AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

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

INTRODUCTION

Section 2 of 9  

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

Background

Respiratory alkalosis is a clinical disturbance due to alveolar hyperventilation. Alveolar hyperventilation leads to a decreased PaCO₂ level (hypocapnia). In turn, the decrease in PaCO₂ level increases the ratio of bicarbonate concentration (HCO₃^-) to PaCO₂ and increases the pH level. Hypocapnia develops when the lungs remove more carbon dioxide than is produced in the tissues. Respiratory alkalosis can be acute or chronic. In acute respiratory alkalosis, the PaCO₂ level is below the lower limit of normal and the serum level is alkalemic. In chronic respiratory alkalosis, the PaCO₂ level is below the lower limit of normal, but the pH level is normal or near normal because of renal compensation.

Respiratory alkalosis is the most common acid-base abnormality observed in patients who are critically ill. It is associated with numerous illnesses and is a common finding in patients undergoing mechanical ventilation. Many cardiac and pulmonary disorders can present with respiratory alkalosis as an early or intermediate finding. When respiratory alkalosis is present, the cause may be minor but more serious disease processes should also be considered in the differential diagnosis.

Pathophysiology

Metabolism generates a large quantity of volatile acid (carbon dioxide) and nonvolatile acid. The metabolism of fats and carbohydrates leads to the formation of a large amount of carbon dioxide. The carbon dioxide combines with water to form carbonic acid (H₂CO₃). The lungs excrete the volatile fraction through ventilation, and acid accumulation does not occur. Significant alterations in ventilation can affect elimination of carbon dioxide and lead to a respiratory acid-base disorder.

PaCO₂ is maintained in the 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 medulla. Ventilation is influenced and regulated by chemoreceptors for PaCO₂, PaO₂, and pH located in the brainstem and by neural impulses from lung stretch receptors and impulses from the cerebral cortex. Various disease processes may cause stimulation of ventilation with subsequent hyperventilation. If hyperventilation is persistent, it leads to hypocapnia.

Acute hypocapnia causes a reduction of serum levels of potassium and phosphate secondary to increased cellular uptake of these ions. A reduction in free serum calcium also occurs. Calcium reduction is secondary to increased binding of Ca⁺⁺ to serum albumin. Many of the symptoms present in persons with respiratory alkalosis are related to the hypocalcemia. Hyponatremia and hypochloremia may also be present.

Acute hyperventilation with hypocapnia causes a small early reduction in serum bicarbonate due to cellular uptake of bicarbonate. Acutely, plasma pH and bicarbonate concentration vary proportionately with the PaCO₂ along a range of 15-40 mm Hg. After a period of 2-6 hours, respiratory alkalosis is renally compensated by a decrease in bicarbonate reabsorption. The expected change in serum bicarbonate concentration ([HCO₃^-]) can be estimated as follows:

• Acute - [HCO₃^-] falls 2 mEq/L for each decrease of 10 mm Hg in the PaCO₂ (Limit of compensation: [HCO₃^-] = 12-20 mEq/L)
• Chronic - [HCO₃^-] falls 5 mEq/L for each decrease of 10 mm Hg in the PaCO₂ (Limit of compensation: [HCO₃^-] = 12-20 mEq/L)

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

• Acute respiratory alkalosis - Change in pH = 0.008 X (40 – PaCO₂)
• Chronic respiratory alkalosis - Change in pH = 0.017 X (40 – PaCO₂)

Frequency

United States

The frequency of respiratory alkalosis varies depending on the etiology. It is the most common acid-base abnormality observed in critically ill patients.

Mortality/Morbidity

Morbidity and mortality of patients with respiratory alkalosis depend on the nature of the underlying cause of the respiratory alkalosis and associated conditions.

CLINICAL

Section 3 of 9  

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

History

Clinical manifestations of respiratory alkalosis vary according to duration and severity and depend on the underlying disease process.

• The hyperventilation syndrome can mimic many conditions that are more serious. Symptoms may include paresthesias, circumoral numbness, chest pain or tightness, dyspnea, and tetany.
• Acute onset of hypocapnia can cause cerebral vasoconstriction. Therefore, an acute decrease in PaCO₂ reduces cerebral blood flow and can cause neurologic symptoms, including dizziness, mental confusion, syncope, and seizures.

Physical

Findings from the physical examination in patients with respiratory alkalosis are usually nonspecific and related to the underlying illness or cause of the respiratory alkalosis.

