apo guidelines1

EVIDENCE BASED GUIDELINES

Management of Acute Pulmonary Oedema

Evidence based guidelines recommended for use in The Royal Melbourne Hospital

Issue Date: April 2004

Review Date: July 2005

Clinical Epidemiology and Health Service Evaluation Unit Supported by funding from the Department of Human Services

Evidence Based Guidelines: Chronic Heart Failure - Management of Acute Pulmonary Oedema

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TABLE OF CONTENTS

INTRODUCTION.....................................................................................................................................4 MULTI-DISCIPLINARY REVIEW GROUP.....................................................................................................4

Other Contributors ..........................................................................................................................4 Systematic Review & Document Preparation ................................................................................4 Intended Audience..........................................................................................................................4 Intent of the guidelines ...................................................................................................................4 Process of guideline development .................................................................................................5 Levels of Evidence for Evaluating the Clinical Research Data ......................................................5

CARDIOGENIC OEDEMA .........................................................................................................................6 NON-CARDIOGENIC OEDEMA .................................................................................................................6 CAUSES OF ACUTE PULMONARY OEDEMA ..............................................................................................6 DIAGNOSIS ...........................................................................................................................................7

Signs of Acute Pulmonary Oedema ...............................................................................................7 Differential Diagnosis: ....................................................................................................................7 Investigations:.................................................................................................................................7

MANAGEMENT ......................................................................................................................................8 INITIAL TREATMENT ...............................................................................................................................8 CARDIAC MANAGEMENT ........................................................................................................................8

Patient with stable cardiac status ...................................................................................................8 Patient with unstable cardiac status...............................................................................................9 General Management.....................................................................................................................9

QUESTION: WHICH TREATMENTS IMPROVE OUTCOMES IN ACUTE PULMONARY OEDEMA?..............................................................................................................................................................10

DRUGS ...............................................................................................................................................10 Morphine.......................................................................................................................................10 Frusemide.....................................................................................................................................11 Nitrates .........................................................................................................................................11 ACE Inhibitors...............................................................................................................................13

NON-PHARMACEUTICAL INTERVENTIONS ..............................................................................................13 Respiratory Management .............................................................................................................13

SUMMARY OF EVIDENCE ..................................................................................................................15

REFERENCES......................................................................................................................................25


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High Dependency Critical Care Management

CONSIDER CLINICAL FEATURES Dyspnoea Central/Peripheral Cyanosis Pallor Tachycardia Tachypnoea Hypotension/Hypertension Cool Extremities Elevated JVP Displaced Apex Beat S3/Basal Crepitations Ankle/Sacral Oedema Differential Diagnosis COPD, Bronchospasm, Pneumonia, Pulmonary Embolism

IMMEDIATE TREATMENT • Sit-up • Maximal Oxygen- 8-10 L via Mask or FiO2 100% • Oxygen Saturation Assess Hypoxia • Nitrates If the BP Systolic >90mmHg

Either Sublingual 0.4-0.8mg OR Topical GTN • IV Access FBE / U&E / Troponin, Enzymes • Arterial Blood Gases • Obtain 12 Lead ECG

CARDIAC MANAGEMENT

Continuous 12 Lead ECG Monitoring

Inotropic Support for Cardiogenic shock

RESPIRATORY MANAGEMENT

CPAP* 10cm H20

BIPAP (Currently lacks supporting evidence) Review ABGs P after 15mins.

Treat : Bronchospasm

Beware : Hypercapnoea / Acidosis / Fatigue

Consider: Intubate and IPPV*

RMH WARD-BASED GUIDELINES FOR MANAGEMENT OF ACUTE PULMONARY OEDEMA

Non-Invasive Ventilation * CPAP=Continuous Positive Pressure Ventilation * BIPAP = B.

Invasive Ventilation * IPPV = Intermittent Positive Pressure Ventilation

6 MINUTE REVIEW

UNSTABLE • Hypoxia O2 sat < 89% • Hypotensive BP < 90mmHg Systolic • Haemodynamically Unstable ->Continuous 12 Lead ECG Atrial Fibrillation or other arrhythmia: treat arrhythmia. Remember: rapid AF can be DUE to sepsis, blood loss, untreated failure.

MEDICAL EMERGENCY TEAM / ICU REFERRAL

STABLE • Diuresis: If not intra-vascularly depleted, Give (IV) usual daily dose frusemide or up to 1-1.5 mg/kg. A higher dose maybe necessary if renal impairment is present • Morphine lose dose 1-2mg increments IV, titrate & Assess for Respiratory Depression and Hypotension Treat underlying cause • IV Nitrate 10-20mcg/ min adjusting rate to response and BP> 100 systolic • Arrhythmias

For Atrial Fibrillation - Refer AF guidelines Ventricular Tachycardia, Heart block - Consider: Drugs, Sepsis, Myocardial Ischaemia, Renal Failure


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INTRODUCTION

Multi-disciplinary Review Group The Guidelines were developed by Dr Thanh Tan Nguyen, Dr Brian Wai, Ana Hutchinson B.N. and Dr Caroline Brand. The following multidisciplinary group reviewed the guidelines. Dr Caroline Brand Acting Director, Clinical Epidemiology & Health Care Evaluation Unit Ms Anastasia Hutchinson Project officer, Clinical Epidemiology Dr Anuradha Aggarwal Cardiologist Dr Leeane Grigg Director Cardiology Ms Monica Kerlin Nurse Consultant Cardiology Dr Alistair Meyer Director of Emergency Dr David Russell Head of Medical Unit Dr Mark Hew Senior Medical Registrar Dr Nancy Huang GP Liasion Ms Petrina Halloran Project Officer, Discharge Planning A/ Prof Don Campbell Director Clinical Epidemiology Mr Barabara Mann Nurse Unit Manager, Ward 6 East, RMH Ms Lauren Andrew Manager, Physiotherapy, Melbourne Health Ms Jane Wiles Care co ordinator, Emergency Department Michael Daly GP Representative Ms Gabrielle Nagel Ex Divisional Director of Nursing Mr Nick Jones Pharmacist Mr Don Ellis Consumer Representative

Other Contributors Dr Peter Greenberg, General Physician and Evidence based medicine CEHSEU A/Prof. David Russell, Director General Medicine Dr Andrew Dent Director of Emergency St Vincents Hospital Melbourne Nursing and Allied Health staff from the general medical wards who participated in focus groups. Systematic Review & Document Preparation The systematic review was prepared by Brian Wai, Thanh Tan Nguyen and Anastasia. Hutchinson and considered by all members of the multi-disciplinary review group. Intended Audience The guideline is for clinicians involved in the care of patients with Acute Pulmonary Oedema Intent of the guidelines This document provides current evidence based guidance about best practice management of Chronic Heart Failure and Acute Pulmonary Oedema. • These guidelines are not a prescriptive standard of medical care. Standards of medical care are

determined on the basis of all clinical data available for an individual patient. • This is a guide to evidence based practice. The guidelines may not include all proper methods of

care or exclude other acceptable methods of care aimed at achieving the same results. • The ultimate choice about treatment options is made by the patient (and/or carer) following

recommendations from the clinician.


