C-CARE
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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.
Guidelines
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
Glucocorticosteroids
- 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
Design
- 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
Population
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
Interventions
- All centres followed anaphylaxis treatment guidelines [2]
Outcomes
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)
Criticisms
- Observational design
- mixed prospective/retrospective design
- only included patients that presented to Emergency Department
Funding
- AllerGen NCE (Networks of Centres of Excellence of Canada)
- Health Canada
Further Reading
- ↑ 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.
- ↑ Cheng A. Emergency treatment of anaphylaxis in infants and children. Paediatr Child Health 2011; 16:35-40