What is the pathophysiology of hydrogen fluoride inhalation lung injury and how should it be managed?

Hydrogen Fluoride Inhalation Lung Injury: Pathophysiology and Management

Pathophysiology

Hydrogen fluoride (HF) inhalation causes direct chemical injury to the respiratory epithelium with rapid systemic fluoride toxicity, leading to acute respiratory failure through alveolar epithelial inflammation, pulmonary edema, and potentially fatal hypocalcemia and hyperkalemia. 1, 2

Mechanism of Injury

• HF penetrates deeply into peripheral respiratory tracts, particularly when present in low concentrations that lack pungent warning properties, allowing direct inhalation without immediate sensory warning 2
• The fluoride ion causes direct cellular toxicity through binding of calcium and magnesium, disrupting cellular enzyme systems and causing liquefactive necrosis of respiratory epithelium 1
• Respiratory depression occurs rapidly, with minute ventilation decreasing to approximately 50% of baseline independent of concentration or exposure duration 3
• Pathological findings demonstrate severe bilateral pulmonary congestion and edema as the primary mechanism of respiratory failure 2

Temporal Pattern of Injury

• Early phase (2 hours post-exposure): Significant reductions in total cell counts, neutrophils, and lymphocytes in bronchoalveolar lavage fluid, with decreased inflammatory markers (IL-6, IL-8, ICAM-1) 4
• Delayed mortality pattern: Deaths typically occur 3-4 days post-exposure from progressive respiratory failure, not immediately during exposure 3
• Systemic toxicity: High serum ionized fluoride concentrations indicate massive systemic absorption with potential for cardiac arrhythmias and multiorgan failure 2

Immediate Management

Decontamination and Initial Stabilization

• Remove patient from exposure source immediately and perform copious irrigation of eyes and skin to reduce morbidity and mortality 1
• Assess for respiratory distress including tachypnea, hypoxemia, and work of breathing, as acute respiratory failure can develop within 30 minutes of severe exposure 2
• Monitor for systemic fluoride toxicity including hypocalcemia, hyperkalemia, and cardiac arrhythmias through serial electrolyte measurements and continuous cardiac monitoring 1, 2

Respiratory Support

For acute hypoxemic respiratory failure, initiate high-flow nasal cannula (HFNC) with close monitoring for escalation to invasive mechanical ventilation if tachypnea or refractory hypoxemia develops. 5

• Lung-protective ventilation strategy with tidal volume 6-8 mL/kg predicted body weight and plateau pressure <30 cmH2O should be implemented if mechanical ventilation is required 6, 5
• Positive end-expiratory pressure (PEEP) of 6-8 cmH2O helps maintain alveolar recruitment and prevent atelectasis 6
• Maintain FiO2 at 100% initially in patients with severe hypoxemia, then titrate to maintain SpO2 >90% 6

Calcium Therapy

Calcium gluconate is the preferred method of detoxifying the fluoride ion, though efficacy is based primarily on anecdotal reports. 1

• Nebulized calcium gluconate should be administered aggressively in patients with respiratory symptoms following HF exposure 7
• Intravenous calcium gluconate for systemic fluoride toxicity and hypocalcemia, with continuous cardiac monitoring 1
• The specific case report from Bagram Air Base demonstrated survival in two patients treated aggressively with nebulized calcium and positive pressure ventilation, compared to three deaths in patients who did not receive this treatment 7

Critical Pitfalls to Avoid

• Do not underestimate low-concentration exposures: Weak HF is not pungent to skin and mucous membranes, allowing deep inhalation into peripheral airways without warning 2
• Do not delay respiratory support: Mortality can occur within 30 minutes to 24 hours of severe exposure, requiring immediate aggressive intervention 2, 7
• Do not assume immediate presentation: Delayed mortality pattern (3-4 days post-exposure) requires prolonged observation even in initially stable patients 3
• Avoid hyperventilation as this can worsen hemodynamic compromise in patients with systemic toxicity 6

Monitoring and Observation

• All significant exposures require evaluation by healthcare personnel familiar with HF toxicity potential 1
• Serial monitoring of respiratory status, arterial blood gases, serum electrolytes (calcium, magnesium, potassium), and cardiac rhythm for minimum 24-48 hours 1, 2
• Lung function measurements may not be immediately affected despite significant injury, requiring clinical vigilance beyond objective testing 4