Use of certain drugs—including opioids, anesthetics, hypnotics, sedatives, and some of the new designer drugs such as Ecstasy—can be a predisposing factor for respiratory acidosis because these drugs decrease the sensitivity of the respiratory center. Other predisposing factors include central nervous system (CNS) trauma because medullary injury may impair ventilatory drive as well as ventilation therapy because the use of high-flow oxygen in chronic respiratory disorders suppresses the patient’s hypoxic drive to breathe. Neuromuscular diseases, such as myasthenia gravis, Guillain-Barré syndrome, and poliomyelitis, can result in respiratory acidosis when the respiratory muscles fail to respond properly to the respiratory drive, decreasing alveolar ventilation.

In addition, respiratory acidosis can result from chronic obstructive pulmonary disease (COPD), asthma, severe acute respiratory distress syndrome, chronic bronchitis, a large pneumothorax; extensive pneumonia, pulmonary edema, and airway obstruction or parenchymal lung disease, which interfere with alveolar ventilation.

A series of reactions leads to in respiratory acidosis. When pulmonary ventilation decreases, PaCO₂ increases, and the CO₂ level rises in all tissues and fluids, including the medulla and cerebrospinal fluid. Retained CO₂ combines with water to form carbonic acid. The carbonic acid dissociates to release free hydrogen and bicarbonate (HCO₃⁻) ions. Increased PaCO₂ and free hydrogen ions stimulate the medulla to increase respiratory drive and expel CO₂.

As pH falls, 2, 3-diphosphoglycerate accumulates in red blood cells, where it alters hemoglobin, causing it to release oxygen. This reduced hemoglobin, which is strongly alkaline, picks up hydrogen ions and CO₂ and removes them from the serum.

As respiratory mechanisms fail, rising PaCO₂ stimulates the kidneys to retain HCO₃⁻ and sodium ions and excrete hydrogen ions. As a result, more sodium bicarbonate is available to buffer free hydrogen ions. Some hydrogen is excreted in the form of ammonium ions, neutralizing ammonia, which is an important CNS toxin.

As the hydrogen ion concentration overwhelms compensatory mechanisms, hydrogen ions move into the cells and potassium ions move out. Without enough oxygen, anaerobic metabolism produces lactic acid. Electrolyte imbalances and acidosis critically depress neurologic and cardiac functions. (See What happens in respiratory acidosis.)

Acute respiratory acidosis produces CNS disturbances that reflect changes in the pH of cerebrospinal fluid rather than increased CO₂ levels in cerebral circulation. Effects range from restlessness, confusion, and apprehension to somnolence, or coma and include:

• headaches resulting from cerebral vasodilation

• fine or flapping tremor (asterixis) caused by continued elevation of CO₂ levels

• dyspnea and tachypnea

• papilledema caused by increased intracranial pressure as a result of cerebral vasodilation

• depressed reflexes related to elevated CO² levels and CNS depression

• hypoxemia

• cardiovascular abnormalities, such as tachycardia, hypertension, and atrial and ventricular arrhythmias

• hypotension with vasodilation (bounding pulses and warm periphery).

• Myocardial depression leading to shock and cardiac arrest

• Profound CNS and cardiovascular deterioration due to dangerously low blood pH (less than 7.15)

• Elevated PaCO2 despite optimal treatment (in chronic lung disease)

• Arterial blood gas (ABG) analysis confirms the diagnosis: PaCO₂ exceeds the normal 45 mm Hg; pH is below the normal range of 7.35 to 7.45 unless compensation has occurred; and HCO₃⁻ is normal in the acute stage but elevated in the chronic stage.

• Chest X-rays, computed tomography scans, and pulmonary function tests can help determine the cause.

Effective treatment of respiratory acidosis requires correction of the underlying source of alveolar hypoventilation. Significantly reduced alveolar ventilation may require mechanical ventilation until the underlying condition can be treated. In COPD, this includes bronchodilators, oxygen, corticosteroids, and antibiotics for infectious conditions; drug therapy for conditions such as myasthenia gravis; removal of foreign bodies from the airway; antibiotics for pneumonia; dialysis or charcoal to remove toxic drugs; and correcting metabolic alkalosis.

Dangerously low blood pH (less than 7.15) can produce profound CNS and cardiovascular deterioration; careful administration of I.V. sodium bicarbonate may be required. In chronic lung disease, elevated CO₂ may persist despite optimal treatment.

• Be alert for critical changes in the patient’s respiratory, CNS, and
cardiovascular functions. Report such changes as well as any variations in ABG values or electrolyte status immediately. Also, maintain adequate hydration.

• Maintain a patent airway and provide adequate humidification if acidosis requires mechanical ventilation. Perform tracheal suctioning regularly and vigorous chest physiotherapy if ordered. Continuously monitor ventilator settings and respiratory status.

Causes of respiratory alkalosis fall into two categories: pulmonary and nonpulmonary. Pulmonary causes include severe hypoxemia, pneumonia, interstitial lung disease, pulmonary vascular disease, and acute asthma. Nonpulmonary causes include anxiety, fever, aspirin toxicity, metabolic acidosis, central nervous system (CNS) disease (inflammation or tumor), sepsis, hepatic failure, and pregnancy.

Respiratory alkalosis results when pulmonary ventilation increases more than needed to maintain normal CO₂ levels, leading to the exhalation of excessive amounts of CO₂. The consequent hypocapnia leads to a chemical reduction of carbonic acid, excretion of hydrogen and bicarbonate (HCO₃⁻) ions, and a rising pH. In defense against the increasing serum pH, the hydrogenpotassium buffer system pulls hydrogen ions out of the cells and into the blood in exchange for potassium ions. The hydrogen ions entering the blood combine with available HCO₃⁻ ions to form carbonic acid, and the pH falls.

Hypocapnia stimulates the carotid and aortic bodies as well as the medulla, increasing the heart rate (which hypokalemia can further aggravate) but not the blood pressure. At the same time, hypocapnia causes cerebral vasoconstriction and decreased cerebral blood flow. It also overexcites the medulla, pons, and other parts of the autonomic nervous system. When hypocapnia lasts more than 6 hours, the kidneys secrete more HCO₃⁻ and less hydrogen. Full renal adaptation to respiratory alkalosis requires normal volume status and renal function, and it may take several days.