Managing Anaphylaxis
Guides anaphylaxis recognition using NIAID/FAAN diagnostic criteria, enforces epinephrine-first treatment protocol, and structures observation timing to capture biphasic reactions.
Why This Skill Exists
Anaphylaxis kills approximately 1,500 people annually in the United States, and the majority of deaths are associated with delayed epinephrine administration. Studies consistently show that patients who receive epinephrine within 5 minutes of symptom onset have near-zero mortality, while delays beyond 30 minutes dramatically increase the risk of fatal cardiovascular collapse. Despite this, epinephrine remains underused—only 50-60% of patients presenting with anaphylaxis to EDs receive epinephrine, often because clinicians fail to recognize anaphylaxis without classic urticaria or wait for "more severe" symptoms before acting.
The biphasic reaction rate of 5-20% means observation decisions directly impact patient safety. Premature discharge has resulted in deaths from recurrent anaphylaxis hours after initial resolution. This skill enforces the evidence-based standard: epinephrine is always first-line, antihistamines and steroids are adjuncts only, and observation duration is risk-stratified.
Checkpoint A: Pre-Draft Intake (Mandatory)
- What was the suspected trigger (food, medication, venom, latex, idiopathic) and time of exposure?
- What symptoms are present and which organ systems are involved (skin, respiratory, GI, cardiovascular)?
- Did the patient self-administer epinephrine (auto-injector) before arrival? If so, how many doses, at what times?
- What is the current hemodynamic status (BP, HR, SpO2, mental status)?
- Is the airway compromised (stridor, voice change, tongue/lip swelling, inability to swallow)?
- Does the patient have a history of prior anaphylaxis, asthma, or mast cell disease?
- Is the patient on beta-blockers or ACE inhibitors (which alter anaphylaxis presentation and treatment response)?
- For pediatric patients: what is the weight?
Documents to Request
- Pre-hospital records (EMS treatments given, timeline of symptom progression)
- Prior allergy/anaphylaxis documentation and testing
- Medication list (beta-blockers, ACE inhibitors, MAOIs)
- Mast cell disease or mastocytosis history
- Prior epinephrine auto-injector prescriptions and use
- Tryptase level timing documentation (if obtained)
- Vital sign trends from onset through treatment
Step 1: Confirm Anaphylaxis Diagnosis Using NIAID/FAAN Criteria
Anaphylaxis is highly likely when any ONE of these three criteria is met:
Criterion 1: Acute onset (minutes to hours) with skin/mucosal involvement (urticaria, angioedema, flushing, pruritus) PLUS at least one of:
- Respiratory compromise (dyspnea, bronchospasm, stridor, hypoxemia)
- Reduced blood pressure or end-organ dysfunction (syncope, incontinence, collapse)
Criterion 2: Two or more of the following occurring rapidly after exposure to a likely allergen:
- Skin/mucosal involvement (urticaria, angioedema, flushing)
- Respiratory compromise
- Reduced BP or associated symptoms
- Persistent GI symptoms (crampy abdominal pain, vomiting)
Criterion 3: Reduced blood pressure after exposure to a known allergen for that patient:
- Adults: SBP <90 mmHg or >30% decrease from baseline
- Pediatric: age-specific low SBP or >30% decrease
Key point: Anaphylaxis can occur WITHOUT skin findings in 10-20% of cases. Do not wait for urticaria or angioedema to diagnose anaphylaxis if respiratory or cardiovascular symptoms are present.
Step 2: Epinephrine-First Treatment Protocol
Epinephrine Dosing
| Population |
IM Dose |
Concentration |
Injection Site |
| Adults (>30 kg) |
0.3-0.5 mg |
1:1,000 (1 mg/mL) |
Anterolateral thigh (vastus lateralis) |
| Children (15-30 kg) |
0.15 mg (junior auto-injector equivalent) |
1:1,000 |
Anterolateral thigh |
| Infants (<15 kg) |
0.01 mg/kg |
1:1,000 |
Anterolateral thigh |
Repeat dosing: May repeat every 5-15 minutes if symptoms persist or recur. Most patients require 1-2 doses; refractory anaphylaxis may require 3+ doses or IV epinephrine infusion.
