LAUSR

To the Editor: Anaphylaxis is an acute, life-threatening systemic hypersensitivity reaction that occurs on re-exposure to a formerly sensitized antigen.1 Since 1960, benzodiazepines have been used clinically as antiepileptics, anxiolytics, for sedation, insomnia, and drug-related agitation.2 The earliest reports of adverse and anaphylactic reactions to benzodiazepines date back to the 1960s.3,4 The most common offending agents are chlordiazepoxide, diazepam, and flurazepam3–5; however, sporadic cases of anaphylaxis because of midazolam have been reported.4,5,7 Several biochemical mediators, including interleukins, leukotrienes, histamine, prostaglandins, and platelet-activating factor released by mast cells and basophils contribute to vasodilation and increased vascular permeability which results in severe hypotension, as 35% of the intravascular volume shifts to the interstitial space.8 Airway edema is an immediate concern, and patients require mechanical ventilation when the reaction does not rapidly improve. Treatment entails supportive measures including immediate evaluation of airway, breathing, and circulation; and varying combinations of administering 100% oxygen, a large volume of fluids, epinephrine, corticosteroids, and antihistamines. Epinephrine is the first-line drug. Along with assistance in vasocontraction, epinephrine has beta-2 agonist action, which helps with bronchial dilation, gastric smooth muscle relaxation, inhibition of further mediator release, and inotropic and chronotropic effects. Epinephrine, however, does not contribute to the relief of airway edema.4,9 After review of Scopus, Cochrane Library, PubMed, and Embase while only sporadic cases of anaphylaxis to midazolam were found,5,6,7 and none secondary to lorazepam were found. We describe a case of a patient with signs of anaphylaxis on 2 separate occasions after lorazepam and midazolam administration. A 68-year-old White man with a history of stage IVA squamous cell carcinoma of the parotid and epiglottis presented with cough, dyspnea, and intermittent hemoptysis. He had no documented history of medication allergies. He was hypoxic to 82% on room air and needed 3L NC oxygen. A Computed Tomography Angiography at admission showed bilateral pneumonia, and the working diagnosis was bacterial pneumonia for which he completed treatment with azithromycin and ceftriaxone. ENT concurred that these symptoms were due to pneumonia and less likely an upper airway obstruction as laryngoscopy was unchanged from previous outpatient encounters. The patient underwent a G-tube placement for nutrition because of the risk of aspiration and was progressing well toward discharge with stable vitals including good saturations on room air on day 7 of admission. The night before anticipated discharge, the patient was increasingly anxious and was given a 1 mg dose of intravenous lorazepam. Within 30 minutes, he became dyspneic with increased accessory respiratory muscle use with suprasternal retractions, developed audible stridor, and rapidly desaturated to 74%. A few minutes later, he developed a pruritic macular rash on his trunk and arms. He was administered racemic epinephrine and was placed on a 12L oxy mask with saturation climbing to 87%. He was intubated using etomidate and propofol, and his glottic opening was notable for significant edema. Although in the intensive care unit the following day, he was given 2 mg IV midazolam for sedation, which dropped his blood pressure to 70/40 mm Hg from 127/83 mm Hg. He was given 1-liter fluid bolus, and his blood pressure improved to 100/60 mm Hg. laryngoscopy, tracheostomy, and biopsy ruled out alternative causes of respiratory compromise. Laryngoscopy showed a friable and necrotic mass around the lingual epiglottis and the posterior pharyngeal wall. Significant supraglottic edema, unrelated to the mass was also seen. A biopsy showed fibro purulent exudate, granulation tissue, and reactive squamous mucosa with no evidence of malignancy. MRI neck revealed extensive edema within the glottis and supraglottis as shown in Figures 1 and 2. He was initiated on methylprednisolone 40 mg IV BID for 3 days, subsequently extubated, and was breathing well at 98% on room air before discharge. American Journal of Therapeutics 0, 1–3 (2020)