Ratio (M-H, Random, 95% CI)7.16 [1.27, 40.50]

    4.2 Nosocomial pneumonia
2152Risk Ratio (M-H, Random, 95% CI)0.35 [0.05, 2.20]

    4.3 Disconfort with mask
5274Risk Ratio (M-H, Random, 95% CI)5.39 [0.97, 30.09]

    4.4 Gastrointestinal bleeding
2170Risk Ratio (M-H, Random, 95% CI)2.32 [0.35, 15.42]

    4.5 Gastric dilatation
264Risk Ratio (M-H, Random, 95% CI)15.87 [0.96, 262.30]

    4.6 Vomiting
5848Risk Ratio (M-H, Random, 95% CI)1.21 [0.47, 3.11]

    4.7 Claustrophobia
1130Risk Ratio (M-H, Random, 95% CI)3.0 [0.12, 72.31]

    4.8 Pneumothorax
2832Risk Ratio (M-H, Random, 95% CI)1.01 [0.11, 9.63]

    4.9 Eye irritation
140Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    4.10 Sinusitis
1130Risk Ratio (M-H, Random, 95% CI)3.0 [0.12, 72.31]

    4.11 Cardiac arrest
2830Risk Ratio (M-H, Random, 95% CI)0.96 [0.25, 3.61]

    4.12 Stroke
1130Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    4.13 Seizures
1130Risk Ratio (M-H, Random, 95% CI)0.33 [0.01, 8.03]

    4.14 Gastric aspiration
1704Risk Ratio (M-H, Random, 95% CI)3.09 [0.13, 75.50]

    4.15 Hypotension
1698Risk Ratio (M-H, Random, 95% CI)0.82 [0.54, 1.23]

    4.16 Arrhythmia
1695Risk Ratio (M-H, Random, 95% CI)1.10 [0.64, 1.90]

    4.17 Progressive respiratory distress
1700Risk Ratio (M-H, Random, 95% CI)0.61 [0.36, 1.03]

 5 CPAP X BILEVEL57593Risk Ratio (M-H, Random, 95% CI)1.18 [0.94, 1.48]

    5.1 Skin damage
5790Risk Ratio (M-H, Random, 95% CI)0.64 [0.19, 2.16]

    5.2 Pneumothorax
2715Risk Ratio (M-H, Random, 95% CI)2.89 [0.12, 70.63]

    5.3 Pulmonary aspiration
3796Risk Ratio (M-H, Random, 95% CI)2.88 [0.12, 70.43]

    5.4 Gastric distension
3172Risk Ratio (M-H, Random, 95% CI)1.49 [0.56, 4.00]

    5.5 Vomiting
4857Risk Ratio (M-H, Random, 95% CI)0.97 [0.43, 2.19]

    5.6 Disconfort with mask
4735Risk Ratio (M-H, Random, 95% CI)1.03 [0.53, 2.00]

    5.7 Increased breathing discomfort
1576Risk Ratio (M-H, Random, 95% CI)1.42 [0.67, 3.02]

    5.8 Hypotension
2758Risk Ratio (M-H, Random, 95% CI)0.98 [0.65, 1.48]

    5.9 Arrhythmia
1677Risk Ratio (M-H, Random, 95% CI)2.00 [1.02, 3.92]

    5.10 Progressive respiratory distress
1679Risk Ratio (M-H, Random, 95% CI)1.19 [0.64, 2.21]

    5.11 Cardiorespiratory arrest
1678Risk Ratio (M-H, Random, 95% CI)1.61 [0.59, 4.38]

    5.12 Pharyngeal damage
180Risk Ratio (M-H, Random, 95% CI)0.95 [0.06, 14.69]

    5.13 Cough
180Risk Ratio (M-H, Random, 95% CI)0.32 [0.01, 7.57]

 
Comparison 15. Hospital or 7-day mortality

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC212263Risk Ratio (M-H, Random, 95% CI)0.72 [0.55, 0.94]

 
Comparison 16. Hospital or 30-day mortality

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC222387Risk Ratio (M-H, Random, 95% CI)0.75 [0.60, 0.95]

 
Comparison 17. General or 7-day ETI rate

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 NPPV (CPAP and BILEVEL) X SMC232417Risk Ratio (M-H, Random, 95% CI)0.55 [0.38, 0.78]

 
Summary of findings for the main comparison. Non-invasive positive pressure ventilation (CPAP and bilevel NPPV) for cardiogenic pulmonary edema

Non-invasive positive pressure ventilation (CPAP and bilevel NPPV) for cardiogenic pulmonary oedema

