AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Respiratory acidosis is a clinical disturbance that is due to alveolar hypoventilation. Production of carbon dioxide occurs rapidly, and failure of ventilation promptly increases the partial arterial pressure of carbon dioxide (PaCO₂). The reference range for PaCO₂ is 36-44. Alveolar hypoventilation leads to an increased PaCO₂ (ie, hypercapnia). The increase in PaCO₂ in turn decreases the HCO₃^-/PaCO₂ and decreases pH. Hypercapnia and respiratory acidosis occur when impairment in ventilation occurs and the removal of CO₂ by the lungs is less than the production of CO₂ in the tissues.

Respiratory acidosis can be acute or chronic. In acute respiratory acidosis, the PaCO₂ is elevated above the upper limit of the reference range (ie, >45 mm Hg) with an accompanying acidemia (ie, pH <7.35). In chronic respiratory acidosis, the PaCO₂ is elevated above the upper limit of the reference range, with a normal or near-normal pH secondary to renal compensation and an elevated serum bicarbonate (ie, HCO₃^- >30 mm Hg).

Acute respiratory acidosis occurs when an abrupt failure of ventilation occurs. This failure in ventilation may be caused by depression of the central respiratory center by cerebral disease or drugs, inability to ventilate adequately due to neuromuscular disease (eg, myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, muscular dystrophy), or airway obstruction related to asthma or chronic obstructive pulmonary disease (COPD) exacerbation.

Chronic respiratory acidosis may be secondary to many disorders, including COPD. Hypoventilation in COPD involves multiple mechanisms, including decreased responsiveness to hypoxia and hypercapnia, increased ventilation-perfusion mismatch leading to increased dead space ventilation, and decreased diaphragm function secondary to fatigue and hyperinflation.

Chronic respiratory acidosis also may be secondary to obesity hypoventilation syndrome (ie, pickwickian syndrome), neuromuscular disorders such as amyotrophic lateral sclerosis, and severe restrictive ventilatory defects as observed in interstitial fibrosis and thoracic deformities.

Lung diseases that primarily cause abnormality in alveolar gas exchange usually do not cause hypoventilation but tend to cause stimulation of ventilation and hypocapnia secondary to hypoxia. Hypercapnia only occurs if severe disease or respiratory muscle fatigue occurs.

Pathophysiology

Metabolism rapidly generates a large quantity of volatile acid (CO₂) and nonvolatile acid. The metabolism of fats and carbohydrates leads to the formation of a large amount of CO₂. The CO₂ combines with H₂O to form carbonic acid (H₂CO₃). The lungs excrete the volatile fraction through ventilation, and acid accumulation does not occur. A significant alteration in ventilation that affects elimination of CO₂ can cause a respiratory acid-base disorder. The PaCO₂ is maintained within a range of 39-41 mm Hg in normal states.

Alveolar ventilation is under the control of the central respiratory centers, which are located in the pons and the medulla. Ventilation is influenced and regulated by chemoreceptors for PaCO₂, PaO₂, and pH located in the brainstem, as well as by neural impulses from lung stretch receptors and impulses from the cerebral cortex. Failure of ventilation quickly increases the PaCO₂.

In acute respiratory acidosis, compensation occurs in 2 steps. The initial response is cellular buffering that occurs over minutes to hours. Cellular buffering elevates plasma bicarbonate (HCO₃^-) only slightly, approximately 1 mEq/L for each 10-mm Hg increase in PaCO₂. The second step is renal compensation that occurs over 3-5 days. With renal compensation, renal excretion of carbonic acid is increased and bicarbonate reabsorption is increased. In renal compensation, plasma bicarbonate rises 3.5 mEq/L for each increase of 10 mm Hg in PaCO₂. The expected change in serum bicarbonate concentration in respiratory acidosis can be estimated as follows:

• Acute respiratory acidosis: HCO₃^- increases 1 mEq/L for each 10-mm Hg rise in PaCO₂.
• Chronic respiratory acidosis: HCO₃^- rises 3.5 mEq/L for each 10-mm Hg rise in PaCO₂.

