Abstract

Résumé

Case presentation

A 42-yr-old male presented to a community hospital with a chief complaint of dyspnea. He reported to have been unwell during the previous days with symptoms of subjective fever, cough, sore throat, and headache. He admitted to inhaling Freon a few days before his symptoms started and reported that he had been inhaling Freon a few times per year for several years. He denied any other drug exposures prior to presentation. His social history included being unemployed with no fixed address as well as prior polysubstance use of inhaled crack cocaine and fentanyl. His home medication was 1,200 mg of slow-release oral morphine daily.

His vital signs on presentation were a temperature of 38°C, heart rate of 104 beats per min in sinus rhythm, and blood pressure of 147/88 mm Hg. His initial oxygen saturation (S_pO₂) was 90% on room air but he quickly progressed to needing a fraction of inspired oxygen of 80% via high flow nasal cannula to attain a S_pO₂ of 90–94%. A chest radiograph showed diffuse reticular nodular opacities throughout both lungs (Fig.1). His initial bloodwork showed signs of elevated inflammatory markers with mild leukocytosis at 11.1 × 10⁹·L^-1 (normal, 4.0–10.5 × 10⁹·L^-1) and C-reactive protein of 218.4 mg·L^-1 (normal, 0.0–2.0 mg·L^-1) but other results were noncontributory. His urine drug screen was positive for amphetamines, cocaine, fentanyl, and opioids. Due to progressive hypoxemic respiratory failure, he was intubated and admitted to the intensive care unit (ICU). Three nasopharyngeal swabs and a tracheal aspirate sample were all negative for SARS-CoV-2. He was treated with intravenous piperacillin-tazobactam, azithromycin, and vancomycin as well as methylprednisolone 40 mg twice daily. A computed tomography (CT) scan of the chest was performed on day 3 of illness and revealed extensive bilateral ground-glass and centrilobular nodular opacities without evidence of pulmonary embolism (Fig.2).

Four days after his admission to hospital, he was transferred to the regional referral centre for higher level of care because of the progressive nature of his respiratory failure refractory to prone positioning and use of inhaled epoprostenol. Upon arrival, he was severely hypercapnic and hypoxemic. He was unable to ventilate effectively at maximal ventilatory settings with full sedation and paralysis and was extremely unstable requiring bag mask ventilation. His arterial blood gas on admission was pH 6.82, P_aCO₂ 202 mm Hg, P_aO₂ 91 mm Hg, and bicarbonate 31 mmol·L^-1 via bag mask ventilation on 100% O₂. A chest radiograph revealed near complete bilateral opacification of the lungs (Fig.1). He was crashed onto vv-ECMO via femoral-femoral configuration with 23 Fr return and 25 Fr access cannulas. Upon cannulation to extracorporeal support, his oxygenation and ventilation significantly improved. A bronchoscopy was subsequently performed and revealed that his airways were filled with fluid. Approximately 1 L of frothy secretions were suctioned with minimal instillment of saline or irrigation (Fig.3). There was no evidence of alveolar hemorrhage on bronchoalveolar lavage, and samples obtained from subsequent bronchoscopies were negative for bacterial and fungal cultures, viral respiratory panel, SARS-CoV-2, Pneumocystis jirovecii, acid-fast bacilli, Leigonella, Cryptococcal antigen, Galactomann, Nocardia, and Acinobacter. He was negative for HIV and hepatitis A, B, and C. Antineutrophil cytoplasmic antibodies, cyclic citrullinated peptide antibodies, and rheumatoid factor were also negative. With a presumptive diagnosis of severe bronchiolitis and pneumonitis secondary to inhalation of Freon, he was treated with 500 mgiv methylprednisolone daily for three days and stepped down to 1 mg·kg^–1 of prednisone for 4–6 weeks.

During the first two weeks of vv-ECMO treatment, he required a high level of ECMO support with blood and sweep gas flows of 6 and 11 L·min^–1, respectively. He was deeply sedated to attain adequate oxygenation. He had near complete consolidation of his lungs and severely poor lung compliance. He was mechanically ventilated using pressure-controlled mode with a positive end-expiratory pressure of 12 cm H₂O and inspiratory pressure of 12 cm H₂O, yielding only tidal volumes of approximately 50 mL per breath. He required daily therapeutic bronchoscopies for bronchial toilet, and his respiratory secretions were noted to be progressively thicker and tenacious. A lengthy bronchoscopy on day 12 of illness yielded multiple large tracheobronchial casts (Fig.3). On microscopic examination, these casts had acute inflammatory cells but were negative for malignant cells, pneumocystis jerovici pneumonia, and fungal and viral inclusions.