Refractory Anaphylaxis (no response to 2-3 IM doses)
- IV epinephrine infusion: 0.1-1 mcg/kg/min, titrate to hemodynamic response
- Volume resuscitation: 1-2 L NS rapid bolus for adults (20 mL/kg for children)—anaphylaxis causes distributive shock with up to 35% intravascular volume shift to extravascular space within minutes
- Glucagon: 1-5 mg IV over 5 minutes for patients on beta-blockers who are epinephrine-resistant (bypasses beta-receptor blockade via direct cAMP activation)
- Vasopressin: 0.01-0.04 units/min as rescue vasopressor in catecholamine-refractory shock
- Methylene blue: 1-2 mg/kg IV over 5-20 min for refractory vasoplegia (inhibits nitric oxide-mediated vasodilation)
Step 3: Adjunctive Therapies
These are NOT substitutes for epinephrine and should never delay its administration:
| Medication |
Dose |
Purpose |
Evidence Level |
| Diphenhydramine (H1) |
25-50 mg IV/IM |
Pruritus and urticaria relief |
Moderate—symptom control only |
| Ranitidine/Famotidine (H2) |
20 mg IV |
Combined H1+H2 may improve urticaria resolution |
Low |
| Methylprednisolone |
125 mg IV |
Theoretically prevents biphasic reaction |
Very low—no RCT evidence of benefit |
| Albuterol |
2.5-5 mg nebulized |
Bronchospasm not responding to epinephrine |
Moderate for isolated bronchospasm |
Steroids: Despite widespread use, no randomized controlled trial has demonstrated that corticosteroids prevent biphasic anaphylaxis. However, they remain standard practice in most guidelines pending definitive evidence. Document as "administered per current practice guidelines, evidence pending."
Step 4: Airway Management in Anaphylaxis
Angioedema-related airway compromise is the most common cause of anaphylaxis death:
- Administer epinephrine immediately—early epinephrine reduces the progression of airway edema
- Prepare for intubation early if voice change, stridor, or visible tongue/uvula swelling
- Use the most experienced airway operator available—laryngeal edema distorts anatomy
- Have surgical airway equipment at bedside (cricothyrotomy kit)
- Nebulized epinephrine (3-5 mL of 1:1,000) can temporize upper airway edema while preparing for definitive airway
- Avoid blind nasotracheal intubation in angioedema—risk of hemorrhage into already edematous tissue
Step 5: Observation and Disposition
Risk Factors for Biphasic Reaction
- Severe initial presentation (hypotension, respiratory failure)
- Delayed epinephrine administration (>30 min from onset)
- Prior history of biphasic reactions
- Unknown trigger (cannot confirm allergen avoidance)
- Wide pulse pressure on presentation
Observation Duration Guidelines
| Risk Category |
Minimum Observation |
Disposition |
| Mild (single system, rapid response to single IM epi) |
4-6 hours |
Discharge with epinephrine auto-injector |
| Moderate (multi-system, responded to 1-2 doses epi) |
8-12 hours |
Observation unit; discharge if stable |
| Severe (required IV epi, intubation, or ICU-level care) |
24+ hours |
ICU admission |
| Refractory (ongoing vasopressor or ventilator support) |
Until resolved + 24 hours |
ICU |
Step 6: Discharge Planning
- Prescribe epinephrine auto-injector (2 devices—one for use, one backup) and ensure affordability
- Provide written anaphylaxis action plan
- Refer to allergist/immunologist within 4-6 weeks for trigger identification and potential immunotherapy
- Educate on trigger avoidance (food label reading, venom avoidance, medication alternatives)
- Recommend medical alert identification (bracelet or necklace)
- Document serum tryptase if obtained (draw within 1-3 hours of onset; elevated >11.4 ng/mL supports mast cell degranulation)
- Address medication conflicts: discuss beta-blocker alternatives with PCP given increased anaphylaxis risk
Checkpoint B: Post-Draft Alignment (Mandatory)
- Was epinephrine administered as the first-line treatment (not antihistamines or steroids first)?
- Are the NIAID/FAAN diagnostic criteria explicitly documented showing which criterion was met?
- Is the observation duration appropriate for the severity of the episode?
- Was an epinephrine auto-injector prescribed at discharge with demonstration of use?
- Is allergist referral documented with specific timeframe?
