Clinicians should follow the ABCs.  Airway, breathing, circulation.  It is highly recommended that all providers maintain BLS certification.  Epinephrine should be administered as soon as the symptoms of anaphylactic shock are recognized. IM administration of epinephrine causes a rapid rise in serum concentration and is preferred over subcutaneous administration.  IM injection is faster and has fewer adverse effects than IV administration.

Initial management is as follows for anaphylactic shock.

  • Remove offending agent if present.
  • Call EMS or code team in the hospital.
  • IM epinephrine injection to the mid outer aspect of the thigh.
  • Place patient supine with legs held in the air, unless there is airway swelling/obstruction necessitating the patient remains upright.  Pregnant patients should be placed on their left side.
  • Supplemental oxygen.
  • IV fluids.
  • Nebulized albuterol/levalbuterol for airway compromise (for dosing, see SABA module)


IM epinephrine can be repeated in 5-15 min intervals as necessary if there is no or suboptimal response.  A second dose is necessary in 12-36% of cases.  Patients with flushing, diaphoresis, and dyspnea are more likely to require a second dose. The injector will come with instructions for use, but in general, they are as follows:

  • Remove autoinjector from the case.
  • Hold the autoinjector in hand, do not cover either end of the device with fingers.
  • Remove safety cap(s).
  • Children and non-cooperative patients should have their legs held to prevent administration errors.
  • Press the tip firmly into the outer thigh; the needle is able to penetrate clothes.
  • Hold in place for 2-3 seconds (may differ based on manufacturer).


H1 and H2 antihistamines can also be administered; however, there is a paucity of evidence regarding their effectiveness in anaphylactic shock. H1 (diphenhydramine, cetirizine, etc.) antihistamines relieve itching and urticaria but do not ameliorate airway obstruction or hypotension.  The onset of action of these agents orally is 30-40 minutes; therefore, IV/IM administration is preferred if available.  Rapid IV infusion of H1 antihistamines may potentiate hypotension. H2 antihistamines (ranitidine, famotidine, etc.) may provide relief for urticaria when given with H1 antihistamines.  Like H1 antihistamines, there is a paucity of evidence regarding efficacy.  Glucocorticoids are frequently given as well to prevent biphasic reactions as their onset of action is several hours.  Data validating use for anaphylactic shock is lacking.

Tale 5 – Drug Information




Common Adverse Effects


Epinephrine - Stimulates ɑ1, β1 and β2 adrenergic receptors resulting in bronchodilation, cardiac stimulation, and vasodilation in skeletal muscle (large doses have a reciprocal effect due to increased ɑ1 activation.)

Adults: 0.3 mg IM using 1mg/ml injector, may repeat q5-15 min as necessary

Dosing Pediatric: Children 7.5-14kg 0.1 mg IM 15-29kg 0.15 mg IM >/= 30kg see adult dosing, may repeat q5-15 min as necessary


  • Cardiac disease: May result in arrhythmias, ischemia, and hypertension.
  • Diabetes: May increase or decrease blood sugars.
  • Parkinson’s disease: May lead to psychomotor agitation.
  • Pheochromocytoma: May lead to severe hypertension.
  • Thyroid disease: Use with caution.
  • Pregnancy risk factor: C, Epinephrine crosses the placenta and may cause uterine vasoconstriction, decrease in uterine blood flow, and fetal hypoxia.  Pregnant women requiring treatment should be closely monitored for signs of fetal compromise. 
  • Breastfeeding:  It is unknown if epinephrine is excreted in breast milk.  Caution is recommended by the manufacturer when administering to breastfeeding women.
  • Tachy/bradyarrhythmias
  • Chest pain
  • Hypertension
  • Anxiety
  • Dizziness 
  • Agitation
  • Diaphoresis, Gangrene at injection site
  • Hyper or hypoglycemia.

See manufacturer recommendations; different formulations may require different preparation instructions and length of time to administer the dose. Do not reinsert needles.  Do not inject at the same site if repeated injections are necessary.  Do not inject into buttocks, hands, or feet.  In obese children, the lower half of the thigh may be the preferred site to ensure IM injection.  In severely obese children, the calf may be used to ensure IM injection. 

Diphenhydramine - Binds to and inhibits H1 receptors

Adults: 25-50 mg q4-8h max 300 mg/day.  IM 10-100 mg q4-8h, max 400 mg daily

Anaphylaxis (off label): IV,IM 25-50 mg

Pediatrics: Allergy reaction 2-6y (off label)  6.25 mg q4-6h max 37.5 mg daily 6-12y 12.5 mg q 4-6h max 150 mg/day >12y see adult dosing

Anaphylaxis (off label use): IV,PO,IM 1-2mg/kg/dose max 50 mg


  • Hypersensitivity to diphenhydramine or any structurally related antihistamine. 
  • Breastfeeding.
  • When used for self-medication, do not use in children under 6


  • CNS: May cause CNS depression.
  • CV: Use with caution in cardiovascular disease due to the potential for side effects.
  • Glaucoma: Use with caution as symptoms may worsen.
  • Urinary obstruction: May worsen/cause urinary obstruction.
  • Pregnancy risk factor: B, Antihistamines used directly before birth may cause respiratory distress in newborns.   Antihistamines are not recommended for the treatment of pruritis due to cholestasis of pregnancy.  
  • Geriatrics: Diphenhydramine is on the beer’s list due to anticholinergic side effects.  Avoid using if possible; however, it can be used for allergic reactions.


Local necrosis may occur with subcutaneous or intradermal injection

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