• Many patients with hyperventilation syndrome appear anxious, and tachycardia is frequently present. Understandably, tachypnea is a frequent finding.
• Positive Chvostek and Trousseau signs may be elicited.
• Patients with underlying pulmonary disease may have signs suggestive of pulmonary disease, such as crackles and rhonchi. Cyanosis may be present if the patient is hypoxic.
• If the cause is neurologic, focal neurologic signs or a depressed level of consciousness may be present.
• Cardiovascular effects of hypocapnia in healthy and alert patients are minimal, but in patients who are anesthetized, critically ill, or receiving mechanical ventilation, the effects can be more significant. Cardiac output and systemic blood pressure may fall due to the effects of sedation and positive-pressure ventilation of venous return, systemic vascular resistance, and heart rate.
• Cardiac rhythm disturbances may occur because of increased tissue hypoxia related to the leftward shift of the hemoglobin-oxygen dissociation curve.

Causes

Respiratory alkalosis may have numerous etiologies, including the following:

• Central nervous system
• • Pain
  • Hyperventilation syndrome
  • Anxiety
  • Psychosis
  • Fever
  • Cerebrovascular accident
  • Meningitis
  • Encephalitis
  • Tumor
  • Trauma
• Hypoxemia
• • High altitude
  • Severe anemia
  • Right-to-left shunts
• Drugs
• • Progesterone
  • Methylxanthines
  • Salicylates
  • Catecholamines
  • Nicotine
• Endocrine
• • Pregnancy: Progesterone levels are increased during pregnancy. Progesterone causes stimulation of the respiratory center, which can lead to respiratory alkalosis.
  • Hyperthyroidism
• Stimulation of chest receptors
• • Pneumothorax/hemothorax
  • Pneumonia
  • Pulmonary edema
  • Pulmonary embolism
  • Aspiration
  • Interstitial lung disease
• Miscellaneous
• • Sepsis
  • Hepatic failure
  • Mechanical ventilation
  • Heat exhaustion
  • Recovery phase of metabolic acidosis

DIFFERENTIALS

Section 4 of 9  

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

Other Problems to be Considered

Thyrotoxicosis

The differential diagnosis of respiratory alkalosis is broad, and all the potential diagnoses listed in the previous section should be considered. A thorough history, physical examination, and laboratory evaluation are generally helpful in limiting the differential diagnosis.

The diagnosis of hyperventilation syndrome should be a diagnosis of exclusion. Rule out all organic medical conditions, including pulmonary embolism, cardiac ischemia, and hyperthyroidism, before establishing a diagnosis of hyperventilation syndrome.

WORKUP

Section 5 of 9  

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

Lab Studies

• Arterial blood gas
• • Alkalemia is documented by the presence of an increased pH level (>7.44) on arterial blood gas determinations.
  • The presence of a decreased PaCO₂ level (<36 mm Hg) indicates a respiratory etiology of the alkalemia.
• Serum chemistries
• • Acute respiratory alkalosis causes minor changes in electrolyte balances. Minor intracellular shifts of sodium, potassium, and phosphate levels are present. A minor reduction in free calcium occurs due to an increased protein-bound fraction.
  • Compensation for respiratory alkalosis is by increased renal excretion of bicarbonate. In acute respiratory acidosis, the bicarbonate concentration level decreases by 2 mEq/L for each decrease of 10 mm Hg in the PaCO₂ level. In chronic respiratory acidosis, the bicarbonate concentration level decreases by 5 mEq/L for each decrease of 10 mm Hg in the PaCO₂ level. Plasma bicarbonate levels rarely drop below 12 mm Hg secondary to compensation for primary respiratory alkalosis.
• Complete blood cell count
• • An elevation of the WBC count may indicate early sepsis as a possible etiology of respiratory alkalosis.
  • A reduced hematocrit value may indicate severe anemia as the potential cause of respiratory alkalosis.
• Liver function test findings may be abnormal if hepatic failure is the etiology of the respiratory alkalosis.
• Cultures of blood, sputum, urine, and other sites should be considered, depending on information obtained from the history and physical examination. Sepsis and bacteremia are potential causes of respiratory alkalosis.

Imaging Studies

• Chest radiograph
• • Perform a chest radiograph (CXR) to help rule out pulmonary disease as a cause of hypocapnia and respiratory alkalosis.
  • Potential etiologies that may be confirmed based on CXR findings include pneumonia, pulmonary edema, aspiration pneumonitis, pneumothorax, and interstitial lung disease.
• CT scan
• • CT scan of the chest may be performed if CXR findings are inconclusive or a pulmonary disorder is strongly considered as a differential diagnosis. CT scan is more sensitive for helping detect disease, and findings may reveal abnormalities not seen on the CXR.
  • Consider a ventilation-perfusion scan of the lungs or spiral CT angiography of the chest if pulmonary embolism is suggested.
  • Consider a CT scan of the brain if a central cause of hyperventilation and respiratory alkalosis is suggested. Specific etiologies that may be diagnosed based on brain CT scan findings include cerebrovascular accident, CNS tumor, and CNS trauma.
• Brain MRI
• • If a central cause of hyperventilation and respiratory alkalosis is suggested and the initial brain CT scan findings are negative or inconclusive, an MRI of the brain can be considered.
  • MRI images may reveal abnormalities that are not seen on CT scan images. Possible etiologies based on MRI images include cerebrovascular accident, CNS tumor, and CNS trauma.

