Respiratory failure

Respiratory failure is a failure of gas exchange: the lungs, the chest wall, the respiratory muscles or the central drive can no longer keep arterial oxygen and carbon dioxide within a range compatible with cellular function. It presents as breathlessness, confusion, drowsiness, cyanosis or an abnormal blood gas in a patient who may look deceptively comfortable. The diagnosis rests on an arterial blood gas, not on appearance.

Clinical relevance. It is a common end point for pneumonia, chronic obstructive pulmonary disease (COPD) exacerbation, acute pulmonary oedema, pulmonary embolism, asthma, neuromuscular weakness and sepsis. Hospital mortality for acute hypercapnic respiratory failure with acidosis is about 10 to 15% when treated early with non-invasive ventilation, and rises sharply when ventilatory support is delayed. The commonest avoidable harm is uncontrolled high flow oxygen in a patient who retains carbon dioxide.

Classification.

• Type 1 (hypoxaemic): PaO2 under 8 kPa (60 mmHg) on air with PaCO2 normal or low. Caused by ventilation-perfusion mismatch, shunt or diffusion limitation.
• Type 2 (hypercapnic, ventilatory): PaCO2 over 6.0 kPa (45 mmHg), with or without hypoxaemia. Acute if pH is under 7.35 with bicarbonate near normal; chronic if pH is near normal with bicarbonate over 30 mmol/L; acute on chronic when both are present.
• Severity grading of hypoxaemia by the PaO2/FiO2 ratio: 200 to 300 mmHg mild, 100 to 200 moderate, under 100 severe. The definition of the acute respiratory distress syndrome, ARDS, also needs bilateral opacities, onset within 1 week and PEEP of 5 cmH2O or more.

Mechanism.

• Hypoxaemia: ventilation-perfusion mismatch (pneumonia, COPD, pulmonary embolism), true shunt (lobar consolidation, ARDS, intracardiac right to left shunt; poorly corrected by oxygen), hypoventilation, diffusion impairment (interstitial disease, exertional) and low inspired oxygen (altitude).
• Hypercapnia: alveolar hypoventilation from reduced central drive (opioids, sedatives, brainstem lesion), neuromuscular failure (Guillain-Barre syndrome, myasthenia, motor neurone disease, high spinal cord lesion), and chest wall disease (obesity, kyphoscoliosis, flail chest).
• Hypercapnia also results from airflow obstruction with increased dead space (COPD, severe asthma) and fatigue from increased work of breathing.
• The alveolar to arterial (A-a) gradient separates the two. A normal gradient (upper limit about age/4 + 4 mmHg) with hypoxaemia and hypercapnia means pure hypoventilation. A raised gradient means a parenchymal, vascular or shunt cause.

History.

• Onset: abrupt (pulmonary embolism, pneumothorax, pulmonary oedema, aspiration, anaphylaxis) versus over days (pneumonia, exacerbation) versus progressive over weeks (interstitial disease, neuromuscular disease).
• Known chronic lung disease, previous hypercapnic admissions, home oxygen, home ventilation, oxygen alert card, baseline saturation.
• Fever, purulent sputum, haemoptysis, pleuritic pain, leg swelling, orthopnoea, paroxysmal nocturnal dyspnoea, wheeze, recent surgery, immobility, malignancy.
• Drugs and toxins: opioids, benzodiazepines, gabapentinoids, amiodarone, nitrofurantoin, methotrexate, bleomycin; smoke inhalation; carbon monoxide; recent aspiration or vomiting.
• Neuromuscular clues: ascending weakness, ptosis, diplopia, dysphagia, voice change, inability to count in one breath, preceding diarrhoeal illness.
• Obesity, snoring, morning headache (nocturnal hypoventilation).

Examination.

