Understanding Drug-Induced Respiratory Alkalosis
Respiratory alkalosis is an acid-base imbalance characterized by a decreased partial pressure of carbon dioxide in the blood (PaCO2) and an elevated blood pH [1.7.2]. This condition is caused by hyperventilation, or over-breathing, which expels carbon dioxide faster than it is produced. While many conditions like anxiety, pain, or fever can trigger this, certain drug overdoses are a significant cause. The most important drug class implicated in causing a primary respiratory alkalosis is the salicylates, with aspirin being the most common example [1.5.1, 1.5.4].
The Primary Culprit: Salicylate Toxicity
Salicylate (aspirin) overdose is a classic and critical cause of respiratory alkalosis [1.2.5]. The toxic effects are complex and evolve in phases. Initially, salicylates directly stimulate the medullary respiratory center in the brainstem [1.4.1, 1.4.2]. This stimulation leads to an increased respiratory rate (tachypnea) and depth (hyperpnea), resulting in hyperventilation. This initial phase of hyperventilation drives off excess CO2, causing a primary respiratory alkalosis [1.4.3]. This is a key diagnostic clue, especially when it occurs alongside other early symptoms like tinnitus (ringing in the ears), nausea, and vomiting [1.2.3].
However, the pathophysiology of salicylate poisoning doesn't stop there. As the toxicity progresses, a second, more dangerous acid-base disturbance emerges. Salicylates uncouple oxidative phosphorylation in the mitochondria, disrupting cellular respiration [1.2.2, 1.4.3]. This leads to:
- Increased production of lactic acid and ketoacids.
- Inhibition of the Krebs cycle.
- Accumulation of inorganic acids due to potential kidney insufficiency.
These processes combine to create a severe, high anion gap metabolic acidosis [1.2.3]. The body's initial respiratory alkalosis is an attempt to compensate for this developing acidosis. The coexistence of respiratory alkalosis and metabolic acidosis is the characteristic acid-base signature of significant salicylate poisoning in adults [1.2.3].
Clinical Presentation and Diagnosis
The symptoms of salicylate toxicity progress with the severity of the overdose.
- Early Symptoms: Tinnitus, vertigo, nausea, vomiting, diaphoresis (sweating), and hyperventilation [1.2.3].
- Progressive Symptoms: As toxicity worsens, patients may develop agitation, delirium, confusion, and lethargy [1.2.3]. Hyperthermia (high body temperature) is a sign of severe toxicity [1.2.3].
- Severe Toxicity: Can lead to seizures, coma, non-cardiogenic pulmonary edema (fluid in the lungs), and cardiovascular collapse [1.2.3, 1.4.6].
Diagnosis relies on a high index of suspicion based on clinical presentation, alongside laboratory tests. Arterial blood gas (ABG) analysis is crucial to identify the mixed respiratory alkalosis and metabolic acidosis [1.7.2]. Serum salicylate levels are measured, though the clinical picture is more important than a single level, especially in chronic toxicity [1.3.1].
Other Drugs Causing Respiratory Alkalosis
While salicylates are the most notable, other substances can also stimulate the respiratory center and lead to respiratory alkalosis, though often with less complex accompanying metabolic disturbances.
- Progesterone: High levels of progesterone, such as those seen in pregnancy or from medication, are a known stimulant of the respiratory center, often causing a chronic, mild respiratory alkalosis [1.5.1, 1.8.2].
- Catecholamines: Drugs like epinephrine and nicotine can also stimulate hyperventilation and cause respiratory alkalosis [1.5.2, 1.9.4].
- Theophylline: An older asthma medication, theophylline can stimulate respiration in toxic doses [1.8.4].
| Drug/Class | Primary Mechanism | Associated Features |
|---|---|---|
| Salicylates (Aspirin) | Direct stimulation of the medullary respiratory center [1.4.1] | Followed by severe high anion gap metabolic acidosis; tinnitus is a classic early symptom [1.2.3]. |
| Progesterone | Stimulation of the respiratory center [1.8.2] | Commonly seen in pregnancy; typically results in a chronic, mild alkalosis [1.8.5]. |
| Catecholamines (e.g., Epinephrine) | Central and peripheral stimulation of respiration [1.5.2] | Often accompanied by other signs of sympathetic activation like tachycardia and hypertension. |
| Theophylline | Central respiratory stimulation [1.8.4] | Narrow therapeutic index; toxicity can also cause seizures and arrhythmias. |
Management of Drug-Induced Respiratory Alkalosis
Treatment must address the underlying cause [1.6.1]. For salicylate toxicity, management is intensive and focuses on two main goals: limiting further drug absorption and enhancing elimination.
- Supportive Care: The first priority is airway, breathing, and circulation. Intubation is avoided if possible, as it can eliminate the patient's compensatory hyperventilation, leading to a rapid drop in pH and cardiac arrest [1.3.1, 1.4.6].
- GI Decontamination: Activated charcoal may be administered to reduce absorption from the gut [1.3.1].
- Urinary and Serum Alkalinization: Intravenous sodium bicarbonate is a cornerstone of therapy. It makes the blood and urine more alkaline. This traps the salicylate in its ionized form, preventing it from crossing the blood-brain barrier into the central nervous system and promoting its excretion by the kidneys [1.2.4, 1.3.1].
- Hemodialysis: In cases of severe poisoning (e.g., very high salicylate levels, altered mental status, kidney failure, or severe acidemia), hemodialysis is the definitive treatment to rapidly remove the salicylate from the blood [1.6.1].
Conclusion
While several substances can cause hyperventilation, the definitive answer to which drug overdose causes respiratory alkalosis points primarily to salicylates. The unique dual presentation of primary respiratory alkalosis followed by severe metabolic acidosis makes salicylate toxicity a critical diagnosis to recognize and manage aggressively in emergency medicine. Understanding this complex pathophysiology is essential for clinicians to anticipate the severe complications and initiate life-saving treatments like sodium bicarbonate and hemodialysis.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. If you suspect an overdose, contact emergency services immediately.
