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==Background==
==Background==
*Type I [[Hypersensitivity Reaction|hypersensitivity reaction]] that is either severe in nature or having two or more organ systems involved.
*'''Acute, life-threatening, systemic allergic reaction''' involving multiple organ systems
*Clinically [[Anaphylaxis]] and its treatment is virtually identical whether it is the traditional IgE dependent anaphylaxis reaction (vast majority), or the IgE independent ''anaphylactoid'' reaction
*IgE-mediated (type I hypersensitivity) in most cases; can also be non-IgE mediated (anaphylactoid)
*Precipitants
*'''Biphasic reaction''' occurs in '''5-20%''' of cases (recurrence 1-72 hours after initial reaction, usually within 8-10 hours)<ref>Lee S, et al. Biphasic anaphylaxis: review of incidence, clinical predictors, and observation recommendations. ''Immunol Allergy Clin North Am''. 2015;35(2):313-326. PMID 25841553</ref>
**Food (most common)
*Epinephrine is the ONLY first-line treatment — delays in administration increase mortality
**Medications
 
**Insect stings
===Common Triggers===
**Latex
*Foods (most common overall): peanuts, tree nuts, shellfish, fish, milk, eggs, wheat, soy
**Aerobic exercise
*Medications: antibiotics (penicillin, cephalosporins), NSAIDs, neuromuscular blocking agents
**Idiopathic (rare)
*Insect stings: Hymenoptera (bees, wasps, hornets, fire ants)
*Latex
*'''Exercise-induced anaphylaxis''' (sometimes food-dependent)
*Idiopathic (~20% — no identifiable trigger)


==Clinical Features==
==Clinical Features==
[[File:Hives2010.jpg|thumbnail|Raised [[urticaria]]]]
*Onset: minutes to hours after exposure (usually within 30 minutes)
[[File:Angioedema2013.jpg|thumbnail|[[Angioedema]] of tongue]]
*Skin/mucosal (90%): urticaria, flushing, angioedema, pruritus
[[File:Angioedema2010.jpg|thumb|Angioedema of face.]]
*Respiratory (70%): laryngeal edema, stridor, bronchospasm, wheezing, dyspnea
*Cutaneous symptoms (90%)
*Cardiovascular (45%): [[hypotension]], [[tachycardia]], distributive [[shock]], syncope, cardiac arrest
**[[Hives]]
*GI (45%): nausea, vomiting, abdominal cramps, diarrhea
**[[Angioedema]]
*'''Neurologic''': anxiety, dizziness, altered mental status
**Itching
*'''Anaphylaxis can occur WITHOUT skin findings''' (~10-20% of cases)
**Morbilliform rash
*Respiratory symptoms (70%)
**[[Wheezing]]
**[[Shortness of breath]]
**Throat itching or tightness
**Hoarseness
**Stridor
**Hypoxia, cyanosis
*Gastrointestinal symptoms (40%)
**Abdominal pain
**Nausea, vomiting
**[[Diarrhea]]
*Cardiovascular symptoms (35%)
**[[Hypotension]]
**Chest pain
**Palpitations
*Central Nervous System
**Uneasiness
**Altered mental status
**Headache, dizziness, confusion
**Syncope


===Expected Course===
===Diagnostic Criteria (Any ONE of Three)===
====Uniphasic (80-90%)====
*Criterion 1: Acute onset with skin/mucosal involvement AND respiratory compromise OR hypotension
*Symptoms peak within 30 minutes to 1 hour after onset, resolve within 30 minutes to 1 hour of receiving treatment<ref>Ewan PW. '''ABC of allergies – Anaphylaxis,''' ''BMJ'' 1998; 316: 1442-1445 </ref>
*Criterion 2: Two or more systems involved rapidly after likely allergen: skin, respiratory, cardiovascular, GI
====Biphasic (10-20%)====
*Criterion 3: Hypotension after exposure to known allergen (SBP <90 or >30% decrease from baseline)
''Biphasic reactions are rare and can occur anywhere from 10 minutes up to six days after an initial reaction.''<ref> Milne K. Biphasic Allergic Reactions: Observation, Treatment Guidelines http://www.acepnow.com/article/biphasic-allergic-reactions-observation-treatment-guidelines/</ref>
*Uniphasic response, followed by asymptomatic period of hour or more, then return of symptoms
*The second phase does not necessarily resemble the first!
*More likely with a severe initial presentation or repeated epinephrine doses. Additionally hypotension, widened pulse pressure, unknown trigger, and drug trigger in children<ref>Ellis AK, Day JH: Incidence and characteristics of biphasic anaphylaxis: A prospective evaluation of 103 patients. Ann Allergy Asthma Immunology. 2007; 98:64-69</ref><ref name="aaaai"/>
*Little evidence to support the use of discharge steroids to prevent a biphasic reaction
*0.4% of patients with anaphylaxis had a rebound event while in the ED<ref name="biphasic"/>


