Evaluation of respiratory acidosis

Required for diagnosis of COPD.[24]Global Initiative for Chronic Obstructive Lung Disease. ​Global strategy for prevention, diagnosis and management of COPD: 2025 report​. 2024 [internet publication]. https://goldcopd.org/2025-gold-report

Obstructive ventilatory deficit may or may not be reversible after bronchodilator use.

Post-bronchodilator FEV1/FVC ratio <0.70 confirms airflow limitation.[24]Global Initiative for Chronic Obstructive Lung Disease. ​Global strategy for prevention, diagnosis and management of COPD: 2025 report​. 2024 [internet publication]. https://goldcopd.org/2025-gold-report

The 2024 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report recommends a repeat spirometry test on a separate occasion if the post-bronchodilator FEV1/FVC ratio is between 0.6 and 0.8.[24]Global Initiative for Chronic Obstructive Lung Disease. ​Global strategy for prevention, diagnosis and management of COPD: 2025 report​. 2024 [internet publication]. https://goldcopd.org/2025-gold-report ​​​

The 2024 GOLD report states that pre-bronchodilator spirometry can be used as an initial test to investigate whether symptomatic patients have airflow obstruction.[24]Global Initiative for Chronic Obstructive Lung Disease. ​Global strategy for prevention, diagnosis and management of COPD: 2025 report​. 2024 [internet publication]. https://goldcopd.org/2025-gold-report ​ If this doesn’t show obstruction, then post-bronchodilator spirometry is not required unless there is a very high clinical suspicion of COPD.[24]Global Initiative for Chronic Obstructive Lung Disease. ​Global strategy for prevention, diagnosis and management of COPD: 2025 report​. 2024 [internet publication]. https://goldcopd.org/2025-gold-report

CXR is useful to support the diagnosis of COPD. Additionally, it can exclude other causes of wheeze or triggers of exacerbation (heart failure, pneumonia, pneumothorax, pulmonary embolism).[24]Global Initiative for Chronic Obstructive Lung Disease. ​Global strategy for prevention, diagnosis and management of COPD: 2025 report​. 2024 [internet publication]. https://goldcopd.org/2025-gold-report

Air-trapping (increased RV) and hyperinflation (increased TLC) are typically present in patients with emphysema.

Should be done if pulse oximetry measurements ≤92%.[24]Global Initiative for Chronic Obstructive Lung Disease. ​Global strategy for prevention, diagnosis and management of COPD: 2025 report​. 2024 [internet publication]. https://goldcopd.org/2025-gold-report ​ Hypercapnia typically accompanies severe cases of COPD.

CXR is the first diagnostic test to confirm pneumonia.

CT of the chest is rarely needed but may provide better visualization of the extent of the disease.

If the patient's clinical state permits, microbiologic cultures should be taken before initiating antibiotics.

CXR can serve to localize foreign bodies if they have passed below the carina. For supracarinal obstruction, symptoms are often severe enough to require emergent intervention (abdominal thrusts [Heimlich maneuver], intubation).

Laryngoscopy and bronchoscopy are useful as diagnostic tests when history of aspiration is unclear, and radiographs are inconclusive (e.g., pediatric patients).

Toxicology testing should include screening for opioids, barbiturates, benzodiazepines, and ethanol.

An osmolar gap (between measured and calculated plasma osmolality) is useful to screen for ethanol, ethylene glycol, or methanol ingestion.

The chronic hypercapnia associated with moderate to severe COPD leads to a change in the normal stimulus for respiration (from hypercapnia and acidosis to hypoxemia). Excessive supplemental oxygen can lead to both a blunting of the hypoxic vasoconstriction of the pulmonary vascular bed, leads to increase in dead space ventilation and a diminished stimulus for breathing.

