Respiratory acidosis

Respiratory acidosis is a primary rise in arterial carbon dioxide (PaCO2 over 45 mmHg or 6.0 kPa) from alveolar hypoventilation, with an arterial pH under 7.35 unless renal compensation is complete. It is a sign of ventilatory failure from airway, lung, chest wall, neuromuscular or central causes.

Clinical relevance. Hypercapnic respiratory failure complicates acute exacerbations of chronic obstructive pulmonary disease, obesity hypoventilation, neuromuscular disease, opioid overdose and severe asthma. Acute hypercapnia with a pH under 7.25 is associated with high mortality, and non-invasive ventilation reduces the need for intubation and death in COPD exacerbations.

Physiology. PaCO2 depends on carbon dioxide production and alveolar ventilation. Acute hypercapnia lowers pH by about 0.08 for each 10 mmHg rise in PaCO2 and raises bicarbonate by 1 mmol/L for each 10 mmHg. Chronic hypercapnia (over 3 to 5 days) is compensated by renal bicarbonate retention, so bicarbonate rises by 3.5 to 4 mmol/L for each 10 mmHg and pH falls by only 0.03 for each 10 mmHg.

Classification by duration.

• Acute: pH under 7.35 with PaCO2 over 45 mmHg and a normal or slightly raised bicarbonate (under 30 mmol/L).
• Chronic: PaCO2 over 45 mmHg, near normal pH and bicarbonate over 30 mmol/L.
• Acute on chronic: a raised bicarbonate with a pH under 7.35 and a higher PaCO2 than the patient's baseline.

Classification by severity.

• Mild: PaCO2 45 to 55 mmHg with pH over 7.30.
• Moderate: PaCO2 56 to 70 mmHg or pH 7.25 to 7.30.
• Severe: PaCO2 over 70 mmHg or pH under 7.25.

Classification by cause.

• Airway obstruction: foreign body, laryngeal and upper airway obstruction, angioedema, epiglottitis, bronchospasm, and COPD.
• Lung and pleural disease: severe asthma, pneumonia, pulmonary oedema, acute respiratory distress syndrome, pneumothorax, large effusion, and interstitial lung disease with exhaustion.
• Chest wall and diaphragm: flail chest, obesity hypoventilation, kyphoscoliosis, ankylosing spondylitis, diaphragmatic paralysis, and abdominal distension.
• Neuromuscular: Guillain-Barre syndrome, myasthenic crisis, motor neurone disease, muscular dystrophy, spinal cord injury, botulism, organophosphate poisoning, and critical illness neuromuscular weakness.
• Central: opioids, benzodiazepines, general anaesthesia, stroke, brainstem lesions, central sleep apnoea, hypothyroidism, and head injury.
• Increased CO2 production: sepsis, fever, overfeeding, malignant hyperthermia, thyroid storm, and seizures.
• Iatrogenic: inadequate ventilator settings, excessive dead space, and oxygen therapy in patients with hypercapnic drive.

Key distinctions. An elevated bicarbonate with a near normal pH implies chronic hypercapnia, and the patient should not be normalised rapidly. A falling pH with a PaCO2 rising on repeat gases indicates ventilatory failure.

History.

• Breathlessness, orthopnoea, cough and sputum, wheeze, morning headache, daytime sleepiness, snoring, witnessed apnoea, weight gain, and ankle swelling.
• Known COPD, asthma, neuromuscular disease, scoliosis, obstructive sleep apnoea, obesity, heart failure, spinal injury, or previous respiratory failure and ventilation.
• Drugs and ingestions: opioids, benzodiazepines, other sedatives, alcohol, muscle relaxants, aminoglycosides, and anaesthesia.
• Recent surgery, trauma, infection, chest pain (pneumothorax), swallowing difficulty (aspiration), and weakness or dysphagia.
• Oxygen use: home oxygen, previous hypercapnia on oxygen, and a COPD alert card.

Examination.

• Respiratory rate and pattern (rapid shallow, paradoxical breathing, use of accessory muscles), oxygen saturation, chest expansion, air entry, wheeze, crackles, and tracheal position.
• Neurological: drowsiness, confusion, asterixis (flapping tremor), myoclonus, papilloedema, small pupils (opioids), reduced power, and bulbar weakness.
• Cardiovascular: warm vasodilated peripheries, bounding pulse, raised jugular venous pressure and oedema (cor pulmonale), and blood pressure.
• Body mass index, neck circumference, and spinal deformity.
• Single breath count, forced vital capacity and negative inspiratory force in neuromuscular disease.