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Process of guideline development The development of these guidelines arose in response to variations in APO management between individual clinicians, unit/department recommendations at Melbourne Health and a perceived need for consensus based on current levels of evidence. The guideline is based on existing international and national guidelines** relating to management of Chronic Heart Failures, supplemented by additional systematic the literature searches. The guidelines were developed with regular consultation with a multidisciplinary working party. **Guidelines on the contemporary management of the patient with chronic failure in Australia. National Heart Foundation and The Cardiac Society of Australia and New Zealand, 2002. ACC/ AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult. 2001 The American College of Cardiology and the American Heart Association, Inc. Information on the cost of different treatment options was not specifically included in the search strategies and is not considered in the guidelines. Levels of Evidence for Evaluating the Clinical Research Data The Australian National Health and Medical Research Council’s levels of evidence have been used when evaluating clinic research data (1). Level Type of Evidence I II III –1 III –2 III –3 IV

Evidence obtained fro a systematic review of all relevant randomised controlled trials (RCTs) Evidence obtained from at least one properly designed RCT Evidence obtained from well designed controlled trials without randomisation Evidence obtained from well designed cohort or case control analytic studies, preferably from more than one centre or research group Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this type of evidence Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.

Search strategy Cochrane Library and OVID Medline 1966-2003 were accessed The following search strategy was used to access Medline database: exp Heart Failure, Congestive / or heart Failure.mp.; Pulmonary Edema/ or cardiogenic pulmonary oedema.mp.; exp Randomized Controlled Trials/ or randomised controlled trials.mp. and was combined with the treatment modality; CPAP.mp.;BiPAP.mp.; Frusemide.mp. or exp Frusemide; diuretics.mp. or exp DIURETICS/; nitrates.mp. or exp NITRATES/; ACE Inhibitors.mp. or exp Angiotensin-Converting Enzyme Inhibitors/ These searches were limited to those published in English and randomized controlled trials. However, as there were no controlled trials in the use of diuretics or morphine in the management of acute cardiogenic pulmonary oedema, all relevant literature pertaining to these agents were retrieved.


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Bibliographies of selected articles were reviewed for other relevant articles. Definitions: Pulmonary Oedema Movement of fluid at the capillary region occurs due to an imbalance in the hydrostatic and osmotic pressures acting at the capillary-interstitial fluid exchange. Pulmonary oedema ensues when the fluid filtration exceeds clearance capability by the lymphatics. This most often occurs when there is marked elevation of pulmonary capillary pressure leading to alveolar oedema. The clinical picture is of cardiac failure with extreme breathlessness, and may include; expectoration of blood-tinged fluid, rales or crackles over the lung fields, elevated JVP and peripheral oedema. Pulmonary Oedema maybe a consequence of cardiac or non-cardiac problems.

Cardiogenic Oedema In congestive cardiac failure, oedema occurs as a result of an increase in the pulmonary venous pressure. The patient clinical picture depends on the magnitude and the duration of the elevated intravascular pressure. Mild tachypnoea occurs with engorgement of the pulmonary vasculature resulting in reduced lung compliance that increases the respiratory workload. Alveolar and airway oedema are seen in severe clinical pulmonary oedema, when the sustained high intravascular pressure has disrupted the tight junctions between alveolar lining cells, with outpouring of fluid with cellular and macromolecules contents.

Non-Cardiogenic Oedema In non-cardiogenic oedema, there is usually minimal elevation of pulmonary capillary pressure, except in volume overload due to oliguric renal failure. It may reflect altered alveolar-capillary membrane permeability, such as Acute Respiratory Distress Syndrome (ARDS), and also lymphatic insufficiency following lung transplant or lymphangitic carcinomatosis. It may occur but is uncommon in diminished plasma oncotic pressure in hypoalbuminemic states such as severe liver disease, nephrotic syndrome and protein-losing enteropathy. Negativity of interstitial pressure has been implicated in oedema following the rapid removal of pneumothorax. The mechanisms for non-cardiogenic oedema are unknown in some occasions such as in narcotic overdose, high-altitude or neurogenic pulmonary oedema.

Causes of Acute Pulmonary Oedema Exacerbations of CCF The causes of acute exacerbations of congestive cardiac failure are conveniently summarized by the acronym MADHATTER - Myocardial infarct, Anaemia, Drugs or dietary high fluid or salt intake, Hypertension, Arrhythmias, Thyrotoxicosis, Toxic i.e. infection, Endocarditis or embolism (pulmonary), Renal failure or pregnancy (‘ruptured placenta’)

Myocardial infarct, Anaemia, Drugs or dietary high fluid or salt intake, Hypertension, Arrhythmias, Thyrotoxicosis, Toxic i.e. infection, Endocarditis or embolism (pulmonary), Renal failure or pregnancy (‘ruptured placenta’)


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Diagnosis In some patients, breathlessness may be the only symptom or sign. Do not wait for other manifestations before considering the diagnosis of pulmonary oedema! The chest Xray (CXR) is important, but treatment should commence empirically beforehand if the patient is unwell. It is sometimes appropriate to treat for bronchospasm at the same time if the diagnosis is unclear. Signs of Acute Pulmonary Oedema

Dyspnoea, Tachypnoea, Central/Peripheral Cyanosis, Pallor Tachycardia, Hypotension/Hypertension, Cool Extremities Elevated JVP Displaced Apex Beat S3, Basal Crepitations Ankle/Sacral Oedema

It is important to note that not all of these signs may be present.

Differential Diagnosis:

Bronchospasm Exacerbation COPD Pneumonia Pulmonary Embolism

Specific reversible precipitants should be considered.

Myocardial Ischemia (and AMI) Anaemia Fluid overload Arrhythmia: eg: Atrial Fibrillation Acute Oliguric Renal Failure

Investigations: Continuous oxygen saturation monitoring Arterial blood gas FBE, electrolytes, cardiac enzymes ECG CXR


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MANAGEMENT

Initial Treatment General Management

Rationale Level of evidence

Sit Patient Up Improve Gas Transfer IV Maximal Oxygen- 8-10 L via Mask or FiO2 100%

Maintain normal PaO2 Prevent further cardiac ischaemia

IV Nitrates

If the BP Systolic >90mmHg Either sublingual 0.4-0.8mg

or topical GTN

Decrease fluid overload and improve gas transfer

II

Obtain a 12 Lead ECG Establish cardiac rhythm and/or ischaemic changes IV

Cardiac Management Patient with stable cardiac status General Management


Continuous ECG Monitoring Monitor for cardiac arrhythmias, ischaemic changes IV

Diuresis: If not intra-vascularly depleted, Consider if

-Patient withheld regular dose -Fluid Overload secondary to Renal Failure Give (IV) usual daily dose frusemide or 40mg-100mg intravenously. Additional boluses are given until adequate response.