• Respiratory rate (over 25 breaths/minute is abnormal; a falling rate with worsening drowsiness is ominous), use of accessory muscles, intercostal recession, paradoxical abdominal movement, inability to speak a full sentence.
• Colour: central cyanosis (needs about 5 g/dL of deoxygenated haemoglobin, so it appears late and is absent in severe anaemia).
• Features of carbon dioxide retention: bounding pulse, warm peripheries, vasodilated face, flapping tremor, papilloedema (rare), drowsiness, confusion.
• Chest: wheeze, crackles, bronchial breathing, reduced air entry, hyper-resonance with tracheal deviation (tension pneumothorax), stridor.
• Cardiovascular: raised jugular venous pressure, third heart sound, peripheral oedema, pulmonary embolism signs (tachycardia, loud P2).
• Neurological: neck flexion weakness, single breath count (under 20 suggests forced vital capacity under about 1.5 L), reduced reflexes.

Red flags.

• Silent chest, exhaustion, inability to speak, rising PaCO2 with falling respiratory rate.
• Drowsiness or confusion, pH under 7.25, PaO2 under 8 kPa despite high flow oxygen.
• Stridor or drooling (upper airway obstruction).
• Hypotension, lactate over 2 mmol/L, new arrhythmia.
• Single breath count under 20, forced vital capacity under 20 mL/kg or a fall of over 30% from baseline, inability to lift the head from the pillow.
• Unilateral absent breath sounds with shock (tension pneumothorax).

Causes are grouped by the blood gas pattern and the presence of a normal or raised A-a gradient.

• Type 1 with raised A-a gradient: pneumonia, acute pulmonary oedema (cardiogenic and non-cardiogenic), ARDS, pulmonary embolism, pneumothorax, interstitial lung disease acute exacerbation, pulmonary haemorrhage, aspiration, severe asthma early (before fatigue), pulmonary hypertension, right to left cardiac shunt.
• Type 2 with normal A-a gradient (pure hypoventilation): opioid or sedative overdose, brainstem stroke or encephalitis, Guillain-Barre syndrome, myasthenic crisis, motor neurone disease, high cervical cord injury, obesity hypoventilation syndrome, severe hypothyroidism, flail chest, kyphoscoliosis, post-operative residual neuromuscular blockade.
• Type 2 with raised A-a gradient: acute exacerbation of COPD, life-threatening asthma with fatigue, cystic fibrosis or bronchiectasis end stage, large pneumonia in a patient with limited reserve.
• Mimics that need exclusion:
  • metabolic acidosis with compensatory hyperventilation (diabetic ketoacidosis, salicylate toxicity)
  • panic hyperventilation
  • methaemoglobinaemia (low saturation on the oximeter with a normal PaO2 and chocolate-brown blood)
  • carbon monoxide poisoning (normal oximeter saturation, true oxyhaemoglobin saturation low on co-oximetry)
  • severe anaemia (breathlessness with normal gases)

1. Start oxygen and monitoring before investigations. Record a baseline saturation, respiratory rate, pulse, blood pressure, temperature and conscious level.
2. Arterial blood gas on a documented FiO2: PaO2, PaCO2, pH, bicarbonate, base excess and lactate. Interpret pH first: pH under 7.35 with PaCO2 over 6.0 kPa is respiratory acidosis.
   • In acute hypercapnia bicarbonate rises about 1 mmol/L for each 10 mmHg (1.3 kPa) rise in PaCO2.
   • In chronic hypercapnia it rises about 3.5 to 4 mmol/L for the same rise, so a bicarbonate far higher than that implies chronic retention.
3. Calculate the PaO2/FiO2 ratio and the A-a gradient to separate parenchymal disease from hypoventilation.
4. Chest radiograph immediately (pneumothorax, consolidation, oedema, effusion, hyperinflation). Bedside lung ultrasound if available (B-lines, pleural sliding, effusion).
5. Electrocardiogram and troponin; natriuretic peptide if heart failure is uncertain (N-terminal pro-B-type natriuretic peptide under 300 ng/L makes acute heart failure unlikely).
6. Blood tests: full blood count, urea and electrolytes, bone profile, liver profile, glucose, C-reactive protein, procalcitonin if available, blood cultures, thyroid stimulating hormone, creatine kinase, carboxyhaemoglobin and methaemoglobin by co-oximetry.
7. Targeted tests: CT pulmonary angiography (embolism), high resolution CT (interstitial disease), sputum and respiratory viral polymerase chain reaction, urinary pneumococcal and legionella antigens, toxicology screen.
8. Neuromuscular assessment: serial forced vital capacity and maximal inspiratory pressure every 4 to 6 hours; nerve conduction and lumbar puncture for Guillain-Barre syndrome; acetylcholine receptor antibodies.
9. After recovery, assess for chronic hypoventilation: overnight oximetry with transcutaneous carbon dioxide, daytime arterial or capillary gas, and lung function.