Procedures

• Perform a lumbar puncture if the history and physical examination findings are suggestive of a CNS infectious process. Perform cytologic analysis in patients suggested to have meningeal metastasis.

TREATMENT

Section 6 of 9  

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

Medical Care

Treatment of respiratory alkalosis is primarily directed at correcting the underlying disorder.

• Respiratory alkalosis itself is rarely life threatening; therefore, emergent treatment is usually not indicated unless the pH level is greater than 7.5. Because respiratory alkalosis usually occurs in response to some stimulus, treatment is usually unsuccessful unless the stimulus is controlled.
• If the PaCO₂ is corrected rapidly in patients with chronic respiratory alkalosis, metabolic acidosis may develop due to the previous compensatory drop in serum bicarbonate.
• In respiratory alkalosis complicating mechanical ventilation, changes that can lead to improvement and resolution involve decreasing the tidal volume and respiratory rate. For patients who are receiving mechanical ventilation and are breathing above the set ventilator rate, adequate sedation and control of pain may also be helpful in controlling hyperventilation.
• In hyperventilation syndrome, patients benefit from reassurance, rebreathing into a paper bag during acute episodes, and treatment for underlying psychological stress. Sedatives should be reserved for patients who have not responded to conservative treatment. Beta-adrenergic blockers may help control the manifestations of the hyperadrenergic state that may lead to the hyperventilation syndrome in some patients.

Consultations

Consider consultation with pulmonologists, neurologists, or nephrologists for assistance with the evaluation and management of respiratory alkalosis. Findings from the history, physical examination, and available laboratory studies should guide selection.

FOLLOW-UP

Section 7 of 9  

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

Prognosis

• The prognosis of respiratory alkalosis is variable and depends on the underlying cause and the severity of the underlying illness.

Patient Education

• Patients with hyperventilation syndrome as the etiology of their respiratory alkalosis may particularly benefit from patient education. The underlying pathophysiology should be explained in simple terms, and patients should be instructed in breathing techniques that may be used to relieve the hyperventilation. Reassurance is key for these patients.

MISCELLANEOUS

Section 8 of 9  

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

Medical/Legal Pitfalls

• The most important factor in managing respiratory alkalosis is to recognize that it may be associated with serious medical disorders. Many of these conditions may be life threatening if not diagnosed early. If the cause of respiratory alkalosis cannot be readily determined, a list of differential diagnoses should be developed and all serious medical conditions should be excluded.

REFERENCES

Section 9 of 9

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

• Chang CH, Kuo PH, Hsu CH, Yang PC. Persistent severe hypocapnia and alkalemia in a 40-year-old woman. Chest. Jul 2000;118(1):242-5. [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].
• Gordon JB, Rehorst-Paea LA, Hoffman GM, Nelin LD. Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets. Pediatr Res. Dec 1999;46(6):735-41. [Medline].
• Imanaka H, Nishimura M, Takeuchi M, et al. Autotriggering caused by cardiogenic oscillation during flow-triggered mechanical ventilation. Crit Care Med. Feb 2000;28(2):402-7. [Medline].
• Javaheri S, Kazemi H. Metabolic alkalosis and hypoventilation in humans. Am Rev Respir Dis. Oct 1987;136(4):1011-6. [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. Apr 2005;21(2):329-46. [Medline].
• Kirsch DB, Jozefowicz RF. Neurologic complications of respiratory disease. Neurol Clin. Feb 2002;20(1):247-64, viii. [Medline].
• Krapf R, Beeler I, Hertner D, Hulter HN. Chronic respiratory alkalosis. The effect of sustained hyperventilation on renal regulation of acid-base equilibrium. N Engl J Med. May 16 1991;324(20):1394-401. [Medline].
• Martinez-Maldonado M, Sanchez-Montserrat R. Respiratory acidosis and alkalosis. Clin Nephrol. May 1977;7(5):191-200. [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. Current status of acid-base quantitation in physiology and medicine. Anesth Clin North Am. 1998;16:211-34.
• Wiseman AC, Linas S. Disorders of potassium and acid-base balance. Am J Kidney Dis. May 2005;45(5):941-9. [Medline].

Article Last Updated: Jun 30, 2005