Acute Pulmonary Oedema

Pulmonary oedema occurs when fluid leaks from the pulmonary capillary network into the lung interstitium and alveoli. It forms when there is:¹

• Imbalance of Starling forces (increased pulmonary capillary pressure, decreased plasma oncotic pressure, increased negative interstitial pressure)
• Damage to the alveolar-capillary barrier
• Lymphatic obstruction

It is frequently caused by disease affecting the left heart but there is a wide range of other possible causes that should be considered.
Pulmonary oedema may or may not complicate the presentation of acute heart failure (AHF). In some patients with AHF, reduced cardiac output or tissue hypoperfusion are the more dominant features.

• Raised pulmonary capillary pressure:
  • Heart:
    • Ischaemic heart disease - acute coronary syndromes, mechanical complications of acute myocardial infarction (MI) such as ventricular septal rupture, right ventricular infarction
    • Valvular - acute aortic or mitral regurgitation, severe aortic stenosis, endocarditis
    • Severe hypertension
    • Acute arrhythmia
    • Acute myocarditis
    • Left atrial myxoma
    • Cardiac tamponade
    • Aortic dissection
    • Cardiomyopathy, e.g. postpartum cardiomyopathy
    • Drugs: myocardial depression, e.g. alcohol; fluid retention, e.g. NSAIDs
  • Renal:
    • Acute renal failure, chronic renal failure
    • Renal artery stenosis
  • Iatrogenic fluid overload
  • Cerebrovascular insult
  • High output heart failure, e.g. septicaemia, thyrotoxic crisis, anaemia, shunts
• Increased pulmonary capillary permeability:
  • Acute respiratory distress syndrome (ARDS)
  • High altitude
  • Inhaled or aspirated toxic substances
  • Radiation
  • Liver failure
  • Fat embolism or amniotic fluid embolism
• Lymphatic obstruction, e.g. mediastinal carcinomatosis, silicosis
• Acute or chronic upper airway obstruction

Acute pulmonary oedema is a very frightening experience for the patient and represents a genuine medical emergency. This does not preclude a systematic assessment with a rapid, focused history and examination.

• Signs:
  • Patient is usually severely breathless, sweaty, nauseated and anxious.
  • Initially they may have a dry or productive cough (sometimes with pink, frothy sputum).
  • Patients may also develop paroxysmal nocturnal dyspnoea or orthopnoea.
• History:
  • Check for a past history of relevant conditions, for example:
    • IHD
    • Valvular heart disease
    • Chronic obstructive pulmonary disease (COPD)
    • Hypertension
    • Cerebrovascular disease
    • Diabetes
    • Recent infection
    • Family history of cardiomyopathy
    • Systemic disease such as sarcoid or amyloid
    • Anaemia
    • Thyroid disease
  • Review current medication.
  • Ask about smoking and alcohol use.
• Signs:
  • Patient is in respiratory distress, pale, sweaty, tachypnoeic and tachycardic.
  • They may be cyanosed, have evidence of congested neck veins and a raised JVP.
  • Bibasal/widespread rales or fine crackles are usually heard listening to the chest.
  • Oxygen saturation is usually <90% on room air.
  • Assess for a gallop rhythm (3rd heart sound) and murmurs suggestive of valve stenosis or regurgitation.
  • Hypotension - the triad of hypotension (SBP <90 mmHg), oliguria, and low cardiac output is known as cardiogenic shock
  • In hypertensive heart failure, a high blood pressure, tachycardia, vasoconstriction present with signs of pulmonary oedema without extensive systemic congestion.
  • Where pulmonary oedema occurs in association with right heart failure, hepatomegaly and peripheral oedema are usual.

These will not be available in the pre-hospital setting. For severe acute heart failure, treatment should be started immediately and the condition stabilised before results of investigations are available.