The expected change in pH with respiratory acidosis can be estimated with the following equations:

• Acute respiratory acidosis: Change in pH = 0.008 X (40 - PaCO₂)
• Chronic respiratory acidosis: Change in pH = 0.003 X (40 - PaCO₂)

Respiratory acidosis does not have a great effect on electrolyte levels. Some small effects occur on calcium and potassium levels. Acidosis decreases binding of calcium to albumin and tends to increase serum ionized calcium levels. In addition, acidemia causes an extracellular shift of potassium, but respiratory acidosis rarely causes clinically significant hyperkalemia.

Mortality/Morbidity

The morbidity and mortality of respiratory acidosis depends on the underlying cause of the respiratory acidosis, associated conditions, the patient's compensatory mechanisms, and ease of access to medical care.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The clinical manifestations of respiratory acidosis often are those of the underlying disorder. Manifestations vary depending on the severity of the disorder and on the rate of development of hypercapnia. Mild-to-moderate hypercapnia that develops slowly usually has minimal symptoms.

Patients may be anxious and may complain of dyspnea. Some patients may have disturbed sleep and daytime hypersomnolence. As the PaCO₂ increases, the anxiety may progress to delirium, and patients become progressively more confused, somnolent, and obtunded. This condition sometimes is referred to as CO₂ narcosis.

Physical

The findings on physical examination in patients with respiratory acidosis usually are nonspecific and related to the underlying illness or the cause of the respiratory acidosis.

• During thoracic examination, patients with obstructive lung disease may have diffuse wheezing, hyperinflation (ie, barrel chest), decreased breath sounds, hyperresonance on percussion, and prolonged expiration. Rhonchi also may be heard.
• Cyanosis may be noted if accompanying hypoxemia is present, and the finding of clubbing may indicate the presence of a chronic respiratory disease.
• Mental status may be depressed in severe elevations of PaCO₂. Patients may have asterixis, myoclonus, and seizures.
• Papilledema may be found during the examination. Conjunctival and superficial facial blood vessels also may be dilated.

Causes

Respiratory acidosis may have numerous etiologies, including the following:

• Chronic obstructive pulmonary disease
• • Emphysema
  • Severe asthma
  • Chronic bronchitis
• Neuromuscular diseases
• • Amyotrophic lateral sclerosis
  • Diaphragm paralysis
  • Severe kyphoscoliosis
  • Guillain-Barré syndrome
  • Myasthenia gravis
  • Muscular dystrophy
• Obesity hypoventilation syndrome
• CNS depression
• • Drugs - Narcotics, barbiturates, benzodiazepines, other CNS depressants
  • Neurologic disorders - Encephalitis, brainstem disease, trauma
  • Primary alveolar hypoventilation

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Amyotrophic lateral sclerosis
Muscular dystrophy
Severe kyphoscoliosis
Guillain-Barré syndrome
Myasthenia gravis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Arterial blood gas
• • Acidemia is documented by the presence of a decreased pH ( <7.35) on ABG analysis.
  • The presence of an increased PaCO₂ (>47 mm Hg) indicates a respiratory etiology of the acidemia.
• Hypoxemia may be present and frequently is associated with pulmonary diseases that may cause respiratory acidosis.
• Serum chemistries: The most common finding in chronic respiratory acidosis is the presence of a compensatory increase in serum bicarbonate concentration.
• Complete blood count: Many patients with chronic hypercapnia and respiratory acidosis also are hypoxemic. These patients also may have a secondary polycythemia.
• Drug screens: Drug and toxicology screens should be performed in patients presenting with unexplained hypercapnia and respiratory acidosis. Screen for specific drugs, including opiates, barbiturates, and benzodiazepines.