Red flags.

• pH under 7.25, or PaCO2 rising on repeat gases.
• Drowsiness, confusion, falling Glasgow Coma Scale, or asterixis.
• Respiratory rate under 10 breaths/min, or exhaustion with paradoxical breathing.
• Forced vital capacity under 15 to 20 mL/kg, or negative inspiratory force weaker than minus 20 to minus 30 cmH2O (neuromuscular failure).
• Upper airway obstruction (stridor, angioedema, epiglottitis).
• Tension pneumothorax or massive effusion.
• Opioid or sedative overdose with respiratory depression.
• Severe asthma with a silent chest.
• Haemodynamic instability.

Special groups. Patients with chronic hypercapnia rely partly on hypoxic drive and need controlled oxygen. Children and neonates have limited reserve and tire quickly. Pregnancy has a lower normal PaCO2 (about 30 mmHg), so a PaCO2 of 40 mmHg is abnormal. Older adults and frail patients may present with confusion only.

Acute respiratory acidosis. Opioid or sedative overdose, severe asthma, acute exacerbation of COPD, upper airway obstruction, aspiration, pneumonia, acute pulmonary oedema, tension pneumothorax, flail chest, acute neuromuscular failure (Guillain-Barre syndrome, myasthenic crisis, botulism), cervical spinal cord injury, status epilepticus, brainstem stroke, severe head injury, and cardiac arrest.

Chronic respiratory acidosis with acute deterioration. COPD, obesity hypoventilation syndrome, neuromuscular disease (motor neurone disease, muscular dystrophy), chest wall deformity, interstitial lung disease, central hypoventilation, hypothyroidism, chronic sleep apnoea, and previous polio.

Ventilator associated and iatrogenic. Inadequate minute ventilation, excessive dead space, high CO2 load from overfeeding, permissive hypercapnia (planned), and oxygen induced hypercapnia in COPD.

Metabolic and electrolyte causes of weakness. Hypophosphataemia, hypokalaemia, hypomagnesaemia, hypocalcaemia, and severe metabolic alkalosis (hypoventilation).

Conditions that mimic or accompany. Mixed acid base disorders (respiratory acidosis with metabolic acidosis in cardiac arrest, sepsis or kidney failure), carbon monoxide poisoning, anxiety, pulmonary embolism, and cardiac failure.

Step 1. Take an arterial blood gas (the reference test for hypercapnia, but a venous gas with PCO2 under 6.5 kPa or 50 mmHg excludes significant hypercapnia in most patients and a higher venous PCO2 needs arterial confirmation). Note the inspired oxygen concentration. Interpret pH, PaCO2, bicarbonate and base excess, and compare with the patient's baseline.

Step 2. Bedside assessment: oxygen saturation, respiratory rate, Glasgow Coma Scale, peak flow (asthma), single breath count, forced vital capacity and negative inspiratory force (neuromuscular disease), and capillary glucose.

Step 3. Laboratory tests: full blood count, electrolytes (potassium, magnesium, phosphate, calcium), urea, creatinine, glucose, lactate, creatine kinase, thyroid function, troponin, BNP, drug and toxicology screen, cultures, and CRP.

Step 4. Imaging and cardiac tests: chest radiograph (pneumothorax, pneumonia, oedema, effusion, hyperinflation, spinal deformity), ECG (cor pulmonale, arrhythmia), lung ultrasound, echocardiography, and CT chest or CT pulmonary angiogram where indicated. CT head for suspected central cause.

Step 5. Further tests for chronic hypercapnia: spirometry, lung volumes, diffusion capacity, sleep study and overnight oximetry with transcutaneous CO2, neuromuscular tests (nerve conduction, anti-acetylcholine receptor antibodies), and spinal imaging.

Interpretation. A PaCO2 over 6.0 kPa (45 mmHg) with pH under 7.35 is acute or acute on chronic ventilatory failure. A PaCO2 over 6.0 kPa with a normal pH and a bicarbonate over 30 mmol/L is chronic. A pH under 7.25 after initial treatment in a COPD exacerbation is an indication for non-invasive ventilation and intensive care review.

