Anaphylaxis & Anaphylactic Shock · ICU Topics

Overview & definition

Anaphylaxis — the severe, the life-threatening, the systemic hypersensitivity reaction. The rapid onset (minutes to hours). The multiple systems: the skin/mucosal, the respiratory, the cardiovascular, the GI. The leading cause of death: the airway obstruction (the laryngeal oedema) and the circulatory collapse (the vasodilation + the myocardial depression). The IM adrenaline 0.5 mg is the first-line treatment.[1][1]

Cinematic ICU scene of a patient with a rash on the arm, oxygen mask, cardiac monitor tachycardia and hypotension, adrenaline auto-injector and IV adrenaline at the bedside, clinical-blue lighting — FigureThe anaphylaxis — the IM adrenaline 0.5 mg FIRST. The 100% O2. The IV fluid. The observation 6-24 h (the biphasic). The tryptase for the diagnosis.

[1]

The clinical — the WAO criteria

The WAO 2020 criteria for the diagnosis of the anaphylaxis (any ONE of the three):[1]

The acute onset (minutes-hours) of the skin/mucosal (the urticaria, the angioedema, the flushed) + at least ONE of: the respiratory (the wheeze, the stridor, the dyspnoea), the cardiovascular (the hypotension, the collapse), the end-organ (the GI, the dizziness).[1]
The TWO OR MORE of the following after the exposure to a likely allergen: the skin/mucosal, the respiratory, the cardiovascular, the GI (the vomiting, the diarrhoea, the cramping).[1]
The hypotension after the exposure to a known allergen (the adult SBP below 90 or the 30% drop from the baseline).[1]

The NIAID/FAAN diagnostic criteria — the foundational 2006 consensus

The NIAID/FAAN (the National Institute of Allergy and Infectious Diseases / the Food Allergy and Anaphylaxis Network) second symposium 2006 criteria — the diagnostic framework later adopted and refined by the WAO. The anaphylaxis is highly likely when ANY ONE of the three criteria is fulfilled:[3][4]

Criterion 1. The acute onset (the minutes to the several hours) of an illness with the involvement of the skin and/or the mucosal tissue (the generalised urticaria, the pruritus or the flush, the swollen lips-tongue-uvula) AND at least ONE of the following:

The respiratory compromise (the dyspnoea, the wheeze, the stridor, the hypoxaemia, the reduced PEF).
The reduced BP or the associated symptoms of the end-organ dysfunction (the collapse, the syncope, the incontinence).
The severe GI symptoms (the crampy abdominal pain, the repetitive vomiting), especially after a food allergen. [1]

Criterion 2. The TWO OR MORE of the following that occur rapidly AFTER the exposure to a LIKELY allergen for that patient (a food, a drug, an insect sting, a contrast agent, a latex, an exercise):

The skin/mucosal (the urticaria, the flush, the angioedema, the pruritus).
The respiratory compromise (the wheeze, the stridor, the hypoxaemia).
The reduced BP or the associated symptoms (the collapse, the syncope, the dizziness).
The persistent GI symptoms (the vomiting, the cramping, the diarrhoea). [1]

Criterion 3. The reduced BP after the exposure to a KNOWN allergen for that patient:

The adults — SBP below 90 mmHg (or the 30 per cent drop from the baseline).
The infants and the children — SBP below 70 mmHg (1 month-1 yr), below 70 + (2 × age) (1-10 yr), below 90 (11-17 yr).[3]

The NIAID/FAAN criteria — the sensitivity around 95 per cent, the specificity the high. The limitation: the 5 per cent missed (the cardiovascular collapse alone WITHOUT the skin; the perioperative — the skin hidden under the drapes; the food anaphylaxis with the normal tryptase).[4]