==Differential Diagnosis==
==Differential Diagnosis==
{{Acute Allergic DDX}}
*[[Angioedema]] (hereditary or ACE-inhibitor — no urticaria)
{{Shock DDX}}
*Vasovagal syncope (bradycardia; no urticaria/wheezing)
{{Erythematous rash DDX}}
*[[Asthma]] exacerbation
*[[Urticaria]] alone (without systemic involvement)
*Carcinoid syndrome, mastocytosis, scombroid fish poisoning
*[[Anxiety]] / panic attack
*[[Vocal cord dysfunction]]


==Evaluation==
==Evaluation==
''[[Anaphylaxis]] is highly likely when ANY ONE of the following criteria is fulfilled''<ref>Brown SGA, Mullins RJ and Gold MS. '''Anaphylaxis: diagnosis and management,''' ''MJA'' 2006; 185: 283–289  </ref><ref>Lieberman P et al. '''The diagnosis and management of anaphyalxis: An updated practice parameter,''' ''J Allergy Clin Immunol'' 2005;115;3:S483-S523 </ref>
*'''Anaphylaxis is a clinical diagnosis''' — do NOT delay treatment for labs
*Serum tryptase: elevated supports diagnosis (draw within 1-3 hours of onset)
**Normal tryptase does NOT exclude anaphylaxis
**Useful for postmortem diagnosis and distinguishing from other causes
*Monitor: continuous ECG, pulse oximetry, blood pressure
*Consider: CBC, BMP, troponin (Kounis syndrome — allergic MI)


===Criterion 1 (90% of patients)===
==Management==
*Acute onset of an illness involving the skin, mucosal tissue, or both AND at least one of the following:
===Epinephrine (Cornerstone of Treatment)===
**Respiratory Compromise
*Epinephrine 0.3-0.5 mg (1:1,000) IM in anterolateral thigh (vastus lateralis)
**Reduced blood pressure or associated symptoms ([[Syncope]], [[Dizziness]])
**Pediatric: 0.01 mg/kg (max 0.3 mg) IM
**Repeat every 5-15 minutes as needed
**'''Do NOT delay''' — there are NO absolute contraindications to epinephrine in anaphylaxis
*If refractory or in shock:
**Epinephrine infusion: 0.1-0.5 mcg/kg/min IV (mix 1 mg in 250 mL NS = 4 mcg/mL)
**IV epinephrine bolus (only for cardiac arrest or refractory shock): 0.1 mg of 1:10,000 IV
*IM > SC (faster absorption; SC absorption unreliable in shock)


===Criterion 2 (10-20% of patients)===
===Adjunctive Therapies===
*TWO OR MORE of the following that occur rapidly after exposure to a LIKELY allergen for that patient
*IV fluids: aggressive NS bolus (1-2L in adults; 20 mL/kg in children) — distributive shock with massive third-spacing
**Involvement of the skin-mucosal tissue (hives, swollen lips-tongue-uvula)
*Albuterol 2.5-5 mg nebulized for bronchospasm (does not replace epinephrine)
**Respiratory compromise
*'''H1 antihistamine''': diphenhydramine 25-50 mg IV (treats urticaria/pruritus; does NOT treat life-threatening features)
**[[Reduced BP|Hypotension]] or associated symptoms
*H2 antihistamine: famotidine 20 mg IV (adjunctive)
**Persistent gastrointestinal symptoms: ([[Vomiting|vomiting]], [[Diarrhea|diarrhea]], crampy [[Abd Pain|abdominal pain]])
*Corticosteroids: methylprednisolone 125 mg IV or prednisone 1 mg/kg PO
**Theoretical benefit in preventing biphasic reaction (limited evidence)
**'''Do NOT rely on steroids as primary treatment''' (slow onset: 4-6 hours)
*Glucagon 1-5 mg IV for patients on beta-blockers (resistant to epinephrine)