1. Blood tests:
   • U&Es, creatinine, sodium, potassium, glucose, cardiac enzymes, liver function tests, clotting tests (INR)
   • Arterial blood gases and pH
   • Brain natriuretic peptides (BNPs) - thought to be helpful in distinguishing acute pulmonary oedema from other causes of dyspnoea,^2,3 but no consensus regarding reference values in acute heart failure. Raised BNP levels are also found in acute coronary syndromes (ACSs), pulmonary embolism and acute severe dyspnoea not due to heart failure.⁴
2. ECG: look for evidence of arrhythmia, myocardial infarction or other cardiac disease, e.g. left ventricular hypertrophy.
3. Chest X-ray: to exclude other causes of breathlessness and confirm pulmonary oedema.
4. Echocardiogram: ESC guidelines suggest that all patients with AHF should be evaluated with echocardiogram as soon as possible, as it frequently determines treatment strategy.⁵
5. Non invasive monitoring: body temperature, respiratory and heart rate, urine output, pulse oximetry and ECG telemetry, daily weights.
6. A urinary catheter enables accurate measurement of urinary output which helps rapidly to assess diuretic response and fluid balance.
7. More invasive monitoring required for intensive support, including arterial and central venous pressure lines and pulmonary artery catheters.

Treatment should be directed at reversing the specific cause - although this may not be possible. Management is otherwise supportive and directed at improving oxygenation, perfusion and haemodynamics, and preventing further cardiac and/or renal damage.

Initial treatment

• Resuscitation - as necessary.
• Sit the patient up.
• Give oxygen (if available) by face mask: 100% if no pre-existing lung disease (but even in patients with COPD, give high oxygen flow initially but monitor with blood gases to ensure hypercapnia is avoided). Aim for oxygen saturations ≥95% (>90% in those with COPD).
• Judge clinical severity, patient's wishes (has the patient made a future directive for this situation?) and consider hospitalisation. Call 999 for an urgent ambulance if appropriate.
• Insert an IV cannula and give:
  • Analgesia and sedation where the patient is in pain or distressed. Diamorphine 2.5-5 mg IV slowly (or morphine 5-10 mg IV slowly) relieves anxiety, pain and distress, as well as both producing transient venodilation and reducing myocardial oxygen demand. An anti-emetic may be required.
  • Nitrates are first-line vasodilators where SBP >90 mmHg and there is no serious obstructive valvular disease. Give sublingual or buccal nitrate, e.g. GTN spray 2 puffs sublingual, or 1-3 mg buccal isosorbide dinitrate.
  • Furosemide 20-40 mg IV (slowly) produces transient venodilation and subsequent diuresis. This may need to be repeated based on response of clinical symptoms - diuretic effectiveness is greatly reduced in presence of hypotension and where patients are chronic oral diuretic users. The total furosemide dose should not exceed 100 mg in the first 6 hours of treatment.

Further treatment - in hospital

Oxygen and artificial ventilation

• Monitor arterial blood gases closely.
• Increase inspired oxygen to maintain arterial oxygen above 10 kPa.
• Early non-invasive ventilation (NIV), either non-invasive positive pressure ventilation (NIPPV) or continuous positive airways pressure (CPAP), reduces the need for intubation and short-term mortality in acute cardiogenic pulmonary oedema.⁶
• Mechanical ventilation, with or without endotracheal intubation, is required where oxygen delivery by mask or NIV is inadequate, in those with increasing respiratory failure or exhaustion with rising pCO₂ and in those unable to maintain their airway.

Vasodilators

Vasodilators reduce pre-load and are an important early treatment for most patients with acute heart failure. Intravenous infusions of nitrates (glyceryl trinitrate, isosorbide dinitrate, nitroprusside and nesiritide) are all used in patients with SBP >110 mmHg. Caution is required when SBP is between 90-110 mmHg and nitrates should not be used when SBP is <90 mmHg. Be particularly vigilant to avoid hypotension in those with renal dysfunction. IV nitroglycerin is most widely used:

• Commence IV nitroglycerin infusion at 10-20 μg/min.
• Titrate dose up in increments of 5-10 μg/min every 3-5 minutes.
• Frequent BP measurements are required to avoid large drops in SBP.
• An arterial line is not mandatory but does ease titration in patients with borderline SBP.

