What Is Respiratory Alkalosis

Respiratory alkalosis is a condition characterised by an elevation in arterial blood pH beyond the normal range of 7.35-7.45 due to a reduction in l carbon dioxide levels in the blood). This occurs due to hyperventilation and the expulsion of carbon dioxide from the blood at a rate faster than the body's production of carbon dioxide.¹ The primary disturbance is a low Partial pressure of CO2 (PaCO2), leading to an excess of bicarbonate ions and increased pH. 

Causes

 One of the most common causes is anxiety, pain or emotional stress. This stimulates the respiratory centre in the medulla, leading to faster and deeper breathing, which decreases CO2 levels. Other conditions like fever, sepsis, salicylate toxicity, early stages of hypoxia, pregnancy and cirrhosis also directly stimulate the respiratory centre, driving respiratory alkalosis.² Pulmonary embolism is another important cause, as clot formation triggers the release of thromboxane enzyme, which acts as a powerful respiratory stimulant.³ Infections like pneumonia, bronchitis, pertussis and asthma can induce tachypnea and hyperventilation through inflammatory mechanisms.⁴ CNS disorders like stroke, tumours and trauma can increase the respiratory drive by disrupting the regulation of breathing.  High-altitude environments are low in oxygen, which drives ventilation to increase oxygenation.⁵ This hypocapnia from altitude is called high-altitude respiratory alkalosis. Some medications may also contribute, like salicylates, progesterone and morphine, by directly stimulating breathing centres.⁶

In a minority of cases, respiratory alkalosis is not caused by hyperventilation but rather by a forced expiration against a closed glottis, which impedes full exhalation of CO2. This is called mechanical respiratory alkalosis, which is seen in whooping cough, breath-holding spells, cystic fibrosis, and some vocal cord disorders. Finally, iatrogenic respiratory alkalosis can occur due to excessive mechanical ventilation parameters in ICU patients. Lowering the tidal volume, respiratory rate, and minute ventilation on the ventilator can help prevent the blowing off of too much CO2.⁷

Pathophysiology

 The reduction in arterial PCO2 is the primary disturbance causing the alkalosis.¹ Under normal conditions, the lungs absorb oxygen (O2) and excrete carbon dioxide (CO2) that is produced by cellular respiration. Oxygen binds to haemoglobin and is delivered to tissues. CO2 diffuses into the alveoli and is exhaled. The kidneys help maintain acid-base balance by excreting acids or retaining bicarbonate.¹

In respiratory alkalosis, hyperventilation abnormally blows off CO2 before it can reach the lungs. Rapid, deep breathing decreases arterial PCO2 below the normal range. For each mmHg drop in PaCO2, the blood pH rises by 0.01 units.⁸ With lower PaCO2, the equilibrium of carbonic acid is disrupted. More bicarbonate (HCO3^-) accumulates relative to hydrogen ions (H⁺), increasing the pH. The kidneys initially excrete more HCO3- to compensate. But in chronic alkalosis, the kidneys conserve HCO3- to prevent excessive rise in pH. The phosphate buffering system in the blood also helps normalise pH by releasing phosphate ions. Haemoglobin binds more hydrogen ions to offset the alkalosis. Over time, these renal and cellular buffering mechanisms work to bring the pH back to normal ranges.8 However, if the hyperventilation persists, full compensation may not occur. Elevated pH can have adverse neurological and cardiovascular effects. Cerebral vasoconstriction occurs due to alkalosis, potentially impaired oxygen delivery to the brain. 

Clinical presentation

 Respiratory alkalosis can produce an array of neurological, cardiovascular, and metabolic signs and symptoms. The degree of symptoms is correlated with the severity of the alkalosis and how quickly it develops.

Neurological manifestations 

Including anxiety, apprehension, confusion, lightheadedness, tingling or numbness of the extremities and perioral area, and muscle cramps. Dizziness, vertigo, and a floating sensation may also occur. Severe alkalosis can even produce tetany, seizures, muscle spasms, and loss of consciousness due to hypocalcemia.⁹ Many of these neurological symptoms are related to cerebral vasoconstriction induced by alkalosis, which can reduce oxygen delivery to the brain. Lower calcium ion levels also play a role in causing neuromuscular irritability.⁹

Cardiovascular effects

Include palpitations, peripheral vasodilation with low blood pressure, and hypoxic pulmonary vasoconstriction, which shifts blood flow away from poorly ventilated lung segments. This hypoxic vasoconstriction aims to optimize ventilation-perfusion matching but can elevate pulmonary pressures. Metabolic changes can include intracellular shifts of potassium, phosphate, and calcium, causing deficits in serum levels. Magnesium levels may drop. The metabolic demands of hyperventilation can increase carbohydrate utilization. Respiratory alkalosis tends to cause less metabolic disturbance than metabolic alkalosis.¹⁰

Gastrointestinal effects

Effects like nausea may occur indirectly due to anxiety and hyperventilation. Some patients experience chest pain or discomfort, possibly related to increased breathing work, though ischemic causes should also be evaluated.¹¹

Diagnosis

The diagnosis of respiratory alkalosis is made through arterial blood gas analysis, which directly measures the pH and carbon dioxide levels. 

