Acute and chronic respiratory failure

At a glance

• Respiratory failure is failure of gas exchange: type 1 (hypoxaemic), PaO2 under 60 mmHg, or type 2 (hypercapnic), PaCO2 over 45 mmHg.
• pH tells acute from chronic: a high PaCO2 with a normal pH and high bicarbonate is chronic compensation.
• TSANZ 2022: SpO2 target 92 to 96% for most adults, 88 to 92% if at risk of hypercapnia. Too much oxygen kills too: higher targets raise mortality (IOTA meta-analysis).
• NIV is first-line for acute hypercapnic acidosis in COPD. High-flow nasal oxygen suits most acute hypoxaemic failure.
• Chronic hypercapnic failure from COPD, obesity or neuromuscular disease often needs home NIV.

Mechanisms

Hypoxaemia

Mechanism	A-a gradient	Responds to oxygen?	Example
V/Q mismatch	Raised	Yes	Pneumonia, COPD, PE, asthma
Shunt	Raised	Poorly	ARDS, lobar collapse, intracardiac shunt, AV malformation
Diffusion impairment	Raised (on exercise)	Yes	ILD
Hypoventilation	Normal	Yes	Opioids, neuromuscular disease
Low inspired oxygen	Normal	Yes	Altitude

• A-a gradient: PAO2 = (FiO2 x 713) - (PaCO2 / 0.8). On room air, PAO2 is about 150 - 1.25 x PaCO2. Normal is under about (age / 4) + 4 mmHg.
• Pitfall: a normal SpO2 on high-flow oxygen can hide a large A-a gradient. Check the gradient, or the PaO2/FiO2 ratio.

Hypercapnia

PaCO2 rises when alveolar ventilation falls. The causes sort by where the "pump" fails:

Level	Examples
Central drive	Opioids, benzodiazepines, brainstem stroke, central hypoventilation
Spinal cord and nerve	High cervical cord injury, motor neurone disease, Guillain-Barré syndrome
Neuromuscular junction and muscle	Myasthenia gravis, myopathy, hypophosphataemia
Chest wall	Kyphoscoliosis, obesity, flail chest
Airways and lung	COPD, severe asthma, cystic fibrosis

Oxygen-induced hypercapnia

In COPD, high-flow oxygen raises PaCO2 mainly through worsened V/Q matching (release of hypoxic vasoconstriction) and the Haldane effect, not through loss of hypoxic drive. Austin's prehospital trial (Austin et al, BMJ 2010, Tasmania) showed titrated oxygen to 88 to 92% cut mortality by over half compared with high-flow oxygen.

Recognition

• Hypoxaemia: breathlessness, tachypnoea, cyanosis (late), confusion, tachycardia, arrhythmia.
• Hypercapnia: drowsiness, headache, flapping tremor, bounding pulse, warm peripheries, papilloedema.
• Neuromuscular failure: paradoxical abdominal movement, weak cough, single-breath count under 15, orthopnoea. Pulse oximetry and gases are late markers.
• Pitfall: in Guillain-Barré or myasthenic crisis, watch FVC. Under 20 mL/kg (or a fall by 30%) means ICU review; under 15 mL/kg usually means intubation. A normal SpO2 doesn't reassure.

Investigations

• Arterial blood gas: pH, PaO2, PaCO2, bicarbonate, lactate. A venous gas is fine to follow pH and screen PaCO2 (a normal venous PCO2 excludes arterial hypercapnia), but not to judge oxygenation.
• Chest X-ray, ECG, FBC, electrolytes including phosphate, magnesium and potassium, CRP, cultures.
• Targeted: CTPA, echo and BNP, drug screen, creatine kinase, acetylcholine receptor antibodies, spirometry or FVC.
• Chronic hypercapnia work-up: spirometry lying and sitting (a fall over 20% on lying suggests diaphragm weakness), maximal inspiratory pressure, sleep study with transcutaneous CO2, thyroid function.

Management of acute respiratory failure

Oxygen (TSANZ 2022)

• Prescribe oxygen with a target range, like a drug.
• Most adults: start if SpO2 under 92%, target 92 to 96%.
• At risk of hypercapnia (COPD, obesity hypoventilation, neuromuscular or chest wall disease, cystic fibrosis, bronchiectasis): start if SpO2 under 88%, target 88 to 92%, use venturi masks or low-flow nasal prongs, and check a gas.
• Rising oxygen needs (FiO2 0.4 or more, or 6 L/min or more by simple face mask) mean the patient needs senior review now; FiO2 0.5 or more, or 8 L/min or more by face mask, needs ICU review.
• BTS 2017 uses 94 to 98% for most patients. BTS is developing an update on target saturations.