Patient or population: patients with cardiogenic pulmonary oedema
Settings: Emergency Department or Intensive Care Unit
Intervention: Non-invasive positive pressure ventilation (CPAP and bilevel NPPV)

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlNon-invasive positive pressure ventilation (CPAP and bilevel NPPV)

Hospital mortalityYStudy population1RR 0.66
(0.48 to 0.89)
1107
(20 studies)
⊕⊕⊕⊕
high2,3

204 per 1000135 per 1000
(98 to 182)

Moderate1

200 per 1000132 per 1000
(96 to 178)

Endotracheal intubation rateStudy populationRR 0.52
(0.36 to 0.75)
1261
(22 studies)
⊕⊕⊝⊝
low4,5

249 per 1000130 per 1000
(90 to 187)

Moderate

300 per 1000156 per 1000
(108 to 225)

Incidence of acute myocardial infarction (During intervention)Study populationRR 1.24
(0.79 to 1.95)
461
(8 studies)
⊕⊕⊕⊝
moderate5,6

153 per 1000190 per 1000
(121 to 299)

Moderate

169 per 1000210 per 1000
(134 to 330)

Incidence of acute myocardial infarction (After intervention)Study populationRR 0.7
(0.11 to 4.26)
154
(4 studies)
⊕⊝⊝⊝
very low5,7

26 per 100018 per 1000
(3 to 111)

Moderate

13 per 10009 per 1000
(1 to 55)

Intolerance to allocated treatmentStudy populationRR 0.47
(0.29 to 0.77)
1848
(13 studies)
⊕⊕⊕⊝
moderate8,9,10

234 per 1000110 per 1000
(68 to 180)

Moderate

350 per 1000165 per 1000
(101 to 269)

Hospital length of stayThe mean hospital length of stay in the intervention groups was
0.8 lower
(2.1 lower to 0.51 higher)
542
(10 studies)
⊕⊝⊝⊝
very low11,12

Intensive care unit length of stay (Copy)The mean intensive care unit length of stay (copy) in the intervention groups was
0.89 lower
(1.33 to 0.45 lower)
222
(6 studies)
⊕⊕⊝⊝
low5,13

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 The most studies have mixed populations (with different levels of severity and co-morbidities).
2 Was included only two quasi-randomised trials, but sensitivity analysis with quasi-randomised studies exclusion (Bersten 1991; Weitz 2007), showed the results to remain statistically significant. L'Her 2004 was interrupted early due to a greater number in deaths and complications in the control group.
3 Although there is less 300 events in meta-analysis, when add Gray's study that analysed the mortality in 30 days, our meta-analysis of hospital mortality show that these study reinforce the favourable use of NPPV in ACPE with more 300 events.
4 Was included only two quasi-randomised trials, but sensitivity analysis with quasi-randomised studies exclusion (Bersten 1991; Weitz 2007), showed the results to remain statistically significant. Park 2004 was interrupted early due to a difference in the frequency of intubations. Lin 1991 lost 35 of the 80 (44%) randomised patients for having fulfilled the criteria of exclusion or having presented failures on the received intervention.
5 There is less 300 events in meta-analysis.
6 Although two studies (Sharon 2000; Thys 2002) were interrupted early due to the incidence of acute myocardial infarction and the second due to a batch of failures of treatment and clinical decline.
7 Was included one quasi-randomised trial (Weitz 2007). Lin 1991 lost 35 of the 80 (44%) randomised patients for having fulfilled the criteria of exclusion or having presented failures on the received intervention.
8 Was included two quasi-randomised trials (Bersten 1991; Weitz 2007). L'Her 2004 was interrupted early due to a greater number in deaths and complications in the control group and not present the results in relation to autonomy for the activities of daily living, patient comfort and some planned adverse effects to be observed. Lin 1991 lost 35 of the 80 (44%) randomised patients for having fulfilled the criteria of exclusion or having presented failures on the received intervention. Thys 2002 was interrupted early due to a batch of failures of treatment and clinical decline.
9 The grouping of the studies demonstrated relevant heterogeneity which was eliminated with the exclusion of Gray 2008 study, but we have not found plausible justification for this result
10 RR < 0.5
11 Was included two quasi-randomised trials (Bersten 1991; Weitz 2007). L'Her 2004 and Thys 2002 were interrupted early, the first due to a greater number in deaths and in the control group and the second due to a batch of failures of treatment and clinical decline. L'Her 2004 did not present the results in relation to autonomy for the activities of daily living, patient comfort and some planned adverse effects to be observed. Lin 1991 lost 35 of the 80 (44%) randomised patients for having fulfilled the criteria of exclusion or having presented failures on the received intervention.
12 The grouping of the studies demonstrated relevant heterogeneity.
13 Was included two quasi-randomised trials (Bersten 1991; Weitz 2007). Thys 2002 was interrupted early due to a batch of failures of treatment and clinical decline.
 
