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Key points

• Anaphylaxis is a rapidly evolving generalised multi-system allergic reaction to an allergen or trigger characterised by respiratory and/or cardiovascular features that can be fatal.
• Anaphylaxis is under-recognised as symptoms may have resolved prior to ED presentation.
• Adrenaline IM into the thigh is the first line treatment for anaphylaxis.
• Severe anaphylaxis is a challenging clinical scenario that requires the most skilled clinicians available and rapid escalation of life saving measures.
• Caregivers of a child who has suffered anaphylaxis must receive two Adrenaline autoinjectors along with education on use and an individualised action plan on discharge from ED.
• Adrenaline autoinjectors must be prescribed (and if possible dispensed) to all children who have suffered any allergic reaction (mild, moderate or severe) secondary to nut exposure as subsequent exposures may lead to more severe reactions (including anaphylaxis) and are less predictable compared to other foods.

Purpose

This document provides clinical guidance for all staff involved in the care and management of a child presenting to an Emergency Department (ED) in Queensland with symptoms suggestive of an acute allergic reaction or anaphylaxis.

This guideline has been developed by senior ED clinicians and Paediatricians across Queensland, with input from Immunologists, Queensland Children’s Hospital, Brisbane. It has been endorsed for use statewide by the Queensland Emergency Care of Children Working Group in partnership with the Queensland Emergency Department Strategic Advisory Panel and the Healthcare Improvement Unit, Clinical Excellence Queensland.

Introduction

An allergic reaction is an immunologically-mediated adverse reaction which occurs when a person’s immune system reacts to a substance (allergen) in the environment which would normally be innocuous. Allergens can enter the body via a number of different portals, including inhalation, ingestion, contact with skin and injection (parenteral medication or insect stings and bites).

Up to 40% of children in Australia and New Zealand are affected by allergic disorders at some time during their life, with 20% having current symptoms. Allergic diseases have approximately doubled in western countries over the last 25 years. The most common allergic conditions in children are food allergies, eczema, asthma and hayfever (allergic rhinitis).¹

Most allergic reactions do not cause major problems, even though for many people they may be a source of extreme irritation and discomfort. A small number of people may experience a severe allergic reaction called anaphylaxis.

Anaphylaxis is an acute systemic allergic reaction in response to an allergen or trigger. It is caused by an IgE-mediated release of histamine, leukotrienes and prostaglandins from tissue mast cells and peripheral blood basophils.^1,2 This reaction is multisystem in nature with systemic cardiovascular and/or respiratory symptoms and involvement of other systems such as the skin and gastrointestinal tract. Anaphylaxis may also be accompanied by signs of general allergic reaction.^1,3 Urticaria / skin symptoms may be transient or subtle. Emergency departments tend to miss the diagnosis of anaphylaxis if the symptoms have resolved or if there is not a previous history of anaphylaxis.⁴

Non-immunologic anaphylaxis or ‘anaphylactoid’ reaction is an acute systemic reaction which is clinically identical to anaphylaxis. This occurs as a result of direct mast cell stimulation in response to a trigger and requires the same treatment.^3,5

Food allergies are the most common cause of anaphylaxis in children. Common allergens include peanuts, tree nuts, wheat, sesame, egg, cow’s milk, fish, shellfish and on rare occasions spices, fruit and soy.⁵ Other causative agents include drugs, insects, latex, allergen therapy and, less commonly, exercise, cold and immunisations. In up to 30% of reactions, a cause cannot be identified.¹

The prevalence of anaphylaxis in the paediatric population is estimated to be 1 in 1000.⁶ Admission rates for anaphylaxis are increasing in Australia with food allergies affecting 4 – 8% of children less than five years of age.¹ Deaths from anaphylaxis are relatively rare but they are increasing in Australia with 324 deaths recorded between 1997 and 2013.⁷

Risk factors for fatal anaphylaxis include:^1,8

• asthma
• delayed administration of adrenaline
• age (teenagers and adults are at higher risk)
• nut allergy

Assessment

Emergency care should always involve a rapid primary survey with evaluation of (and immediate management of concerns with) airway, breathing, circulation and disability (ABCD). Pre-hospital treatment with IM adrenaline (see dosing advice below) should be initiated if any clinical suspicion of anaphylaxis.

History

History taking should include specific information on allergic symptoms prior to hospital presentation with particular emphasis on cardiovascular or respiratory symptoms.

Once the patient is stabilised, the allergen trigger for the event should be identified (if possible).

Questioning should identify:

• all foods and medications consumed several hours before the reaction
• any possible stings or bites
• current medications such as beta-blockers (as may affect response to treatment)
• co-morbid diseases such as asthma (as can affect the severity of the reaction)

Examination

Source: The Australian Society of Clinical Immunology and Allergy¹

Differential diagnosis

Investigations

Investigations are not routinely recommended. Histamine levels fall too rapidly to be clinically useful.  Occasionally tryptase levels collected within three hours of symptom onset may be useful but should only be collected on advice from Immunologist/Allergist.

