Anaphylaxis

OVERVIEW

• Anaphylaxis is a severe, life-threatening, generalised or systemic hypersensitivity reaction
• It is characterised by rapidly developing life-threatening airway (pharyngeal or laryngeal edema) and/or breathing (bronchospasm and tachypnea) and/or circulation (hypotension and tachycardia) problems usually associated with skin and mucosal changes
• a patient can have anaphylaxis without any urticaria or mucosal signs
• in the patient with known allergies, anaphylaxis may present as isolated hypotension
• early recognition and treatment is important — delay in adrenaline adminstration is associated with increased mortality and increased rates of biphasic reactions

DEFINITION

Multiple definitions exist —  the definition of anaphylaxis below is that of the National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network.

• Anaphylaxis is highly likely when any 1 of the following 3 criteria are fulfilled:

1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) AND at least 1 of the following:

• Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
• Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence)

2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):

• Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula)
• Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
• Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence); persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)

3. Reduced BP after exposure to known allergen for that patient (minutes to several hours):

• Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP
• Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline

PATHOPHYSIOLOGY

• IgE mediated hypersensitivity reaction to an antigen
• leads to profound histamine and serotonin release from basophil and mast cell degranulation.

Biphasic reactions

• the recurrence of anaphylaxis symptoms soon after the initial episode
• occur about 5% of the time
• may occur >24 hours after the initial episode
• usually less severe than the initial episode
• possible risk factors include:
  1. delayed administration of adrenaline
  2. slow response to adrenaline
  3. need for repeated doses of adrenaline
  4. need for IV fluids

CLINICAL FEATURES

Exposure to antigen:

• stings
• foods
• antibiotics
• contrast media
• thrombolytics
• NSAIDs
• suxamethonium
• non-depolarising neuromuscular blockers

Rapid onset (within minutes) of some combination of:

• Angioedema
• Stridor
• Respiratory distress
• Bronchospasm
• Hypotension and cardiovascular collapse
• Abdominal cramps
• Diarrhoea
• Flushing or pallor
• Urticaria
• Coagulopathy

INVESTIGATIONS

Emergency tests

• anaphylaxis is primarily a clinical diagnosis but tests may help longterm management
• histamine levels (rarely performed, peak at 10 minutes, back to baseline at 1 hour)
• serum tryptase (see below)

Serum tryptase

• released from secretory vesicles of mast cells
• take at 1, 6 and 24 hours
• serum separated and stored at 20 C
• normal: <1ng/mL
• non-specific and anaphylactoid reactions: 1-15ng/mL
• true anaphylaxis levels: >15ng/mL

RAST testing

• radioallergosorbent test for antigen-specific IgE antibodies

CAP testing

• an antigen coated capsule is exposed to the patients serum under laboratory conditions
• if serum contains antigen specific IgE a measurable colour change is produced
• superceded RAST testing
• available for testing pencillin, sux and latex allergy – sensitivity low -> thus negative result requires skin testing

Skin or intradermal testing

• skin testing has been shown to be diagnostic for anaphylaxis (but not for anaphylactoid reactions)
• should take place 4-6 weeks post event to allow regeneration of IgE
• antihistamines should not have been given within the last 5 days
• use skin prick testing first
• test all drugs given before the event
• use a saline as a negative control
• use histamine solution as a positive control
• weal >2mm wider than saline = positive
• repeat positive test with a 1:10 dilution to reduce the chance of a false positive
• once positive drug detected -> test other drugs in same class
• if history is strong, but skin prick test negative -> test intradermally with diluted drugs

MANAGEMENT

Address potential life threats

• Stop trigger
• Call for help
• Position supine (head down)
• O2 (FiO2 1.0 if possible)
• Exclude alternatives

Pulse present

• Adrenaline 0.5mg IM
• IV access
• Fluid boluses if SBP <90mmHg
• Promethazine 25-50mg IV
• Hydrocortisone 250mg IV
• Persistant hypotension/bronchospasm -> repeat Adrenaline 0.5mg IM after 5 minutes; if still persists after 5 minutes start adrenaline infusion

