The question

The recommendation
 (strength/ certainty)

Summary of evidence
 (the most important references)

Remarks
(for implementation)

1.

Is adrenaline effective for the treatment of anaphylaxis?

We recommend adrenaline as the first line treatment for anaphylaxis in ED
(strong recommendation, moderate certainty evidence)

There is little doubt that sufficient levels of adrenaline lead to the resolution of symptoms, while delayed administration can lead to prolonged reactions, hypotension, and fatal outcomes ^{13 14}.

A clear definition of anaphylaxis should be provided and demonstrated through the ABCDE approach (see Annex 2,3), to discriminate it from allergic skin reaction which is not an emergency.

2.

What is the optimal timing of adrenaline in the treatment of anaphylaxis?

We recommend that adrenaline should be administered early once symptoms of anaphylaxis have been recognized or suspected
(weak recommendation, very low certainty evidence).

Although there is a lack of high-certainty evidence to differentiate the effect of early versus delayed administration of adrenaline on clinical outcomes, it is reasonable to recommend administering adrenaline as soon as symptoms of anaphylaxis appear ^{7 13}.

It seems reasonable to ensure the availability of adrenaline in ED to be given as soon as features of anaphylaxis are apparent.

3.

What is the optimal route of adrenaline to treat anaphylaxis?

The intramuscular (IM) route is recommended for initial adrenaline treatment for anaphylaxis
(strong recommendation, very low certainty evidence).

There are currently no trials comparing the effectiveness of different ways of administering adrenaline to patients during anaphylaxis. The use of IM adrenaline as the initial treatment for anaphylaxis due to its favourable safety profile, especially for patients with cardiovascular issues ¹⁵.

The IV route is not recommended for initial management of anaphylaxis, except by those skilled and experienced in its use.

4.

What is the optimal dose of intramuscular adrenaline in the treatment of anaphylaxis?

We recommend IM adrenaline dosage

listed according to age

(strong recommendation, low certainty evidence)

The dosing regimen listed has been proven safe and effective in clinical practice for over 20 years. International guidelines recommend a dose of 0.01 mg/kg (maximum 500 micrograms) for children, which should be titrated to achieve a clinical response.

Several guidelines also recommend simplifying the dosing schedule based on age categories, making it safer and more practical for emergency use by simplifying the preparation and injection process ^{1 16 17}.

.

Table with doses and equivalent ml should be available in ED.

Adults: 500 ug (0.5 mg) IM (0.5 mL of 1 mg/ml [1:1000])

Children >12 years:
same as adult dose and 300 ug (0.3 ml) if child is small

Children 6-12 years:
300 micrograms IM (0.3 mL)

Children 6 months-6 years:

150 micrograms IM (0.15ml)

Children <6 months: 100-150 micrograms IM (0.1 0.15 mL)

5.

Is adrenaline effective in the treatment of anaphylaxis reactions refractory to initial treatment with adrenaline?

We recommend that:
1- Subsequent doses of IM adrenaline should be given every 5 min, titrated to clinical response, in patients whose symptoms are refractory to initial treatment (weak recommendation, very low certainty evidence).

2- Low dose intravenous (IV) adrenaline infusions appear to be effective and safe to treat refractory anaphylaxis.
 ( weak recommendation,

very low certainty evidence).

The absorption of adrenaline following intramuscular injection follows a biphasic profile, with the initial peak occurring within 5-10 minutes ¹⁸. Therefore, IM adrenaline should be repeated every 5-15 min where features of anaphylaxis persist ¹⁵.  The rationale for waiting longer than 5 min when symptoms have failed to respond to adrenaline is unclear.

Low-dose adrenaline infusions are effective in case series of human anaphylaxis ^{19 20} and are included as the treatment of choice for refractory anaphylaxis in national guidelines in Australia for the acute management of anaphylaxis; 2024 ²¹.

Where respiratory and/or cardiovascular features of anaphylaxis persist despite 2 appropriate doses of adrenaline (administered by IM or IV route), urgent expert help (e.g. from experienced critical care clinicians) should be sleeked to establish an intravenous adrenaline infusion to treat refractory anaphylaxis. Complications due to adrenaline occur regardless of route

but are more common after IV administration.

6.

Are intravenous fluids effective as an adjuvant treatment for anaphylaxis?

In case of anaphylaxis with haemodynamic instability, IV crystalloid fluids should be given.
 (weak recommendation, very low certainty evidence)

Crystalloid infusion was more effective in restoring venous return when compared to a single dose of IM adrenaline ²².

IV access should be obtained as early as possible, as a single bolus of IV crystalloid can be used in refractory anaphylaxis.