Quality Audit
| # |
Criterion |
Pass/Fail |
| 1 |
Anaphylaxis diagnosed using NIAID/FAAN criteria with criterion number documented |
|
| 2 |
Epinephrine IM administered as first medication |
|
| 3 |
Time from recognition to first epinephrine documented |
|
| 4 |
Epinephrine dose appropriate for weight |
|
| 5 |
Repeat epinephrine documented with timing intervals |
|
| 6 |
IV access established and fluid resuscitation given for hypotension |
|
| 7 |
Airway assessment and management plan documented |
|
| 8 |
Observation duration meets minimum for severity category |
|
| 9 |
Biphasic reaction risk factors assessed and documented |
|
| 10 |
Epinephrine auto-injector prescribed at discharge (two devices) |
|
| 11 |
Allergist referral placed with timeframe |
|
| 12 |
Trigger identified or documented as unknown with avoidance counseling |
|
| 13 |
Beta-blocker/ACE inhibitor use assessed and addressed |
|
| 14 |
Serum tryptase drawn within window if indicated |
|
Guidelines
- Epinephrine IM in the anterolateral thigh achieves peak plasma levels faster than subcutaneous or deltoid injection—thigh is the only acceptable site
- Never substitute antihistamines for epinephrine—H1 blockers treat urticaria only; they have zero effect on bronchospasm, laryngeal edema, or cardiovascular collapse
- IV epinephrine bolus (as opposed to infusion) in a patient with a pulse is dangerous—it can cause fatal arrhythmia; use 1:10,000 concentration in 10-20 mcg increments only if infusion unavailable
- Biphasic reactions typically occur 4-12 hours after initial episode but have been reported up to 72 hours later—ensure patients understand this risk at discharge
- Beta-blocker patients may present with paradoxical bradycardia during anaphylaxis and may be epinephrine-resistant; glucagon is the critical rescue medication
- Exercise-induced anaphylaxis and food-dependent exercise-induced anaphylaxis are distinct entities requiring specific counseling about exercise timing relative to meals
- Tryptase levels are most useful when compared to a baseline level drawn weeks after the episode; a single elevated level supports but a normal level does not exclude anaphylaxis
- Mast cell disorders (mastocytosis, MCAS) should be considered in patients with recurrent idiopathic anaphylaxis—baseline tryptase >20 ng/mL warrants hematology referral
1---2name: managing-anaphylaxis3description: Guides anaphylaxis recognition and epinephrine-first treatment protocol with observation timing. Use when managing allergic reactions, treating anaphylaxis, or planning post-anaphylaxis observation.4---5
6# Managing Anaphylaxis
7
8Guides anaphylaxis recognition using NIAID/FAAN diagnostic criteria, enforces epinephrine-first treatment protocol, and structures observation timing to capture biphasic reactions.
9
10## Why This Skill Exists
11
12Anaphylaxis kills approximately 1,500 people annually in the United States, and the majority of deaths are associated with delayed epinephrine administration. Studies consistently show that patients who receive epinephrine within 5 minutes of symptom onset have near-zero mortality, while delays beyond 30 minutes dramatically increase the risk of fatal cardiovascular collapse. Despite this, epinephrine remains underused—only 50-60% of patients presenting with anaphylaxis to EDs receive epinephrine, often because clinicians fail to recognize anaphylaxis without classic urticaria or wait for "more severe" symptoms before acting.
13
14The biphasic reaction rate of 5-20% means observation decisions directly impact patient safety. Premature discharge has resulted in deaths from recurrent anaphylaxis hours after initial resolution. This skill enforces the evidence-based standard: epinephrine is always first-line, antihistamines and steroids are adjuncts only, and observation duration is risk-stratified.
15
16---
17
18## Checkpoint A: Pre-Draft Intake (Mandatory)
