C. Diffuse Alveolar Hemorrhage
Discussion
The chest CT image above show diffuse ground glass opacities,
predominantly in the bilateral lower lobes. The bronchoscopic images
show dark red blood in the proximal airways and the three traps
containing fluid from BAL. After BAL with three sequential 60 mL
aliquots of normal saline, the return became progressively bloodier
which is diagnostic of diffuse alveolar hemorrhage (DAH). The patient
was admitted to the medical intensive care unit and was placed on
high-flow nasal cannula while autoimmune, infectious, inflammatory,
pulmonary vascular, and malignant causes of DAH were pursued.
Concurrently, the outside hospital was contacted, and it was revealed
that patient had received general anesthesia with sevoflurane for his
recent surgical procedure. All BAL cultures were negative, as were
blood cultures and a respiratory viral panel. Autoimmune serologies
including ANA, anti-PR3 antibody, anti-MPO antibody, and anti-GBM
antibody were negative, studies of coagulation were normal, and the rest
of the workup was negative. The patient rapidly improved and was
discharged home on room air without any immunosuppressive agents or
antimicrobials. At discharge, the final diagnosis was
sevoflurane-induced DAH.
DAH is an uncommon cause of hemoptysis and can have severe
consequences if not recognized clinically. DAH is defined as diffuse
intra-alveolar accumulation of erythrocytes and can arise from a variety
of pathologic conditions (1). Patients with DAH commonly present with
hemoptysis and diffuse opacities on chest radiography. Many patients,
depending on the chronicity of the alveolar hemorrhage and underlying
etiology, can also present with microcytic or normocytic anemia, as did
the patient in this case. Pulmonary function testing can be normal or
may show restriction to ventilation in cases of chronic DAH. Acute DAH
can cause an increase in the diffusion capacity of carbon monoxide
(DLCO) secondary to binding of carbon monoxide to hemoglobin that has
extravasated into the alveolar space (1).
DAH can be broadly classified by its chronicity and by its underlying
cause. In general, causes of DAH can be categorized into disorders of
coagulation, capillaritis, diffuse alveolar damage, bland pulmonary
hemorrhage, and idiopathic (2). Depending on the medication, all four
aforementioned etiologies are possible pathogenic mechanisms for DAH.
For example, propylthiouracil and phenytoin cause a pulmonary
capillaritis, amiodarone and nitrofurantoin cause bland pulmonary
hemorrhage, and crack cocaine causes diffuse alveolar damage (2).
Sevoflurane is an inhaled anesthetic gas frequently used in general
anesthesia that has been associated with DAH (3, 4). Although no
definitive mechanism for sevoflurane-induced DAH has been elucidated,
theories include direct endothelial damage or pulmonary toxicity from
the main metabolite of sevoflurane, fluoromethyl-
2,2-difluoro-1-(trifluoromethyl) vinyl ether (4). Although no large
case series of sevoflurane-induced DAH are available, patients are
expected to improve with withdrawal of the offending agent, as the
patient did in this case.
References
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Murray, J. F. and Nadel, J. A. (2010). Textbook of Respiratory Medicine (5th ed.). Philadelphia, PA: Elsevier.
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Lara AR, Schwarz MI. Diffuse Alveolar Hemorrhage. Chest. 2010; 137(5): 1164–71.
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Kim CA, Liu R, Hsia DW. Diffuse alveolar hemorrhage induced by sevoflurane. Ann Am Thorac Soc 2014; 11(5): 853-5.
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Austin A, Modi A, Judson MA, and Chopra A. Sevoflurane Induced Diffuse Alveolar Hemorrhage in a Young Patient. Respiratory Medicine Case Reports 2017; 20: 14-15.