7.

Are antihistamines effective in the treatment of anaphylaxis?

We advise against using antihistamines as part of the initial emergency treatment for anaphylaxis.
(weak recommendation, low certainty evidence)

Antihistamines are not to be utilized in the treatment of respiratory or cardiovascular symptoms associated with anaphylaxis. Their application should not impede the timely administration of adrenaline and intravenous fluids required to address such symptoms ^{1 17 21}.

We suggest antihistamines are used to treat skin symptoms which often occur as part of allergic reactions without delaying timely and appropriate use of adrenaline to treat anaphylaxis

8.

Are corticosteroids effective in the treatment of anaphylaxis?

We advise against using corticosteroids as part of initial emergency treatment for anaphylaxis
(weak recommendation; low certainty of evidence)

Corticosteroids increased the admission rate in the intensive care units and Hospital in a Canadian Emergency Department Anaphylaxis Cohort ²³. Also, corticosteroids may postpone the use of adrenaline which is life saving ²⁴.

Corticosteroids could be included in the management of refractory anaphylaxis and shock.

9.

Are inhaled beta-2 agonists effective in the treatment of anaphylaxis?

We suggest that inhaled beta2 agonist can only be used as an adjunct treatment to adrenalin in the presence of wheezing for anaphylaxis
(weak recommendation low certainty of evidence)

Short-acting beta-2 agonists (inhaled through a nebulizer or spacer) can be used to relieve lower respiratory symptoms and anaphylaxis, such as wheezing and coughing ²⁵.

But it should not be used instead of adrenaline as a first line of treatment for anaphylaxis ²¹.

Considering bronchial asthma as an important differential diagnosis of acute onset dyspnea and wheezes.

Beta 2 agonist should not be used as a treatment for persistent wheezing instead of repeating the IM adrenaline.

10.

How long should patients be observed in hospital following anaphylaxis?

We recommend, minimum 6 hours observation after resolution of symptoms for all patients. Observation for at least 12 hours after the symptoms have resolved should be ensured in the following cases:

- A severe reaction that necessitated more than 2 doses of adrenaline.

- Patients with severe asthma or those who experienced severe respiratory compromise during the reaction.

- Possibility of continued absorption of allergen, such as with slow-release medications.

- Patients who present late at night or may not be able to respond to any deterioration.

- Patients in areas where access to emergency care is difficult.
(weak recommendation, very low certainty evidence)

The optimal duration of observation following anaphylaxis is unknown. We suggest using a risk-stratified approach for discharging patients after anaphylaxis ^{24 26} . 

The rapid discharge of patients within 2-6 hours after anaphylaxis symptoms have been resolved is not considered a safe approach. However, relatively early discharge of stable patients or arranging for safe transfer to another hospital should be considered in the event of limited capacity at busy ED and small hospitals during a medical crisis.

Recommendation

Clinical indicators

Adrenaline as the first line treatment for anaphylaxis.

100 % of patient presented with anaphylaxis shock should be treated with adrenaline.

Adrenaline should be administered early once symptoms of anaphylaxis have been recognized or suspected.

Percentage of experiencing anaphylaxis who are promptly treated with adrenaline.

The IM route is recommended for initial adrenaline treatment.

Percentage of patients treated with adrenaline in ED by appropriate route.

IM adrenaline dosage listed according to age

100 % of patients prescribed adrenaline in treatment anaphylaxis should be for the correct dose

Subsequent doses of adrenaline, titrated to clinical response, in patients whose symptoms are refractory

Percentage of patients with anaphylaxis who received adrenaline 2^nd dose due to refractory reaction after initial dose of adrenaline

IV crystalloid for treating anaphylaxis with haemodynamic instability

Percentage of patients with anaphylaxis who received IV fluid (bolus and maintenance)

Antihistamines shouldn’t be the initial emergency treatment for anaphylaxis

Percentage of patients with anaphylaxis who administrated antihistamines prior to adrenaline

Corticosteroids shouldn’t be the initial emergency treatment for anaphylaxis

Percentage of patients with anaphylaxis who administrated corticosteroids prior to adrenaline

Inhaled beta2 agonist as an adjunct treatment to adrenaline in the presence of wheezing for anaphylaxis

Percentage of patients with lower respiratory symptoms in the context of anaphylaxis inhaled beta-2 agonists

Minimum 6- 12 hours observation after resolution of symptoms of anaphylaxis according to the associated risk

Percentage of patients with an acute episode of anaphylaxis are observed in hospital for duration less than 6 hours.
Hospital revisit or mortality after 6 hours of observations