His respiratory function improved over time. By day 24, his tidal volumes were up to 450 ml/breath while the same ventilatory settings, and ECMO support was weaned. He showed radiographic improvement (Fig.1). He was decannulated from vv-ECMO on day 26 of illness and liberated from the ventilator support and discharged from the ICU on day 28 of illness. He was discharged from ambulatory hospital care on day 50 of illness, requiring no oxygen and tolerating a full diet.

Discussion

Here, we present an unusual case of pulmonary toxicity from intentional inhalation of Freon, leading to severe and refractory respiratory failure requiring salvage institution of vv-ECMO support and high doses of corticosteroids to attain full recovery. We hypothesize that inhalation of Freon caused severe acute bronchiolitis and subsequent pneumonitis leading to respiratory failure.

Bronchiolitis is often used to describe nonspecific inflammatory injury to primarily the small airways, often sparing a considerable portion of the interstitium.⁵ Although tissue biopsies were not taken for histopathology, there were bronchoscopic, clinical, radiographic, and microscopic features that supported the diagnosis of acute bronchiolitis. There is no direct laboratory test for inhalants available clinically, but our patient did admit to inhaling Freon a few days before his acute respiratory failure. Diffuse bronchial injury is supported by the bronchoscopic findings of copious bronchial secretions and later thick tracheobronchial casts. The obstruction of the airways from these secretions and casts led to increased airway resistance and worsening lung compliance shown by extremely low tidal volumes on pressure control ventilation, and near complete lung consolidation on chestx-ray. The casts examined under microscopy were mostly of inflammatory cells with no evidence of malignancy or infection. Moreover, the diffuse distribution of centrilobular nodules shown on CT further supported the nature of inhalational injury. His acute recovery and single system involvement make other inflammatory disorders much less likely.

Inhaled hydrocarbons are known to produce pulmonary toxicity but their CNS and cardiac effects are not well described.⁶ An acute lung injury known as hydrocarbon pneumonitis has been described in the pediatric literature following unintentional ingestion and aspiration of liquid hydrocarbons by young children. Hydrocarbon pneumonitis is similar to aspiration pneumonitis, leading to inflammation and consolidation of dependent lobes such has the middle and lower lobes of the lung.⁷ There have been pediatric case reports of hydrocarbon pneumonitis being successfully treated with ECMO.⁸ Our patient’s presentation is different from hydrocarbon pneumonitis as he intentionally rather than accidentally inhaled Freon and showed a diffuse centrilobular distribution of lung injury. Furthermore, he did not appear to suffer from nonpulmonary manifestations such as cardiac arrhythmias or neurologic disturbances. These features are more prominent during acute intoxication and his lung injury developed a few days after the intentional exposure to Freon.

The treatment of pulmonary toxicity following hydrocarbon exposure is primarily supportive. There is scarce literature to guide us on how to manage such patients, mainly case reports from the pediatric literature describing accidental ingestion and hydrocarbon pneumonitis.⁹ In addition to lung protective strategies during mechanical ventilation for acute lung injury,¹⁰ other described treatment modalities include ECMO and the administration of glucocorticoids, antibiotics, and exogenous surfactants.¹¹ Our patient received all of these except for exogenous surfactant. In our case, vv-ECMO was a lifesaving strategy. Given the initial blood gases and clinical deterioration on presentation to our ECMO referral centre, he would not have survived without extracorporeal support. The toxicological exposure leading to rapid progressive respiratory failure in an otherwise healthy man provided a good indication for ECMO to recover lung function. While exogenous surfactant use has been well-studied in both adult and pediatric patients with acute lung injuries, its therapeutic benefit in the adult population has unfortunately not been shown.¹² Supportive management such as lung protective ventilator strategies along with frequent bronchoscopy for bronchial toileting allowed for enough time for lung recovery.

In summary, we report the first case of pulmonary toxicity from recreational inhalation of Freon, leading to severe and refractory hypoxemic respiratory failure requiring salvage vv-ECMO and high doses of corticosteroids to attain full recovery.

Acknowledgments

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