The NIAID/FAAN 2006 vs the WAO 2020 — the diagnostic criteria

Feature	The NIAID/FAAN 2006	The WAO 2020
Criterion 1	Skin/mucosa + (respiratory OR reduced BP/end-organ OR severe GI)	Skin/mucosa + (respiratory OR cardiovascular OR end-organ/GI)
Criterion 2	2+ systems after a LIKELY allergen	2+ systems after a LIKELY allergen
Criterion 3	Reduced BP after a KNOWN allergen	Reduced BP after a KNOWN allergen
The GI	Criterion 1 (severe) + Criterion 2	A standalone system
The paediatric BP	Explicit age-based thresholds	Adult thresholds adapted
The clinical use	The foundational criteria — still widely cited	The current international standard

[1]

The severity grading — the Brown 3-grade system

The Brown SGA 2004 three-grade severity grading — the practical bedside and the research tool.[6]

Grade 1 (mild): the skin and the subcutaneous tissue only (the urticaria, the flush, the angioedema) — WITHOUT the respiratory, the cardiovascular, or the severe GI.
Grade 2 (moderate): the grade 1 features PLUS the mild-to-moderate respiratory (the wheeze, the dyspnoea), the cardiovascular (the tachycardia, the mild hypotension), OR the GI.
Grade 3 (severe): the hypoxaemia (the cyanosis, the SpO2 below 92 per cent), the hypotension (the collapse, the syncope), and/or the neurological compromise (the confusion, the collapse, the incontinence). The highest risk of the biphasic and the death.[6]

The grade 3 reaction → the longer the observation (the 12-24 h); the grade 1 may be observed the 6 h if the rapid response. The grade predicts the biphasic and the adrenaline requirement. [1]

The pathophysiology

The IgE-mediated (most) — the allergen binds the IgE on the mast cells and the basophils → the degranulation → the release of the histamine, the tryptase, the leukotrienes, the prostaglandins, the platelet-activating factor. The non-IgE (the anaphylactoid) — the direct mast cell activation (the contrast media, the opioids, the vancomycin, the NSAIDs).[1][1]

The mediators → the vasodilation (the hypotension), the capillary leak (the oedema), the bronchoconstriction (the wheeze), the increased mucus secretion, the increased gut motility, the myocardial depression (the histamine — the direct the negative the inotropy).[1]

The triggers — the allergens and the agents

The anaphylaxis triggers — the IgE-mediated (the true allergy — the drugs, the foods, the venoms, the latex) and the non-IgE (the direct mast cell activation — the radiocontrast, the opioids, the vancomycin, the NSAIDs, the exercise, the cold). The idiopathic — the 20 per cent (the no trigger found despite the work-up).[5][14]

The common anaphylaxis triggers — the community vs the perioperative

Trigger	The mechanism	The community (the ED)	The perioperative (the theatre/ICU)	The notes
The drugs — beta-lactams (penicillins, cephalosporins)	IgE	The #1 drug trigger	15-20 per cent of perioperative	The penicillin-cephalosporin cross-reactivity the low (1-2 per cent with the modern side chains)
The drugs — NMBAs (rocuronium, suxamethonium, vecuronium)	IgE to the quaternary ammonium	Rare	The #1 perioperative trigger (60-70 per cent)	The cross-reactivity between the NMBAs the 60-70 per cent. The sugammadex reverses the NMBA — NOT the anaphylaxis
The drugs — NSAIDs (aspirin, ibuprofen, diclofenac)	Non-IgE (the COX-1 inhibition → the leukotriene)	Common	—	The class effect within the strong COX-1 inhibitors; the COX-2 selective (the celecoxib) usually tolerated
The drugs — radiocontrast media (the iodinated)	Non-IgE (the direct mast cell activation)	Common (the radiology)	—	The "iodine allergy" is the myth — the reaction is to the contrast molecule, NOT the iodine. The premedication (the steroid + the antihistamine) for the prior reactors
The drugs — vancomycin	Non-IgE (the direct degranulation — the Red Man Syndrome)	—	Common	The rate-dependent — slow the infusion (the NOT the anaphylaxis if the infusion slowed resolves it)
The foods (the peanut, the tree nut, the shellfish, the milk, the egg, the sesame)	IgE	The #1 cause in the children	—	The peanut and the tree nut — the most likely to be the severe and the fatal
The insect stings (the bee, the wasp, the hornet, the fire ant)	IgE to the venom	Common (the adults)	—	The beekeeper and the prior large local reaction — the higher risk
The latex	IgE (the Hevea proteins)	Decreasing (the healthcare workers, the spina bifida)	The decreasing — the latex-free theatre	The type I (anaphylaxis); NOT the type IV (the contact dermatitis)
The chlorhexidine	IgE	Under-recognised	5-8 per cent perioperative (the skin prep, the central line, the urinary catheter lubricant)	The ubiquitous — the test if the unexplained perioperative reaction
The Patent Blue / the dyes	IgE	Rare	2-4 per cent (the lymph node mapping — the breast, the melanoma)	The falsely low SpO2 for 1-2 min
The exercise / the cold / the co-factors	Non-IgE / the cofactor-augmented	The exercise-induced (the food + the exercise), the cold-induced	—	The cofactors (the NSAID, the alcohol, the exercise, the menstruation, the intercurrent infection) lower the threshold
The idiopathic	Unknown	20 per cent	5-10 per cent	The work-up (the tryptase, the skin testing, the component testing) — the referral to the allergy clinic

