Refractory Hypoxaemia

Refractory hypoxaemia is persistent arterial hypoxaemia (saturation under 88% or PaO2 under 8.0 kPa) despite high inspired oxygen (FiO2 0.8 or more) and PEEP in a ventilated patient, usually with a PF ratio under 100. It marks the most severe form of hypoxaemic respiratory failure.

Epidemiology. It arises mostly in severe ARDS and carries mortality of 40 to 60%.

Causes and associations. Severe ARDS, massive pneumonia, large shunt through collapsed or consolidated lung, pulmonary embolism, intracardiac right to left shunt (patent foramen ovale opened by high pulmonary pressure), pulmonary arteriovenous malformation and hepatopulmonary syndrome.

Mechanical causes to exclude. Endotracheal tube malposition or blockage, tension pneumothorax, lobar or lung collapse, mucus plug, ventilator or circuit fault, bronchospasm and main stem intubation.

Pathophysiology. Shunt fraction is the dominant cause, and added oxygen does not correct it. Reduced cardiac output and increased oxygen consumption (fever, shivering, agitation) worsen venous desaturation and arterial hypoxaemia.

Presentation is falling saturation despite maximal oxygen with tachycardia, cyanosis and haemodynamic instability. Check chest movement, breath sounds and ventilator waveforms for a sudden cause.

Red flags.

• Abrupt fall in saturation (tube, pneumothorax, plug).
• Right ventricular failure, shock or arrhythmia.

Exclude reversible causes at once: check tube position and patency (suction catheter, bronchoscopy), chest radiograph or ultrasound for pneumothorax, collapse and effusion, and ventilator function. Obtain arterial and mixed or central venous gas, lactate, haemoglobin, echocardiography with bubble study for right to left shunt and right heart strain, and CT pulmonary angiography when stable.

Differential diagnosis. Methaemoglobinaemia and carboxyhaemoglobinaemia (low saturation by oximetry with a normal PaO2, or a normal oximetry reading with true hypoxia), and poor oximeter signal.

Escalate in order, with early referral to an extracorporeal centre.

1. Optimise lung protective ventilation. Tidal volume 6 mL/kg predicted body weight, plateau pressure 30 cmH2O or less, and higher PEEP titrated to compliance and haemodynamics. Recruitment manoeuvres (for example PEEP of 35 to 40 cmH2O for 40 seconds) are used cautiously and not as a routine.

2. Prone position. At least 16 hours daily.

3. Neuromuscular blockade. Cisatracurium 15 mg IV bolus then 37.5 mg/h for up to 48 hours.

4. Reduce oxygen consumption and improve delivery. Deep sedation, treat fever and shivering, transfuse to haemoglobin of 70 to 80 g/L (higher if myocardial ischaemia), and optimise cardiac output and avoid excess fluid.

5. Inhaled pulmonary vasodilators. Nitric oxide 5 to 20 ppm, or nebulised epoprostenol 50 nanogram/kg/min. These improve oxygenation without proven survival benefit. Stop if there is no response in 30 to 60 minutes. Monitor methaemoglobin with nitric oxide.

6. Extracorporeal membrane oxygenation. Venovenous support for PF ratio under 80 for over 6 hours, or under 50 for over 3 hours, or pH under 7.25 with PaCO2 60 mmHg or more for over 6 hours. Contraindications include irreversible disease, prolonged high pressure ventilation (over 7 days) and bleeding that prevents anticoagulation.

Treat the cause. Thrombolysis or embolectomy for massive pulmonary embolism, pleural drainage and removal of mucus plugs.

Monitoring. Continuous oximetry and arterial gas, lactate, mixed venous saturation, right heart function by echocardiography, and airway pressures.

Referral and escalation. Contact an ECMO centre early. Do not delay transfer until the patient is unstable.

Special groups. In pregnancy, early ECMO should be considered, and delivery is discussed with obstetrics. In right ventricular failure, avoid high plateau pressures and hypercapnia.