Limits.

• Pulse oximetry misreads in carbon monoxide poisoning, methaemoglobinaemia, poor perfusion, nail varnish and dark skin pigmentation. With dark skin pigmentation it can overestimate true saturation by 2 to 4 percentage points.
• Venous gas gives pH and bicarbonate reliably but PaCO2 only to within about 0.8 kPa of the arterial value. It cannot give oxygenation.
• A normal PaO2 on high FiO2 can hide severe lung injury, so always record the FiO2.

Oxygen.

• Target saturation 94 to 98% in patients without hypercapnic risk. Start 15 L/minute by reservoir mask in critical illness and titrate down.
• Target 88 to 92% in patients with COPD, obesity hypoventilation, chest wall or neuromuscular disease, or a previous hypercapnic episode. Use a Venturi mask 24% (2 to 4 L/minute) or 28% (4 L/minute) and repeat the blood gas in 30 to 60 minutes. Never withhold oxygen in hypoxia that is life threatening; the aim is controlled, not absent, oxygen.
• High flow nasal oxygen 30 to 60 L/minute with FiO2 titrated to target is effective for hypoxaemic failure and reduces intubation in selected patients.

Non-invasive ventilation.

• Indication: acute hypercapnic acidosis with pH 7.25 to 7.35 persisting after 1 hour of optimal medical therapy; also pH under 7.25 in a patient who is alert and cooperative, in a monitored setting with intubation ready.
• Starting settings: inspiratory positive airway pressure (IPAP) 10 cmH2O, expiratory pressure (EPAP) 4 to 5 cmH2O.
• Raise IPAP by 2 to 5 cmH2O every 10 to 20 minutes to 20 cmH2O (maximum about 30) as tolerated, FiO2 titrated to 88 to 92%.
• Repeat blood gas at 1 hour; failure to improve pH or rising PaCO2 means escalate.
• Continuous positive airway pressure (CPAP) 5 to 10 cmH2O for cardiogenic pulmonary oedema.
• Contraindications: untreated pneumothorax, vomiting with unprotected airway, facial trauma, fixed upper airway obstruction, severe agitation. Drowsiness from carbon dioxide narcosis is a relative, not absolute, contraindication.

Cause directed treatment.