[1]

The differential diagnosis — the mimics of the anaphylaxis

The anaphylaxis — the commonly over-diagnosed AND the under-diagnosed. The mimics — the vasovagal, the anxiety, the asthma, the carcinoid, the mastocytosis, the scombroid, the hereditary angioedema.[5][9]

The anaphylaxis vs the mimics — the distinguishing features

Condition	The key distinguishing features	The trap
The vasovagal syncope	The pallor (NOT the flush/urticaria), the bradycardia (NOT the tachycardia), the nausea, the rapid resolution on the supine, the precipitant (the pain, the sight of blood). The NO urticaria, the NO bronchospasm, the normal tryptase	The over-diagnosis of the vasovagal in the young — the bradycardia can occur in the anaphylaxis too (the Bezold-Jarisch reflex from the empty ventricle)
The anxiety / the panic attack	The dyspnoea WITHOUT the wheeze/hypoxaemia, the tingling fingers (the hyperventilation → the respiratory alkalosis), the NO urticaria, the NO hypotension, the normal tryptase	The genuine anaphylaxis dismissed as the panic — the fatal error
The asthma	The isolated bronchospasm — the NO urticaria, the NO hypotension, the NO GI, the history of the asthma	The anaphylaxis may present as the isolated bronchospasm. The severe asthma after a food/drug → the anaphylaxis until proven otherwise
The carcinoid syndrome	The flush (NOT the urticaria), the diarrhoea, the right-heart valvular disease, the wheeze — the elevated 24-h urinary 5-HIAA, the NOT the tryptase	The flush in the carcinoid is the prolonged and the patchy — the anaphylaxis flush is the acute and the generalised
The systemic mastocytosis	The recurrent unexplained anaphylaxis, the urticaria pigmentosa, the Darier sign, the baseline tryptase elevated (above 20 mcg/L), the KIT D816V mutation	The trigger may be trivial (the wasp sting, the temperature change). The baseline tryptase above 20 → the mastocytosis
The scombroid poisoning	The histamine from the spoiled fish (the tuna, the mahi-mahi) — the flush, the urticaria, the diarrhoea, the wheeze, the minutes after the ingestion. The NOT IgE — the histamine intoxication. The response to the antihistamine (the adrenaline NOT the first-line unless the severe)	The multiple diners affected — the clue
The hereditary angioedema (the C1-inhibitor deficiency)	The angioedema WITHOUT the urticaria (the bradykinin — NOT the histamine), the family history, the low C4, the NOT the bronchospasm, the NOT the hypotension. The NOT the response to the adrenaline — the C1-inhibitor concentrate or the icatibant	The laryngeal angioedema → the intubation. The bradykinin-mediated
The shock from the other cause (the septic, the cardiogenic, the hypovolaemic)	The NO urticaria, the NO bronchospasm, the appropriate history	The anaphylaxis can be the isolated shock (the Criterion 3) — the skin may be absent