The use of other laboratory and radiological tests should be guided by patient co-morbidities and circumstances, including incidental trauma.⁹

Management

Refer to flowchart [PDF 370 KB] for a summary of the emergency management of children with an acute allergic reaction.

Anaphylaxis

Initial management includes rapid triage and clinical assessment of the patient’s airway patency, breathing (ventilation and oxygenation) and circulation. Intervention and stabilisation should occur immediately. Continuous cardiac and oxygen saturation monitoring is recommended. Children with less severe generalised allergic symptoms may initially appear stable but have the potential for rapid deterioration.⁹

Adrenaline

• Adrenaline IM into the thigh is the recommended first-line treatment of anaphylaxis
• effective for all the symptoms and signs of anaphylaxis²
• associated with a decreased fatality rate if administered promptly¹⁰

Studies have demonstrated that peak plasma levels are achieved significantly faster after IM injection into the thigh compared with SC injection into the arm.^11,12  1 in 10 patients will need more than one dose of adrenaline.¹⁹

Nebulised Adrenaline may help relieve upper airway obstruction and/or bronchospasm but should only be administered in addition to Adrenaline IM.

Where Adrenaline IV is indicated, a continuous low dose Adrenaline infusion is the safest and most effective form of administration.¹³ Significant adverse events including fatal cardiac arrhythmia and cardiac infarction have been reported when Adrenaline IV is administered too rapidly, inadequately diluted or in excessive dose.¹⁴ An Adrenaline IV bolus can be considered for use in the hemodynamically unstable patient while preparing an adrenaline infusion.¹ Staff with specialist training/most senior staff available will be required.

Seek urgent paediatric critical care advice (onsite or via Retrieval Services Queensland (RSQ)) for a child requiring more than two doses of Adrenaline IM or prior to administering Adrenaline IV.

Airway

• Children suffering from anaphylaxis who have respiratory distress without circulatory instability should be initially nursed in a sitting up position.
• Early preparation for advanced airway management
• For persistent stridor, consider nebulised adrenaline and continue to escalate anaphylaxis management Flowchart

Seek senior emergency/paediatric advice as per local practices for a child with airway concerns following administration of Adrenaline IM.

Contact the most senior resources available onsite (critical care/anaesthetic/ENT) prior to intubating a child with anaphylaxis.

Breathing

• high flow supplemental oxygen via non-rebreather mask is recommended
• for persistent wheeze, consider inhaled bronchodilators, magnesium, corticosteroids as per acute asthma management, in addition to escalating anaphylaxis management Flowchart

Circulation

• children with circulatory compromise should be nursed lying down
• elevate the lower extremities to conserve circulating volume
• IV access with two large-bore (age-appropriate) cannula, or intraosseous access, is recommended for children with severe symptoms at risk of circulatory compromise
• fluid resuscitation with sodium chloride 0.9% (in addition to IM adrenaline) for the management of shocked children

• consideration of IV adrenaline infusion for refractory shock
• monitor for signs of overtreatment including pulmonary oedema and hypertension, with careful review and re-assessment of tachycardia, pallor and gastrointestinal symptoms

Seek urgent paediatric critical care advice (onsite or via RSQ) for a child in shock who is not responding to Adrenaline and fluids.'

Advanced Airway Management

Severe anaphylaxis is an incredibly challenging clinical scenario even for experienced clinicians. While most children respond well to IM adrenaline, airway swelling and bronchospasm can occur rapidly, with respiratory arrest being the cause of death in 86% fatal anaphylaxis cases.²⁰

Preparation for early intubation with escalation to the most senior clinician available onsite is recommended if the child is desaturating.  The airway should always be considered difficult, requiring smaller than usual endotracheal tube (ETT) size for age⁹. Caution should also be applied to Rapid Sequence Induction (RSI), requiring lower doses of sedation but maximising paralysis.

For the patient with progressive hypoxia or confusion despite maximum medical management, early intubation needs to be considered with anticipation of high airway pressure. When performing bag valve mask (BVM) ventilation, the pop off valve may need to be closed to achieve pressures required to overcome bronchospasm, while considering risk of inadvertent barotrauma.

Similarly, ventilation settings may need to be adjusted for peak inspiratory pressure (PIP) >50 and increased I:E, with consideration of pneumothorax in the case of secondary deterioration.

In the event intubation is unsuccessful, a clear escalation plan needs to be defined, with a surgical airway to be performed in the CICO situation.²¹

Profound and/or refractory anaphylaxis

Anaphylactic shock displays features of both distributive and hypovolemic shock.  If hypotension continues despite maximal adrenaline administration and large volume fluid resuscitation, additional therapies need to be considered and prepared²².  These include additional vasopressors such as argipressin (vasopressin) (infusion via DERS software pumps at 0.01-0.12 unit/kg/h for < 20kg, 0.6-2.4unit/kg/hour for > 20kg) and methylene blue for profound vasodilatation (single dose 1 to 2 mg/kg by 20min infusion).