Given its relative ease and rapidity, CT scan is the initial diagnostic test of choice.[26]American College of Radiology. ACR appropriateness criteria: cerebrovascular diseases-stroke and stroke-related conditions. 2023 [internet publication]. https://acsearch.acr.org/docs/3149012/Narrative ​ It allows exclusion of intracerebral hemorrhage. Detection of infarction on CT depends on the timing of the imaging relative to the event. Characteristic changes are of an area of low attenuation with surrounding edema and associated sulcal or ventricular effacement.

MRI of the brain is a useful secondary imaging modality, as acute or subtle regions of infarct and hemorrhage may not be easily detected on CT.[26]American College of Radiology. ACR appropriateness criteria: cerebrovascular diseases-stroke and stroke-related conditions. 2023 [internet publication]. https://acsearch.acr.org/docs/3149012/Narrative [27]Intercollegiate Stroke Working Party. National clinical guideline for stroke for the UK and Ireland. May 2023 [internet publication]. https://www.strokeguideline.org ​ MRI characteristics depend on the timing of the imaging relative to the event. However, the distribution of abnormalities can offer clues to the etiology (i.e., wedge-shaped infarcts in thromboembolic disease distal margin ischemia in watershed infarcts related to hypoperfusion).

CT findings include skull fracture, subdural hematoma, or intraparenchymal bleeding.

While a CT scan of the brain is not required prior to a lumbar puncture, it is often performed to screen for elevated intracranial pressure and avoid the risk of herniation. A normal CT scan does not necessarily mean a lumbar puncture is safe and, therefore, should be used in conjunction with the physical exam to determine the risk of herniation.[28]Joffe AR. Lumbar puncture and brain herniation in acute bacterial meningitis: a review. J Intensive Care Med. 2007;22:194-207. http://www.ncbi.nlm.nih.gov/pubmed/17712055?tool=bestpractice.com

Apart from screening for evidence of increased intracranial pressure prior to performing a lumbar puncture, a CT scan may reveal an alternative diagnosis for the presenting signs and symptoms (e.g., tumor, abscess).

CT features of increased intracranial pressure include sulcal effacement, loss of gray-white matter distinction, and obliteration of the normal ventricular space.

Serum bicarbonate level <27 mEq/L⁻¹ has a 97% negative predictive value for excluding obesity hypoventilation syndrome.[29]Masa JF, Pépin JL, Borel JC, et al. Obesity hypoventilation syndrome. Eur Respir Rev. 2019 Mar 14;28(151):180097. https://pmc.ncbi.nlm.nih.gov/articles/PMC9491327 http://www.ncbi.nlm.nih.gov/pubmed/30872398?tool=bestpractice.com A level ≥27 mEq/L⁻¹ should be followed by daytime ABG analysis​.[29]Masa JF, Pépin JL, Borel JC, et al. Obesity hypoventilation syndrome. Eur Respir Rev. 2019 Mar 14;28(151):180097. https://pmc.ncbi.nlm.nih.gov/articles/PMC9491327 http://www.ncbi.nlm.nih.gov/pubmed/30872398?tool=bestpractice.com ​ Daytime hypercapnia is seen on ABG with PCO₂ ≥45 mmHg.

While obstructive sleep apnea (OSA) often accompanies hypoventilation syndrome in obesity, the presence of OSA is not an absolute requirement in this disorder.[30]Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med. 2005;118:948-956. http://www.ncbi.nlm.nih.gov/pubmed/16164877?tool=bestpractice.com [31]National Institute for Health and Care Excellence. Obstructive sleep apnoea/hypopnoea syndrome and obesity hypoventilation syndrome in over 16s. Aug 2021 [internet publication]. https://www.nice.org.uk/guidance/ng202 ​​

There are no differentiating signs on CXR between pleural effusion and hemothorax.

Point-of-care ultrasound may be used to guide intervention.[32]Laursen CB, Clive A, Hallifax R, et al. European Respiratory Society statement on thoracic ultrasound. Eur Respir J. 2021 Mar 4;57(3):2001519. https://publications.ersnet.org/content/erj/57/3/2001519 http://www.ncbi.nlm.nih.gov/pubmed/33033148?tool=bestpractice.com [33]Expert Panel on Thoracic Imaging, Morris MF, Henry TS, et al. ACR appropriateness criteria® workup of pleural effusion or pleural disease. J Am Coll Radiol. 2024 Jun;21(6s):S343-52. https://www.jacr.org/article/S1546-1440(24)00254-0/fulltext http://www.ncbi.nlm.nih.gov/pubmed/38823955?tool=bestpractice.com ​​

CT scan aids in evaluating the etiology of the effusion.