[1]

The practical rule: the acute unexplained bronchospasm + the hypotension within the minutes of a drug/food/sting → the anaphylaxis until proven otherwise.[9]

The management — the ABCDE

Vertical timeline with three numbered steps: IM adrenaline (red syringe), 100% O2 + IV fluid (blue mask), positioning (green legs-raised), on a white clinical-blue background — FigureThe three priorities: the IM adrenaline 0.5 mg (the FIRST), the 100% O2 + the IV fluid, the positioning (the supine + the legs raised — the cardiovascular; the sitting up — the respiratory distress).

[1]

Escalation pathway infographic for anaphylaxis: IM adrenaline, oxygen and fluids, IV adrenaline infusion, glucagon if beta-blocked, tryptase sampling timeline — FigureRefractory pathway: IV adrenaline infusion, glucagon if beta-blocked, consider vasopressin/methylene blue; sample tryptase on a timed schedule and observe for biphasic reactions.

1. The IM adrenaline 0.5 mg (the FIRST-LINE).[1][2]

The 0.5 mg (0.5 mL of the 1:1000) IM in the anterolateral thigh. The repeat every 5 minutes if no response (up to 2 doses before the IV).[1]
The alpha-1 (the vasoconstriction — the BP, the oedema reduction), the beta-1 (the increased the inotropy and the chronotropy), the beta-2 (the bronchodilation).[1]

2. The airway + the breathing.[1][1]

The 100% O2 (the high-flow, the non-rebreather). The early intubation if the airway oedema (the laryngeal — the rapidly progressive; the intubate before the impossible).[1]
The nebulised adrenaline (5 mg) for the upper airway oedema (the laryngeal).[1]

3. The circulation.[1][1]

The IV fluid (the 20 mL/kg crystalloid rapidly — the vasodilation + the capillary leak → the relative the hypovolaemia).[2]
The vasopressor (the noradrenaline) if the refractory. The IV adrenaline infusion (the 0.05-0.1 mcg/kg/min — for the refractory to the IM).[1]

4. The adjuncts.[1][1]

The antihistamine (the chlorphenamine 10 mg IV — the H1; the H2 — the famotidine; the secondary — NOT the first-line).[1]
The corticosteroid (the hydrocortisone 200 mg IV — the prevent the biphasic; the delayed onset 4-6 h).[1]
The bronchodilator (the salbutamol nebulised — the bronchospasm refractory to the adrenaline).[1]
The glucagon (1-2 mg IV) for the beta-blocked patient (the adrenaline ineffective; the glucagon bypasses the receptor).[1]

5. The positioning.[1]

The supine + the legs raised (the cardiovascular collapse — the venous return).[1]
The sitting up (the respiratory distress — the easier the breathing).[1]
The left lateral (the pregnant — the vena cava).[1]

The diagnosis — the tryptase

The serum tryptase — the mast cell degranulation marker. The peak 1-2 h; the return to the baseline 4-6 h. The sampling: the acute (as soon as possible), the 1-2 h, and the baseline (at least 24 h later). The rise above 1.2 x the baseline + 2 mcg/L → the anaphylaxis (the sensitivity not perfect — the food anaphylaxis may have a normal tryptase).[1]

The biphasic reaction

The biphasic — the recurrence of the symptoms 4-24 h after the initial resolution (without the re-exposure). The incidence 5-20 per cent. The risk factors: the delayed the adrenaline, the severe the initial reaction, the multiple the doses the adrenaline, the biphasic the history. The observation 6-24 h (the severe → the longer). The corticosteroid + the antihistamine (the prevention — the evidence weak).[1]

Refractory anaphylaxis — the escalation beyond the standard therapy

The refractory anaphylaxis — the no improvement despite the 2 doses of the IM adrenaline + the IV fluids + the IV adrenaline infusion. The incidence the 3-5 per cent. The pathophysiology: the profound NO-mediated vasoplegia (the refractory to the alpha-agonists), the extremely high circulating mediators (the histamine, the PAF, the NO), the beta-blocker therapy blocking the adrenaline's beta-effects.[7][11]