Imaging Studies

• Chest radiography
• • Perform chest radiography to rule out pulmonary disease as a cause of hypercapnia and respiratory acidosis.
  • Findings on chest radiography that may help determine an etiology of respiratory acidosis include hyperinflation and diaphragm flattening secondary to severe obstructive airway disease, infiltrates secondary to pneumonias, elevated diaphragm related to diaphragmatic weakness or paralysis, pneumothorax, and atelectasis.
  • With complicating pulmonary hypertension, the hilar vascular shadows are prominent, and the cardiac silhouette may show evidence of right ventricular enlargement.
• CT scanning of the chest: A CT scan of the chest may be obtained if the results of chest radiography are inconclusive or a pulmonary disorder is high on the differential diagnosis. CT scanning is more sensitive for detecting disease and may reveal abnormalities that are not observed on chest radiography.
• CT scanning of the brain: Perform imaging of the brain if a central cause of hypoventilation and respiratory acidosis is suspected. Specific etiologies that may be diagnosed using brain CT scanning include stroke, CNS tumor, and CNS trauma. Attention particularly should be directed to the brainstem for lesions in the pons and medulla.
• MRI of the brain: If a central cause of hypoventilation and respiratory acidosis is suspected and initial findings on brain CT scanning are negative or inconclusive, consider MRI of the brain. MRI may disclose abnormalities that are not observed on CT scanning, particularly in the brainstem.
• Fluoroscopy: A fluoroscopic "sniff test," in which paradoxical elevation of the paralyzed diaphragm is observed with inspiration, can confirm diaphragmatic paralysis, even in the presence of a normal appearance on chest radiography.

Other Tests

• Pulmonary function testing
• • These measurements are required for the diagnosis of obstructive lung disease and assessment of the severity of disease.
  • Forced expiratory volume in 1 second (FEV1) is the most commonly used index of airflow obstruction.
  • The forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio is reduced and is the diagnostic variable in airflow obstruction.
  • Lung volume measurements may document an increase in total lung capacity, functional residual capacity, and residual volume.
  • Measurement of maximal inspiratory and expiratory pressures may be useful in screening for respiratory muscle weakness.
• Electromyography and nerve conduction velocity: Electromyography (EMG) and nerve conduction velocity (NCV) are useful in diagnosing neuromuscular disorders (eg, myasthenia gravis, Guillain-Barré, amyotrophic lateral sclerosis), which may cause ventilatory muscle weakness. These studies may reveal a neuropathic or a myopathic pattern, depending on the etiology.
• Measurement of transdiaphragmatic pressure
• • This study is useful in documenting respiratory muscle weakness but is difficult to perform and usually is carried out in specialized pulmonary function laboratories.
  • This test is performed by placing an esophageal catheter with an esophageal balloon and a gastric balloon. The difference between the pressures measured at the 2 balloons is the transdiaphragmatic pressure.
  • Patients with diaphragmatic dysfunction and paralysis have a decrease in maximal transdiaphragmatic pressure (Pdimax).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The treatment of respiratory acidosis primarily is directed at correcting the underlying disorder. Exercise caution when correcting chronic hypercapnia. Rapid correction of the hypercapnia can alkalinize the cerebrospinal fluid, causing seizures and also inducing a metabolic alkalemia.