Diuretics

Diuretics are continued in hospital if there is fluid retention. IV infusions of furosemide are preferable to very high bolus doses in severe acute heart failure (5-40 mg/h). Total dose of furosemide should not exceed 240 mg in the first 24 hours. Bumetanide and torasemide are alternative loop diuretics that may be used.
Where problems are encountered with resistance to loop diuretics:

• A thiazide, e.g. hydrochlorothiazide, or metolazone can be added, avoiding very high doses of loop diuretics.
• Spironolactone or eplerenone can be also be used in association with loop diuretics. Potassium should be checked prior to initiation in view of the risk of hyperkalaemia.

Where the above strategies fail, inotropes should be added. Haemodialysis and ultrafiltration are sometimes considered as the treatments of last resort if fluid overload cannot be controlled by diuretic therapy.⁴

Inotropes

Inotropes are used in patients with low output states or where signs of hypoperfusion or congestion persist despite the use of vasodilators and diuretics. They may stabilise patients at risk of circulatory collapse or provide a bridge to further treatment such as ventricular assist devices or transplant. They increase the risk of arrhythmias so continuous monitoring is required.

• Dopamine infusion improves myocardial contractility and cardiac output as well as renal blood flow and diuresis at low dose (≤2-3 mg/kg/min).
• Dobutamine infusion is usually started at 2-3 μg/kg/min and then adjusted to response. Doses must be substantially increased in patients on beta blockers.
• Phosphodiesterase inhibitors (milrinone and enoximone) may be preferred to dobutamine in patients on beta blocker therapy or with inadequate response to dobutamine. They are peripheral vasodilators and should only be used if SBP is adequate. They may increase mortality in those with coronary artery disease.
• Levosimendan is a calcium sensitiser that appears effective in patients with decompensated chronic heart failure already on beta blockers.

Arrhythmias

Where there is fast atrial fibrillation, give digoxin 0.75-1.25 mg orally (or 0.5 mg slowly IV if very urgent). Treat other arrhythmias as appropriate, e.g. pacing, anti-arrhythmics, cardioversion.

Surgical management

Options include coronary revascularisation, correction of anatomic lesions, valve replacement or reconstruction, mechanical assist devices for temporary circulatory support and heart transplantation.

Continuing management

• Monitor BP and pulse rate frequently; restrict fluids; measure urine output; adjust medical therapy to clinical response.
• Measure U&Es daily initially watching for renal impairment/failure; perform serial ECGs and cardiac enzymes.
• It is important to examine the patient repeatedly. Are there any new murmurs? For example, the patient who has severe pulmonary oedema following a myocardial infarction may go on to develop a VSD or mitral regurgitation (confirm with echocardiogram).
• Current guidelines⁵ state that ACE inhibitors are not indicated in the early stabilisation of patients with acute heart failure. However, an ACE inhibitor or angiotensin receptor antagonist should be started once the acute symptoms of pulmonary oedema have settled following a myocardial infarct or in those with evidence of LV systolic dysfunction. There is no current consensus as to the ideal time for initiation, but common practice is to initiate them prior to leaving hospital.
• For ongoing management, see separate article on Heart Failure Management. Review patient's current medication and care needs.

A recent European survey revealed that the median stay in hospital following AHF was 9 days. Almost half are rehospitalised within the following year. Risk of death or rehospitalisation within 60 days of admission with acute heart failure is between 30-50%.⁷The Killip classification further subdivides prognosis:⁸

• Class I (no signs of left ventricular dysfunction): hospital mortality 6%
• Class II (S3 gallop with mild/moderate pulmonary congestion): hospital mortality 30%
• Class III (severe pulmonary oedema): hospital mortality 40%
• Class IV (cardiogenic shock): hospital mortality 80-90%

Given these figures, emergency medical care must also attend to the need for good end of life and palliative care.