Aspiration of pleural fluid and fluid analysis could help reach a definitive diagnosis.

Tension pneumothorax (presence of mediastinal shift) is a medical emergency, and its treatment should be initiated on the basis of a clinical diagnosis and should not be delayed in order to undertake a CXR.

While vital capacity and total lung capacity are reduced in obesity, some studies suggest that reduction in functional residual capacity better correlates with the degree of obesity.[34]Jones RL, Nzekwu MM. The effects of body mass index on lung volumes. Chest. 2006;130:827-833. http://journal.publications.chestnet.org/article.aspx?articleid=1084654 http://www.ncbi.nlm.nih.gov/pubmed/16963682?tool=bestpractice.com

Radiography can help confirm the diagnosis by revealing distortions of the spine. Moreover, it can help identify curvature patterns, identify certain underlying etiologies, and the magnitude of the distortion (i.e., Cobb angle).

Total lung capacity, functional residual capacity, and residual volume are reduced in kyphoscoliosis.

Other electrolytes, such as magnesium, should also be evaluated, as abnormalities in these values may provide clues as to the primary cause of hypokalemia.

Bilateral lower lobe shadowing is due to alveolar edema, and Kerley B lines are due to interstitial edema.

While useful for the diagnosis of pulmonary fibrosis, CXR findings may be nonspecific.

While a CXR can be useful for the diagnosis of pulmonary fibrosis, high-resolution CT scanning offers more information regarding the extent of the disease and staging for prognosis.[25]Sung A, Swigris J, Saleh A, et al. High-resolution chest tomography in idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia: utility and challenges. Curr Opin Pulm Med. 2007;13:451-457. http://www.ncbi.nlm.nih.gov/pubmed/17940493?tool=bestpractice.com

The development of hypoxemia indicates the need for consideration of mechanical ventilation.

Peak expiratory flow is useful for monitoring response to therapy and is predicted based on the patient's age, height, and sex (charts available to identify predicted value).

Condition presents with acute onset of wheeze or dyspnea after accidental aspiration of liquids, mucus, or food, or immediately post extubation. Clinical exam reveals frequent coughing, stridor, and increased work of breathing with or without inability to phonate.

Hereditary angioedema can be assessed by testing the activity level of C1 esterase inhibitor. Diagnosis of idiopathic angioedema is based on clinical grounds.

The condition predominantly presents in men ages 20-50 years, with lethargy, fatigue, dyspnea at rest, daytime hypersomnolence, and frequent night-time awakening. Clinical exam reveals hypersomnolence and signs of cor pulmonale (dyspnea on minimal exertion, hepatomegaly, peripheral edema, jugular venous distention).

CXR findings are areas of patchy atelectasis due to hypoventilation.

CT scans help evaluate the extent and location of the empyema, which may help guide definitive drainage procedures.

There are no differentiating signs on CXR between hemothorax and pleural effusion.

CT scan aids in evaluating the extent and etiology of hemothorax.

CXR is the most rapid way to confirm the diagnosis. Fractures of three or more ribs are required to generate instability of the thoracic cage, leading to a flail chest. Respiratory acidosis is more often due to the underlying lung injury.

CT scan aids in evaluating the possibility of damage to the adjacent lung and mediastinal structures.

Serologic diagnosis of scleroderma includes a panel of autoimmune antibodies, including antinuclear antibodies, topoisomerase antibodies, and antiribonucleoprotein antibodies.[35]Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005;35:35-42. http://www.ncbi.nlm.nih.gov/pubmed/16084222?tool=bestpractice.com

High-resolution CT is useful for determining the presence and severity of pulmonary involvement in scleroderma. Early findings include ground glass infiltrates suggestive of alveolitis. As the disease progresses, fibrosis, honeycombing, and traction bronchiectasis predominate.