Decrease fluid overload and improve gas transfer

III B

Morphine : Monitor blood pressure; Dose 1-2mg increments IV, titrate & Assess for respiratory depression and hypotension

Relieve pain & anxiety

empirical evidence only, about the use of morphine in APO

IV

IV Nitrate 10-20mcg/ min adjusting rate to response and BP> 100 systolic

Decrease fluid overload and improve gas transfer II


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Patient with unstable cardiac status General Management


Inotropic Support for Cardiogenic shock

• Renal Dose Dopamine 1-2 mcg/kg/min • Dobutamine Infusion: 2-20mg/kg/min • Adrenaline Infusion 1-2-mcg/hr • Adrenaline Stat Dose 1:10, 000 solution

ie 0.1mg/ml and slowly inject IV, • 1 ml increments up to a total of 3 ml.

(0.3mg)

Hypotensive BP < 90mmHg Systolic Haemodynamically Unstable

II

Arrhythmias Atrial Fibrillation or other arrhythmia: treat arrhythmia. Remember: rapid AF can be DUE to sepsis, blood loss, untreated failure, pulmonary embolism Ventricular Tachycardia, Heart block Consider: Drugs, Sepsis, Myocardial Ischaemia, Renal Failure


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QUESTION: WHICH TREATMENTS IMPROVE OUTCOMES IN ACUTE PULMONARY OEDEMA?

Drugs Morphine Although morphine has been used for years in the treatment of pulmonary oedema, the mechanism of its effect is not completely understood. There have been no randomised controlled trials regarding the use of morphine in acute cardiogenic pulmonary oedema. Its precise mode of action is not known. Animal studies suggest that morphine produces a significant peripheral venodilation and moves significant quantities of blood from the central to the peripheral circulation1. Studies of venous tone changes in normal subjects and patients with mild stable acute pulmonary oedema demonstrate initial venodilation after a dose of Morphine2. The magnitude of the venodilation induced by morphine however, has been shown to be quite minimal, and the amount of blood that could be pooled in the limbs has been calculated to be quite small (70ml in normal subjects and 116mls in patients with acute pulmonary oedema2. This is insufficient to cause significant clinical improvement in patients’ with APO. Alternative mechanisms of action include pooling of blood in the splanchnic circulation caused by arteriolar dilation and passive filling of previously under perfused venous segments2. Morphine’s capacity to dilate resistance vessels, resulting in afterload reduction may be of more importance than its ability to dilate veins2. Morphine’s other mechanisms of action such as the reduction in dyspnoea, the work of breathing and the inducement of a central nervous system euphoria may be the primary factors in relieving pulmonary oedema2 Benefits: Reduction in dyspnoea and anxiety. Potentially improves cardiac output by reducing afterload on the heart or the redistribution of blood volume Harms: Morphine has the potential to produce deleterious consequences in patients with other conditions, such as chronic lung disease, that may be confused with pulmonary oedema. The respiratory and central nervous system depressant effects of morphine may cause significant deterioration in such patients. Comment: Small doses of Morphine (1-2 Mg IV) maybe used in APO to relieve anxiety. Patients should be closely monitored for signs of drowsiness or decreased consciousness state.


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Frusemide Frusemide was first used in the treatment of oedema in the early 1960’s 3. The earliest published trial was by Kleinfelder in the University of Wurzburg, in which the drug was used in 51 patients, 36 of whom had oedema of cardiac origin and none had APO 4. Before frusemide, the available therapeutic options were digoxin, spironolactone, thiazide and intramuscular mercurials diuretics but many patients were refractory to these treatments 5 6

A number of unblinded, non-randomised clinical studies showed that frusemide was safe, more effective and faster acting diuretic 5 4 7 8 9 10 11. As there were initially no effective alternatives, treatment with Frusemide became standard practice in the management of Acute Pulmonary Oedema without the level of investigation which would be required today. Benefits: Studies of patients with acute left ventricular failure have shown that intravenous frusemide has an early venodilating effect thus decreasing cardiac preload. The reduction in cardiac filling pressures and decreased pulmonary congestion prior to significant diuresis 12 13 14 15 16. The initial effect, within 5-15 minutes of dosing, is vascular, and causes a rise in renal plasma flow and increased venous capicitance. Peak increase in urine output occurs by 30 minutes and peak natriuretic effect at 60 minutes 14. The lowering of intracardiac filling pressures from diuresis lowers the intravascular pressure, permitting mobilization of fluid from the insterstium and therefore minimising the reduction in intravascular volume. This means that haemodynamics are usually maintained even with a rapid diuresis. Harms: There is some reservation regarding frusemide as it can cause a variety of changes that are theoretically undesirable. A different haemodynamic response maybe seen in patients with advanced chronic heart failure, in whom, intravenous loop diuretics may result in an acute increase in plasma renin and norepinephrine levels from activation of the sympathetic and renin-angiotensin systems. This leads to tachycardia, vasoconstriction and a rise in systemic blood pressure 3 13 16 17. This increase in afterload reduces cardiac output and increases cardiac filling pressures resulting in worsening respiratory distress. In combination with reducing stroke volume, frusemide has the potential to increase myocardial oxygen demand and aggravate ischaemia 13 16. Dose: There has been no current trial to establish the most effective starting dose for patient in acute pulmonary oedema. The usual starting dose for frusemide is 40mg-100mg intravenously. Additional boluses are given until adequate response 18 19 20 21 16 Nitrates Benefits: The ideal treatment of acute pulmonary oedema would relieve pulmonary congestion by decreasing preload without activating the neurohumoral axis or the renin angiotensin system, thus avoiding an increase in cardiac afterload. Nitrates are potent venodilators and have been shown to increase cardiac output and reduce both preload and afterload via infusion 22 or sublingual 23 routes. Recent studies have shown that the use of nitrate vasodilators are safe and effective in heart failure 24 20 25 26 27 19. Two randomised controlled studies have directly compared the haemodynamic effects of intravenous frusemide and morphine versus nitrates in patients with acute pulmonary oedema 26 27. Frusemide and morphine reduced left heart filling pressure and cardiac output and transiently raised systemic blood-pressure. In contrast, nitrates reduced systemic blood pressure and peripheral resistance with the result that cardiac output was maintained despite a fall in pulmonary vascular and left heart filling pressures 27. These studies demonstrate that reducing preload by venodilation is haemodynamically superior to diuresis 26 27. However, the sample sizes were small and patients were not unstable nor in respiratory distress. A randomised controlled trial (RCT) comparing the safety and efficacy of high dose nitrates (with low-dose frusemide) versus high-dose frusemide (with low dose nitrates) in patients with severe pulmonary oedema found that high dose nitrates were more effective 25. High dose nitrates reduced the need for mechanical ventilation (p=0.0041) and the rates of myocardial infarction (p= 0.047) 25. In this study the number needed to treat to prevent one episode of mechanical ventilation was 4 (95%CI [2-9]) standard-treatment patients. A RCT of patients with acute pulmonary oedema without


