From Wiki Journal Club
Jump to: navigation, search
Gebrielli S, et al. "Evaluation of Prehospital Management in a Canadian Emergency Department Anaphylaxis Cohort". J Allergy Clin Immunol Pract. 2019. Sep-Oct 7(7):2232-2238.
PubMedFull textPDF

Clinical Question

In adult and pediatric patients that present to the Emergency Department with symptoms of allergic anaphylaxis, what factors contribute to patient admission, use of multiple doses of epinephrine, and intravenous fluids within the Emergency Department?

Bottom Line

Receiving pre-hospital doses of epinephrine and antihistamines may help avoid admission to ward or ICU, and more severe reactions, drug triggers, or peanut triggers may be associated with requiring admission and worse outcomes.

Major Points

Anaphylaxis may kill within 5 minutes of symptom onset. Epinephrine, antihistamines, and glucocorticoids are the mainstay of most guidelines and treatment algorithms. Randomized-control trials of these interventions would be very challenging to create, given the ethical implications of withholding therapy. Given the slower onset of glucocorticoids, the question as to their role in the per-hospital setting has been made; they have a clear role in management of asthma.

This observational trial conducted across 5 Canadian provinces, including 9 centres, as part of the C-Care Registry (Cross-Canada Anaphylaxis Registry) enrolled 3498 participants between April 2011 and October 2017. Treatment in the prehospital setting included epinephrine in 31% of cases, antihistamines in 2% of cases, and glucocorticoids in 46% of cases. Epinephrine decreased the likely hood of hospital/ICU admission (OR 0.23, 95% CI 0.14-0.38) and antihistamines (OR 0.61, 95% CI 0.44-0.85) whereas prehospital glucocorticoids increased the risk of hospital admission (OR 2.84, 95% CI 1.55-6.97).

There are some limitations with this trial. Being an observational design, there is some risk of bias that cannot be eliminated. With the low utilization of antihistamine there is an area for improvement in their utilization but the concern of sedation may be leading to their low utilization. The signal of worse outcomes associated with glucocorticoids needs to be explored further as their cannot be deemed causative.


Guideline for acute therapy and management of anaphylaxis[1], 2014, adapted

Primary pharmacologic therapy include vaso-active agents:

  • epinephrine (adrenaline), IM if stable and IV if requiring volume resuscitation or unstable
    • secondarily may include: norepinepherine, dopamine, vasopressin

Primary pharmacologic therapy for respirator distress:

  • beta-adrenergic agents including salbutamol or terbutaline

Manifest respiratory or cardiovascular reactions:

  • give 100% Oxygen therapy

Volume resuscitation, initially and then titrated to response

  • Children 20 ml/kg body weight
  • Adults 0.5–1 liters

Histamine blockade

  • H1 blockers are slower to act than vasoactive agents, with few side effects (sedation being the major concern)
  • H2 blockers have little evidence to support their use


  • slow onset, may have a minor role in the acute phase but their role in stabilizing acute asthma or preventing a protracted or biphasic reaction is effecive


  • Multicenter, double-blind, parallel-group, randomized, controlled trial
  • N=3498
  • Setting: 9 centres across 5 Canadian provinces
  • Enrollment: April 2011 - October 2017
  • Analysis: Generalized linear mixed model
  • Primary Outcome: Admission to ICU/ward, use of multiple doses of epinephrine in ED, use of IV fluids in ED


Inclusion Criteria

  • All children and adults presenting to Emergency Department with symptoms consistent with anaphylaxis, defined as:
    • ≥ 2 organ systems involved after exposure to a possible allergen, or
    • hypotension after exposure to a known allergen

Exclusion Criteria

  • cases not meeting the definition of anaphylaxis

Baseline Characteristics

  • Demographics: median age 8.0, 19.7% adults, 55.6% male
  • Allergen trigger: 79.2% specific food, 2.3% venom, 5.4% drug, 3.3% other, 9.8% unknown
  • Reaction location: 5% during exercise, 54.6% at home
  • Reaction severity: 18.9% Mild (eg rash), 74.2% moderate (eg “barky cough” and moderate wheezing), 6.9% severe (eg respiratory arrest)
  • Comorbidities: 16.0% Asthma, 49.9% known food allergy, 0.3% Ischemic Heart Disease
  • Previously prescribed medications: 1.1% Beta-blockers, 1.3% regular NSIADs, 0.8% ACE inhibitors, 0.2% Tricyclic antidepressants,
  • admission: 0.7% to intensive care unit, 1.9% to ward


  • All centres followed anaphylaxis treatment guidelines [2]


Primary Outcomes

Admission to ICU/Hospital Ward
Pre-hospital corticosteroids (OR 2.88, 95% CI 1.13-7.36)
Severe reaction (OR 11.50, 95% CI 4.51-29.33)
Peanut trigger (OR 2.18, 95% 1.23-3.88)
Drug trigger (OR 4.88, 95% CI 2.21-10.77)
≥2 doses of Epinephrine in Emerg
Pre-hospital epinephrine (OR 0.22, 95% CI 0.13-0.37)
Pre-hospital antihistamines (OR 0.58, 95% CI 0.41-0.82)
Male (OR 1.56, 95% CI 1.11-2.19)
Severe reaction (OR 5.68, CI3.2-10.08)
Utilization of IV fluids in Emerg
Severe reaction (OR 4.95, 95% CI 4.95)
Peanut trigger (OR 1.60, 95% CI 1.12-2.29)

Subgroup Analysis

Patients with known food allergy
Admission to ICU/Ward
Pre-hospital corticosteroids (OR 5.69, 95% CI 1.52-21.32)
Regular treatment with ACE inhibitors (OR 15.8, 95% CI 1.07-233.12)
Trigger Drug (OR 5.33, 95% CI 1.19-23.97)
≥2 doses of Epinephrine in Emerg
Prehospital epinepherine (OR 6.29, 95% CI 1.22-32.58)
Regular treatment with NSAIDs (OR 0.58, 95% CI 0.41-0.82)
Male (OR 1.56, 95% CI 1.11-2.19)
Trigger Other (OR 0.55, 95% CI 0.32-0.96)
Utilization of fluids in ED
Pre-hospital corticosteroids (OR 3.08, 95% CI 1.13-8.36)
Regular treatment with NSAIDs (OR 5.67, 95% CI 1.54-19.59)
Male (OR 1.47, 95% CI 1.00-2.16)
Age <18 years (OR 0.14, 95% CI 0.09-0.21)
Trigger Peanut (OR 1.96, 95% CI 1.29-1.53)


  • Observational design
  • mixed prospective/retrospective design
  • only included patients that presented to Emergency Department


  • AllerGen NCE (Networks of Centres of Excellence of Canada)
  • Health Canada

Further Reading

  1. Ring J et al. Guideline for acute therapy and management of anaphylaxis: S2 Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Association of German Allergologists (AeDA), the Society of Pediatric Allergy and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Austrian Society for Allergology and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Society for Psychosomatic Medicine (DGPM), the German Working Group of Anaphylaxis Training and Education (AGATE) and the patient organization German Allergy and Asthma Association (DAAB). Allergo J Int 2014. 23:96-112.
  2. Cheng A. Emergency treatment of anaphylaxis in infants and children. Paediatr Child Health 2011; 16:35-40