• COPD exacerbation: salbutamol 5 mg and ipratropium 500 micrograms nebulised, driven by compressed air with oxygen by nasal cannula 1 to 4 L/minute to hold 88 to 92%; prednisolone 30 mg orally daily for 5 days; antibiotics if sputum is purulent (doxycycline 200 mg on day 1 then 100 mg daily for 5 days, or amoxicillin 500 mg every 8 hours for 5 days).
• Life-threatening asthma: oxygen to 94 to 98%, salbutamol 5 mg nebulised repeated every 15 to 20 minutes or continuously, ipratropium 500 micrograms, prednisolone 40 to 50 mg or hydrocortisone 100 mg intravenously, magnesium sulphate 2 g intravenously over 20 minutes; early critical care referral.
• Cardiogenic pulmonary oedema: sit upright, CPAP, furosemide 40 to 80 mg intravenously, glyceryl trinitrate 10 to 200 micrograms/minute if systolic blood pressure over 110 mmHg.
• Pneumonia: antibiotics within 1 hour if septic (co-amoxiclav 1.2 g every 8 hours intravenously with clarithromycin 500 mg twice daily for severe community-acquired disease).
• Pulmonary embolism: anticoagulate on suspicion if bleeding risk is acceptable (rivaroxaban 15 mg twice daily for 21 days then 20 mg daily, or enoxaparin 1 mg/kg twice daily); alteplase 100 mg over 2 hours for haemodynamic collapse.
• Opioid toxicity: naloxone 400 micrograms intravenously, repeated every 2 to 3 minutes up to 2 mg, then an infusion at two thirds of the total effective dose each hour.
• Tension pneumothorax: immediate needle decompression then chest drain.
• Neuromuscular failure: intubate early for forced vital capacity under 20 mL/kg, rapid decline, bulbar failure or ineffective cough. Avoid suxamethonium in prolonged immobility or denervation (hyperkalaemic cardiac arrest).
• ARDS: lung protective ventilation with tidal volume 6 mL/kg predicted body weight, plateau pressure under 30 cmH2O; prone positioning for at least 16 hours/day when the PaO2/FiO2 ratio is under 150 mmHg; conservative fluid strategy once shock resolves.

Intubation criteria. Failure of non-invasive ventilation (worsening pH or PaCO2 after 1 to 2 hours), exhaustion, GCS 8 or under without a reversible cause, inability to protect the airway, refractory hypoxaemia, haemodynamic instability.

Monitoring. Continuous saturation and electrocardiogram, respiratory rate every 15 minutes initially, blood gas at 30 to 60 minutes after each change in oxygen or ventilation and then every 4 to 6 hours, urine output, lactate trend, daily chest radiograph in ventilated patients.

Referral and escalation.

• Critical care review for pH under 7.25 despite non-invasive ventilation, PaO2 under 8 kPa on FiO2 of 0.6 or more, rising lactate, shock, or a need for invasive support.
• Respiratory team for all hypercapnic episodes; neurology for neuromuscular causes; toxicology for drug overdose.
• Discuss ceilings of treatment and resuscitation status early in patients with advanced chronic disease.

Admission or disposition. All patients with acute respiratory failure are admitted; level 2 or 3 care for non-invasive ventilation, high flow oxygen at high FiO2, ARDS or neuromuscular failure. Type 2 respiratory failure with a pH under 7.35 should not be managed on an open ward without a non-invasive ventilation unit.

Safety netting. Before discharge:

• oxygen alert card for hypercapnic patients
• inhaler technique
• written exacerbation plan with rescue steroid and antibiotic supply where appropriate
• smoking cessation: nicotine patch 21 mg/24 hours for 6 weeks, then 14 mg for 2 weeks, then 7 mg for 2 weeks; or varenicline 0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks
• vaccination
• pulmonary rehabilitation referral
• a review within 2 weeks

Reassess for long term oxygen if PaO2 is under 7.3 kPa (or 7.3 to 8 kPa with polycythaemia, pulmonary hypertension or peripheral oedema) on two measurements at least 3 weeks apart when stable.

Special groups.

• Pregnancy: normal PaCO2 is lower (about 4.0 kPa), so 5 kPa is already abnormal; aim for saturation of 95% or more to protect the foetus; left lateral tilt.
• Obesity: reverse Trendelenburg and ramped positioning for preoxygenation; higher PEEP needs.
• Frail older patients: involve the patient and family early in decisions about invasive ventilation.
• Immunosuppression or HIV: consider pneumocystis pneumonia (co-trimoxazole 120 mg/kg/day in divided doses for 21 days with prednisolone 40 mg twice daily for 5 days when PaO2 is under 9.3 kPa).