To the Editor, A previously healthy 16-year-old male presented to a peripheral hospital with a 2-day history of right lower quadrant abdominal pain and two episodes of non-bilious, non-bloody emesis. An abdominal ultrasound confirmed acute appendicitis, and an appendectomy was performed under general anesthesia with propofol (200 mg), rocuronium (20 mg), hydromorphone (0.4 mg), ketorolac (15 mg) and sevoflurane. The surgery was uncomplicated. Within an hour post-operatively, the patient developed oxygen desaturation requiring supplemental oxygen (2 L/min), followed by several episodes of hemoptysis (approximately 60 mL). Clinical examination revealed decreased breath sounds, particularly over the right hemithorax. Chest radiography showed bilateral ill-defined airspace opacities, more prominent on the right (Figure 1A). A flexible laryngoscopy did not reveal any bleeding source in the upper airway. The patient was transferred to our institution for further management. Supplemental oxygen was promptly weaned off after arrival. He had no systemic complaints, and the review of systems, particularly pertaining to autoimmune manifestations was negative. There was no significant past medical history, family history, previous surgeries or exposure to general anesthesia. His clinical examination was normal except for a low weight-for-age (< −2.3 Z-score), mild tachypnea and the appendectomy surgical scar. He subsequently had two additional episodes of hemoptysis (3 mL of clotted blood) on day 1 of admission. His initial hemoglobin level was 124 g/L with a nadir of 106 g/L at the end of Day 1. He received 3 doses of intravenous tranexamic acid (15 mg/kg/dose), inhaled tranexamic acid for 72 h (500 mg every 6 h), fresh frozen plasma (10 mL/kg) once, and intravenous ceftriaxone for 48 h. He proceeded to a chest CT that revealed bilateral asymmetric ground-glass and airspace opacities with coalescent opacification more marked on the right, suggestive of diffuse alveolar hemorrhage. There were no findings of pulmonary infection, mass, airway abnormality, aberrant vessel, or vascular malformation (Figure 1B). The echocardiogram was normal. Flexible bronchoscopy confirmed normal upper and lower airway anatomy with no active bleeding present. Pink-tinged bronchoalveolar lavage fluid (BALf) was retrieved from the right middle lobe, which was positive for hemosiderin-laden macrophages (~50%) in keeping with a recent pulmonary hemorrhage. Bacterial, fungal and mycobacterial BALf cultures were negative. Blood investigations were unremarkable apart from mildly elevated International Normalized Ratio (INR) 1.3 (0.9–1.2), low-titre anti-double stranded DNA antibody (anti-dsDNA Ab) and antinuclear antibody (ANA) Table S1. Tuberculin skin test was negative. Histopathology of the appendix confirmed acute appendicitis without signs of vasculitis. The patient's symptoms resolved spontaneously approximately 3 days after presentation, and he was discharged 6 days post-surgery. No anti-inflammatory therapy was administered. There was marked improvement in chest imaging performed 1 month later (Figure 1C). At the 2-month follow-up, pulmonary function testing revealed a moderate restrictive ventilatory defect, moderately decreased diffusing capacity of the lungs for carbon monoxide (DLCO), and normal carbon monoxide transfer coefficient (KCO) Table 1. A CT chest performed 3 months later was normal (Figure 1D). The INR normalized without treatment and repeat ANA and anti-dsDNA Ab were negative. He was followed for 2 years and remained asymptomatic with a weight for age that remained at −2.3 Z-score without any clear explanation. His last chest imaging at 15 months post-DAH remained normal despite the unchanged moderate restrictive ventilatory defect on pulmonary function testing. His KCO remained normal, indicating that his DLCO, when corrected for alveolar volume, remained normal (Table 1). Given the absence of baseline pulmonary function data in our case, it remains unclear whether the moderate restrictive ventilatory defect observed at follow-up was a consequence of the DAH or a pre-existing condition. The patient's body habitus and the noted reduction in posterior-anterior diameter on imaging suggest that reduced lung volumes or mechanical restriction may have been present prior to the acute illness. As per The Hospital for Sick Children institutional policy, this review was deemed IRB exempt. Written informed consent was provided by the participants’ legal guardian/next of kin for this manuscript. Diffuse alveolar hemorrhage (DAH) is a potentially life-threatening disorder with multiple potential etiologies, including systemic autoimmune rheumatic disease (e.g., lupus), vasculitis, coagulation disorders, toxic exposures, cardiac disease, infection, trauma, as well as idiopathic 1. Sevoflurane is a widely used inhalational anesthetic agent for both induction and maintenance of general anesthesia. It undergoes degradation to pentafluoroisopropenyl fluoromethyl ether (PIFE), also known as “Compound A,” which has demonstrated nephrotoxicity in rats, although its involvement in lung toxicity is not clear in humans 2. However, the exact mechanism by which DAH may occur following sevoflurane exposure remains unclear. Other lipid-soluble volatile agents, such as halothane, cyclopropane, and nitrous oxide, have been shown to activate the arachidonic acid cascade within cell membranes. This cascade may lead to increased oxidative stress, enhanced alveolar-capillary permeability, and pulmonary vasoconstriction 3. Clinical features typically include hypoxia, dyspnea, hemoptysis, new pulmonary infiltrates on chest imaging, and/or anemia 4. Several case reports have described sevoflurane-associated DAH, predominantly in adult male patients, with only one case previously reported in a pediatric patient 5. In these patients, alternative causes of DAH, including coagulopathies, autoimmune conditions, vasculitis, and infections, were excluded. Our patient presented with bilateral airspace opacities and right sided prominence on chest imaging, comparable to the findings of previous case reports where patients had bilateral involvement with increased prominence noted in various regions of the lung (Table S2). Patients were successfully managed with supportive therapy, including low-flow oxygen, high-flow oxygen therapy, or invasive ventilation. Adjunctive intravenous methylprednisolone was administered in select cases. Most patients experience complete resolution of symptoms within 1 week, with normalization of chest imaging within 1–3 months. There are no long-term pulmonary function outcome data published (Table S2). Sevoflurane-associated DAH should be considered in the differential diagnosis of acute pulmonary hemorrhage following general anesthesia, particularly after exclusion of other etiologies. Longitudinal follow-up, including pulmonary function testing (i.e. DLCO, full body plethysmography) to assess the patient's trend and chest imaging (to ensure resolution) may help characterize the natural history and potential long-term sequelae of this rare complication. Despite the absence of definitive data on the mechanism, recurrence rate and cross-reactivity with other agents, lifelong avoidance of sevoflurane and other halogenated inhalational agents (e.g., halothane, enflurane, isoflurane, desflurane) is recommended in affected individuals. Adeline Yi Ling Lim: conceptualization, data curation, formal analysis, writing – original draft, writing – review and editing. Amani AlBijadi: data curation, formal analysis, writing – original draft, writing – review and editing. Han Byul Kang: formal analysis, supervision, writing – review and editing. Ruud Hendrikus Johannes Verstegen: formal analysis, supervision, writing – review and editing. Ronald Melvin Laxer: formal analysis, supervision, writing – review and editing. Fiona Elize Kritzinger: conceptualization, data curation, formal analysis, supervision, writing – review and editing. The authors received no specific funding for this work. As per The Hospital for Sick Children institutional policy, this review was deemed IRB exempt. Written informed consent was provided by the participants' legal guardian/next of kin for this manuscript. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Lim et al. (2026) studied this question.