Table 1. IPAP Level and EPAP Level and time of intervention

StudyIPAP level

(cmH2O)
EPAP in bievel NPPV

(cmH2O)
PEEP in CPAP (cmH2O)Time of bilevel NPPV

(hours)
Time of CPAP

(hours)

Bautin 20055.1 (SD 0.3)9.8 (SD 1.1)

Bellone 20045101.6 (SD 0.6)1.7 (SD 0.7)

Bellone 20055103.41 (SD 1.1)3.6 (SD 1.3)

Bersten 1991109.3 (SD 4.9)

Crane 200415510

Ferrari 200715 (SD 3.1)7 (SD 1.2)8.8 (SD 1.9)6.0 (SD 4.7)8.1 (SD 8.3)

Ferrari 200914 (SD 3.1)6.7 (SD 1.4)8.8 (SD 1.7)5.9 (SD 4.0)8.4 (SD 7.1)

Fontanella 201018 (SD 3)10 (SD 2)8 (SD 2)

Frontin 201010

Gray 200914 (SD 5)7 (SD 3)10 (SD 4)2.0 (SD 1.3)2.2 (SD 1.5)

Kelly 20027.5

L'Her 20047.58 (SD 6)

Liesching 200312410

Martin-Bermudez 20021.3 (SD 0.8)1.8 (SD 1)

Masip 200015.2 (SD 2.4)54.2 (SD 1.5)

Mehta 199714.35 (SD 1.73)510.08 (SD 1.24)7.1 (SD 4.7)6.4 (SD 5.8)

Moritz 200712 (SD 3.2)4.9 (SD 0.9)7.7 (SD 2.1)2.82.3

Nava 200314.5 (SD 21.1)6.1 (SD 3.2)11.4 (SD 3.6)

Park 20011247.52.5 (SD 0.6)2.8 (SD 1.5)

Park 200417 (SD 2)11 (SD 2)11 (SD 2)2.0 (SD 1.0)1.7 (SD 0.6)

Rasanen 198510

Sharon 20009.3 (SD 2.3)4.2 (SD 3.1)

Takeda 199711.9 (SD 8.4)

Thys 200216.5 (SD 3.3)6.1 (SD 1.5)1.2 (SD 0.2)

Weitz 200712.5 (SD 1.2)5

 CPAP - continuous positive airway pressure; EPAP - expiratory positive airway pressure; IPAP - inspiratory positive airway pressure; PEEP - positive expiratory end pressure; SD - standard deviation; * statistically significant.
 
Table 2. Summary of adverse events

Adverse eventsNumber of events (CPAP)Total number CPAPNumber of event (bilevel NPPV)Total number (bilevel NPPV)RR (95% CI)

Skin damage2472174580.06 (0.01, 0.43)*

Pneumonia0401760.63 (0.03, 15.03)

Pulmonary aspiration047613830.27 (0.01, 6.57)

Gastric distention51788510.18 (0.06, 0.52)*

GI bleeding0113851.02 (0.06, 18.63)

Vomitting738194190.86 (0.32, 2.27)

Pneumothorax044014300.33 (0.01, 7.97)

Asphyxia/claustrophobia0201651.05 (0.04, 24.76)

Mask discomfort15364224400.82 (0.43, 1.57)

Sinusitis0431650.50 (0.02, 12.00)

Conjunctivitis070

Eye irritation020

Cardiac arrest6333134100.57 (0.22, 1.48)

Stroke065

Seizure065

Hypotension36332373461.01 (0.66, 1.56)

Arrhythmia requiring treatment12332253450.50 (0.25, 0.98)*

Progressive respiratory distress17333213460.84 (0.45, 1.57)

Increase breathing discomfort16287192910.85 (0.45, 1.63)

 CI - confidence interval; CPAP - continuous positive airway pressure; RR - relative risk; SD - standard deviation; * statistically significant..
 