The refractory anaphylaxis — the rescue agents

Agent	The dose	The mechanism	The indication
The IV adrenaline infusion	0.05-0.5 mcg/kg/min, the titrate to the MAP above 65	The alpha-1 + the beta-1 + the beta-2	The first escalation after the 2 doses IM + the fluids
The IV noradrenaline	0.05-0.5 mcg/kg/min	The alpha-1 predominant (the vasoconstriction)	The vasoplegia refractory to the adrenaline
The vasopressin	0.01-0.04 U/min	The V1 receptor — the independent pathway (NOT the alpha)	The second vasopressor — the catecholamine-resistant vasoplegia
The methylene blue	1-2 mg/kg IV over 20 min (the repeat in 30-60 min if the partial response)	The inhibits the soluble guanylate cyclase → the blocks the NO-cGMP-mediated vasoplegia	The NO-mediated refractory vasoplegia (the case reports and the series). The caution: the SSRI interaction (the serotonin syndrome), the MAOI. The NOT in the G6PD deficiency (the haemolysis). The interferes with the pulse oximetry (the falsely low SpO2)[11]
The glucagon	1-5 mg IV over 5 min, then the 5-15 mcg/min infusion	The activates the adenylate cyclase via the glucagon receptor (the bypasses the beta-receptor) → the cAMP → the positive inotropy + the chronotropy	The beta-blocked patient (the adrenaline ineffective). The emesis is the common (the have the antiemetic and the airway protected)[7]
The atropine	0.5-1 mg IV	The muscarinic antagonist	The severe bradycardia from the Bezold-Jarisch reflex (the profound vasodilation + the empty ventricle → the vagal reflex)
The VA-ECMO	—	The mechanical circulatory support	The last resort — the refractory cardiovascular collapse or the cardiac arrest (the bridge to the recovery)

The refractory anaphylaxis — the escalation protocol

The ASSESS at 5 minutes after the second IM adrenaline + the 20 mL/kg fluid — the BP, the wheeze, the skin, the mental state. The refractory = the persistent hypotension/wheeze.
The IV adrenaline infusion — the 1 mg in the 100 mL 0.9 per cent saline (the 10 mcg/mL), the start the 0.05 mcg/kg/min, the titrate the every 2-5 min to the MAP above 65. The NOT the IV bolus (the risk of the VF, the intracranial haemorrhage) unless the cardiac arrest.
The second vasopressor (the noradrenaline) if the adrenaline infusion inadequate — the central access when the safe.
The methylene blue 1-2 mg/kg IV over 20 min — the NO-mediated vasoplegia. The monitor the SpO2 (the falsely low — the co-oximetry if the available).
The glucagon 1-5 mg IV over 5 min then the infusion — the beta-blocked (the check the medication history the early).
The vasopressin 0.01-0.04 U/min — the catecholamine-resistant.
The VA-ECMO — the refractory collapse. The call the early.

[1]

The tryptase — the mast cell degranulation marker (the expanded)

The serum tryptase — the enzyme released from the mast cell granules (NOT from the basophils — the basophils contain the little). The peak at the 1-2 hours; the half-life the 2 hours; the return to the baseline by the 6-8 hours. The diagnostic sampling — the THREE samples:[12][13]

The acute sample — the ASAP (the within 30 min, the ideally before the adrenaline — but the NOT the delay the treatment).
The 1-2 hour sample — the peak.
The baseline sample — the at least 24 hours after the resolution (the serial tryptase — the most informative).

