Case Presentation: AB is a 48-year-old patient with a medical history significant for undifferentiated inflammatory polyarthritis and anaphylaxis to numerous food and medications. Ten minutes after sampling a new cracker flavor, AB noted dysphonia, dysphagia, and difficulty handling her secretions. She self-administered epinephrine 0.3mg intramuscularly (IM). Fifteen minutes later, her symptoms continued to progress, so she self-administered a second dose. This second dose was also ineffective, prompting her to call 911. Although she had a prior history of anaphylaxis requiring IM epinephrine use, this was the first time that it did not lead to symptom resolution. She denied any other symptoms of anaphylaxis or allergic reactions. Emergency services administered 50mg IM diphenhydramine and brought her to the emergency department, where she was noted to be afebrile with blood pressure of 139/92 mmHg, heart rate of 113 beats per minute, respiratory rate of 19 breaths per minute, and oxygen saturation of 100% on room air. She was given dexamethasone 10mg intravenously (IV), additional epinephrine 0.5mg IV, and famotidine 20mg IV. Otolaryngology evaluation showed an edematous right arytenoid and 50% airway closure around the glottic area. The patient was started on IV fluids and an epinephrine drip at 0.03 mcg/kg/min, which led to gradual resolution of her edema and corresponding symptoms. An electrocardiogram (ECG) obtained 3 hours after initiation of the epinephrine drip showed a prolonged corrected QT interval (QTc) of 628ms, compared to an initial QTc of 408ms two hours prior to starting the epinephrine drip (see images). Her home hydroxychloroquine and venlafaxine were held due to QT prolongation, and she was placed on continuous telemetry monitoring. This abnormality resolved after the epinephrine drip was weaned off, with a repeat ECG twenty hours later showing a QTc of 443ms. She was discharged the next day on all her home medications.
Discussion: This case provides insight into the clinical management of refractory anaphylaxis, defined as anaphylaxis unresponsive to treatment with at least two doses of epinephrine 0.3mg IM (1,2). Occurring in roughly 1% of all anaphylaxis cases (1), refractory anaphylaxis is associated with significantly higher mortality rates, and, as our case shows, can present in patients historically responsive to treatment. Although little data exists on the appropriate management of refractory anaphylaxis, our case demonstrates that continuous IV epinephrine may be an appropriate first step in treatment. Physicians should be prepared to intubate and/or consider second-line medications, such as IV dopamine or methylene blue (3.4), in case of continued refractory symptoms. Our case study supports the continued use of epinephrine in patients presenting with anaphylactic shock even despite potential QT prolongation. However, 1-2 grams IV magnesium, continuous ECG monitoring (5), holding of other QT-prolonging medications, and prompt discontinuation of epinephrine once symptoms abate should be done to minimize the risk of developing lethal cardiac arrhythmias.
Conclusions: Anaphylaxis is a medical emergency that typically resolves with IM epinephrine. Our case study suggests use of continuous intravenous epinephrine as an appropriate first step in refractory anaphylaxis, followed by IV magnesium, continuous EKG monitoring, and prompt discontinuation of epinephrine when appropriate to prevent fatal arrhythmias due to QT prolongation.