Table 3. Adverse events by NPPV versus SMC

Adverse eventsStudiesNPPV groupSMC groupRR (95% CI)

Skin damage11 studies (Rasanen 1985, Bersten 1991, Takeda 1998, Masip 2000, Kelly 2002, Thys 2002, Nava 2003, Crane 2004, L'Her 2004, Park 2004, Bautin 2005)17/3180/2766.62 (1.20, 36.55)*

Pneumonia3 study (Lin 1991, Nava 2003, Bautin 2005)1/1164/1160.35 (0.05, 2.20)

Pulmonary aspiration5 studies (Rasanen 1985, Bersten 1991, Lin 1991, Kelly 2002, Gray 2008)1/7870/4681.58 (0.06, 38,61)

Gastrointestinal
bleeding
3 study (Takeda 1998, Masip 2000, Nava 2003)3/962/961,37 (0.27, 6.89)

Gastric distension8 studies (Rasanen 1985, Bersten 1991, Lin 1991, Takeda 1998, Thys 2002, Park 2004, L'Her 2004, Frotin 2010)13/2530/23113.26 ( 0.82, 215.12)

Vomiting5 studies (Masip 2000, Thys 2002, Crane 2004, Park 2004, Gray 2008)16/8008/4291.06 (0.46, 2.47)

Asphyxia2 study (Bersten 1991, Nava 2003)1/850/853.00 (0.12, 72.31)

Pneumothorax6 studies (Bersten 1991, Kelly 2002, Nava 2003, L'Her 2004, Gray 2008, Frotin 2010)1/8941/5800.72 (0.08, 6.89)

Conjunctivitis2 studies (Kelly 2002, L'Her 2004)0/700/77inestimable

Sinusitis2 study (Nava 2003, L'Her 2004)1/1080/1113.00 (0.12, 72.31)

Mask discomfort7 study (Masip 2000, Nava 2003, L'Her 2004, Park 2004, Bautin 2005, Weitz 2007, Frotin 2010)7/2650/2475.39 (0.97, 30.09)

Hypotension1 study (Gray 2008)73/67846/3520.82 (0.58, 1.16)

Arrhythmia1 study (Gray 2008)37/67723/3500.83 (0.50, 1.38)

Progressive respiratory distress2 studies (L'Her 2004, Gray 2008)39/72236/4000.58 (0.37, 0.89)*

Neurological failure (coma)1 study (L'Her 2004)1/4411/460,10 (0.01, 0,71)*

Cardiorespiratory arrest3 studies (Nava 2003, L'Her 2004, Gray 2008)21/78622/4660.60 (0.29, 1.26)

Eye irritation1 study (Masip 2000)0/200/20inestimable

Stroke1 study (Nava 2003)0/650/65inestimable

Seizure1 study (Nava 2003)0/651/650.33 (0.01, 8.03)

 CI - confidence interval; NPPV - noninvasive positive pressure ventilation; RR - relative risk; SMC - standard medical care; * statistically significant.
 
Table 4. Adverse events by CPAP versus SMC

Adverse EventsStudiesCPAP groupSMC groupRR (95% CI)

Skin damage7 studies (Rasanen 1985, Bersten 1991, Takeda 1998,

Kelly 2002, Crane 2004, L'Her 2004, and Park 2004)
1/1680/1753.00 (0.13, 69.52)

Pneumonia1 study (Lin 1991)0/400/40inestimable

Pulmonary aspiration5 studies (Rasanen 1985, Bersten 1991, Lin 1991,

Kelly 2002, Gray 2008)
0/4400/468inestimable

Gastrointestinal
bleeding
1 study (Takeda 1998)0/111/110.33 (0.02,7.39)

Gastric distension7 studies (Rasanen 1985, Bersten 1991, Lin 1991,

Takeda 1998, Park 2004, L'Her 2004, Frotin 2010)
5/2210/22611.00 ( 0.64, 189.65)

Vomiting3 studies (Crane 2004, Park 2004, Gray 2008)7/3818/4040.93 (0.34, 2.54)

Asphyxia1 study (Bersten 1991)0/200/20inestimable

Pneumothorax5 studies (Bersten 1991, Kelly 2002, L'Her 2004,

Gray 2008, Frotin 2010)
0/4830/515inestimable

Conjunctivitis2 studies (Kelly 2002, L'Her 2004)0/700/77inestimable

Sinusitis1 study (L'Her 2004)0/430/46inestimable

Mask discomfort3 studies (L'Her 2004, Park 2004, Frotin 2010)0/1300/135inestimable

Hypotension1 study (Gray 2008)36/33246/3520.83 (0.55, 1.25)

Arrhythmia1 study (Gray 2008)12/33223/3500.55 (0.28, 1.09)

Progressive respiratory distress2 studies (L'Her 2004, Gray 2008)18/37636/4000.53 (0.31, 0.92)*

Neurological failure (coma)1 study (L'Her 2004)1/4411/460,10 (0.01, 0,71)*

Cardiorespiratory arrest2 studies (L'Her 2004, Gray 2008)8/37621/4010.41 (0.18, 0.91)*

 CI - confidence interval; CPAP - continuous positive airway pressure; RR - relative risk; SMC - standard medical care; * statistically significant.
 