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myocardial infarction demonstrated that nitrates were as effective as morphine and frusemide in improving gas exchange in these patients 20. In a retrospective cohort study of 172 patients with acute cardiogenic pulmonary oedema presenting to two emergency departments in the UK, the use of nitrates in the emergency department was associated with improved survival to hospital discharge (odds ratio 3.04, 95% CI 1.15-8.01). Nitrates were recommended for all patients whose presenting blood pressure would allow their use 16. In summary, while diuretic action of frusemide is useful in patients with total body fluid overload, pulmonary oedema in many cases is produced by inefficient cardiac pumping, rather than fluid volume increase, such as in recent myocardial infarction or acute rhythm disturbances. Nitrates have minimal side effects, the advantage of venodilation without changing the cardiac output and minimal neurohumoral activation 24 Harms: Systematic review of large randomised controlled trials of Nitrate treatment in AMI found no significant harm associated with routine use of nitrates 28, (ISIS-4) Collaborative Group. Comment: Initial management of APO should include sub-lingual or topical glyceryl trinitrate provided that the systolic blood-pressure is greater than or equal to 90mmHg. In high-dependency environments intravenous nitrates can be commenced at 10-20mcg /min and titrated to patients clinical response. Clinical parameters should include, heart rate, respiratory rate, dyspnoea score and pulmonary artery wedge pressure, when available.


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ACE Inhibitors Benefits: Two small studies have demonstrated that there may be some role for ACE inhibitors in APO 29 21. Results are promising but larger studies need to be performed to establish Level 1 Evidence for this treatment. Hamilton’s prospective randomised double-blind placebo controlled trial of 48 patients with pulmonary oedema compared the efficacy of sublingual captopril with placebo when added to standard treatment for pulmonary oedema. There was greater improvement in symptoms of clinical distress (“APEX score”) in the captopril group at 25 minutes 21, but the improvement was not sustained beyond 25 mins. (The “APEX Score” is a composite score derived from a patient dyspnoea scale, patient diaphoresis score, a measure of respiratory distress by the treating physician and the patients’ capacity to tolerate lying flatter 21. The validity of the APEX score as a measure of clinical distress and clinical outcomes is not well established.) Adigun et al conducted a small randomised controlled trail of 17 patients comparing the use of captopril and prazosin with hydralazine and nitrates in treatment of acute pulmonary oedema29. There was a faster improvement in heart rate and respiratory rate in captopril group. The power of this study is limited by the small number. Comment: There is insufficient evidence to recommend the use of ACE inhibitors in the emergency management of APO.

Non-Pharmaceutical Interventions Respiratory Management

Respiratory Management

Indication Level of Evidence

CPAP 10cm H20 APO Dyspnoea Hypoxia

II

BIPAP The use of BIPAP for the Acute management of APO is not currently supported by controlled trials.

(Currently lacks supporting evidence)

Salbutamol Bronchospasm Diagnosis Unclear Possible COPD Exacerbation

IV

Intermittent Positive Pressure Ventilation

Hypoxia Hypercapnoea Acidosis Fatigue

IV Continuous Positive Airways Pressure (CPAP) Benefits: There have been four randomized controlled studies which have demonstrated better outcomes for patients treated with Continuous Positive Airway Pressure (CPAP) via face mask 30 31 32 33. Three of the four studies demonstrated improvements in gas exchange and decreased intubation rates in the CPAP group: 35% versus 0% (p<0.005) 34, 36% versus 16% (p<0.01) 32, 73% versus 18% (p 0.03) 33. One study demonstrated improvements in mortality for patients in the CPAP group: 64% oxygen versus 9 % CPAP group, (p 0.02), the power of this study was limited by small sample size 33. These four studies did not demonstrate any difference in length of hospital stay. A more recent randomised concealed, unblinded trial, failed to show significant improvement in patients using CPAP, but the patients in this study had PaCO2 <50mmHg at entry 35. A systematic review conducted by Pang et al found that pooled data demonstrated decreased intubation rates (risk difference – 26%, 95% CI –13 to –38) and a trend towards decreased in hospital mortality (risk difference –6.6%; 95% CI 3 to –16) 36.


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Comments: Patients in respiratory distress may find it difficult to tolerate the CPAP mask and will not receive the full benefit from the CPAP modality as the seal is not maintained on the patients’ face. Patients’ with a decreased conscious state who are unable to maintain their own airway are not suitable for treatment with CPAP. Patients in severe failure (PaO2<70mmHg with FiO2 100%), severe cardiogenic shock, or decreased conscious state on arrival to the emergency department were excluded from the above studies. The evidence available supports the use of CPAP in cardiogenic pulmonary oedema, the greatest benefit may be obtained in those in acute ventilatory failure (PaCO2 >50mmHg). There is currently no evidence that CPAP causes harm in patients with cardiogenic pulmonary oedema, however, the evidence available is insufficient to exclude this concern 36.

Non-Invasive Ventilation: Bi-level Positive Airway Pressure (BIPAP) Bi-Level Positive Airway Pressure (BIPAP) is an alternative mode of non-invasive ventilation in which positive pressure is delivered to the airways during both the inspiratory and expiratory cycles. Whereas CPAP delivers a constant continuous positive airway pressure throughout the respiratory cycle, BiPAP delivers a higher pressure during the inspiratory cycle. There has been some controversy surrounding the use of BIPAP for patients with acute pulmonary oedema as potentially the positive pressure during the inspiratory cycle may decrease blood flow down the coronary arteries and exacerbate myocardial ischaemia. Harms: Previous RCTI’s have reported higher rates of adverse events in patients randomised to BIPAP, although differences in baseline characteristics of the studied groups may have been a stronger contributing factor than the experimental treatment 37 38, 18. In the study by Mehta comparing BIPAP versus CPAP there were no differences in intubation rates, mortality or length of hospital stay between the BIPAP and CPAP group. The BIPAP group showed a faster improvement in physiological parameters but a higher incidence of AMI (71% BIPAP versus 31% CPAP p=0.06) 38. There was no difference in intubation rates, or in hospital mortality between the two groups. One limitation of this finding is that a larger number of patients in the BIPAP group had central chest pain prior to randomization, (10/14 versus 4 /13) it is possible that these patients had myocardial infarction prior to the commencement of treatment. The study was stopped early due to these adverse events and as a result, the findings are limited by small numbers 38. Masip et al. compared oxygen via venture mask to BIPAP and found lower intubation rate in ventilated group (33% versus 5 % p= 0.037) but no overall difference in mortality 37. Sharon et al compared high dose intravenous isosorbide dinitrate or BiPAP ventilation with low dose intravenous isosorbide dinitrate and found better outcomes in those patients managed with high dose nitrates 18. Intubation rates were higher in the BIAP group (80% / 20%; p= 0.0004) and the incidence of myocardial infarction was higher BiPAP group (55% / 10%; p=0.006) 18 The results, however, are difficult to interpret as to whether they demonstrate the efficacy of nitrates or the limitations of BiPAP therapy. Comments: CPAP has been shown to be effective in patients with cardiogenic pulmonary oedema who remain hypoxic despite maximal medical treatment. The use of BIPAP in patients presenting with respiratory distress due to cardiogenic pulmonary oedema is not currently supported by controlled trials, as its safety and efficacy are still unclear.