Limitations. Pulse oximetry cannot detect hypercapnia. Venous PCO2 overestimates arterial PCO2 by about 0.5 to 0.8 kPa. Bicarbonate on venous samples varies. Rapid correction of chronic hypercapnia may cause post hypercapnic alkalosis.

Principles. Secure the airway, support ventilation, give controlled oxygen, treat the cause, and avoid sedation. Aim to return the patient to their baseline PaCO2, not to normal values, when chronic hypercapnia is present.

Airway and oxygen.

• Clear the airway and treat obstruction: jaw thrust, airway adjuncts, suction, and urgent senior airway review.
• For angioedema or anaphylaxis give adrenaline 0.5 mg (0.5 mL of 1 in 1000) IM into the anterolateral thigh every 5 minutes.
• Use controlled oxygen with a target saturation of 88 to 92% in patients at risk of hypercapnia (COPD, obesity hypoventilation, neuromuscular disease, chest wall disease). Use a 24 to 28% venturi mask or nasal cannula at 1 to 2 L/min. Target 94 to 98% in others.
• Do not withhold oxygen from a hypoxic patient, because hypoxia kills sooner than hypercapnia. Repeat a gas within 30 to 60 minutes of any oxygen change.

Non-invasive ventilation (NIV).

• Indications: acute or acute on chronic hypercapnic respiratory failure with pH under 7.35 and PaCO2 over 6.5 kPa (49 mmHg) persisting after 1 hour of optimal medical treatment. This includes COPD exacerbation, obesity hypoventilation, neuromuscular and chest wall disease, and cardiogenic pulmonary oedema with hypercapnia.
• Contraindications: unprotected airway or reduced consciousness (unless in intensive care), vomiting, facial trauma or surgery, fixed upper airway obstruction, undrained pneumothorax, haemodynamic instability, and copious secretions.
• Initial settings: inspiratory positive airway pressure 10 to 12 cmH2O, expiratory positive airway pressure 4 to 5 cmH2O, backup rate 12 to 16 breaths/min. Add oxygen to keep saturation 88 to 92%.
• Increase inspiratory pressure by 2 to 5 cmH2O every 10 to 30 minutes as tolerated, up to 20 to 30 cmH2O.
• Check a gas at 1 hour and at 4 hours. A fall in PaCO2 and rise in pH indicates success.
• Failure (pH falling, PaCO2 rising, worsening consciousness, exhaustion, or intolerance at 1 to 4 hours): intubate unless a ceiling of care has been set.

Invasive ventilation. Intubation for pH under 7.25 not responding to NIV, respiratory arrest, severe hypoxia, airway protection, or contraindication to NIV.

Use rapid sequence induction: ketamine 1 to 2 mg/kg IV or etomidate 0.3 mg/kg IV with rocuronium 1.2 mg/kg IV. Suxamethonium 1 to 1.5 mg/kg IV is acceptable if there is no hyperkalaemia or neuromuscular disease. Give fentanyl 1 to 2 micrograms/kg IV for the pressor response, have a vasopressor ready, and plan post intubation sedation.

Ventilate with tidal volume 6 to 8 mL/kg of predicted body weight, a low respiratory rate (10 to 14 breaths/min) and a long expiratory time in obstructive disease to avoid dynamic hyperinflation. Aim for a PaCO2 at the patient's baseline with a pH over 7.20 (permissive hypercapnia). Reduce PaCO2 slowly (not faster than 10 mmHg each hour in chronic hypercapnia) to avoid alkalosis and seizures.

Cause specific.