• Infusion of sodium bicarbonate rarely is indicated. It may be considered in cardiopulmonary arrest at extremes of pH ( <7.0-7.1). In most other situations, it has no role in the treatment of respiratory acidosis.
• Bronchodilators such as beta-agonists (eg, albuterol, salmeterol), anticholinergic agents (eg, ipratropium bromide, tiotropium), and methylxanthines (eg, theophylline) are helpful in treating patients with obstructive lung disease and severe bronchospasm. In addition, theophylline may improve diaphragm muscle contractility and may stimulate the respiratory center.
• Treatment also should be aimed at assisting or increasing ventilation. Therapeutics that may be life saving include endotracheal intubation with mechanical ventilation and noninvasive ventilatory techniques such as nasal continuous positive pressure ventilation and nasal bilevel ventilation.
• Drugs aimed at reversing the effects of certain sedative drugs also may be helpful in the event of an overdosage. Naloxone (Narcan) may be used to reverse the effects of narcotics. Flumazenil (Romazicon) may be used to reverse the effects of benzodiazepines.
• Oxygen therapy
• • Because many patients with hypercapnia also are hypoxemic, oxygen therapy may be indicated. Oxygen therapy is indicated to prevent the sequelae of long-standing hypoxemia.
  • Patients with COPD who meet the criteria for oxygen therapy have been shown to have decreased mortality when treated with oxygen.
  • Oxygen therapy also has been shown to reduce pulmonary hypertension.
  • Oxygen therapy should be used with caution because it may worsen hypercapnia in some situations. In patients with COPD, the presence of worsening hypercapnia following oxygen therapy is felt by many to be primarily a consequence of ventilation-perfusion mismatching, rather than a reduction in ventilatory drive. However, definitive studies are lacking and the pathophysiology remains controversial.
  • Hypercapnia is best avoided by titration of oxygen delivery to maintain oxygen saturations in the low 90% range and a PaO₂ of 60-65 mm Hg.
• Respiratory stimulants have been used but have limited efficacy in respiratory acidosis.
• • Medroxyprogesterone increases the central respiratory drive and is effective in treating obesity-hypoventilation syndrome.
  • Acetazolamide is a diuretic that increases bicarbonate excretion and causes a metabolic acidosis. The metabolic acidosis subsequently stimulates ventilation.
  • Theophylline increases diaphragm muscle strength and stimulates central ventilatory drive.

Consultations

Consider consultation with pulmonologists and neurologists for assistance with evaluation and treatment of respiratory acidosis. The history, physical examination, and available laboratory studies should guide the selection of consultants.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No drugs are used specifically to treat respiratory acidosis. Medical therapies can be used to treat some of the more common etiologies of hypoventilation and, therefore, respiratory acidosis.

Drug Category: Bronchodilators

These agents decrease muscle tone in both small and large airways in the lungs, increasing ventilation. This category includes beta-andrenergics, methylxanthines, and anticholinergics.

Drug Category: Benzodiazepine antagonists

Used in reversing the CNS-depressant effects of benzodiazepine overdose. Ability to reverse the benzodiazepine-induced respiratory depression is less predictable.

Drug Category: Opioid antagonists

Opioid abuse, toxicity, and overdose are potential etiologies of hypoventilation and respiratory acidosis. Can be used to reverse the effects of opiates and to improve ventilation.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• ICU admission
• • The criteria for admission to the ICU vary from institution to institution but include confusion, lethargy, respiratory muscle fatigue, and low pH.
  • All patients who require tracheal intubation acutely and mechanical ventilation require ICU admission.
  • Most acute care facilities require that all patients being treated with noninvasive ventilation be admitted to the ICU as well.

Further Outpatient Care

• Oxygen therapy
• • Oxygen therapy should be continued in the outpatient setting in patients who meet the specific criteria for long-term oxygen therapy.
  • The specific criteria for long-term oxygen therapy include a PaO₂ of less than 55 mm Hg or a PaO₂ of less than 59 mm Hg with evidence of polycythemia or cor pulmonale.
  • Patients should be reevaluated 1-3 months after initiating therapy for ongoing need for long-term oxygen therapy.
• Noninvasive ventilation: Noninvasive ventilation can be continued in the outpatient setting. Nasal bilevel ventilation can be used long-term to treat patients with neuromuscular disorders, COPD with hypercapnia, primary alveolar hypoventilation, and obesity-hypoventilation syndrome.

Prognosis

• The prognosis for patients with respiratory acidosis varies and depends on the severity of the underlying cause of respiratory acidosis.

Patient Education

• For excellent patient education resources, see eMedicine's Lung and Airway Center and patient education article Chronic Obstructive Pulmonary Disease (COPD).