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SUMMARY OF EVIDENCE Morphine

First author Year Study design Setting Subject Age, Sex Intervention Vismara, L.A. Circulation Vol 53, No.2

1976 Case Series N=22 Normal N= 13 Mild Pulmonary Oedema

Cardiology, Medical Centre Hershey, Pennsylvania, USA Follow up

Inclusion Criteria Acute Pulmonary Oedema partially stanilized by Oxygen therapy & Bed rest

Mean Age 51.8years Age Range (35-64 years)

Morphine Sulphate (0.1mg/kg)

Results Comment Limitation Evidence Resp Rate Decreased from 24.3+/- 2.5 to 17.2 bpm (p<0.01) Venous pressure (Hand) Inc from 34.2+/- 4.9 to 39.0 +/- 4.6 mmHg (p<0.01); Fell To 24.4+/- 3.6mmHg (p<0.01) Venous Volume (Venous Capacitance) Prior Post 1.74 +/-0.08cc/100cc 2.22 +/- 0.13/100cc (p<0.01)

Study documents that the administration of Morphine Sulphate does not cause major pooling of blood in the limbs in either normal subjects or subjects in acute pulmonary oedema. Mechanisms of action in Pulmonary Oedema caused by other mechanisms such as splanchnic pooling, after-load reduction or decreased work of Breathing.

Non Randomised or Blinded Case Series III-2

Morphine First author Year Study design Setting Subject Age, Sex Intervention Vasko, J.S. 1966 American Journal of

Cardiology National heart Institute Bethesda, Maryland. USA Follow up

Animal Model Pulmonary Oedema created by artificially creating, aortic or mitral regurgitation, mitral stenosis or AMI 18 dogs

Morphine 0.5mg/kg administered intravenously

Results Comment Limitation Evidence Decreases in Pulmonary arterial flow and pressure, Central venous pressure occurred within 5 minutes of administration of Morphine and remained low for the following 30 minutes. Systemic arterial pressure decreased at 5 minutes but progressively increased to baseline values by 30 minutes.

The beneficial effects of Morphine in APO were associated with the effects of the drug on capacitance vessels of the peripheral circulation.

Animal Model of Acute Pulmonary Oedema


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Frusemide

First author Year Study design Setting Subject Age, Sex Intervention Dikshit, K. The New England Journal of Medicine Vol 288 (21) 1087-1090

1973 Case Series N=20

Follow up

Inclusion Criteria Clinical Signs of Left Ventricular Failure following AMI Rales Third heart Sound PAWP > 15mmHg

44-81 years F= 4 M= 16

0.5mg-1.0mg /kg Frusemide

Results Comment Limitation Evidence Outcome Central Haemodynamic Effects

Baseline 5 mins p-value

Left Ventricular end-diastolic (PAWP)

20.4+/- 1.4 17.0 +/- 1.8 0.0001

HR 90 +/- 3 90 +/-2 NS BP 90+/- 6 90+/-10 NS Urine Output Renal Plasma Flow Glomerular Filtration Rate

NS NS Ns

Study documents that significant renal and extrarenal effects of frusemide and suggests that the earliest and frequently clinically important hemodynamic changes are produced by vascular rather than diuretic mechanisms

Non Randomised case Series III-2

Frusemide Vs Nitrate First author Year Study design Setting Subject Age, Sex Intervention Beltrame J Journal of Cardiac Failure 4(4) 271-79 N=69

Dec ‘98 Open-label Randomised design study

ED/ICU in Hosp Follow up

Inclusion Criteria 1.Acute SOB within 6hrs 2.↑RR, use Acces. Muscle. , Resp crepes 3.No Hx. suggest infection / aspiration 4.CXR – APO Exclusion criteria: 1.Hx suggest non-cardiac PO 2.SPB<90mmHg 3.ST elevation AMI, severe angina 4.Severe valvular disease 5.COAD + CO2 retention 6.Need immediate Intubation 7.Cardiac arrhythmia 8.CRF (Cr >250mcmol/L)

F/M:NTG/NAC Age 77:76 (M/F) 14/18:17/20 Baseline: PH 7.28:7.26 PaO2 79:74 PaCO2 52:52

1. Frusemide / Morphine, n=32 Frusemide 40mg iv / 2x usual dose Equivalent 2nd dose in 60mins if inadequate response Morphine 1-2mg/5min max of 10mg 2. NTG/NAC, n=37 Nitroglycerin 2.6mcg/min → 5 N-acetylcysteine 6.6mcg/min →10 (if inadequate response in 60mins) over 24hrs. Calcium antagonist, Beta-blocker – ceased If on long acting nitrate continue nitrate if in F/M gp, cease if in NTG/NAC gp Continue Diuretic + ACE I

Results Comment Limitation Evidence Outcome NTG/NAC p-value Clinical status Dyspnoea score, RR, PR, SBP, Crepes Score

No significant difference

Gas Exchange: pH, PaO2,PaO2, PaO2/FiO2, PaCO2

No significant difference

Need Vent Support No significant difference

No significant difference in the rate of improvement of clinical status and gas exchange and need for vent support in either group.

II


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Frusemide Vs Nitrate

First author Year Study design Setting Subject Age, Sex Intervention Cotter G Lancet;351(9100): 389-93 N=104

1998 Feb7

Randomised controlled trial

Follow up

Inclusion criteria: Pulmonary oedema on CXR SaO2 <90% Exclusion criteria Oral nitrate > 40mg/d Frusemide >80mg/d BP<110/70 Previous adverse reaction to study drug

Gp A:Gp B Age 74:74 (M/F) 26/26:28/24 Baseline: SaO2 78:79

O2 10L/min, morphine 3mg, Frusemide 40mg Gp A (n=52) : ISDN 3mg bolus every 5 mins Gp B (n=52) 80mg Frusemide every 15 mins and ISDN 1mg/hr (increase 1mg/hr every 10mins) Endpoint: SaO2 >96 % SBP <90mmHg, less than 30% of baseline Intubation: SaO2<80% for >20 mins, progressive dyspnoea, apnoea, sever arrhythmia.