===Criterion 3===
===Refractory Anaphylaxis===
*[[Reduced BP|Hypotension]] after exposure to a KNOWN allergy for that patient (minutes to hours):
*Epinephrine infusion + aggressive volume resuscitation
**Adults: systolic blood pressure (SBP) <90 mmHg or >30% reduction from baseline
*Vasopressin 1-2 units IV bolus for refractory hypotension
**Pediatrics
*Glucagon for beta-blocker use
***1 month - 1 year: SBP <70 mmHg
*Consider methylene blue 1-2 mg/kg IV for refractory vasoplegia
***1 year - 10 years: SBP <(70 mmHg + [2 x age])
*Secure airway early if airway edema progressing (may require surgical airway)
***11 years - 17 years: SBP <90 mmHg
 
==Management==
*'''[[Epinephrine]]'''
**1:1000 '''IM''' 0.3 - 0.5mg (0.3 - 0.5mL) every 5 - 15 minutes<ref>Dhami S. et al. Management of anaphylaxis: a systematic review. Allergy. 69 (2014) 168–175. http://onlinelibrary.wiley.com/store/10.1111/all.12318/asset/all12318.pdf?v=1&t=hrspdbpk&s=8067bfd5903c7ffebf4a274f062a71633ebe0507</ref><ref>Sheikh A, Shehata YA, Brown SGA, Simons FER. '''Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock.''' ''Cochrane Database of Systematic Reviews'' 2008, Issue 4. Art. No.: CD006312. DOI:10.1002/14651858.CD006312.pub2</ref>
**Give as soon as possible
**Always IM initially <ref>Simons FER, Gu X, Simons KJ. '''[[Epinephrine]]absorption in adults: Intramuscular versus subcutaneous injection,''' ''J Allergy Clin Immunol'' 2001;108:871-3 </ref>
**If response to IM is inadequate: give epinephrine infusion 1:10,000 2 - 10 µg/min
**'''How to make a quick epinephrine drip:''' ''Take your code-cart epinephrine (it does not matter if it is 1:1,000 or 1:10,000) and inject 1mg into a liter bag of NS.  Final concentration is 1mcg/ml.  Run at 1cc/min and titrate to effect''.
*Pediatric: [[Epinephrine]] '''1:1000 0.01mg/kg (max 0.5mg) IM''' every 5 to 15 minutes
**IV infusion: 0.05 - 1 mcg/kg/min
*'''Supplemental oxygen'''
**''Consider [[Intubation|endotracheal intubation]] if airway edema present''
*'''Normal saline bolus'''
**If unresponsive to [[epinephrine]] assume distributive [[Shock|shock]] and give 1 - 2 liters of normal saline
*'''Also consider'''
**[[Albuterol]] for bronchospasm resistant to IM epinephrine
**[[Antihistamines]] (for symptom control AFTER hemodynamically stable)
***[[Diphenhydramine]]: 25 to 50mg IV (1mg/kg in children)
***[[Ranitidine]]: 50mg IV (0.5mg/kg in children) (has been found to improve urticaria but not angioedema at 2 hours<ref>Lin, RY et al. Improved Outcomes in Patients With Acute  Allergic Syndromes Who Are Treated With  Combined H1 and H2 Antagonists. Annals of Emergency Medicine. 36:5 NOVEMBER 2000.</ref>)
***AVOID promethazine as this can worsen hypotension
**Glucocorticoid
***MAY blunt biphasic reaction although little evidence to support usage<ref>Choo KJ, Simons E, Sheikh A: Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy 2010; 65:1205-1211.</ref>
***[[Methylprednisolone]]: 125mg IV (2mg/kg in children)
***[[Dexamethasone]]: 10mg IV or PO (0.6mg/kg in children)
**[[Glucagon]]
***1 - 5mg IV over 5 minutes followed by infusion of 5 - 15 µg/min<ref>Campbell RL, et al. Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol. 2014; 113:599e608.</ref>
***If taking beta-blocker AND unresponsive to [[Epi|epinephrine]]
**Consider adding additional pressor support if persistent hypotension present
***For example: '''[[vasopressin]]''' 2-8 units for persistent refractory shock (case series only)<ref>Schummer et al. The Pivotal Role of Vasopressin in Refractory Anaphylactic Shock. Anesthesia & Analgesia: August 2008 - Volume 107 - Issue 2 - pp 620-624.</ref><ref>Dünser et al. Treatment of Anaphylactic Shock: Where Is the Evidence? Anesthesia & Analgesia: August 2008 - Volume 107 - Issue 2 - pp 359-361</ref>
***[[Norepinephrine]] 0.05 to 0.5 mcg/kg per minute


