Anaphylaxis Treatment

ANAPHYLAXIS TREATMENT

ADRENALINE

Adrenaline is the drug of choice for the emergency treatment of severe allergic reactions to food, insect stings, medication, latex, exercise, and other allergens. 1, 2, 3, 4 It should be administered as soon as anaphylaxis is suspected, as there is clear evidence that failure to do so has contributed to fatal outcomes. 3 A 2008 Cochrane review concluded that most people who died from anaphylaxis did not receive prompt adrenaline treatment. 2 Delayed injection of adrenaline can also increase the likelihood of a biphasic reaction. 5

Adrenaline acts fast and rapidly treats all of the most dangerous symptoms of anaphylaxis, including throat swelling, difficulty breathing, and low blood pressure. 6 It also helps alleviate itching, rash, swelling, gastrointestinal and genitourinary symptoms. 7 It works most effectively if it is given within the first few minutes of a severe allergic reaction. 6

Mean time to peak plasma concentrations of adrenaline is 8±2 minutes after administration. 8 This is important as respiratory or cardiac arrest can occur as early as 6 minutes for food-triggered reactions and 4 minutes for venom-triggered reactions (median times 30 and 15 minutes, respectively). 9

ADRENALINE MOA

Adrenaline for EpiPen

Through its action on alpha-adrenergic receptors, adrenaline lessens the vasodilation and increased vascular permeability that occurs during an anaphylactic reaction that can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, adrenaline causes bronchial smooth muscle relaxation that helps alleviate bronchospasm, wheezing, and dyspnoea that may occur during anaphylaxis.10 Beta-adrenergic action also works on the heart to enhance coronary blood flow and increase cardiac output to increase blood pressure.6

Two mechanisms have been proposed for the cardiac effects, which counteract the vasoconstrictor effects of adrenaline on the coronary arteries:10

  • increased duration of diastole compared to systole
  • vasodilator effect due to increased myocardial contractility.

DOSAGE AND ADMINISTRATION

The emergency dose of adrenaline is 0.01 mg/kg of a 1 mg/mL (1:1000) dilution to a maximum dose of 0.5 mg in an adult and 0.3 mg in a child.6

Adrenaline can be given intramuscularly (IM), intravenously (IV) or subcutaneously (SC). However, IV administration must be given by a healthcare professional; in practice adrenaline is generally given by the IM route using an auto-injector, such as EpiPen®, as it is more quickly absorbed than when given by SC injection.8 This is an important consideration because rapid absorption of adrenaline is critical to reversing the symptoms of anaphylaxis.

Up to 35% of patients need more than one dose of adrenaline to reverse anaphylaxis symptoms.

For this reason it is important that patients at risk of anaphylaxis carry 2 auto-injectors with them at all times.11

Adrenaline can be administered every 5 to 15 minutes until there is resolution of anaphylaxis or signs of adrenaline toxicity occur (e.g. palpitations, tremor, uncomfortable apprehension and anxiety).7 It is important that patients administer no more than two doses, with any additional treatment only given by a healthcare professional.

Reports show as many as 20% of patients will go on to develop a second anaphylactic response several hours later in response to the initial allergen exposure.10 The second phase, known as a biphasic reaction, usually occurs after an asymptomatic period of 1 to 72 hours, but most occur within 8 hours after the initial reaction.10 About one third of the second-phase reactions are more severe, one third are as severe,12 and one third are less severe, and so patients should be observed for at least 6 hours after the initial symptoms of anaphylaxis subside, and maybe for 12 hours if considered appropriate.1,13

SIDE EFFECTS AND PRECAUTIONS

Transient side-effects such as pallor, tremor, anxiety, palpitations, headache and dizziness can occur within 5 to 10 minutes of injection, but these are usually mild and confirm that a therapeutic dose has been given.5

Although serious events such as pulmonary oedema or hypertension have been reported with adrenaline, these are usually associated with overdose and with the IV, rather than the IM or SC route.5

While the use of adrenaline requires caution in patients with coronary artery disease, it should be noted that untreated anaphylaxis is also associated with cardiac risks and adrenaline can actually improve blood flow in the coronary arteries.5

Anyone taking beta-blockers for cardiovascular disease may not respond well to adrenaline. Beta-blockers interact with one of the receptor sites for adrenaline, antagonising its cardiostimulating and bronchodilating effects and potentially worsening anaphylaxis.5

However, there is no absolute contraindication to the use of adrenaline in a life-threatening situation.6


REFERENCES:

  1. Resuscitation Council (UK) Guidelines. January 2008.
    Available at: http://www.resus.org.uk/pages/reaction.pdf Last accessed November 2014.
  2. Sheikh A, Shehata YA, Brown SGA, et al. Cochrane Database Syst Rev.2008; Issue 4: CD006312.
  3. McLean-Tooke APC, Bethune CA, Fay AC, et al. BMJ 2003;327:1332–1335.
  4. Muraro A, Roberts G, Clark A, et al. Allergy 2007;62:857–871.
  5. Simons FER.J Allergy Clin Immunol 2010;125:S161-81.
  6. Simons FER et al. J Allergy Clin Immunol 2011; 127(3):587-93.
  7. EpiPen® Summary of Product Characteristics, MEDA Pharmaceutical Ltd, February 2016.
  8. Simons FER et al. J Allergy Clin Immunol 1998;101(Part 1):33-7.
  9. Pumphrey RS. Clin Exp Allergy.2000;30(8):1144-1150.
  10. Kemp SF et al. World Allergy Org J 2008;1(7):S18-S26.
  11. Drug Safety Update Volume 7 Issue 10, May 2013: A3.
  12. Ellis AK, Day JH. Can Med Ass J 2003;169(4):307-12.
  13. NICE clinical guideline 134. Anaphylaxis: assessment to confirm an anaphylactic episode and the decision to refer after emergency treatment for a suspected anaphylactic episode. Issued December 2011.

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