Results Comment Limitation Evidence Outcome ISDN Frusemide P-value Clinical status ∆ PR ∆ RR

-15 -11

-9 -5

0.024 <0.0001

SaO2 18 13 0.0063 Death 2% 6% 0.61 Intubate 13% 40% 0.0041 AMI 17% 37% 0.047

SIg improvement in clinical status and SaO2 in both group but greater sig improvement in ISDN gp. Sig less intubation rate in ISDN Gp. No sig difference in death. Intention to treat analysis.

Use bolus iv ISDN – unsure of availability in Australia. ? Use SaO2, PaO2 not published.

II

Frusemide Vs Nitrate First author Year Study design Setting Subject Age, Sex Intervention Crane S. European Journal of Medicine 2002 Vol. 9 (4): 320-324 n= 172

2002 Retrospective Cohort Study

@ Acute Hospital Emergency Dept. U.K.

Acute, Cardiogenic Pulmonary Oedema Presenting Emergency Acidotic pH <7.35

F. n = 87 M. n = 85 Median Age 77 years

Retrospective Audit Use of Frusemide, Narcotics and Nitrates in APO Sub-lingual Nitrates IV Nitrates IV Frusemide IV Narcotics

Results Comment Limitation Evidence Treatment given No Pts Median dose SL Nitrates 47 (27.3%) 3 (2-5mg) IV Nitrates 60 (34.9%) Variable rate IV Frusemide 165 (96%) 80 (80-100) mg IV Diamorphine 80 (46.5%) 2.5 (2.5-6) mg IV Morphine 9 (5.2%) 5 (5) mg

Logistic Regression Analysis demonstrated increased survival to Hospital discharge of patients treated with Nitrates (odds ratio 3.04; 95% CI 1.15-8.01) Less than 70% of patients received Nitrates

Retrospective Cohort Study

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18

ACE Inhibitor

First author Year Study design Setting Subject Age, Sex Intervention Diuretics vs Venodilator vs Arteriodilator vs Positive Inotropic Agents

First author Year Study design Setting Subject Age, Sex Intervention Verma, S.P. Journal of Cardiovascular Pharmacology 1987. 10 38-46 n= 48

1987 Prospective Randomised Single-Blind Parallel-Group Study

Coronary Care Unit Leeds U.K.

Acute Lelt Ventricular Failure following Myocardial Infarction PAWP >20mmHg Excluded patients with Unstable Arrhythmias Valvular Disease Requiring Surgical Treatment

48 male Age 35-68 years

Diuretic: Frusemide Venodilator: Isosorbide Dinitrate Arteriolar Dilator: Hydralazine Positive Inotope: Prenalterol

Results Comment Limitation Evidence Clinical status

Frusemide ISDN Hydralazine Prenalterol

∆ PR No change No change Increased (P <0.01)

Increased (P <0.01)

∆ PAWP Dec (p<0.01)

Dec (p<0.01) Dec (p<0.05)

Dec (p<0.05)

∆ CI No change No change Increased CI (P<0.01) Increased Stroke Vol (p <0.01)

Increased (P <0.01) Stroke Volume Unchanged

∆ Systemic VR

No change Dec (p<0.01) Dec (p<0.01) Dec (p<0.01)

∆ BP Dec BP 90mins (p=0.05)

Dec Systolic BP (p<0.01) Dec Diastolic (p< 0.01)

Dec Systolic BP (p<0.05) Dec Diastolic (p< 0.01)

Dec Systolic BP (p<0.05)

Frusemide and ISDN reduced left Ventricular filling pressure at an unchanged cardiac index. Hydralazine and Prenalterol reduced SVR with limited reduction in Left Vent filling Pressures. A combination expected to confer additional haemodynamic advantages.

II

Hamilton RJ Acad Emerg Med 3(3):205-12 n=48

1996 Mar

Prospective, randomized, double-blind, placebo-controlled clinical trial

urban teaching hospital ED

Inclusion Criteria 1.Acute SOB, Diaphoresis, Rales (Ax by Ed physician/PGY4 ED resident) Exclusion Criteria SBP<90mmHg Pregnancy ACE allergy Age<18

Cap:Pla Age 71:66 (M/F) 11/12:15/10 Baseline: APEX 252:265

O2 100% by mask Nitroglycerin 0.4mg SL every 5 mins (3 doses) Morphine 2mg increment Iv frusemide min 40mg 1.Captopril Gp n=23 SL captopril 25mg if SBP≥ 110mmHg, 12.5mg if SBP 90-110 repeated at 60mins 2. Placebo Gp (lactose powder) n=25 placebo tablet SL

Results Comment Limitation Evidence Outcome Captopril Placebo p-value At 25 mins APEX improved to

65% 79% 0.03

MAP NS Need Mech vent 9% 20% NS

APEX – sig greater improvement in captopril group at 25 mins, continue to 45 mins but not sig. No sig difference with 2nd dose. APEX = total score on visual analog of patient reported dyspnoea, observer-reported resp distress and diaphoresis No sig difference in intubation rate.

Validity of APEX in assessing severity of disease, no mentioned correlation with SaO2/PaO2 etc. ? Criteria for intubation Validity of APEX not well established

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19

First author Year Study design Setting Subject Age, Sex Intervention Adigun AQ Int J Cardiol 67(1):81-6 n=17

1998 Nov 30

Randomised single blind trial

Follow up

Inclusion Criteria 1.BP>140/90 2.CXR –APO Exclusion Criteria 1.Previous Rx for heart failure with vasodilator 2.Diab Mellitus 3.thyrotoxicosis

CP:HI Age 49:42 M/F 6/3:5/3

100% O2 Aminophylline 250mg iv Frusemide Gp 1 n=9 Captopril po 25mg twice Prazosin 1mg Gp 2 n=8 Hydralazine 10mg iv 3times ISDN po 10mg 3 times

Results Comment Limitation Evidence Outcome Captopril Hydralazine p-value BP No sig difference HR Captopril greater sig decrease RR Cap greater sig decrease Self paced exercise capacity

5 patient can ambulate

None can ambulate

Small population

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20

ACE Inhibitor

First author Year Study design Setting Subject Age, Sex Intervention Annane D Circulation 94(6):1316-24 N=20