==Disposition==
==Disposition==
===Admit===
*Observe minimum 4-6 hours after last dose of epinephrine (biphasic reaction monitoring)
*Severe and moderate presentations especially if symptoms did not respond promptly to epinephrine or required repeat dosing
*Extended observation (8-24 hours) if:
*Labs that may be requested by allergist/admitting team if uncertain diagnosis
**Severe initial reaction (hypotension, intubation)
**Histamine level - serum elevation 30-60 min following anaphylaxis, window easily missed
**History of biphasic reactions
**Tryptase - peaks at 2-4 hrs, remains elevated 6-12 hrs
**Delayed presentation
 
**Poor access to medical care
===Discharge===
*Discharge with:
*Consider discharge after 1 hour observation per AAAAI recommendations if no severe symptoms and no repeat epinephrine doses <ref name="aaaai">Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol 2020; 145:1082. https://www.aaaai.org/Aaaai/media/Media-Library-PDFs/Professional%20Education/Podcasts/Anaphylaxis-2020-grade-document.pdf</ref>
**Epinephrine auto-injector prescription (EpiPen or equivalent) — prescribe 2 devices
**NPV of 1-hour observation was 95%, with NPV for biphasic anaphylaxis after >6 hours of observation of 97.3% <ref>Shaker M, Wallace D, Golden DBK, Oppenheimer J, Greenhawt M. Simulation of health and economic benefits of extended observation of resolved anaphylaxis. JAMA Netw Open 2019;2:e1913951.</ref>
**Antihistamine (diphenhydramine or cetirizine) for 3 days
*Classical teaching Symptom-free for at least 4 hours and mild initial presentation
**Prednisone 40-60 mg PO daily × 3-5 days
*Send home with an [[epinephrine]] autoinjector! (Epi-Pen)
**Allergist referral
*Up to 6% of the people with anaphylaxis have a repeat ED visit for anaphylaxis within 7 days<ref name="biphasic">Grunau BE et al. Incidence of Clinically Important Biphasic Reactions in Emergency Department Patients With Allergic Reactions or Anaphylaxis. Ann Emerg Med. 2013 Nov 13</ref>
**'''Written anaphylaxis action plan'''
**Strict avoidance of trigger
**'''Return precautions''': return immediately if symptoms recur


==See Also==
==See Also==
*[[Allergic Reaction]]
*[[Angioedema]]
*[[Angioedema]]
*[[Urticaria]]
*[[Asthma]]
*[[Shock]]
*[[Epinephrine]]


==References==
==References==
<references/>
<references/>
*Lieberman P, et al. Anaphylaxis — a practice parameter update 2015. ''Ann Allergy Asthma Immunol''. 2015;115(5):341-384. PMID 26505932
*Cardona V, et al. World Allergy Organization anaphylaxis guidance 2020. ''World Allergy Organ J''. 2020;13(10):100472. PMID 33204386
*Simons FER, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. ''World Allergy Organ J''. 2011;4(2):13-37. PMID 23268454
*Shaker MS, et al. Anaphylaxis — a 2020 practice parameter update. ''J Allergy Clin Immunol''. 2020;145(4):1082-1123. PMID 32001253


[[Category:Allergy and Immunology]]
[[Category:Critical Care]]
[[Category:Critical Care]]

Revisión actual - 09:23 22 mar 2026

Background

  • Acute, life-threatening, systemic allergic reaction involving multiple organ systems
  • IgE-mediated (type I hypersensitivity) in most cases; can also be non-IgE mediated (anaphylactoid)
  • Biphasic reaction occurs in 5-20% of cases (recurrence 1-72 hours after initial reaction, usually within 8-10 hours)[1]
  • Epinephrine is the ONLY first-line treatment — delays in administration increase mortality

Common Triggers

  • Foods (most common overall): peanuts, tree nuts, shellfish, fish, milk, eggs, wheat, soy
  • Medications: antibiotics (penicillin, cephalosporins), NSAIDs, neuromuscular blocking agents
  • Insect stings: Hymenoptera (bees, wasps, hornets, fire ants)
  • Latex
  • Exercise-induced anaphylaxis (sometimes food-dependent)
  • Idiopathic (~20% — no identifiable trigger)

Clinical Features

  • Onset: minutes to hours after exposure (usually within 30 minutes)
  • Skin/mucosal (90%): urticaria, flushing, angioedema, pruritus
  • Respiratory (70%): laryngeal edema, stridor, bronchospasm, wheezing, dyspnea
  • Cardiovascular (45%): hypotension, tachycardia, distributive shock, syncope, cardiac arrest
  • GI (45%): nausea, vomiting, abdominal cramps, diarrhea
  • Neurologic: anxiety, dizziness, altered mental status
  • Anaphylaxis can occur WITHOUT skin findings (~10-20% of cases)