Radiographs should be in the anteroposterior plane.

HLA-B27 antigen is not required for the diagnosis of ankylosing spondylitis. It is positive in 92% of white patients with the disease but can have a variable presence in other racial groups.

TSH above the upper limit of the laboratory reference range is considered elevated. If TSH is elevated, free thyroxine (FT4) should be assessed. Elevated TSH associated with low FT4 is consistent with primary hypothyroidism.[36]Devdhar M, Ousman YH, Burman KD. Hypothyroidism. Endocrinol Metab Clin North Am. 2007;36:595-615. http://www.ncbi.nlm.nih.gov/pubmed/17673121?tool=bestpractice.com

If TSH is elevated, FT4 should be assessed. Elevated TSH associated with low FT4 is consistent with primary hypothyroidism.[36]Devdhar M, Ousman YH, Burman KD. Hypothyroidism. Endocrinol Metab Clin North Am. 2007;36:595-615. http://www.ncbi.nlm.nih.gov/pubmed/17673121?tool=bestpractice.com

Diagnosis is made by promptly recognizing potential exposure to offending agents and excluding other causes for presenting symptoms (e.g., infection). Condition presents with history of recent exposure to paralytic agents (e.g., induction for anesthesia) or organophosphates (e.g., insecticides) and, with the latter, is associated with increased secretions, abdominal pain, fatigue, and confusion, depending on the agent ingested. Clinical exam may reveal ataxia, slurred speech, coma, miosis, diaphoresis, or fasciculations, depending on the exposure.

CT imaging of the cervical spine is the standard of care test in suspected high cord trauma.

Three views of the cervical spine should be obtained: anterior-posterior, lateral, and odontoid.

The condition presents with ascending weakness and/or tingling beginning in the lower extremities, which can spread to the upper body and arms, incontinence, back pain, and difficulty speaking. An antecedent viral infection or tick bite may also be reported. Clinical exam reveals the cardinal signs of hyporeflexia or areflexia combined with symmetrical lower extremity weakness, as well as cranial nerve and sensory deficits, and ileus.

While the diagnosis is typically made on clinical grounds, a lumbar puncture may assist in excluding other etiologies for the presenting symptoms. A normal lumbar puncture does not exclude this diagnosis.

FVC <30 mL/kg should prompt monitoring in an intensive care unit. If FVC is <15-20 mL/kg, prophylactic intubation should be considered.[37]Lawn ND, Fletcher DD, Henderson RD, et al. Anticipating mechanical ventilation in Guillain-Barré syndrome. Arch Neurol. 2001 Jun;58(6):893-8. https://jamanetwork.com/journals/jamaneurology/fullarticle/779520 http://www.ncbi.nlm.nih.gov/pubmed/11405803?tool=bestpractice.com

Values below these thresholds should be considered an indication for prophylactic intubation.

Gadolinium contrast administration allows visualization of active plaques.

Visual or somatosensory nerve stimulation

If myasthenia gravis is suspected as the etiology of respiratory acidosis, management of impending respiratory failure is key.[23]Cabrera Serrano M, Rabinstein AA. Usefulness of pulmonary function tests and blood gases in acute neuromuscular respiratory failure. Eur J Neurol. 2012;19:452-456. http://www.ncbi.nlm.nih.gov/pubmed/21974753?tool=bestpractice.com FVC should be monitored every 4 hours and if <15 mL/kg or the patient is unable to clear secretions, elective intubation should be considered.

The degree of degeneration depends on the stage of the disease.