19
201. What was the suspected trigger (food, medication, venom, latex, idiopathic) and time of exposure?
212. What symptoms are present and which organ systems are involved (skin, respiratory, GI, cardiovascular)?
223. Did the patient self-administer epinephrine (auto-injector) before arrival? If so, how many doses, at what times?
234. What is the current hemodynamic status (BP, HR, SpO2, mental status)?
245. Is the airway compromised (stridor, voice change, tongue/lip swelling, inability to swallow)?
256. Does the patient have a history of prior anaphylaxis, asthma, or mast cell disease?
267. Is the patient on beta-blockers or ACE inhibitors (which alter anaphylaxis presentation and treatment response)?
278. For pediatric patients: what is the weight?
28
29### Documents to Request
30
31- Pre-hospital records (EMS treatments given, timeline of symptom progression)
32- Prior allergy/anaphylaxis documentation and testing
33- Medication list (beta-blockers, ACE inhibitors, MAOIs)
34- Mast cell disease or mastocytosis history
35- Prior epinephrine auto-injector prescriptions and use
36- Tryptase level timing documentation (if obtained)
37- Vital sign trends from onset through treatment
38
39---
40
41## Step 1: Confirm Anaphylaxis Diagnosis Using NIAID/FAAN Criteria
42
43Anaphylaxis is **highly likely** when any ONE of these three criteria is met:
44
45**Criterion 1**: Acute onset (minutes to hours) with skin/mucosal involvement (urticaria, angioedema, flushing, pruritus) PLUS at least one of:
46- Respiratory compromise (dyspnea, bronchospasm, stridor, hypoxemia)
47- Reduced blood pressure or end-organ dysfunction (syncope, incontinence, collapse)
48
49**Criterion 2**: Two or more of the following occurring rapidly after exposure to a likely allergen:
50- Skin/mucosal involvement (urticaria, angioedema, flushing)
51- Respiratory compromise
52- Reduced BP or associated symptoms
53- Persistent GI symptoms (crampy abdominal pain, vomiting)
54
55**Criterion 3**: Reduced blood pressure after exposure to a known allergen for that patient:
56- Adults: SBP <90 mmHg or >30% decrease from baseline
57- Pediatric: age-specific low SBP or >30% decrease
58
59**Key point**: Anaphylaxis can occur WITHOUT skin findings in 10-20% of cases. Do not wait for urticaria or angioedema to diagnose anaphylaxis if respiratory or cardiovascular symptoms are present.
60
61---
62
63## Step 2: Epinephrine-First Treatment Protocol
64
65### Epinephrine Dosing
66
67| Population | IM Dose | Concentration | Injection Site |
68|---|---|---|---|
69| Adults (>30 kg) | 0.3-0.5 mg | 1:1,000 (1 mg/mL) | Anterolateral thigh (vastus lateralis) |
70| Children (15-30 kg) | 0.15 mg (junior auto-injector equivalent) | 1:1,000 | Anterolateral thigh |
71| Infants (<15 kg) | 0.01 mg/kg | 1:1,000 | Anterolateral thigh |
72
73**Repeat dosing**: May repeat every 5-15 minutes if symptoms persist or recur. Most patients require 1-2 doses; refractory anaphylaxis may require 3+ doses or IV epinephrine infusion.
74
75### Refractory Anaphylaxis (no response to 2-3 IM doses)
76
771. **IV epinephrine infusion**: 0.1-1 mcg/kg/min, titrate to hemodynamic response
782. **Volume resuscitation**: 1-2 L NS rapid bolus for adults (20 mL/kg for children)—anaphylaxis causes distributive shock with up to 35% intravascular volume shift to extravascular space within minutes
793. **Glucagon**: 1-5 mg IV over 5 minutes for patients on beta-blockers who are epinephrine-resistant (bypasses beta-receptor blockade via direct cAMP activation)
804. **Vasopressin**: 0.01-0.04 units/min as rescue vasopressor in catecholamine-refractory shock
815. **Methylene blue**: 1-2 mg/kg IV over 5-20 min for refractory vasoplegia (inhibits nitric oxide-mediated vasodilation)
82
83---
84
85## Step 3: Adjunctive Therapies
86
87These are NOT substitutes for epinephrine and should never delay its administration:
88
89| Medication | Dose | Purpose | Evidence Level |
90|---|---|---|---|
91| Diphenhydramine (H1) | 25-50 mg IV/IM | Pruritus and urticaria relief | Moderate—symptom control only |
92| Ranitidine/Famotidine (H2) | 20 mg IV | Combined H1+H2 may improve urticaria resolution | Low |
93| Methylprednisolone | 125 mg IV | Theoretically prevents biphasic reaction | Very low—no RCT evidence of benefit |
94| Albuterol | 2.5-5 mg nebulized | Bronchospasm not responding to epinephrine | Moderate for isolated bronchospasm |
95
96**Steroids**: Despite widespread use, no randomized controlled trial has demonstrated that corticosteroids prevent biphasic anaphylaxis. However, they remain standard practice in most guidelines pending definitive evidence. Document as "administered per current practice guidelines, evidence pending."
