Anaphylaxis National Pediatric Nighttime Curriculum Written by Nicole Paradise Black, M.D. Shands Children’s Hospital at University of Florida

Case 1 (interns): Text page from a nurse, “Pt in room 4244 has hives” What do you think about this situation? What do you need to do? What are your initial steps? Do you need to do any work up? Teacher’s Guide: What do you think about this situation? Could this be anaphylaxis, yes, but you need to know more. What do you need to do? What are your initial steps? Do you need to do any work up? Go see the patient immediately to assess the clinical status of the patient. Anaphylaxis is a clinical diagnosis that requires rapid identification, so you need to confirm the findings of the nurse and determine if other signs or symptoms exist to support the diagnosis (such as respiratory, CV, GI or other cutaneous findings.) You’ll also want to understand any recent exposures.

Case 1 (interns): Text page from a nurse, “Pt in room 4244 has hives” Information received upon arrival to the room: 7 yo patient started IVIG infusion 15 minutes ago who has generalized hives, RR= 54, HR 154, BP = 68/38 and says his chest “feels tight” What do you need to do? Teacher’s Guide: What do you need to do? This is clearly anaphylaxis: you have a known inciter for anaphylaxis, with cutaneous, respiratory and cardiovascular signs & symptoms, the biggie is uncompensated shock! You identified it and have to act fast Have another individual call your senior resident stat (who will help you and also notify PICU and primary attending), you may also need to initiate the appropriate rapid escalation of care team (e.g., Rapid Response Team) Assess ABC’s, stop IVIG, Epinephrine IM, IV access and fluids, hemodynamic and pulse oximetry monitoring, recumbent position

Case 2 (seniors) receiving sign out as night float & receive text from intern “Pt B is set to go home but c/o belly pain and a loose stool” What do you think about this situation? What do you need to do? Teacher’s Guide: What do you think about this situation? You haven’t received sign out yet on this patient and obviously need to know more. You ask the senior from the day and he says that is a patient from a cross cover team and all he was told is, “the patient is going home.” What do you need to do? You have a decision to make, do you keep going with sign out or do you assess the situation 1st? Since this is a talk on anaphylaxis, hmm….the answer is pretty obvious, but if this was real life and not embedded in this talk you would at least talk to the intern to ascertain more.

Case 2 (seniors) receiving sign out as night float & receive text from intern “Pt B is set to go home but c/o belly pain and a loose stool” Upon calling the intern back you find out: 8 yo female admitted with pneumonia 3 days prior due to respiratory distress. She has been on ceftriaxone IV and azithromycin po, and after improvement in her symptoms she was changed to all oral antibiotics today in preparation for discharge. The abdominal pain has persisted over the last hour and is crampy and disabling, she has had one loose stool. What do you do?? Teacher’s guide: What do you do? You should see the patient to evaluate her clinical status and understand what may have instigated this sudden change.

Case 2 (seniors) receiving sign out as night float & receive text from intern “Pt B is set to go home but c/o belly pain and a loose stool” She received her 1st dose of Augmentin 2 hours ago and has started to develop hives and some itching Is this anaphylaxis? What do you need to do? Teacher’s guide: Is this anaphylaxis? Yes this is anaphylaxis…she was recently given an agent that is a likely allergen (Augmentin) and proceeded to have cutaneous and GI symptoms. Two important points- anaphylaxis that occurs with an oral exposure (vs. parental exposure) can manifest slower/later and will more commonly include GI symptoms. What do you need to do? See last case and the rest of the talk Get PICU involved and notify attending physician.

Objectives Define the diagnostic criteria for anaphylaxis Recognize anaphylaxis Know the common etiologies of anaphylaxis in the inpatient setting Carry out a proper treatment plan for a patient experiencing anaphylaxis

Anaphylaxis An acute and potentially life-threatening systemic allergic reaction Usually, but not always, mediated by an immunologic mechanism Caused by the sudden release of biologically active mediators from mast cells and basophils Leading to symptoms involving the skin, respiratory tract, and cardiovascular and GI systems. Teacher’s guide: interaction of an allergen and a cell-bound IgE anaphylactoid reactions are IgE independent As with any IgE mediated reaction patients much 1st be exposed to the allergen in order to generate Ab’s (though parents are often unaware of prior exposure) More rapidly it occurs after the exposure the more likely for it to be severe and potentially life-threatening Onset of symptoms may vary: delayed with ingested allergen vs. more rapidly with injected 8

Causes you may see in hospitalized patients Medications Antibiotics (penicillin most common cause) Chemotherapy Muscle relaxants Blood products (including IVIG) Contrast dye Latex Food Teacher’s guide Latex 3 groups are at higher risk of reaction: health care workers, children with spina bifida and genitourinary abnormalities, and workers with occupational exposure to latex

Differential diagnosis Vasodepressor (vasovagal-neurocardiogenic) syncope Syndromes that can be associated with flushing (e.g., metastatic carcinoid) Postprandial syndromes (e.g., scombroid food poisoning) Systemic mastocytosis Psychiatric disorders (e.g., panic attacks or vocal cord dysfunction syndrome) Angioedema (e.g., hereditary angioedema) Other causes of shock (e.g., cardiogenic) Other cardiovascular or respiratory events

Diagnostic criteria: anaphylaxis likely if 1 of the following… Acute onset of illness with skin and/or mucosal involvement and… Two or more of the following after exposure to a likely allergen Reduced blood pressure* after exposure to known allergen Signs or symptoms of respiratory compromise 1. Skin and/or mucosal changes and/or 2. Signs or symptoms of respiratory compromise 2. Reduced blood pressure* or end-organ dysfunction (e.g., syncope) 3. Reduced blood pressure* or end-organ dysfunction (e.g., syncope) *reduced BP either hypotension for age or 30% decrease in systolic BP 4. Persistent GI symptoms Teacher’s guide: Ski/mucosa: hives, pruritis, flushing, swollen tongue and uvula Respiratory compromise: dyspnea, wheeze/bronchospasm, stridor, hypoxemia End-organ dysfunction: hypotonia, collapse, incontinence GI: crampy abdominal pain, vomiting Adapted from UpToDate, Anaphylaxis: Rapid Recognition and Treatment 11

