Evaluation of respiratory alkalosis

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Evidence last reviewed: 13 Oct 2026

Topic last updated: 05 Nov 2026

Respiratory alkalosis is a systemic acid-base disorder characterized by a primary reduction in arterial partial pressure of carbon dioxide (PaCO₂), which produces an elevation in pH above 7.45, and consequent decrease in bicarbonate (HCO₃-) concentration, as buffering mechanisms.[1] It may occur as a simple primary disorder, a sole respiratory abnormality in which a decrease in PaCO₂ results from excess alveolar CO₂ excretion relative to CO₂ production. Respiratory alkalosis may also occur as compensation for an underlying process, such as metabolic acidosis, or as a separate component of a mixed acid-base disorder, in which case the PaCO₂, HCO₃-, and pH are determined by the combined effects of the underlying acid-base disorders.[2]

Respiratory alkalosis can be classified clinically into three categories:[3]

as a component of disease processes
accidentally induced
deliberately induced (therapeutic)

Accidental respiratory alkalosis develops as a consequence of inappropriate settings of mechanical ventilation or associated with extracorporeal membrane oxygenation (ECMO).[3] Although therapeutic respiratory alkalosis or hypocapnia has historically been applied to temporarily treat intracranial hypertension or neonatal pulmonary artery hypertension, this practice is no longer recommended for these indications.[4][5][6][7]

Epidemiology

Respiratory alkalosis is common. Two large studies of inpatients from the US evaluating arterial blood samples showed a respiratory alkalosis prevalence of 22.5% to 44.7%.[8][9] Because arterial blood was withdrawn at various times in the patients' hospital course, these figures probably represent instances of respiratory alkalosis from disparate categories. In an Italian study, arterial blood samples obtained from 110 consecutive patients at the time of hospital admission demonstrated respiratory alkalosis in 24%.[10] A 2016 analysis of 10-year data from the prospective Health, Aging, and Body Composition Study, which enrolled participants from two US states, identified respiratory alkalosis via arterial blood gas measurements in 16% (372) of 2287 black and white adults ages 70-79 years. Respiratory alkalosis was also associated with mortality in this cohort.[11]

During the COVID-19 pandemic, the prevalence of respiratory alkalosis among inpatients with COVID-19 or with acute respiratory distress syndrome (ARDS) on noninvasive respiratory support was within the range of earlier studies at 30.3% (COVID-19) and 40% (ARDS).[10][12][13] Respiratory alkalosis was unrelated to the degree of hypoxemia or respiratory rate.[13]

The occurrence of accidentally induced respiratory alkalosis may be inferred from a retrospective study of intubated patients with burns (146 people) who received mechanical ventilation for aeromedical transport. The frequency of respiratory alkalosis was 19%, in which 39% of patients received volume-assist control and 17% of patients on intermittent mandatory ventilation experienced hypocapnia.[14][15] A 2022 retrospective study of 375 patients admitted to the intensive care unit in one hospital in Cape Town, South Africa found respiratory alkalosis in 4.3% of mechanically ventilated patients.[16] Respiratory alkalosis is also associated with extracorporeal membrane oxygenation (ECMO). A secondary analysis of neonatal and pediatric ECMO patients showed the frequency of hypocapnia in the study group (484 patients) across eight US hospitals to be 20.2%.[17]

Therapeutic respiratory alkalosis or hypocapnia has historically been applied to temporarily treat intracranial hypertension or neonatal pulmonary artery hypertension.[4][5][7] However, this practice is no longer recommended for these indications because the benefit of therapeutic hypocapnia is unproven.[7][18] However, the benefit of therapeutic hypocapnia remains unproven and it should be limited to life-threatening elevated intracranial pressure.[6][19] Guidelines on the management of traumatic brain injury recommend avoiding hypocapnia as it is associated with worse outcomes for patients.[6]

Physiology

In respiratory alkalosis, initial suppression of the respiratory center and reduction in plasma bicarbonate concentration attenuate the rise in pH. Excess CO₂ excretion (alveolar hyperventilation) and the resulting low arterial PaCO₂ (hypocapnia) inhibits the respiratory centre through a negative feedback loop. The systemic effect of the initial reduction in PaCO₂ can be described by the modified Henderson-Hasselbalch equation as follows:

(H+)=24(PaCO₂/HCO₃-)

The decrease in PaCO₂ reduces the PaCO₂/HCO₃- ratio, hence reducing the H+ concentration, which results in alkalemia. The decrease in PCO₂ also leads to a reduced rate of H+ secretion and increased rate of bicarbonate excretion by the renal tubules as an intracellular buffering mechanism. Within the renal tubular cells, CO₂, under the influence of carbonic anhydrase enzyme, combines with H₂O to form carbonic acid (H₂CO₃), which then dissociates into HCO3- and H+. Alkalemia inhibits carbonic anhydrase activity, resulting in reduced H+ secretion into the renal tubule.[20] HCO₃- reabsorption is dependent on combining with H+ to form carbonic acid, which later dissociates into H₂O and CO₂. Owing to the reduced H+ concentration in the renal tubule, there is inadequate H+ concentration to react with the filtered HCO₃-. HCO₃- reabsorption decreases, resulting in reduced plasma HCO₃- concentration and attenuation of pH.