Pulse absent

• CPR
• Raise legs
• 2 large IVs
• 2 L IVF
• Increasing Adrenaline (adult – 1-4mg) (children – 10-100mcg/kg)
• H1 and H2 antagonists
• Extended CPR

Persisting hypotension

• Ranitidine (H2 antagonism)
• Adrenaline/Noradrenaline infusion
• Invasive monitoring
• Colloid

Persistant bronchospasm

• As per asthmatic emergencies

Persisting angioedema

• Nebulised adrenaline (1mg)
• ETT
• Cricothyroidotomy
• Tracheostomy

Seek and treat underlying causes and complications

DISPOSITION

• observe minimum 6 hours in most cases (according to expert consensus guidelines)

Admit if:

• severe anaphylaxis
• uncontrolled asthma
• slow response to adrenaline
• need for bolus fluids
• need for a second dose of adrenaline

Prior to discharge ensure:

• provide appropriate discharge instructions (e.g. written action plan)
• teach use of adrenaline auto-injector
• provide prescriptions and ensure that the patient is able to fill them
• ensure that the patient can access to emergency medical services (e.g. phone, not too remote)
• arrange follow up (GP, allergist, report reaction to Med Safe, medic alert bracelet)
• appropriate documentation (record allery in clinical notes)

References and Links

LITFL

• CCC — Anaphylaxis DDX
• CCC — Paediatric anaphylaxis

Journal articles

• Bjornsson HM, Graffeo CS. Improving diagnostic accuracy of anaphylaxis in the acute care setting. West J Emerg Med. 2010 Dec;11(5):456-61. PubMed PMID: 21293765; PubMed Central PMCID: PMC3027438.
• Brown SG. The pathophysiology of shock in anaphylaxis. Immunol Allergy Clin North Am. 2007 May;27(2):165-75, v. Review. PubMed PMID: 17493496.
• Brown SG, Mullins RJ, Gold MS. Anaphylaxis: diagnosis and management. Med J Aust. 2006 Sep 4;185(5):283-9. Review. Erratum in: Med J Aust. 2006 Oct 2;185(7):400. Dosage error in article text. PubMed PMID: 16948628. [Free Full Text]
• El-Shanawany T, Williams PE, Jolles S. Clinical immunology review series: an approach to the patient with anaphylaxis. Clin Exp Immunol. 2008 Jul;153(1):1-9. doi: 10.1111/j.1365-2249.2008.03694.x. Review. PubMed PMID: 18577027; PubMed Central PMCID: PMC2432091.
• Kirkbright SJ, Brown SG. Anaphylaxis–recognition and management. Aust Fam Physician. 2012 Jun;41(6):366-70. PubMed PMID: 22675674. [Free Full Text]
• Peavy RD, Metcalfe DD. Understanding the mechanisms of anaphylaxis. Curr Opin Allergy Clin Immunol. 2008 Aug;8(4):310-5. doi: 10.1097/ACI.0b013e3283036a90. Review. PubMed PMID: 18596587; PubMed Central PMCID: PMC2683407.
• Nel L, Eren E. Peri-operative anaphylaxis. Br J Clin Pharmacol. 2011 May;71(5):647-58. doi: 10.1111/j.1365-2125.2011.03913.x. Review. PubMed PMID: 21235622; PubMed Central PMCID: PMC3093071.
• Wölbing F, Fischer J, Köberle M, Kaesler S, Biedermann T. About the role and underlying mechanisms of cofactors in anaphylaxis. Allergy. 2013 Aug 2. doi: 10.1111/all.12193. [Epub ahead of print] PubMed PMID: 23909934. [Free Full Text]

FOAM and web resources

• ALIEM — Paucis Verbis: Anaphylaxis (2012)
• EM Basic — Anaphylaxis Part 1- Diagnosis and Treatment and Anaphylaxis Part 2- Airway (2013)
• Emergency Medicine PharmD — Epinephrine IM for Anaphylaxis (2012)
• EM Lyceum — Anaphylaxis, Questions and “Answers” (2012)
• The Flipped EM Classroom — Anaphylaxis (2012)
• ICN — 101. Rose on Anaphylaxis (2013)
• Resus.ME — Two new anaphylaxis guidelines (2011)