High-flow nasal oxygen (HFNO)

• Delivers heated humidified gas at up to 60 L/min, FiO2 0.21 to 1.0, with a little PEEP and washout of dead space.
• Preferred over conventional oxygen in acute hypoxaemic failure without hypercapnia (ATS 2026, strong). ATS 2026 also suggests NIV or CPAP over conventional oxygen (conditional) and makes no recommendation between HFNO, CPAP and NIV. FLORALI's primary outcome, intubation at 28 days, didn't differ overall; 90-day mortality (secondary) was lower with HFNO.
• Pitfall: in COVID-19 pneumonia, RECOVERY-RS found CPAP, not HFNO, reduced intubation or death compared with conventional oxygen.
• ROX index (SpO2/FiO2 divided by respiratory rate) under 3.85 at 12 hours predicts failure. Don't delay intubation.
• May be considered in selected patients with mild hypercapnic acidosis (for example pH over 7.25) if NIV escalation is immediately available (ATS 2026, conditional, low certainty, as reported in guideline summaries). Also for preoxygenation and after extubation.

Non-invasive ventilation (NIV)

• Indications: COPD with pH under 7.35 and a raised PaCO2 that persists after optimal medical treatment. BTS/ICS 2016 uses PaCO2 over 6.5 kPa (about 49 mmHg); ERS/ATS 2017 and COPD-X use over 45 mmHg. Also obesity hypoventilation, neuromuscular and chest wall disease with acidosis.
• Cardiogenic pulmonary oedema: CPAP or NIV improves breathing and oxygenation quickly.
• Typical bilevel settings: low EPAP, about 3 to 5 cmH2O (enough to flush a vented mask; higher in obesity or OSA), IPAP starting about 12 to 15 and increased to about 20 (up to 30) cmH2O within the first 30 minutes as tolerated, with a backup rate (BTS/ICS 2016 setting guide).
• Recheck a gas at 1 to 2 hours, and at 4 to 6 hours. Decide in advance whether intubation is the next step or NIV is the ceiling.
• Contraindications: can't protect airway, vomiting, untreated pneumothorax, facial injury, upper GI surgery, haemodynamic instability, imminent arrest.
• Pitfall: NIV in de novo hypoxaemic failure can delay intubation and generate injurious tidal volumes. Use it there only with close monitoring.

Invasive ventilation

• Intubate for failure of HFNO or NIV, falling consciousness, inability to protect the airway, exhaustion, or shock.
• ARDS: global definition (2023, published 2024) is acute onset within a week, bilateral opacities on X-ray, CT or ultrasound, not fully explained by heart failure, with PaO2/FiO2 300 or less (or SpO2/FiO2 315 or less with SpO2 97% or less). It now includes patients on HFNO 30 L/min or more.
• Lung-protective ventilation: tidal volume 6 mL/kg predicted body weight, plateau pressure 30 cmH2O or less, driving pressure under 15, permissive hypercapnia.
• Prone positioning at least 12 to 16 hours a day if PaO2/FiO2 under 150 (PROSEVA: mortality fell from 33% to 16%).
• Conservative fluids once shock resolves (FACTT). ECMO in specialist centres for refractory hypoxaemia.

Chronic respiratory failure

Cause	Clues	Long-term treatment
COPD	Persistent PaCO2 over 53 mmHg 2 to 4 weeks after an admission needing NIV	Home NIV plus oxygen (HOT-HMV)
Obesity hypoventilation	BMI 30 or more, PaCO2 over 45 mmHg awake, bicarbonate 27 or more, OSA	CPAP first if severe OSA and stable; bilevel NIV if CPAP fails or with acute-on-chronic failure; weight loss
Motor neurone disease	Refer for NIV assessment with symptoms of hypoventilation (orthopnoea, morning headache) and FVC under about 80%, or with FVC under about 50% or SNIP under about 40 cmH2O even without symptoms (NICE NG42 sets the exact thresholds)	NIV improves survival and quality of life (Bourke, Lancet Neurology 2006)
Duchenne, kyphoscoliosis, post-polio	Nocturnal hypoventilation first	Nocturnal NIV

• Long-term oxygen criteria (PaO2 55 mmHg or less, or 56 to 59 with cor pulmonale or polycythaemia) apply mainly to COPD. Home oxygen funding varies by state.
• Driving: Austroads Assessing Fitness to Drive applies to chronic respiratory failure and to untreated sleep-disordered breathing with daytime sleepiness. Commercial drivers have stricter standards.
• Discuss goals of care and ceilings of treatment early in progressive disease, especially MND.

Complications

• Oxygen toxicity and absorption atelectasis with prolonged high FiO2.
• NIV: pressure ulcers on the nasal bridge, gastric distension, aspiration, dry eyes.
• Ventilator-associated pneumonia, barotrauma, ICU weakness, delirium.
• Refeeding syndrome and hypophosphataemia can delay weaning.

Pitfalls

• Withholding oxygen from a hypoxaemic COPD patient for fear of CO2 retention. Titrate to 88 to 92% instead.
• Trusting SpO2 in carbon monoxide poisoning or methaemoglobinaemia.
• Relying on oxygen saturation to monitor neuromuscular weakness instead of FVC.
• Missing obesity hypoventilation in an obese patient with high bicarbonate admitted with "heart failure".
• Starting NIV without a documented plan for what happens if it fails.