The physicochemical (Stewart or strong ion difference) approach to acid-base analysis similarly shows that acute hyperventilation and fall in PaCO₂ slowly lead to hyperchloremic renal compensation. The hyperchloremia is related to excretion of filtered sodium and potassium with bicarbonate as hydrogen secretion decreases in proximal and distal tubules. As the plasma strong ion difference decreases, the plasma bicarbonate concentration decreases, resulting in the return of serum pH toward normal. Both the traditional and the Stewart approaches illustrate that renal compensation is caused by a change in the ratio of PaCO₂ to bicarbonate (see above modified Henderson-Hasselbalch equation).[21]

Respiratory alkalosis can manifest as acute or chronic. Acute respiratory alkalosis occurs from the onset of hypocapnia for up to 6 hours.[1] Chronic respiratory alkalosis with renal compensatory mechanisms begins 6 hours after the onset of hypocapnia and becomes complete within 2 to 5 days.[1][22][23] In acute respiratory alkalosis, the relationship between the decrease in serum HCO₃- and the decrease in PaCO₂ can be expressed as:

change in HCO₃- (mEq/L ) = 0.1 x change in PaCO₂ (mmHg)

where the decrease in HCO₃- is from a normal value of 24 mEq/L and the decrease in PaCO₂ is from a normal value of 40 mmHg. For instance, an acute decrease in PaCO₂ of 20 mmHg will result in serum HCO₃- of approximately 22 mEq/L : that is, a decrease of 2 mEq/L (0.1 x 20) from the normal value of serum HCO₃- of 24 mEq/L. Notable deviation of serum HCO₃- concentration from the predicted value suggests acid-base disorder other than isolated acute respiratory alkalosis.

In chronic respiratory alkalosis, serum HCO₃- is further reduced owing to suppression of renal tubular H+ secretion and HCO₃- reabsorption. Thus, the magnitude of the decrease in H+ concentration is attenuated to a greater extent than in the acute stage. In chronic respiratory alkalosis, the relation between the decrease in serum HCO₃- and the decrease in PaCO₂ can be expressed as:[24][25]

change in HCO₃- (mEq/L) = 0.4 x change in PaCO₂ (mmHg)

In this instance, a persistent decrease in PaCO₂ of 20 mmHg will decrease serum HCO₃- by 8 mEq/L from its normal value of 24 mEq/L, resulting in serum HCO₃- of 16 mEq/L. In patients with isolated chronic respiratory alkalosis, serum HCO₃- rarely decreases below 12 to 14 mEq/L.[23]

While significant deviations of HCO₃- concentration predicted in acute or in chronic respiratory alkalosis indicate a second primary acid-base process, pH is also a key factor because compensatory mechanisms do not restore the pH entirely.[23] If hypocapnia occurs alongside acidemia, a primary respiratory alkalosis may be present if the degree of hypocapnia exceeds what would be expected as a compensatory response to the coexisting metabolic acidosis.

Respiratory alkalosis leads to increased serum lactate by mildly increasing lactate production and by decreasing lactate clearance.[26][27] Interestingly, in one small study, induced respiratory alkalosis in trained athletes by voluntary hyperventilation has been shown to attenuate performance decline as measured by peak and mean power output in repeated sprinting. This is thought to be due to retardation of the acidosis caused by exercise-induced lactic acidosis.[28]

Respiratory alkalosis also alters electrolyte homeostasis, separate from its renal compensatory mechanisms.

Potassium

Initially, hyperkalemia occurs owing to hyperventilation-induced augmentation of alpha-adrenergic activity. Afterwards, hypokalemia ensues owing to transcellular shift, decreased renal reabsorption, and bicarbonaturia. Bicarbonaturia increases renal potassium excretion.[29][30] Hypokalemia is usually mild but can be severe in pregnant women due to high circulating progesterone levels causing hyperventilation and respiratory alkalosis. One case report described a patient with respiratory alkalosis-induced hypokalemia leading to flaccid paralysis.[22]

Phosphate

In the acute phase, hypophosphatemia may be related to increased cellular uptake.[31][32] Conversely, the chronic phase is associated with hyperphosphatemia together with hypocalcemia due to parathyroid hormone resistance.[33]

Bronchoconstriction is a prominent manifestation of physiologic changes in the lung.[34][35][36] Effects on the pulmonary artery, and pH-related changes in respiratory alkalosis, can induce pulmonary arterial vasodilation. Although therapeutic hypocapnia has historically been used as a temporary treatment for neonatal persistent pulmonary hypertension, this practice has essentially been replaced by pulmonary vasodilator therapy.[5][7][37]