97
98---
99
100## Step 4: Airway Management in Anaphylaxis
101
102Angioedema-related airway compromise is the most common cause of anaphylaxis death:
103
1041. Administer epinephrine immediately—early epinephrine reduces the progression of airway edema
1052. Prepare for intubation early if voice change, stridor, or visible tongue/uvula swelling
1063. Use the most experienced airway operator available—laryngeal edema distorts anatomy
1074. Have surgical airway equipment at bedside (cricothyrotomy kit)
1085. Nebulized epinephrine (3-5 mL of 1:1,000) can temporize upper airway edema while preparing for definitive airway
1096. Avoid blind nasotracheal intubation in angioedema—risk of hemorrhage into already edematous tissue
110
111---
112
113## Step 5: Observation and Disposition
114
115### Risk Factors for Biphasic Reaction
116
117- Severe initial presentation (hypotension, respiratory failure)
118- Delayed epinephrine administration (>30 min from onset)
119- Prior history of biphasic reactions
120- Unknown trigger (cannot confirm allergen avoidance)
121- Wide pulse pressure on presentation
122
123### Observation Duration Guidelines
124
125| Risk Category | Minimum Observation | Disposition |
126|---|---|---|
127| Mild (single system, rapid response to single IM epi) | 4-6 hours | Discharge with epinephrine auto-injector |
128| Moderate (multi-system, responded to 1-2 doses epi) | 8-12 hours | Observation unit; discharge if stable |
129| Severe (required IV epi, intubation, or ICU-level care) | 24+ hours | ICU admission |
130| Refractory (ongoing vasopressor or ventilator support) | Until resolved + 24 hours | ICU |
131
132---
133
134## Step 6: Discharge Planning
135
1361. Prescribe epinephrine auto-injector (2 devices—one for use, one backup) and ensure affordability
1372. Provide written anaphylaxis action plan
1383. Refer to allergist/immunologist within 4-6 weeks for trigger identification and potential immunotherapy
1394. Educate on trigger avoidance (food label reading, venom avoidance, medication alternatives)
1405. Recommend medical alert identification (bracelet or necklace)
1416. Document serum tryptase if obtained (draw within 1-3 hours of onset; elevated >11.4 ng/mL supports mast cell degranulation)
1427. Address medication conflicts: discuss beta-blocker alternatives with PCP given increased anaphylaxis risk
143
144---
145
146## Checkpoint B: Post-Draft Alignment (Mandatory)
147
1481. Was epinephrine administered as the first-line treatment (not antihistamines or steroids first)?
1492. Are the NIAID/FAAN diagnostic criteria explicitly documented showing which criterion was met?
1503. Is the observation duration appropriate for the severity of the episode?
1514. Was an epinephrine auto-injector prescribed at discharge with demonstration of use?
1525. Is allergist referral documented with specific timeframe?
153
154---
155
156## Quality Audit
157
158| # | Criterion | Pass/Fail |
159|---|---|---|
160| 1 | Anaphylaxis diagnosed using NIAID/FAAN criteria with criterion number documented | |
161| 2 | Epinephrine IM administered as first medication | |
162| 3 | Time from recognition to first epinephrine documented | |
163| 4 | Epinephrine dose appropriate for weight | |
164| 5 | Repeat epinephrine documented with timing intervals | |
165| 6 | IV access established and fluid resuscitation given for hypotension | |
166| 7 | Airway assessment and management plan documented | |
167| 8 | Observation duration meets minimum for severity category | |
168| 9 | Biphasic reaction risk factors assessed and documented | |
169| 10 | Epinephrine auto-injector prescribed at discharge (two devices) | |
170| 11 | Allergist referral placed with timeframe | |
171| 12 | Trigger identified or documented as unknown with avoidance counseling | |
172| 13 | Beta-blocker/ACE inhibitor use assessed and addressed | |
173| 14 | Serum tryptase drawn within window if indicated | |
174
175---
176
177## Guidelines
178
1791. **Epinephrine IM in the anterolateral thigh** achieves peak plasma levels faster than subcutaneous or deltoid injection—thigh is the only acceptable site
1802. **Never substitute antihistamines for epinephrine**—H1 blockers treat urticaria only; they have zero effect on bronchospasm, laryngeal edema, or cardiovascular collapse
1813. **IV epinephrine bolus** (as opposed to infusion) in a patient with a pulse is dangerous—it can cause fatal arrhythmia; use 1:10,000 concentration in 10-20 mcg increments only if infusion unavailable
1824. **Biphasic reactions** typically occur 4-12 hours after initial episode but have been reported up to 72 hours later—ensure patients understand this risk at discharge
1835. **Beta-blocker patients** may present with paradoxical bradycardia during anaphylaxis and may be epinephrine-resistant; glucagon is the critical rescue medication
1846. **Exercise-induced anaphylaxis** and food-dependent exercise-induced anaphylaxis are distinct entities requiring specific counseling about exercise timing relative to meals
1857. **Tryptase levels** are most useful when compared to a baseline level drawn weeks after the episode; a single elevated level supports but a normal level does not exclude anaphylaxis
1868. **Mast cell disorders** (mastocytosis, MCAS) should be considered in patients with recurrent idiopathic anaphylaxis—baseline tryptase >20 ng/mL warrants hematology referral