Diagnostic Criteria (Any ONE of Three)

  • Criterion 1: Acute onset with skin/mucosal involvement AND respiratory compromise OR hypotension
  • Criterion 2: Two or more systems involved rapidly after likely allergen: skin, respiratory, cardiovascular, GI
  • Criterion 3: Hypotension after exposure to known allergen (SBP <90 or >30% decrease from baseline)

Differential Diagnosis

  • Angioedema (hereditary or ACE-inhibitor — no urticaria)
  • Vasovagal syncope (bradycardia; no urticaria/wheezing)
  • Asthma exacerbation
  • Urticaria alone (without systemic involvement)
  • Carcinoid syndrome, mastocytosis, scombroid fish poisoning
  • Anxiety / panic attack
  • Vocal cord dysfunction

Evaluation

  • Anaphylaxis is a clinical diagnosis — do NOT delay treatment for labs
  • Serum tryptase: elevated supports diagnosis (draw within 1-3 hours of onset)
    • Normal tryptase does NOT exclude anaphylaxis
    • Useful for postmortem diagnosis and distinguishing from other causes
  • Monitor: continuous ECG, pulse oximetry, blood pressure
  • Consider: CBC, BMP, troponin (Kounis syndrome — allergic MI)

Management

Epinephrine (Cornerstone of Treatment)

  • Epinephrine 0.3-0.5 mg (1:1,000) IM in anterolateral thigh (vastus lateralis)
    • Pediatric: 0.01 mg/kg (max 0.3 mg) IM
    • Repeat every 5-15 minutes as needed
    • Do NOT delay — there are NO absolute contraindications to epinephrine in anaphylaxis
  • If refractory or in shock:
    • Epinephrine infusion: 0.1-0.5 mcg/kg/min IV (mix 1 mg in 250 mL NS = 4 mcg/mL)
    • IV epinephrine bolus (only for cardiac arrest or refractory shock): 0.1 mg of 1:10,000 IV
  • IM > SC (faster absorption; SC absorption unreliable in shock)

Adjunctive Therapies

  • IV fluids: aggressive NS bolus (1-2L in adults; 20 mL/kg in children) — distributive shock with massive third-spacing
  • Albuterol 2.5-5 mg nebulized for bronchospasm (does not replace epinephrine)
  • H1 antihistamine: diphenhydramine 25-50 mg IV (treats urticaria/pruritus; does NOT treat life-threatening features)
  • H2 antihistamine: famotidine 20 mg IV (adjunctive)
  • Corticosteroids: methylprednisolone 125 mg IV or prednisone 1 mg/kg PO
    • Theoretical benefit in preventing biphasic reaction (limited evidence)
    • Do NOT rely on steroids as primary treatment (slow onset: 4-6 hours)
  • Glucagon 1-5 mg IV for patients on beta-blockers (resistant to epinephrine)

Refractory Anaphylaxis

  • Epinephrine infusion + aggressive volume resuscitation
  • Vasopressin 1-2 units IV bolus for refractory hypotension
  • Glucagon for beta-blocker use
  • Consider methylene blue 1-2 mg/kg IV for refractory vasoplegia
  • Secure airway early if airway edema progressing (may require surgical airway)

Disposition

  • Observe minimum 4-6 hours after last dose of epinephrine (biphasic reaction monitoring)
  • Extended observation (8-24 hours) if:
    • Severe initial reaction (hypotension, intubation)
    • History of biphasic reactions
    • Delayed presentation
    • Poor access to medical care
  • Discharge with:
    • Epinephrine auto-injector prescription (EpiPen or equivalent) — prescribe 2 devices
    • Antihistamine (diphenhydramine or cetirizine) for 3 days
    • Prednisone 40-60 mg PO daily × 3-5 days
    • Allergist referral
    • Written anaphylaxis action plan
    • Strict avoidance of trigger
    • Return precautions: return immediately if symptoms recur

See Also

References

  1. ↑ Lee S, et al. Biphasic anaphylaxis: review of incidence, clinical predictors, and observation recommendations. Immunol Allergy Clin North Am. 2015;35(2):313-326. PMID 25841553
  • Lieberman P, et al. Anaphylaxis — a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384. PMID 26505932
  • Cardona V, et al. World Allergy Organization anaphylaxis guidance 2020. World Allergy Organ J. 2020;13(10):100472. PMID 33204386
  • Simons FER, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13-37. PMID 23268454
  • Shaker MS, et al. Anaphylaxis — a 2020 practice parameter update. J Allergy Clin Immunol. 2020;145(4):1082-1123. PMID 32001253
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