Elevation in markers of muscle injury, such as aldolase and creatine kinase, is typically seen in muscular dystrophy.[38]Hathout Y, Seol H, Han MH, et al. Clinical utility of serum biomarkers in Duchenne muscular dystrophy. Clin Proteomics. 2016 Apr 5;13:9. https://pmc.ncbi.nlm.nih.gov/articles/PMC4820909 http://www.ncbi.nlm.nih.gov/pubmed/27051355?tool=bestpractice.com

Creatine kinase elevations are nearly uniformly seen. Additional tests of muscle inflammation (aldolase, erythrocyte sedimentation rate) can also be abnormal.

Imaging may be useful to assist with site of potential muscle biopsy.

Also known as the "sniff test."

The condition presents with painful muscle spasms and stiffness, trismus (lockjaw), and dysphagia in unvaccinated people. Clinical exam reveals muscle spasms, rigidity, autonomic instability, and seizures.

The condition presents with gastrointestinal complaints and cranial nerve paralysis when due to food-borne etiologies and with trauma and fever in wound-associated botulism. Clinical exam reveals cranial nerve deficits, symmetrical descending paralysis, and signs of autonomic involvement (orthostatic hypotension, dry eyes, dry mouth, and ileus).

Serologic types A, B, and E of the botulinum toxin cause the majority of botulism cases in humans, with type E typically found in fish. Toxin levels may also be measured in urine and stomach contents.

Mouse injected with a suspected contaminated sample (with and without botulinum antitoxin) is monitored for botulism.

Reduced amplitude of muscle action potential in response to single or low-frequency stimulation. Increased muscle action potential response following high-frequency or tetanic stimulation.

Distinguishes botulism from Guillain-Barre syndrome.

Positive during the acute phase. Serum should be sent for acute and convalescent titers of the 3 major polioviruses. Appropriate interpretation of antibodies depends on the timing of the infection related to symptoms.[39]WHO. New approaches to poliovirus diagnosis using laboratory techniques: memorandum from a WHO meeting. Bull World Health Organ. 1992;70:27-33. https://pmc.ncbi.nlm.nih.gov/articles/PMC2393343 http://www.ncbi.nlm.nih.gov/pubmed/1348972?tool=bestpractice.com

Blood cultures should be taken immediately, and preferably before antibiotics are started, provided their sampling will not delay administration of antibiotics. Other cultures (e.g., sputum, stool, and urine) should be taken as clinically indicated.

Elevated serum lactate indicates tissue hypoperfusion, and is most reliably assessed using an arterial sample.

WBC count is sensitive but not specific for the diagnosis of sepsis.

Elevated creatinine may occur in sepsis associated with renal dysfunction.

Sepsis can originate from hepatic or peri-hepatic infections.

Comorbid hepatic disease can affect drug metabolism.

Septic shock can compromise hepatic blood flow and metabolism.

An ECG should be arranged to help exclude other differential diagnoses, including myocardial infarction, pericarditis, and myocarditis. Sepsis also predisposes to myocardial dysfunction and arrhythmias.

Performed if meningitis suspected.

The caffeine-halothane contracture test is used; muscle biopsies in malignant hyperthermia elicit contractures at lower levels than those from standardized controls when exposed to caffeine and halothane.[40]Schneiderbanger D, Johannsen S, Roewer N, et al. Management of malignant hyperthermia: diagnosis and treatment. Ther Clin Risk Manag. 2014;10:355-62. https://pmc.ncbi.nlm.nih.gov/articles/PMC4027921 http://www.ncbi.nlm.nih.gov/pubmed/24868161?tool=bestpractice.com [41]Allen GC, Larach MG, Kunselman AR. The sensitivity and specificity of the caffeine-halothane contracture test: a report from the North American Malignant Hyperthermia Registry. The North American Malignant Hyperthermia Registry of MHAUS. Anesthesiology. 1998 Mar;88(3):579-88. https://journals.lww.com/anesthesiology/fulltext/1998/03000/the_sensitivity_and_specificity_of_the.6.aspx http://www.ncbi.nlm.nih.gov/pubmed/9523799?tool=bestpractice.com

The condition presents with a history of recent laparoscopic surgery. The clinical exam can be normal or demonstrate a distended abdomen or postoperative changes associated with recent surgery.