Respiratory Alkalosis

Description

Respiratory alkalosis is a physiologic state of high pH (>7.45) and low partial pressure of carbon dioxide (paCO₂) (<35 mm Hg).
This clinical condition is caused by hyperventilation that results in excessive elimination of CO₂.
Respiratory alkalosis is commonly classified as either:
- Acute respiratory alkalosis: Low paCO₂, high pH, onset of 6–24 hours.
- Chronic respiratory alkalosis: Low PaCO₂, near normal pH, onset of >6–24 hours. The longer duration allows the body time to compensate by excreting sodium bicarbonate ions renally.
Since pH homeostasis is essential for proper protein function, and consequently organ function, its derangement affects multiple organ systems including the cerebral, cardiovascular, renal, pulmonary, and GI systems.

Epidemiology

Incidence

In the general, in-patient population, the incidence can be as high as 26% (1).

Prevalence

Varies greatly with disease etiology

Etiology/Risk Factors

Central nervous system (CNS). The medullary respiratory center is affected by disease processes and input from peripheral and central receptors, as well as voluntary control from the cerebral cortex:
- Infection
- Tumor
- Brain injury
- Drug poisoning such as salicylates
- Caffeine
- Liver failure
- Fever
- Pain
- Anxiety
Pulmonary
- Hypoxia governs breathing to a greater extent than CO₂, thereby triggering the respiratory center to increase the respiratory rate and tidal volume (minute ventilation). It can result from pulmonary emboli, pneumonia, pneumothorax, pulmonary edema, aspiration, interstitial lung disease, asthma, emphysema or chronic bronchitis. Additionally, ascent to high altitudes can decrease the fraction of inspired oxygen.
- Iatrogenic: Mechanical hyperventilation
Cardiovascular: Congestive heart failure, right-to-left shunt, and anemia result in low-oxygen states that stimulate peripheral receptors.
Catecholamines increase ventilation via direct dilation of the smooth muscles of the bronchi.
Nicotine and acetylcholine stimulate the carotid and aortic bodies.
Hyperthyroidism increases the respiratory drive in response to hypoxemia and hypercapnia. The specific mechanism is not known.
Systemic sepsis results in tissue hypoxia as well as metabolic acidosis. In addition, the lungs provide a large surface area for heat exchange thus helping to control body temperature via neural input from the hypothalamus.
Pregnancy: Respiratory alkalosis is a normal physiologic response. A sustained elevation of progesterone causes a hypoxic ventilatory response as a result of its effect on carotid bodies, while estrogen acts on the CNS thereby augmenting carotid sinus nerve activity on ventilation.

Physiology/Pathophysiology

Carbon dioxide is a product of cellular metabolism and is excreted via the lungs. It is transported in blood in three main ways:
- Bicarbonate ions in red blood cells (RBCs) and plasma (majority). After entering the RBC, CO₂ combines with water via carbonic anhydrase to form carbonic acid; it is then broken down to H⁺ and HCO₃^-. The H⁺ binds to deoxyhemoglobin, while HCO₃^- is extruded from the cell in exchange for a Cl^- ion to maintain electroneutrality. This reaction also occurs in the plasma, but at a slower rate due to the lack of carbonic anhydrase. This mechanism for transport also serves to buffer the extracellular fluid compartment against pH derangements.
- Bound to hemoglobin (Hgb) (carbaminohemoglobin) and protein
- Dissolved in blood; a small percentage exists in the gas form and exerts partial pressure that can be measured on an arterial blood gas reading.
Chemoreceptors exist in the central and peripheral system and serve to detect changes in CO₂ and pH; they send input to the medullary respiratory center.
- Central chemoreceptors are the primary regulators of respiratory rate and are located on the ventrolateral surface of the medulla oblongata in the brain; they detect changes in pH of CSF. Since CSF is separated from the blood, electrolytes do not diffuse freely into CSF. However, volatile gases such as carbon dioxide can move easily through the barrier. Once CO₂ is in the CSF, it can react with water to eventually produce hydrogen ions and bicarbonate and thereby alter the CSF pH. With time, the chemoreceptor will eventually desensitize to the derangement.
- Peripheral chemoreceptors: aortic body and carotid body. Unlike the central chemoreceptors, they do not desensitize to stimulus. The aortic body receptors detect changes in the paO₂ and paCO₂ of the blood, whereas the carotid body receptors detect changes in the paO₂, paCO₂, and pH of the blood. The chemoreceptors serve to increase or decrease the respiratory rate and tidal volume, hence adjusting ventilation. Output from the peripheral receptors reaches the central respiratory centers, which in turn affect the ventilation.
High altitude and hypoxia govern breathing to a greater extent than CO₂. When the paO₂ falls below 100 mm Hg, neural activity from peripheral receptors begins to increase. However, the paO₂ needs to reach 60–65 mm Hg for a substantial increase in minute ventilation to occur and make the individual dependent on hypoxic ventilatory drive. This, consequently can result in respiratory alkalosis.
pH derangements result when the buffering mechanisms are overwhelmed.
- Henderson Hasselback equation:
- HCO₃^- + H⁺ H₂CO₃ CO₂ + H₂O
- Acute: pH = 0.008 × (40–paCO₂) and the HCO₃^- = 0.2 × paCO₂
- Chronic: pH = 0.017 × (40–paCO₂) and the HCO₃^- = 0.5 × paCO₂
Electrolyte derangements
- Hypokalemia. To offset the pH imbalance, hydrogen ions shift from intracellular to the extracellular space via the Na⁺-H⁺ ion exchanger (Na⁺ moves into the cell). The increase in intracellular Na⁺ stimulates the Na⁺-K⁺-ATPase, which results in a secondary intracellular shift of K⁺.
- Hypocalcemia. Alkalosis results in an increased negative charge on albumin that leads to increased Ca⁺⁺ binding and decreased unbound Ca⁺⁺ ions. Additionally, calcium binds to bone in exchange for hydrogen ions stored in bone material. Hypocalcemia can result in tetany and paresthesias.
Decreased cerebral blood flow (CBF). CBF is directly proportional to paCO₂ values between 20 and 80 mm Hg. Normal brain blood flow is 50 mL/100 g/min. A paCO₂ value of 20 mm Hg will result in severely decreased CBF to 25 mL/100 g/min. Acute decreases below this value can produce EEG signs of cerebral ischemia.
Cardiovascular system. Hypocalcemia can result in dysrhythmias and vasodilation.
Pulmonary system. Hypocarbia can result in decreased pulmonary vascular resistance as well as increased bronchial smooth muscle tone from hypocalcemia.
Medications. Respiratory alkalosis can potentiate the effects of nondepolarizing neuromuscular blockade secondary to hypokalemia and alkalemia.

