Approach

Once respiratory acidosis has been identified by arterial blood gas (ABG) analysis, the approach to narrowing the differential diagnosis and determining the severity of the patient's condition is aided by establishing its acuity (acute or chronic). This is done through the synthesis of information from the ABG, history, and physical examination.[19]

Historical findings may immediately point to the underlying cause, such as head trauma and drug ingestion, or provide only limited information, as with the obtunded patient.

The physical examination should focus on assessing the neurological and respiratory systems, with careful examination of the lung fields, which can yield useful information regarding the presence of underlying parenchymal disease. The examination can be augmented with point-of-care ultrasonography (POCUS), which is a rapid and cost-effective tool that can help narrow down the differential diagnosis.[20]

Further laboratory studies are warranted when metabolic abnormalities or specific systemic diseases are suspected aetiologies. Radiographic imaging is key to the evaluation of respiratory acidosis, as it can provide rapid screening for head, cervical, or chest pathology.

Arterial blood gas analysis

Step 1: Is there acidosis?

  • Acidosis is indicated by an ABG pH below the normal range (i.e., <7.35)

Step 2: Respiratory or metabolic?

  • Respiratory acidosis is indicated by an increase in the arterial carbon dioxide levels above the normal range of 35 to 45 mmHg (4.7 to 6.0 kPa).

  • It is important to note that the degree of acidosis and the potential concerns are different depending on whether the problem is respiratory or metabolic.

  • An equivalent pH in metabolic acidosis (e.g., 7.0) is a much worse clinical sign, as the body has dual buffering and compensatory mechanisms for metabolic acid (the carbamate-bicarbonate system: bicarbonate buffer and carbon dioxide elimination). On the other hand, elevated carbon dioxide causes a dramatic fall in pH, but the patient is less sick as there is little buffering capacity for carbon dioxide. Studies in critical illness have demonstrated that patients tolerate hypercapnic acidosis well.

Step 3: Is the respiratory acidosis acute or chronic?

  • Knowing whether respiratory acidosis is acute or chronic is important, as it helps identify the underlying cause of acidosis.

  • Knowledge of the condition's chronicity also helps identify the patient's ability to tolerate the rise in carbon dioxide. Acute respiratory acidosis tends to have a more serious (often life-threatening) clinical presentation compared to patients with chronic respiratory acidosis.

  • Common causes of respiratory acidosis are summarised. See Aetiology.

  • In acute respiratory acidosis, for every 10 mmHg increase in PaCO₂, the pH decreases by 0.08 and the serum bicarbonate and base excess are within the normal range, due to the acute nature of the underlying process.[21]​ 

  • To calculate the anticipated compensation in chronic respiratory acidosis, recall that the pH in chronic respiratory acidosis decreases by only 0.03 units for every 10 mmHg increase in PaCO₂. For patients with compensated chronic respiratory acidosis (e.g., in COPD), the pH may be within the normal range despite an elevated PaCO₂.

  • Renal mechanisms of compensation can correct respiratory acidosis within 24 hours.

  • Changes in pH outside these ranges suggest a superimposed metabolic abnormality (either acidosis or alkalosis).

Step 4: Is there hypoxaemia?

  • The presence of hypoxaemia with respiratory acidosis can help to narrow down the differential diagnosis.

  • Hypoxaemia may occur with processes that cause profound alveolar hypoventilation, such as sedative overdose and CNS infarction, or regional ventilation-perfusion mismatch, such as multilobar pneumonia.

History

Signs and symptoms of acute hypercapnia are often non-specific (e.g., headache, somnolence, mild dyspnoea, and hypoxaemia). For patients who are at high risk of hypoventilation: for example, patients with advanced COPD, patients who are sedated or anaesthetised after procedures, or obese patients with obstructive sleep apnoea, a high index of suspicion could prevent a delay in diagnosis.

Respiratory acidosis affects many organ systems, and patients may present with manifestations of hypercapnia and /or signs and symptoms of the underlying disorder.

Experienced clinicians have noted that while patients with neuromuscular disorders exhibit some tachypnoea or respiratory distress when they are hypercapnic, patients with disorders of the respiratory centre often hyperventilate without any sensation of dyspnoea or obvious respiratory distress. Furthermore, tachypnoea does not equate with an increase in alveolar ventilation. In fact, patients may be hypoventilating with respiratory rates that are either in the normal range, decreased, or even increased.

Impaired consciousness is often a late development in hypercapnic patients; those who are normocapnic at baseline may not become somnolent until PaCO₂ rises to more than 75-80 mmHg (9.9 to 10.9 kPa), whereas previously hypercapnic patients may not develop impairment of consciousness until PaCO₂ rises acutely to >90-100 mmHg (11.9 to 13.3 kPa).[22]​​ Thus, a delay in diagnosis of acute hypercapnia could lead to the development of coma, seizures, cardiovascular collapse, and death. Early recognition of acute hypercapnia by ABG analysis could circumvent such adverse outcomes.

Onset of symptoms

  • The degree of acuity and magnitude of symptoms helps to narrow the differential diagnosis.