Tachycardia is also consistent with physiologic changes inherent in respiratory alkalosis and is related to increased sympathetic activity and to hypokalemia.[29][38] Chest pain may occur through coronary vasospasm or decreased myocardial oxygen delivery owing to increased O₂ affinity to hemoglobin.[39] Data also suggest that respiratory alkalosis significantly decreased in vivo microcirculatory flow as measured by reflectance confocal microscopy during states of sustained hypocapnia (PaCO₂ 20.9 ± 2.9 mmHg). This was seen without concomitant decrease in cardiac output.[40] Ventricular and atrial arrhythmias have also been reported in acute and chronic respiratory alkalosis.[41][42][43]

Gastrointestinal and hepatic symptoms are seen in acute (but not in chronic) respiratory alkalosis. Acute respiratory alkalosis produces nausea, vomiting, and increased gastrointestinal motility.[44] The mechanism for increased colonic tone is dependent on the presence of hypocapnia (and not eucapnic hyperventilation), which seems to have a direct effect on colonic smooth muscle.[45] Peripheral and central nervous system (CNS) effects of hypocapnia occur at a threshold of PaCO₂ <20 mmHg.[46] Symptoms include vertigo, dizziness, anxiety, euphoria, clumsiness, forgetfulness, hallucinations, and seizure.[47] Unilateral somatic symptoms have also been reported, including partial seizures, migraines, or stroke-like symptoms. CNS symptoms are initiated by changes in pH (rather than changes in PaCO₂), which reduce cerebral blood flow, causing cerebral ischemia that ultimately accounts for neurologic symptoms.[48] Peripheral manifestations include tetany and paresthesia. These neurologic manifestations are mediated by hyperventilation-induced increased neural excitability caused by hypocalcemia and, possibly, hypophosphatemia.[48][49][50]

Differentials

Common

Pulmonary embolism
Sepsis
Acute respiratory distress syndrome (ARDS)
Pneumonia
Cardiogenic shock
Pulmonary edema
Ischemic stroke
Hemorrhagic stroke
Salicylate poisoning
Pseudorespiratory alkalosis
Pregnancy
Asthma in adults
Asthma in children
Hypoxemia
Cirrhosis
Cardiopulmonary bypass

Full details

Uncommon

Pneumothorax
Meningitis
Encephalitis
Brain tumor
Traumatic brain injury
Mechanical ventilation
High altitude-related illness
Generalized anxiety disorder
Idiopathic pulmonary arterial hypertension
Interstitial pulmonary fibrosis
Central sleep apnea
Hypovolemic shock
Severe anemia
Lung contusion
Central neurogenic hyperventilation
Hyperventilation syndrome
Hyperthermic hyperpnea
Cyanotic heart disease
Hemoglobinopathy
Extracorporeal membrane oxygenation (ECMO)
Fulminant hepatic failure
Hepatopulmonary syndrome
Portopulmonary hypertension
Nicotine, xanthines, catecholamines, respiratory stimulants, progestational agents
Situational anxiety

Full details

Contributors

Authors

Radhika Reddy, MD

Assistant Clinical Professor of Medicine

University of California

Irvine, CA

Disclosures

None

Catherine S. Sassoon, MD

Emeritus Professor of Medicine

University of California

Irvine, CA

Disclosures

None

Acknowledgements

Dr Catherine S. Sassoon and Dr Radhika Reddy would like to gratefully acknowledge Dr Brian Dang, Dr Asad Qasim, Dr Wilson Yan, Dr Jeremy Murdock, and Dr Sterling L. Malish, previous contributors to this topic. BD, AQ, WY, JM, and SLM declare that they have no competing interests.

Peer reviewers

Feras Hawari, MD

Chief of Pulmonary and Critical Care

King Hussein Cancer Center

Amman

Jordan

Disclosures

FH declares that he has no competing interests.

John G. Laffey, MD

Professor and Head

Department of Anesthesia

Galway University Hospitals

Galway

Ireland

Disclosures

JGL is an author of a number of references cited in this topic.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Laffey JG, Kavanagh BP. Hypocapnia. N Engl J Med. 2002 Jul 4;347(1):43-53. Abstract

Lulla A, Lumba-Brown A, Totten AM, et al. Prehospital guidelines for the management of traumatic brain injury - 3rd edition. Prehosp Emerg Care. 2023;27(5):507-38.Full text Abstract

Berend K, de Vries AP, Gans RO. Physiological approach to assessment of acid-base disturbances. N Engl J Med. 2014 Oct 9;371(15):1434-45. Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

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Evaluation of respiratory alkalosis

Summary

Epidemiology

Physiology

Differentials

Common

Uncommon

Contributors

Authors

Radhika Reddy, MD

Disclosures

Catherine S. Sassoon, MD

Disclosures

Acknowledgements

Peer reviewers

Feras Hawari, MD

Disclosures

John G. Laffey, MD

Disclosures

Peer reviewer acknowledgements

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Patient information

Videos

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