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• All potential causes of respiratory acidosis should be considered. These include lung disease, neuromuscular diseases, and central neurologic depression.
• The effects of sedating drugs such as narcotics and benzodiazepines in depressing the central ventilatory drive and causing respiratory acidosis always should be considered. These sedative drugs should be avoided in patients with respiratory acidosis. In patients without an obvious source of hypoventilation and respiratory acidosis, a drug screen should be performed.
• Oxygen therapy should be used cautiously in patients with COPD and respiratory acidosis because higher fractions of inspired oxygen can worsen hypoventilation.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Adnet F, Plaisance P, Borron SW, et al. Prolonged severe hypercapnia complicating near fatal asthma in a 35-year-old woman. Intensive Care Med. Dec 1998;24(12):1335-8. [Medline].
• Brimioulle S, Berre J, Dufaye P, et al. Hydrochloric acid infusion for treatment of metabolic alkalosis associated with respiratory acidosis. Crit Care Med. Mar 1989;17(3):232-6. [Medline].
• Caruana-Montaldo B, Gleeson K, Zwillich CW. The control of breathing in clinical practice. Chest. Jan 2000;117(1):205-25. [Medline].
• Cham GW, Tan WP, Earnest A. Clinical predictors of acute respiratory acidosis during exacerbation of asthma and chronic obstructive pulmonary disease. Eur J Emerg Med. Sep 2002;9(3):225-32. [Medline].
• Ehrsam RE, Heigenhauser GJ, Jones NL. Effect of respiratory acidosis on metabolism in exercise. J Appl Physiol. Jul 1982;53(1):63-9. [Medline].
• Epstein SK, Singh N. Respiratory acidosis. Respir Care. Apr 2001;46(4):366-83. [Medline].
• Fall PJ. A stepwise approach to acid-base disorders. Practical patient evaluation for metabolic acidosis and other conditions. Postgrad Med. Mar 2000;107(3):249-50, 253-4, 257-8 passim. [Medline].
• Gluck SL. Acid-base. Lancet. Aug 8 1998;352(9126):474-9. [Medline].
• Hoo GW, Hakimian N, Santiago SM. Hypercapnic respiratory failure in COPD patients: response to therapy. Chest. Jan 2000;117(1):169-77. [Medline].
• Hooper RG, Browning M. Acid-base changes and ventilator mode during maintenance ventilation. Crit Care Med. Jan 1985;13(1):44-5. [Medline].
• Kassirer JP, Madias NE. Respiratory acid-base disorders. Hosp Pract. Dec 1980;15(12):57-9, 65-71. [Medline].
• Kazmaier S, Weyland A, Buhre W, et al. Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease. Anesthesiology. Oct 1998;89(4):831-7. [Medline].
• Kellum JA. Determinants of plasma acid-base balance. Crit Care Clin. 2005;21 (2):329-46. [Medline].
• Kirsch DB. Neurologic complications of respiratory disease. Neurol Clin. 2002;20 (1):247-64. [Medline].
• Krachman S, Criner GJ. Hypoventilation syndromes. Clin Chest Med. Mar 1998;19(1):139-55. [Medline].
• Martinez-Maldonado M, Sanchez-Montserrat R. Respiratory acidosis and alkalosis. Clin Nephrol. May 1977;7(5):191-200. [Medline].
• Nowbar S, Burkart KM, Gonzales R. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med. Jan 1 2004;116(1):1-7. [Medline].
• Plant PK, Owen JL, Elliott MW. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration. Thorax. Jul 2000;55(7):550-4. [Medline].
• Schlichtig R, Grogono AW, Severinghaus JW. Human PaCO2 and standard base excess compensation for acid-base imbalance. Crit Care Med. Jul 1998;26(7):1173-9. [Medline].
• Schlichtig R, Grogono AW, Severinghaus JW. Current status of acid-base quantitation in physiology and medicine. Anesthesiol Clin North America. 1998;16 (1):211-233.
• Sterns RH. Fluid, Electrolyte, and Acid-Base Disturbances. Journal of the American Society of Nephrology. 2003;2 (1):1 - 33.
• Theerthakarai R, El-Halees W, Javadpoor S. Severe pectus excavatum associated with cor pulmonale and chronic respiratory acidosis in a young woman. Chest. Jun 2001;119(6):1957-61. [Medline].
• Wiseman AC. Disorders of potassium and acid-base balance. Am J Kidney Dis. 2005;45 (5):941-9. [Medline].

Article Last Updated: Jul 7, 2005