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If there is only a local isolated reaction, patient comfort and pain relief are all that is necessary. However, if the patient has a systemic allergic response, there is an immediate need for additional medications. Several medications are useful in this setting, and their use will depend on the severity of the patient’s symptoms, vital signs, and past medical history. Before administering any medication, the clinician should ensure that the patient has no medication allergies. The clinician should also determine if the patient has taken any of his or her own medication (e.g., epinephrine autoinjector, oral diphenhydramine, or other oral antihistamine) before EMS arrival that may be masking the severity of the reaction or affect any of the medications EMS will administer. If the patient has his or her own autoinjector, EMS personnel of all qualification levels may assist with administration. Research has further demonstrated that epinephrine can be safely administered either via autoinjectors or nonautoinjection by EMTs at all training levels in the treatment of anaphylaxis in the field [12, 13].

Antihistamines are by far the most commonly used class of medication. Antihistamines block the action of histamine at H1 receptors, but do not decrease histamine release. Diphenhydramine is the most common medication in this class and can be given orally, intravenously, intraosseously, or intramuscularly in a typical dose of 25‐50 mg for adults, depending on their weight and the severity of the reaction. Research suggests that H2 blockers have a synergistic action when used in conjunction with diphenhydramine, blocking both H1 and H2 cellular histamine receptors [14]. Both famotidine and ranitidine are useful H2 blockers, but cimetidine is not recommended due to its multiple drug interactions. Adult doses are IV famotidine 20 mg or IV ranitidine 50 mg. Corticosteroids, either orally or intravenously, may also be useful to prevent return of symptoms once other medications are metabolized, but they are not effective immediately. Peak onset of action of corticosteroids is 2‐4 hours, and there is evidence that corticosteroid administration prevents biphasic allergic reactions if coadministered with epinephrine and antihistamines. Nebulized beta‐agonists, such as albuterol, can be used for patients with persistent bronchospasm. Nebulized ipratropium bromide may also be used in conjunction with albuterol but should not be used alone. Although both the multidose inhaler and the nasal spray formulations of ipratropium contain an ingredient that may cause an allergic reaction in patients with known peanut allergies (soy lecithin, used to keep the medication in suspension), the nebulized formulation typically used by EMS and emergency departments lacks this ingredient [3]. All of the aforementioned drugs may also be used in children, but, as with any pediatric medication, dosages must be calculated based on the child’s weight (Table 21.1).

Local allergic reactions can progress from one body system to anaphylaxis involving several systems, including skin, respiratory, and circulatory. If untreated, this can progress to anaphylactic shock with circulatory collapse and hypotension. Epinephrine is the first‐line medication for a patient with severe allergic reactions or anaphylaxis and should be given as soon as possible. Delaying administration has been associated with poor outcomes. While generally safe, caution may be advised in patients with known coronary artery disease or in cases with life‐threatening tachydysrhythmias. Infrequently, myocardial ischemia and infarction have been reported, especially if administered IV [15]. Two different concentrations of epinephrine may be used, and the clinician must be attentive to using the proper dosage and formulation when administering it. In adults, 0.3 mL of epinephrine 1:1,000 solution can be given subcutaneously or intramuscularly except when the patient is on the verge of cardiovascular collapse. The intramuscular route at the lateral thigh is preferred. This route produces higher peak plasma concentrations in less time than subcutaneous injection or intramuscular injection in the deltoid [16]. Faster absorption from intramuscular injection in the thigh is thought to be due to the increased vascularity of the vastus lateralis muscle [16].

Table 21.1 Pediatric anaphylaxis medication doses

Drug	Weight‐based dose
Epinephrine	1:1000 IM (0.3 mL maximum) 1 mL of 1:10,000 mixed with 10 mL NS 0.5 mL of 1:1000 in 2.5 mL NS nebulized
Diphenhydramine	1 mg/kg IM/IV/IO/PO (max. 50 mg)
Methylprednisolone	1‐2 mg/kg
Famotidine	0.5 mg/kg to max. of 20 mg IV/IO
Ranitidine	2‐4 mg/kg to max. of 50 mg IV/IO

IM, intramuscular; IO, intraosseous; NS, normal saline; PO, by mouth.

If the patient is hemodynamically unstable, 1 mL of epinephrine 1:10,000 mixed with 10 mL of normal saline can be given slowly by IV or intraosseous push over 5‐10 minutes. Caution is advised. On the one hand, epinephrine given intravenously to a patient who is not in cardiac arrest can be risky, resulting in hypertension or myocardial ischemia [15]. On the other hand, it can be lifesaving and should not be delayed in the case of a hemodynamically unstable or “crashing” patient. Epinephrine may also be nebulized by placing 0.5 mL of 1:1000 solution in 2.5 mL of normal saline.

If the patient is hypotensive, rapid fluid resuscitation with 1‐2 L of normal saline (20 mL/kg in children) is indicated in addition to the aforementioned medications. Patients often will become intermittently hypotensive and require multiple fluid boluses and additional medications, so frequent monitoring of vital signs is imperative. At least two large‐bore IV lines are desirable.

Localized angioedema is typically treated as an allergic reaction with antihistamines and steroids, along with epinephrine in severe cases. However, little actual benefit or significant improvement has been shown with these medications. As with medication‐induced angioedema, hereditary angioedema is generally not responsive to antihistamines, steroids, or epinephrine, although they are routinely administered [3]. The mainstay of treatment is supportive, with ongoing monitoring and early consideration of intubation if there is airway compromise.

EMS clinicians should anticipate that any airway intervention for a patient with an allergic reaction or angioedema is likely to be especially difficult. The edema can extend to the glottic and subglottic regions and not be externally visible. The only clue the clinician might have is that the patient’s voice is hoarse or different from normal. Oral‐pharyngeal, glottic, and subglottic edema can obscure anatomical landmarks and decrease airway caliber to alter the effective sizes of airway tools. If bronchospasm is present, ventilation before and between intubation attempts may be difficult, adding pressure for expedient success. Thus, it is imperative that the clinician is prepared for a difficult airway with airway skills, adjuncts, and emergency rescue devices and techniques, such as cricothyrotomy, especially if rapid sequence intubation is also being performed [17].