This should be discussed early with a senior physician in the paediatric intensive care unit or with the paediatric medical coordinator (PMC) via Retrieval Service Queensland (phone number 1300 799 127).

Adjuvant Therapy

Nebulised adrenaline

• nebulised Adrenaline may help relieve upper airway obstruction (stridor)

Inhaled bronchodilators

• may help relieve bronchospasm if lower airway obstruction (wheeze) is a concern¹⁸

Corticosteroids

• not recommended unless there is a component of asthma aggravation with anaphylaxis, which should be treated concurrently as per the Asthma Guideline.

While corticosteroids are commonly recommended as second-line treatment internationally, little evidence supports their use in anaphylaxis. No randomised controlled trials (in adults or children) were identified in a Cochrane Systematic Review of glucocorticoids for the treatment of anaphylaxis.¹⁵ The primary action of glucocorticoids is down-regulation of the late-phase eosinophilic inflammatory response, as opposed to the early-phase response. Short-term glucocorticoid treatment is seldom associated with adverse effects.¹⁶ The proposed rationale for corticosteroid administration is to prevent biphasic or protracted reactions.² However, in two paediatric studies of biphasic reactions the administration of steroids did not appear to be preventative.²

Antihistamines

• not recommended in acute anaphylaxis as there is no evidence to support use¹⁷

Generalised and local allergic reaction

Antihistamines

• H₁ antagonists are recommended to treat allergy symptoms including urticaria, angioedema and itchiness
• two-to-four-day-course taken orally is recommended to alleviate persistent symptoms after a severe allergic reaction

Antihistamine dosing for the treatment of allergic reaction in children

*Loratadine, Fexofenadine and Desloratadine are not available within QH Hospitals but are available in the community. Fexofenadine and Desloratadine can be prescribed to infants 6 months and over.

Escalation and advice outside of ED

Critically unwell or rapidly deteriorating child

Non-critical child

Inter-hospital transfers

Disposition

When to consider discharge from ED

Children with a localised or general allergic reaction

Children with a localised allergic reaction may be safely discharged.

Children with a general allergic reaction may be safely discharged provided symptoms have not progressed and are improving within one hour of observation.

On discharge

• parents / carers should be educated on allergic reactions and instructed to return immediately if symptoms recur
• Adrenaline autoinjectors must be prescribed (and if possible dispensed) to all children who have suffered any allergic reaction (mild, moderate or severe) secondary to nut exposure as subsequent exposures may lead to more severe reactions (including anaphylaxis) and are less predictable compared to other foods

Follow-up

• with GP within a week.

For children with a generalised allergic reaction, consider referral to a local Immunologist (via ED or GP) on discharge. Refer to the ASCIA website (https://allergy.org.au/) for registered local Immunologists. Refer to local Paediatrician if no local Immunology service.

Children with anaphylaxis

Consider discharge for children who meet the following criteria:

• resolution of respiratory and CVS symptoms
• an observation period of four hours following administration of Adrenaline IM.

Prior to discharge, consider other factors including the time of day, parents/carers comprehension and compliance, access to transport should return be required and distance to the local hospital.

On discharge

• caregivers must receive:
  • two Adrenaline autoinjectors (AAI) (see table below). If dispensing from afterhours cupboard (in relevant hospitals) a non-PBS script can be provided for a single AAI and script a second AAI on PBS to take with the family. Make family aware of short expiry dates on AAI.
  • education on how and when to administer the AAI (refer to ﷟ How to give Epipen – Australasian Society of Clinical Immunology and Allergy (ASCIA)). And when to administer the AAI (refer to ﷟ https://www.allergy.org.au/hp/anaphylaxis/first-aid-for-anaphylaxis).
  • an individualised Action Plan (see Action Plan for Anaphylaxis on ASCIA website)
  • general information regarding allergies and anaphylaxis management (see ASCIA website)
• the child and their caregiver/s should be encouraged to document the circumstances leading up to an episode of anaphylaxis (up to six to eight hours prior to symptoms)

Follow-up

• refer (via ED or GP) to Immunologist/Allergy specialist if available locally, otherwise refer to local Paediatrician
• if allergen known to be food related, consider referral to local dietician

When to consider admission

Facilities without a Short Stay Unit (SSU)

Admission is recommended for children with anaphylaxis who:

• have persistent symptoms four hours after treatment
• required more than two Adrenaline doses (due to possibility of recurrent symptoms)

Facilities with a Short Stay Unit (SSU)

Consider admission to a SSU for children who are responding to treatment but require a period of observation prior to meeting the criteria for discharge.

When to consider admission to inpatient ward from SSU

Admission to an inpatient service is recommended for children who require more than two Adrenaline doses (due to possibility of recurrent symptoms) or who are failing to improve after 12 hours of care.