Table 5. Adverse events by bilevel NPPV versus SMC

Adverse EventsStudiesBilevel NPPV GroupSMC GroupRR (95% CI)

Skin damage6 studies (Masip 2000, Thys 2002, Nava 2003, Crane 2004, Park 2004, Bautin 2005)16/1480/1487.16 (1.27, 40.50)*

Pneumonia2 study (Nava 2003, Bautin 2005)1/764/760.35 (0.05, 2.20)

Gastrointestinal
bleeding
2 studies (Nava 2003, Masip 2000)3/851/852.32 (0.35, 15.42)

Gastric distension2 studies (Thys 2002, Park 2004)8/320/3215.87 (0.96, 262.30)

Vomiting5 studies (Masip 2000, Thys 2002, Crane 2004, Park 2004, Gray 2008)9/4198/4291.21 (0.47, 3.11)

Pneumothorax2 study (Nava 2003, Gray 2008)1/4111/4211.01 (0.11, 9.63)

Eye irritation1 study (Masip 2000)0/200/20inestimable

Sinusitis1 study (Nava 2003)1/650/653.00 (0.12, 72.31)

Mask discomfort5 studies (Masip 2000, Nava 2003, Park 2004, Bautin 2005, Weitz 2007)7/1350/1395.39 (0.97, 30.09)

Claustrophobia1 study (Nava 2003)1/650/653.00 (0.12, 72.31)

Cardiac arrest2 study (Nava 2003, Gray 2008)13/41017/4200.96 (0.25, 3.61)

Stroke1 study (Nava 2003)0/650/65inestimable

Seizure1 study (Nava 2003)0/651/650.33 (0.01, 8.03)

Pulmonary aspiration1 studies (Gray 2008)1/3470/3573.09 (0.13, 75.50)

Hypotension1 study (Gray 2008)37/34646/3520.82 (0.54, 1.23)

Arrhythmia1 study (Gray 2008)25/34523/3501.10 (0.64, 1.90)

Progressive respiratory distress1 study (Gray 2008)21/34635/3540.61 (0.36, 1.03)

 CI - confidence interval; NPPV - noninvasive positive pressure ventilation; RR - relative risk; SMC - standard medical care; * statistically significant.
 
Table 6. Adverse events by bilevel NPPV versus CPAP

Adverse eventsSstudiesBilevel NPPV groupCPAP groupRR (95% CI)

Skin damage5 studies (Mehta 1997, Martin-Bermudez 2002, Crane 2004, Park 2004, Gray 2008)4/4006/3900.64 (0.19, 2.16)

Pulmonary aspiration3 studies (Mehta 1997, Martin-Bermudez 2002, Gray 2008)1/4070/3892.88 (0.12, 70.43)

Gastric distension3 studies (Mehta 1997, Martin-Bermudez 2002, Park 2004)8/895/831.49 (0.56, 4.00)

Vomiting4 studies (Martin-Bermudez 2002, Crane 2004, Park 2004, Gray 2008)11/43711/4200.97 (0.43, 2.19)

Pneumothorax2 studies (Mehta 1997, Gray 2008)1/3650/3502.89 (0.12, 70.63)

Mask discomfort4 studies (Mehta 1997, Martin-Bermudez 2002, Park 2004, Gray 2008)17/37516/3601.03 (0.53, 2.00)

Increased breathing discomfort1 study (Gray 2008)16/29111/2851.42 (0.67, 3.02)

Hypotension2 studies (Martin-Bermudez 2002, Gray 2008)41/38740/3710.98 (0.65, 1.48)

Arrhythmia1 study (Gray 2008)25/34512/3322.00 (1.02, 3.92)*

Progressive respiratory distress1 study (Gray 2008)21/34617/3331.19 (0.64, 2.21)

Cardiorespiratory arrest1 study (Gray 2008)10/3456/3331.61 (0.59, 4.38)

Pharyngeal damage1 study (Martin-Bermudez 2002)1/411/390.95 (0.06, 14.69)

Cough1 study (Martin-Bermudez 2002)1/411/390.32 (0.01, 7.57)

 CI - confidence interval; CPAP - continuous positive airway pressure; NPPV - noninvasive positive pressure ventilation; RR - relative risk; SMC - standard medical care; * statistically significant.