• COPD exacerbation: salbutamol 2.5 to 5 mg nebulised every 4 to 6 hours, driven by air, not oxygen, with nasal oxygen added. Monitor tremor, tachycardia and potassium. Give ipratropium 500 micrograms nebulised every 6 hours.
• COPD exacerbation: prednisolone 30 to 40 mg orally once daily for 5 days (monitor glucose).
• COPD exacerbation with purulent sputum: doxycycline 200 mg orally on day 1 then 100 mg once daily (total 5 days), with photosensitivity and separation from calcium, iron and antacids. Alternatively amoxicillin with clavulanic acid 625 mg orally every 8 hours for 5 days (reduce when CrCl is under 30 mL/min).
• Consider theophylline in COPD only in specialist hands.
• Severe asthma: salbutamol 5 mg nebulised continuously or every 15 to 20 minutes, ipratropium 500 micrograms nebulised, hydrocortisone 100 mg IV or prednisolone 40 to 50 mg orally, and magnesium sulphate 2 g IV over 20 minutes (single dose; monitor blood pressure).
• In asthma, a normal or rising PaCO2 is a sign of impending arrest. Arrange early critical care for a rising PaCO2.
• Opioid overdose: naloxone 0.4 to 2 mg IV (or 0.4 to 0.8 mg IM) repeated every 2 to 3 minutes to a maximum of 10 mg. In opioid dependent patients titrate to respiratory rate and not consciousness (0.04 to 0.1 mg increments, to avoid withdrawal).
• For long acting opioids follow with an infusion of two thirds of the effective bolus dose each hour. Monitor for at least 4 to 6 hours after the last dose of naloxone.
• Avoid flumazenil in benzodiazepine overdose because of the risk of seizures. Use supportive ventilation instead.
• Neuromuscular failure (Guillain-Barre syndrome, myasthenic crisis): measure forced vital capacity and negative inspiratory force every 2 to 4 hours.
• Intubate for forced vital capacity under 15 to 20 mL/kg, negative inspiratory force weaker than minus 20 to minus 30 cmH2O, bulbar failure, or rising PaCO2.
• Use immunoglobulin 0.4 g/kg IV once daily for 5 days (monitor renal function and thrombosis) or plasma exchange, in consultation with neurology.
• Pulmonary oedema: furosemide 40 to 80 mg IV, glyceryl trinitrate infusion, and NIV.
• Pneumothorax: needle or finger decompression for tension, then chest drain.
• Pneumonia: antibiotics within 1 hour for sepsis, for example amoxicillin 1 g orally or IV every 8 hours with clarithromycin 500 mg every 12 hours (adjust for kidney function; monitor QTc).
• Obesity hypoventilation: NIV, weight loss, and avoid sedatives; long term home NIV with specialist review.
• Hypophosphataemia, hypokalaemia and hypomagnesaemia: replace potassium chloride 40 mmol in 1 litre of isotonic saline over 4 hours (maximum 10 mmol/hour peripherally).
• Replace phosphate 10 to 20 mmol IV over 6 to 12 hours, and magnesium sulphate 2 g IV over 20 minutes (reduce in kidney impairment).
• Hypothyroidism: levothyroxine under endocrine advice.
• Sepsis, fever and overfeeding raise carbon dioxide production: treat infection, avoid excess carbohydrate loads, and cool.

Bicarbonate. Not used routinely; it increases CO2 production. It may be considered for severe mixed acidosis (pH under 7.1) with metabolic acidosis once ventilation is optimised.

Monitoring. Arterial blood gas at 30 to 60 minutes after any change of oxygen or ventilation, then every 2 to 4 hours; continuous saturation and ECG; respiratory rate and Glasgow Coma Scale hourly; forced vital capacity for neuromuscular disease; electrolytes and glucose daily; and ventilator pressures and volumes.

Referral and escalation. Critical care for pH under 7.25, NIV failure, invasive ventilation, or neuromuscular failure. Respiratory medicine for COPD and chronic ventilatory failure. Neurology for neuromuscular disease. Anaesthesia for difficult airway. Palliative care and ceiling of care decisions for advanced disease.

Admission criteria. pH under 7.35 with PaCO2 over 6.0 kPa, new drowsiness, rising PaCO2, neuromuscular weakness, overdose, or inability to manage at home. Stable chronic hypercapnia with a near normal pH can be managed by respiratory teams as an outpatient.

Discharge and safety netting. Discharge when pH and PaCO2 are at baseline on room air or home oxygen, the patient is stable for 24 hours, treatment is oral, and follow up is arranged within 2 weeks. Written advice on home NIV, oxygen alert card, inhaler technique, and avoidance of sedatives. Patients return for worsening breathlessness, drowsiness, morning headache, confusion or swelling.