1996 Sep

placebo-controlled, randomized, double-blind study

Follow up

Pre-Inclusion Criteria (all Criteria) 1.Mild-severe CHF (NYHA class III-IV) 2.APO (RR>30,bilat rales, PaO2<80, PCWP>25, CXR Ch. 3.SBP>80mmHg 4.Cr<180mcmol/L Inclusion Criteria (post initial Rx) 1.Substantial improvement after initial Rx Exclusion Criteria (any one) 1.Need Mech Vent 2.AMI/unstable angina within 3mth 3.severe stenotic valvular dis 4.active infection/ severe hepatic/haematological dis 5.Hx of cancer/AIDS 6.On ACE I during 2 wks preceding APO 7.Previous digoxin Rx

Ena:Pla Age: 77:77 (M/F) 6/5 : 5/4 Baseline: NYHA III/IV 4/7 : 4/5 PaO2 58:64 RR 36:34 PR 99:92 SBP 135:128

1st period 6-12 hrs diagnosis Iv frusemide ISDN 2nd period 6 hrs Randomised 3rd period 8 hrs 1.iv enalaprit over 2hrs (n=11) 2.Placebo (n=9) oral enalapril 2,5mg at the end of 3rd period

Results Comment Limitation Evidence Outcome Enalaprit Placebo p-value Systemic Hd DBP MAP

71→56 91→75

70→70 88→87

0.0092 0.0255

Pulm Hd MPBP PCWP

38→33 27→20

34→34 21→22

0.0464 0.0013

Regional Hd BBF BVR

39→68 162→90

40→43 145→124

0.036 0.017

Hormonal PCEA

13.1→3.1

16.2→11.1

0.0014

PaO2 83→85 77→65 0.0411

The study shows that its safe to use enalaprit in APO With favourable outcome in measured parameters (i.e. haemodynamic).

Availability of enalaprit in Australia Shows only modest improvement in PaO2 Exclusion criteria is patient who was on ACE I with heart failure.

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21

CPAP Vs Conventional Oxygen

First author Year Study design Setting Subject Age, Sex Intervention Bersten AD N Engl J Med 26;325(26):1825-30 n=39

1991 Dec

Randomised controlled trial (block randomisation)

Hospital in Australia Follow up

Inclusion criteria 1.Pulmonary oedema + resp distress 2.PaO2<70 mmHg, PaCO2>45mmHg if receive O2 Exclusion criteria: 1.AMI with Shock SBP<90mmHg 2. Severe stenotic valvular dis 3. COAD + known CO2 retention

O2:CPAP Age 75:76 (M/F) 9/11 vs 4/15 APACHE 20.7:20.3

If BP>90mmHg, Nitroglycerin SL/Top. Frusemide iv 40mg/ x2 usual dose. If PaCO2 >55 morphine 1-10mg. n=20 receive O2 60% (Hudson mask) n=19 CPAP endpoint: intubated if PaO2 <70mmHg on 100%FiO2, PaCO2 >55

Bersten AD Results Comment Limitation Evidence O2 CPAP p-value Intubation 35% 0% <0.005 ICU stay (days) 2.7 ± 2 1.2 ± 0.4 0.006

pH,RR, Pa02:FiO2 CPAP faster than O2 <0.01

CPAP improved physiological parameter faster as well as decrease the intubation rate. Decrease ICU stay. No sig difference in hospital stay and mortality.

Modest Sample Size Limited Power II

CPAP Vs Conventional Oxygen First author Year Study design Setting Subject Age, Sex Intervention Lin M Chest;107(5):1379-86 n=100

1995 May


CCU Veteran Gen Hosp Taiwan Follow up1 yr

Inclusion criteria 1.Sign of impeding resp failure – use of accessory muscles, RR>22/min, PaO2/FiO2 200-400,A-a difference 250mmHg 2.typical CXR appearance of APO 3.Clinical finding Hx + Ex Exclusion criteria 1.unresponsive to speech 2.Unable to maintain patent airway 3.cardiogenic shock, vent septal rupture, severe stenotic valvular heart dis. 4.COPD with CO2 retention at rest

O2:CPAP Age 72:73 (M/F) 46/4 vs 44/6

SBP>100mmHg – SL or oral nitrate 40mg frusemide or 2x normal dose PAWP > 25mmHg Nitroprusside Chest pain Nitrate infusion Morphine if PaCO2 <50mmHg N=50 receive O2 only face mask 10L N=50 receive CPAP + O2

Results Comment Limitation Evidence O2 only CPAP p-value Intubation 36% 16% <0.01 Death (1yr) 28% 24% NS Hospital stay 9±4.5 8.5±4.5 NS PaO2, ↓P(A-a)O2 Sig. decrease in CPAP gp PaCO2, pH No diff. b/w 2 gps

Sig lower rate of intubation in CPAP gp. So sig difference in mortality and hospital stay.

No data given for PaO2 at entry for CPAP gp. II


22

CPAP Vs Conventional Oxygen First author Year Study design Setting Subject Age, Sex Intervention Shinhiro Takeda Jpn Circ J 62:553-558 n=22

1998

Randomised controlled trial (RANDOMISATION ENVELOPE)

CCU, ?Nippon Med school Follow up 1yr

Inclusion Criteria 1.patient with AMI 2.Resp distress PaO2 <80mmHg while receiving 50% FiO2 via mask 3.APO-sudden SOB, CXR, Rales Exclusion criteria 1.Hx suggest aspiration/infarction 2. cardiogenic shock → intubated

O2:CPAP Age 75:74 (M/F) 9/2 vs 8/3 APACHE 10.5:10.8

N=7 intubated N=11 O2 via mask N=11 nasal CPAP system Endpoint: 1.mortality 2.intubation (PaO2/FiO2<100 with FiO2 70%, PaCO2 >55mmHg)

Results Comment Limitation Evidence O2 only n=11 CPAP n=11 P-value Intubation 73% n=8 18% n = 2 0.03 Mortality 64% n=7 9% n=1 0.02 Improvement Oxygenation

Greater improvement in CPAP gp in 24hrs and 48 hrs

<0.01

Sig greater % of mortality and intubation in O2 only Group.

Different subject as compared to other studies reviewed. Patient is post AMI. Power is limited by small number.