Signs and symptoms Level of consciousness: impairment might reflect hypoxia Upper and lower airways:, tightness in throat or chest, nasal congestion, nasal discharge, dysphonia, stridor, cough, wheezing, shortness of breath Cardiovascular system: hypotension with or without syncope and/or cardiac arrhythmias, tachycardia Cutaneous/mucosa: diffuse or localized erythema or flushing, pruritis, urticaria, angioedema of lips-tongue-uvula Gastrointestinal system: nausea, vomiting, abdominal cramps, diarrhea Misc: pruritis of mouth and face, lightheadedness, diaphoresis, headache, uterine cramps, feeling of impending doom or apprehension, unconsciousness Teacher’s Guide: Cutaneous: occur in up to 90% of episodes Respiratory symptoms occur in up to 70% of episodes Gastrointestinal symptoms occur in up to 40% of episodes CV symptoms occur in up to 35% of episodes Cutaneous symptoms may be absent, but the acute onset of severe bronchospasm in a previously well asthmatic could indicate anaphylaxis 12

Management Assess Airway, Breathing, Circulation, and level of consciousness Establish and maintain airway Have someone call supervising resident, PICU and attending (if not already done) Administer epinephrine: Aqueous epinephrine 1:1000 dilution (1 mg/mL), 0.01 mL/kg (max dose 0.5mL) intramuscularly every 5 minutes, as necessary Teacher’s guide: Epinephrine can be given subcutaneously, but IM is the recommended route. Epinephrine should be used to control symptoms and increase blood pressure Need for IV administration would be a patient who is severe/ICU-type patient (meaning cardiac arrest or profound hypotension who are refractory to repeated IM epi and fluids). Risk of IV administration includes fatal arrhythmias 13

Management continued… Hemodynamic monitoring and continuous pulse oximetry Place patient in the recumbent position and elevate the lower extremities, as tolerated symptomatically Administer oxygen Intravenous access and normal saline for fluid replacement H1-antihistamine, diphenhydramine: 1 to 2 mg/kg IV or 25 to 50 mg per dose Consider H2-antihistamine, ranitidine: 12.5 to 50 mg IV (1 mg/kg) Consider systemic glucocorticoids: 2mg/kg IV Teacher’s guide: Oxygen should definitely be administered to patients with anaphylaxis who have prolonged reactions, have pre-existing hypoxemia or myocardial dysfunction, receive inhaled b-agonists as part of anaphylaxis or require multiple doses of epinephrine Rapid NS infusion for hypotension unimproved with epinephrine In the management of anaphylaxis, a combination of diphenhydramine and ranitidine is superior to diphenhydramine alone H1-antihistamines are only useful for pruritis and urticaria, NOT for other signs or symptoms and therefore should not be substituted for epinephrine. Can substitute certirazine for diphenhydramine, but not available IV and IV is preferred Other treatments for refractory situations that may be tried in the ICU include IV epinephrine bolus vs drip, inhaled beta-2 agonists, vasopressors, systemic glucocorticosteroids (though glucocorticosteroids will not help acutely…only with protracted or biphasic anaphylaxis) Bronchodilator treatment will help with bronchospasm, but NOT prevent or relieve upper airway edema or shock and should not be substituted for epinephrine 14

Management (later) Period of observation and treatment before discharging home Epinephrine auto-injectors 0.3/0.15mg (EpiPen® & EpiPen Jr®: epipen.com/how-to-use-epipen, video demonstrating use and PDFs for patients) Teacher’s guide: Treatment: around-the-clock H1-antihistamine and H2-antihistamine, and same for systemic glucocorticoids and albuterol if decided to use 24-36 hours of observation with: >30 min exposure to symptoms >60 min from symptoms to epinephrine repeated boluses of fluid or doses of epinephrine were needed history of late-phase reaction.

Take home points Goal of therapy: early recognition and treatment with epinephrine to prevent progression to life-threatening symptoms, including shock If there is any doubt, it is generally better to administer epinephrine Epinephrine and oxygen are the most important therapeutic agents administered in anaphylaxis. Teacher’s guide: Prompt recognition of signs and symptoms of anaphylaxis is crucial Important errors in the treatment of anaphylaxis include failure to administer epinephrine promptly, and delay in epinephrine injection due to over-reliance on antihistamines, albuterol, and glucocorticoids.

References Lieberman, et al. The diagnosis and management of anaphylaxis: An updated practice parameter. J Allergy Clin Immunolo. 2005;115:S463-S McGintee, E.E., Pawlowski, N.A. Allergy and Asthma: Anaphylaxis. In: The Philadelphia Guide: Inpatient Pediatrics, Frank, G., Shah, S.S., Catallozzi, M., Zaoutis, L.B. (Eds), Malden, MA: Blackwell Publishing; 2005:10-11 Sampson, H.A., Leung, D.Y.M. Anaphylaxis. In: Nelson Textbook of Pediatrics, 18th Edition, Kliegman, R.M., Behrman, R.E., Jenson, H.B., Stanton, B.F. (Eds), Philadelphia, PA: Saunders Elsevier; 2007:983-984. Simons, F.E.R., Camargo, C.A. Anaphylaxis: Rapid Recognition and Treatment. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2011. Waibel, K.H. Anaphylaxis. Pediatrics in Review. 2008;29 (8):255-263