Prevantative Measures

Perioperatively, the end-tidal CO₂ should be monitored with adjustments made to the respiratory rate and tidal volume as appropriate. Arterial blood gas (ABG) measurements can confirm paCO₂ and pH values, particularly when there is an increase in dead space ventilation.
Increases in minute ventilation, particularly when spontaneously ventilating, may suggest pain or awareness under anesthesia and administration of opioids or deepening of the anesthetic should be considered.

Respiratory alkalosis is a relatively common abnormality seen in in-patients. It may not always be recognized preoperatively; however, a history of recent infection, liver or thyroid disease, as well as psychological disturbances, may be clues to its presence.
Diagnostic tests and interpretation
- ABG: Identify an elevated pH with a low paCO₂. The pH value can aid with distinguishing between acute and chronic states.
- Chemistry panel: To determine the effect on electrolytes such as K⁺, Cl^-, HCO₃^-, and Ca⁺⁺. The bicarbonate value, which is decreased by the kidneys, can aid with distinguishing between acute and chronic states.
- Liver function tests: To determine if liver failure may be the cause of respiratory alkalosis.
- Chest x-ray: Can help confirm pneumonia, pulmonary congestions, pneumothorax, lung disease, pulmonary edema, cardiac enlargement, and congestion.
- Chest CT: If pulmonary embolism is suspected
- Head CT/MRI: Help to confirm an injury, tumor, or CVA
- CBC: If sepsis is suspected
- Cultures: If sepsis is suspected; if a CSF infection is suspected, perform cultures on CSF fluid.

Differential Diagnosis

Respiratory alkalosis is a unique disorder that is always a sign of some other underlying disease; thus, the etiology is, in itself, the differential diagnosis.

When detected preoperatively, the underlying cause should be sought and corrected. If found intraoperatively, it is most commonly the result of mechanical hyperventilation; however, other causes should also be at least considered.
Medication: If alkalosis is >7.60, careful titration of HCl, ammonium chloride, and arginine hydrochloride can be administered. All three medications must be administered carefully under constant supervision. Although they have other uses, their main function here is as systemic acidifiers. The HCl component of each of the drugs serves to buffer excess bicarbonate.
Additional treatment: If alkalemia is severe, consider patient intubation and mechanical (hypo)ventilation as well as hemodialysis. In cases of chronic respiratory alkalosis, correction to normocarbia needs to be gradual to avoid metabolic acidosis; the body compensates via the kidneys by excreting extra HCO₃^- to normalize the pH.
Complementary and alternative therapies: In cases of anxiety or panic attacks, the patient can be instructed to breathe into a paper bag, thereby causing some of the CO₂ to be rebreathed. Patients can be taught to identify an episode of an acute anxiety attack and practice this maneuver until the panic attack and resultant hyperventilation subsides. They can also carry out relaxation and biofeedback exercises in order to manage the severity of their anxiety and panic attacks.
Surgical treatment of hyperthyroidism and liver disease can return the paCO₂ to normal.

Palange P , Carlone S , Galassetti P , et al. Incidence of acid-base and electrolyte disturbances in a general hospital: A study of 110 consecutive admissions. Recenti Prog Med. 1990;81(12):788–791.
Terzano C , Di Stefano F , Conti V. Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation. PLoS One. 2012;7(4):e35245.
Oh YK. Acid-base disorders in ICU patients. Electrolyte Blood Press. 2010;8(2):66–71.
Quintanilla AP. Acute acid-base disorders. 2. Specific disturbances. Postgrad Med. 1976;60(5):75–83

See Also (Topic, Algorithm, Electronic Media Element)

ICD9

276.3 Alkalosis

ICD10

E87.3 Alkalosis

Perioperatively, the anesthesia provider must keep in mind that respiratory alkalosis can result in

Cerebral ischemia. Rapid correction may alternatively result in vasodilation and intracranial hypertension. Often during surgery, patients are intubated and are placed on mechanical ventilation. Adjustments made to the ventilator tidal volume and respiratory rate can lead to rapid correction of paCO₂ to normal. However, such rapid corrections could result in acute changes in CSF pH and consequently cerebral blood flow.
Cardiac instability from hypotension or dysrhythmias.
An increase in the affinity of O₂ to Hgb will shift the O₂–Hgb dissociation curve to the left. This makes it more difficult for Hgb to offload oxygen to tissues and can potentially cause tissue hypoxia.
Prolonged respiratory depression from opioids (alkalemia).
A potentiated effect of nondepolarizing neuromuscular blockade (hypokalemia and alkalemia).

Mariya Svilik , MD

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