  • COPD commonly presents with acute or chronic respiratory acidosis secondary to an exacerbation caused by a lower respiratory tract infection, pulmonary embolism, pneumothorax (due to bullous rupture), or cor pulmonale.

  • Fever, cough, pleuritic chest pain, and hypoxia suggest an underlying parenchymal process such as pneumonia or empyema.

  • Chronic conditions, including obesity-hypoventilation syndrome, multiple sclerosis, myasthenia gravis, and kyphoscoliosis, may be associated with few or no symptoms.

  • Acute causes of respiratory acidosis often present with more overt symptoms, such as rapidly progressive ascending neurological weakness suggestive of Guillain-Barre syndrome.

Pre-existing medical conditions

  • The presence of chronic diseases associated with respiratory acidosis, including COPD, myasthenia gravis, and multiple sclerosis, can assist in determining the underlying cause.

  • The presence of atherosclerotic disease or atrial fibrillation increases the likelihood of CNS pathology (i.e., infarction).

  • A history of depression may increase suspicion of toxic ingestion.

Medication history

  • Narcotics and analgesics may lead to respiratory depression.

  • A recent increase in continuous oxygen flow rate in a COPD patient can cause hypoventilation.

  • The use of ACE inhibitors or angiotensin receptor blockers increases the risk of angio-oedema.

Excessive daytime sleepiness and headaches on wakening are seen in hypoventilation syndrome in obesity.

Physical examination

Pulmonary examination

  • Abnormal findings on pulmonary auscultation (egophony, crackles, wheeze, dullness to percussion) can help localise chest pathology but are nonspecific.

  • Obstructed breathing patterns include seesaw chest movements, nasal flaring, and supraclavicular and subcostal recession.

  • Paradoxical movement of a portion of the chest wall with spontaneous breathing suggests a flail chest.

Cardiac examination

  • A right ventricular heave and tricuspid regurgitation suggest chronic right ventricular failure (cor pulmonale) associated with COPD and obesity hypoventilation syndrome.

  • An irregular cardiac rhythm, valvular murmurs, or carotid bruits may suggest an embolic source if a CNS event is present.

Neurological examination

  • Obtundation, anisocoria, and abnormal unilateral pupillary reflex signify a possible brainstem infarct.

  • Asterixis, myoclonus, seizures, or miosis may be present depending on the ingested substance.

  • Symmetrical hyporeflexia/areflexia of the lower extremities is a cardinal sign of Guillain-Barre syndrome.

Laboratory evaluation

Initial laboratory assessments should include a full blood count (FBC), serum bicarbonate and electrolytes. Once the patient has been stabilised, subsequent laboratory tests are then directed toward determining the specific cause(s) of hypercapnia (e.g., toxicology screen).

Laboratory assessments may include:

  • Serum electrolyte measurement: to assess potassium and phosphate levels

  • FBC: to evaluate for polycythaemia or elevated white blood cell count

  • Toxicology testing: indicated in the obtunded patient to screen for pharmacological depressants

  • Lumbar puncture: useful to screen for CNS infection

  • Specific tests to screen for systemic diseases:

    • Thyroid-stimulating hormone for hypothyroidism

    • Anti-acetylcholine receptor antibody for myasthenia gravis

    • C1 esterase inhibitor functional assay for hereditary angio-oedema

    • Anti-nuclear antibodies for scleroderma

    • HLA-B27 antigen for ankylosing spondylitis.

  • Microbiological testing: sputum microscopy, culture, and sensitivity for the assessment of pneumonia.

  • Muscle biopsy: may be indicated if muscular dystrophy, malignant hyperthermia, polymyositis, or dermatomyositis is suspected.

Imaging studies

  • Chest x-ray (CXR) and computed tomography (CT) are key to screening for underlying lung and chest wall disease. CXR is a rapid and readily available imaging modality to screen for causes of respiratory acidosis. CT scanning can often add more information.

  • When accessible, POCUS is usually the quickest investigative method and is particularly valuable for identifying immediate life-threatening conditions in an emergency situation.[20]

  • Brain imaging with CT or magnetic resonance imaging is indicated to screen for head trauma, stroke, or haemorrhage.

  • Overnight polysomnography is a useful screening tool for obesity-hypoventilation syndrome and primary alveolar hypoventilation.

  • Dynamic fluoroscopy with deep inspiration (sniff test) can diagnose phrenic nerve damage.

  • Electromyography and nerve conduction testing demonstrate diffuse denervation and abnormal amplitude of compound muscle action potentials with preserved conduction velocities in amyotrophic lateral sclerosis.

Pulmonary function testing

  • Forced vital capacity (FVC) and maximal inspiratory and expiratory pressures are used to evaluate the respiratory system integrity in Guillain-Barre syndrome and myasthenia gravis.

  • FVC, maximal inspiratory pressures (MIP), and maximal expiratory pressures (MEP) should be monitored in all patients with neuromuscular disorders affecting the chest wall muscles and diaphragm.[23]

  • Reduced lung volumes are seen in kyphoscoliosis and obesity.

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