In respiratory alkalosis, arterial pH will be elevated beyond the normal reference range of 7.35-7.45, often over 7.50 in acute cases. The primary acid-base disturbance is a low arterial carbon dioxide pressure (PaCO2) below 35-45 mm Hg, confirming that hypocapnia is driving the alkalosis.¹

Bicarbonate (HCO3-) levels may be slightly low or in the normal range depending on the chronicity and presence of metabolic compensation. Pulse oximetry usually shows normal oxygen saturation unless there is concurrent respiratory disease. Serum electrolytes may reveal hypocalcemia, hypokalemia, and hypophosphatemia.¹²

The arterial blood sample for gases should be drawn anaerobically and immediately placed on ice to avoid erroneous results. Repeat testing may be needed to track changes in the alkalosis. Capnography can continuously monitor end-tidal CO2 levels.¹²

Further testing helps identify the cause of hyperventilation and respiratory alkalosis in each case. Assessment for pulmonary embolism, pneumonia, bronchitis, salicylate toxicity, and diabetic ketoacidosis should be tailored to the clinical scenario.¹³ Looking for signs of anxiety, fever, pregnancy, and pain can reveal triggers like neurologic disorders. Urine pregnancy tests and ECGs might be done. Pulmonary function tests can diagnose asthma, emphysema, and vocal cord dysfunction. CT chest scans help visualize lung pathology.¹⁴ The clinical history and exam are key components to elucidate the origin of each patient’s hyperventilation. Response to treatment and trends in repeat blood gases also aid the diagnosis. Cases due to hypoxemia may improve with supplemental oxygen.¹⁵

Treatment

The primary goal in treating respiratory alkalosis is to address the underlying condition causing hyperventilation. Treating infections, fever, pain, pulmonary emboli, pregnancy complications, or other triggers will help reverse the alkalosis. Providing respiratory support and managing anxiety is key. Rebreathing into a paper bag for short intervals can help restore carbon dioxide levels. Sedative medications like benzodiazepines alleviate anxiety and slow respiratory rate, which allows PaCO2 to normalize.¹⁶

Bronchodilators open the airways in obstructive lung disease, contributing to hyperventilation. Diuretics may be used cautiously to induce a mild metabolic acidosis to compensate for the alkalosis. In chronic cases, acetazolamide can reduce bicarbonate reabsorption.¹⁷ In ICU patients on mechanical ventilation, lowering the respiratory rate, tidal volume, and minute ventilation helps retain some PaCO2. Permissive hypercapnia allows higher CO2 levels to counter the alkalosis. Monitoring arterial blood gases guides ventilator adjustments.¹⁸ Severe refractory cases may require extracorporeal methods to remove excess bicarbonate and add carbonic acid. Hemodialysis with an acetate buffer can filter out bicarbonate. Extracorporeal CO2 addition directly treats the hypocapnia.¹⁸ Symptomatic treatment for muscle cramps, spasms, or seizures includes calcium and magnesium administration. However, caution is needed as excessive calcium risks rebound alkalosis when hyperventilation recurs.¹⁹ Preventing recurrent hypocapnia is key after an alkalosis episode resolves. Gradual breathing techniques help maintain PaCO2 in the normal range. Some patients may benefit from breathing pacemakers or biofeedback devices.¹⁹ In many mild to moderate cases, reassuring the patient and addressing the anxiety or fear can stabilize respiration. 

Prevention and complications

Respiratory alkalosis can often be prevented by promptly treating underlying conditions like infections, fever, pain, and anxiety that elevate respiratory drive. Avoiding triggers like salicylate medications and high altitudes may also help susceptible individuals. Learning relaxation techniques and breathing control can prevent hyperventilation episodes, especially for anxiety disorders.¹⁷ Gradually deep breathing and blowing into cupped hands can abort acute hyperventilation. Complications relate to neurological, cardiovascular, and metabolic effects of hypocapnia and alkalemia. Neuromuscular irritability can lead to tetany or seizures.²⁰ Cerebral vasoconstriction and hypocalcemia impair oxygen delivery.²¹ Arrhythmias may occur with acid-base shifts. Metabolic derangements include electrolyte imbalances.²² Severe alkalosis can worsen hypoxemia through hypoxic pulmonary vasoconstriction. In ICU care, abrupt PaCO2 normalization normalisation risks rebound acidosis.²³ With prompt diagnosis and careful management, respiratory alkalosis is often reversible without permanent adverse effects. Monitoring mental status, electrolytes, and cardiovascular function helps recognize and mitigate complications.

Conclusion

In summary, respiratory alkalosis occurs due to hyperventilation and excessive loss of carbon dioxide, leading to increased blood pH. Prompt treatment of the underlying cause, along with measures to restore normal CO2 levels, can effectively manage this condition and prevent complications. Monitoring arterial blood gases is key for diagnosis and guiding therapy.