II

CPAP Vs Conventional Oxygen First author Year Study design Setting Subject Age, Sex Intervention Delclaux C JAMA 8;284(18):2352-60 n=123

2000 Nov

Randomised concealed unblinded trial (multicentred)

Medical ICU 6 hospitals Multi-centre Randomise ED Follow up

Inclusion criteria 1.Acute resp insuf. (PaO2/FIO2 <300mmHg) after breathing O2 at 10L/min for 15 mins 2.Bilat lung infiltrate 3.Randomised within 3 hrs Exclusion criteria 1.< 18 y..o. 2.Intubation refused/contraindicated 3.Hx of COPD 3.Acute resp acidosis (pH <7.3, PaCO2>50mmHg) 4. SBP<90mmHg 5.Vent arrhythmia 6.Coma, seizure 7. SaO2 <80% with O2 mask 8. Use epinephrine/norepinephrine 9.Inability to clear sputum

O2: CPAP Age (M/F) 40/21 vs 38/24

Cardiac insufficiency – Frusemide Infection - antibiotic 1.Receive oxygen (n=61) 2.Receive oxygen + CPAP Start 7.5cm H2O (n=62) Endpoint 1.Death 2.Endotracheal intubation ( alertness, agitation, clinical exhaustion, haemodynamic instability, cardiac arrest, refractory hypoxemia – SaO2<85% with FIO2 of 100%) 3.Improvement SaO2 >92% without O2 and RR <30

Results Comment Limitation Evidence O2 only CPAP p-value PaO2/FiO2, pH, RR

CPAP better than O2 alone at 1hr, other time no sig diff.

0.001

Intubation, death, hospital stay

39.3 33.9 NS

Any adverse event 10 % 29% 0.01

No sig. difference in intubation rate. Note that 9/62 patient not tolerate CPAP 3 eventually require intubation. Greater No. of adverse effect in CPAP group.

? the use of nitrate, morphine patient is non hypercapnic – PaCO2 <50

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23

BIPAP Vs. CPAP, First author Year Study

design Setting Subject Age, Sex Intervention

Mehta S Crit Care Med Vol 25 No, 4 n=27

1997 Randomised controlled double-blind trial

ED in Uni Hosp Follow up

Inclusion Criteria: 1.acute resp distress (mod-sev SOB, RR>30, PR>100, use accessory muscle, paradoxical abdo movement.) 2.Gallopm Bilat Rales 3.CXR finding Exclusion Criteria 1.Hx suggesting aspiration/infection 2.Resp/cardiac arrest 3.Unstable cardiac rhythm 4.SBP<90 5. Unresponsive, agitated, uncooperative 6.condition that preclude the application of mask to face

BiPAP:CPAP Age 76:77 (M/F) 6/8 vs 5/8 APACHE 2 18.8:17

Frusemide 40mg iv or x2 usual dose (If no diuresis double previous dose every 20 mins) SL/Top Nitroglycerin Morphine IV nitroglycerin in ECG suggest ischaemia IV Nitroprusside if BP increase + no sig ECG change 1.BiPAP (n=14) IPAP 15 cm PEEP 5cm 2.CPAP (n=13) 10cm H2O Intubate if: 1.Discretion of ED/ICU consultant 2.Unrelenting resp distress 3.Unable to tolerate/synchronise with mask system 4.deteriorate vital signs 5.Unable to maintain PaO2>60torr, ↑PaCO2>5torr from baseline

Mehta S Results Comment Limitation Evidence BiPAP CPAP p-Value Intubation 7% 8% NS Death 1 2 NS Hospital stay, d 9.6±6.3 9.2±3.9 NS AMI 71% 31% 0.06 ↑pH,↓HR,↓BP,PaCO2 improved No sig improve

No difference in intubation + mortality between 2 intervention. Faster improvement un physiological parameter. Higher incidence of AMI.

Greater no of patient in BiPAP Gp had PIC at study entry (10/14 vs 4/13). LBBB 3/14 vs 0/13 Study stopped Small number

II

BIPAP vs Conventional O2, BIPAP Vs. CPAP, BiPAP Vs. ISDN First author Year Study design Setting Subject Age, Sex Intervention Masip J Lancet; 356(9248):2126-32 n=37

2000 Dec

Randomized Controlled Trial

Follow up

Inclusion criteria: 1.Acute resp failure 2.SOB sudden onset 3.Clinical + CXR – pulm oedema Exclusion criteria 1.Cardiogenic shock (SBP<90mmHg) 2. Severe COAD without Pulm oedema 3. Renal failure (Cr >0.265) 4. Neurological impairment 5. AMI needing thrombolysis 6. Pneumonia

O2:NIPSV Age 78.5:75.3 (M/F) 11/7 vs 8/11 APACHE 2 15.9:16.1

40mg frusemide, 4mg morphine, GTN infusion 1.5mg/hr 1.Non Invasive Pressure Support Ventilation (NIPSV) via face mask (n=19) 2.venturi mask (n=18) Endpoint: Cardiac and resp arrest Refractory or progressive hypoxaemia (SaO2 < 80%) Clinical sign of muscle fatigue

Masip J Results Comment Limitation Evidence NIPSV O2 p-Value Intubation 5% 33% 0.037 Death 0 2 Hospital stay, d 14.2 14.3 0.93 Resolution time 30mins 105mins 0.002 AMI (cause of APO) 26% 33%

Faster resolution with NIPSV. Intubation less in NIPSV group. No increase AMI (as mentioned in discussion)

APACHE II score is similar, but higher incidence of AMI in control Gp (67%) vs NIPSV gp (26%). Greater number of patient with COAD in control group

II


24

BIPAP vs Conventional O2, BIPAP Vs. CPAP, BiPAP Vs. ISDN

First author Year Study design Setting Subject Age, Sex Intervention Sharon A J Am Coll Cardiol 37(6):1754-5 n=40

2001 May


Follow up

Inclusion criteria: SaO2 <90%, Exclusion criteria: 1. previous Rx nitrate >40mg/day, long acting nitrate>2x/d or short acting>3x/d 2. Frusemide >80mg/d 3. BP<110/70 4. previous adverse effect of nitrate 5. ST elevation AMI 6. absence of Pulm oedema on CXR

ISDN:BiPAP Age 73:72 (M/F) 10/10:9/11 Prior MI 12:14 SaO2 79:80

Morphine 3mg, frusemide 80mg iv 1 n=20 BiPAP 8cmH2O 12 cm (IPAP) 3cm H2O 5 cm (EPAP). + iv ISDN 10mcg/min increase every 5-10mins 2.n=20 iv ISDN 4mg bolus every 4 mins 1 +2 until SaO2>96%, SBP<110mmHg / 30% below baseline endpoint 1.death 2.intubation (if SaO2<80%, increase SOB, altered neuro state) 3. AMI 4. speed of recovery

Results Comment Limitation Evidence Outcome BiPAP ISDN p-value Death 10% 0% 0.49 Intubation 80% 20% 0.0004 AMI 55% 10% 0.006 SaO2 in 50mins 89% 96% 0.017 Resp Rate in 50 mins 36 31 0.011 PR 121 104 0.014

Significantly higher rate of Intubation and AMI in BiPAP Gp.

?Very high rate of Intubation in BiPAP gp 80% cf to other study quoting figure 7% and 5%. IV ISDN not available in Australia

II


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