Risk of Unmanaged Anaphylaxis
Unmanaged anaphylaxis carries a mortality risk and can result in death or serious disability from cardiovascular collapse, respiratory failure, and multi-organ hypoperfusion—risks that far outweigh any concerns about treatment side effects. 1
Life-Threatening Risks of Untreated Anaphylaxis
Cardiovascular Collapse
- Massive intravascular volume depletion occurs within minutes, with up to 35% of intravascular volume shifting into the extravascular space, leading to profound hypotension and shock. 1
- Myocardial ischemia and dysrhythmias can occur in untreated anaphylaxis, even in patients without pre-existing cardiovascular disease. 1
- Refractory hypotension develops when patients do not receive prompt epinephrine and fluid resuscitation. 1
Respiratory Failure
- Laryngeal edema and bronchospasm can rapidly progress to complete airway obstruction and respiratory arrest. 2
- Hypoxia from airway swelling and bronchospasm leads to organ damage and death if untreated. 1
Neurological Complications
- Cerebral hypoperfusion from shock can cause permanent neurological damage or death. 1
- Loss of consciousness and seizures may occur from severe hypotension. 2
Specific High-Risk Patient Populations
Patients at Increased Risk of Fatal Anaphylaxis
- Patients with severe uncontrolled asthma are at significantly higher risk for fatal outcomes. 3
- Patients on beta-adrenergic blockers can develop refractory hypotension and bradycardia that is resistant to epinephrine treatment. 1
- Elderly patients with cardiovascular disease are particularly vulnerable to severe complications. 2
- Patients with peanut and tree nut allergies have higher rates of severe reactions. 4
Complications in Untreated Patients on Beta-Blockers
- These patients require glucagon administration (1-5 mg IV in adults, 20-30 μg/kg in children up to 1 mg maximum) because epinephrine's effects are blocked at β-receptors. 1
- They can develop refractory hypotension and bradycardia that does not respond to standard epinephrine dosing. 1
Biphasic and Protracted Reactions
Risk of Delayed Deterioration
- Biphasic reactions occur in 1-7% of patients, with symptoms recurring hours after initial resolution without re-exposure to the allergen. 5, 4
- Protracted anaphylaxis can develop from ongoing inflammatory cell recruitment and release of long-acting mediators from mast cells. 1
- Patients require observation for 4-6 hours minimum, or longer based on severity of initial reaction. 1, 4
Risk Factors for Biphasic Reactions
- Severe initial presentation requiring multiple doses of epinephrine. 5, 6
- Delayed administration of initial epinephrine. 5, 6
- History of prior severe allergic reactions. 1
Critical Treatment Principles to Prevent Mortality
Immediate Epinephrine Administration
- There are no absolute contraindications to epinephrine use in anaphylaxis—the risk of death from untreated anaphylaxis outweighs all other concerns. 1, 7
- Epinephrine must be given intramuscularly in the anterolateral thigh at 0.01 mg/kg (maximum 0.5 mg in adults) as first-line therapy. 7, 5
- Delayed or absent epinephrine administration is associated with fatal reactions. 8
Volume Resuscitation
- Large-volume fluid resuscitation with normal saline must be initiated immediately in patients with orthostasis, hypotension, or incomplete response to IM epinephrine. 1
- Crystalloids initially, followed by colloid volume substitutes in severe shock. 3
Refractory Anaphylaxis Management
- Repeated doses of epinephrine, IV fluids, corticosteroids, and vasopressor agents may be needed for refractory cases. 1
- Prompt transfer to an acute-care facility and ICU is essential for treatment and monitoring. 1
Common Fatal Pitfalls in Anaphylaxis Management
Using Antihistamines Instead of Epinephrine
- Using antihistamines as primary treatment is the most common reason for not using epinephrine and places patients at significantly increased risk for life-threatening progression. 9
- Antihistamines and corticosteroids should never delay epinephrine administration and do not reduce risk of biphasic reactions. 5, 9
Inadequate Observation Period
- Patients must be observed for 4-6 hours minimum even if symptoms resolve, due to biphasic reaction risk. 1, 7
- Higher-risk patients require longer observation periods of 4-12 hours. 4
Failure to Recognize Early Signs
- Flushing, urticaria, apprehension, and mild respiratory symptoms can rapidly progress to cardiovascular collapse if not treated immediately with epinephrine. 2, 1
- In patients with history of prior severe reactions, epinephrine should be administered at the onset of even mild symptoms. 1
Mortality Statistics
- Fatal anaphylaxis occurs in approximately 1 in 75,000 patients who experience anaphylactic reactions when untreated or inadequately treated. 1
- With appropriate epinephrine treatment, fatal anaphylaxis is very rare, as low as 0.002 deaths per million person-years. 6
- Approximately 98% of anaphylactic episodes respond to 2 or fewer doses of epinephrine when administered promptly. 6