The diagnostic threshold: the peak tryptase above (1.2 × the baseline + 2 mcg/L) → the anaphylaxis (the 92 per cent specificity). The absolute peak above 11.4 mcg/L → the supportive (the not the diagnostic alone).[13]

The limitations:

The sensitivity the 60-90 per cent — the food anaphylaxis may have the NORMAL tryptase (the mast cell burden lower; the food triggers the less tryptase than the drug/venom). The negative tryptase does NOT exclude the anaphylaxis.[13]
The elevated baseline (above 20 mcg/L) → the systemic mastocytosis — the refer for the KIT D816V mutation and the bone marrow biopsy.
The tryptase also elevated in the trauma, the cardiac arrest, the AMI — the NOT the specific to the anaphylaxis.

The observation period — the biphasic risk stratification

The observation — the 6-12 hours for the low-risk; the 12-24 hours for the high-risk. The decision — the balanced (the biphasic risk vs the bed-occupancy).[7][14]

The biphasic reaction — the risk stratification for the observation

The low-risk (the observe 6 h, the may discharge with the action plan)	The high-risk (the observe 12-24 h, the admit to the HDU/ICU)
The grade 1 (the skin only)	The grade 3 (the hypoxia/hypotension/neuro)
The single dose of the adrenaline with the rapid response	The 2+ doses of the adrenaline
The beta-agonist NOT required	The refractory (the IV adrenaline infusion)
The no prior biphasic history	The prior biphasic history
The no beta-blocker	The beta-blocker therapy
The no comorbidity (the asthma, the cardiovascular)	The asthma, the cardiovascular disease, the mastocytosis
The reaction the over 1 hour ago, the stable	The slow onset, the prolonged reaction
The access to the auto-injector + the carer	The social isolation, the no access to the care

[1]

The corticosteroid + the antihistamine — the prevention of the biphasic — the evidence the weak (the largest cohort study the negative). The still the standard (the hydrocortisone 200 mg IV + the chlorphenamine 10 mg IV). The NOT a substitute for the observation.[7]

The perioperative anaphylaxis — the unique ICU/theatre challenge

The perioperative anaphylaxis — the unique: (a) the patient anaesthetised (the NO skin signs visible under the drapes — the hypotension + the bronchospasm may be the ONLY signs), (b) the multiple drugs simultaneously (the trigger the difficult), (c) the patient intubated (the bronchospasm = the high airway pressures + the hypoxia), (d) the vasoplegia attributed to the anaesthetic agents (the delayed recognition).[8][9]

The triad of the perioperative anaphylaxis: the sudden hypotension + the high airway pressures (the bronchospasm) + the tachycardia (or the paradoxical bradycardia from the Bezold-Jarisch reflex). The skin signs — the often absent (the under the drapes; the check the exposed skin, the ask the surgeon). The #1 trigger — the NMBAs (the 60-70 per cent; the rocuronium the most common).[8]

The perioperative anaphylaxis — the theatre protocol

The SUSPECT — the sudden hypotension + the high airway pressures + the tachycardia/bradycardia within the minutes of a drug (the induction, the antibiotic, the skin prep, the dye). The ask the surgeon to check the skin.
The STOP all the potential triggers — the most recently administered agent (the NMBA, the antibiotic, the contrast, the dye, the chlorhexidine). The NOT give more.
The CALL FOR HELP — the senior anaesthetist, the ICU team, the stop the surgery if possible.
The POSITION — the supine with the legs elevated (the Trendelenburg).
The IM adrenaline 0.5-1 mg (the 1:1000) — the IM even in the anaesthetised (the anterolateral thigh).
The IV fluids — the 20-50 mL/kg crystalloid rapidly (the massive capillary leak; the consider the colloid cautiously — the colloid itself can be the trigger).
The IV adrenaline infusion if the refractory. The vasopressin/methylene blue/glucagon as the above.
The SAMPLES — the tryptase the acute, the 1-2 h, the 24 h. The send the saved serum (the drug-specific IgE later). The refer to the allergy clinic at the 4-6 weeks for the skin testing (the NOT the earlier — the false negative in the first 4 weeks).[8]

Prognosis

The mortality the low (1-3 per cent) if the prompt the IM adrenaline. The death from the airway (the laryngeal oedema) or the circulatory collapse (the myocardial depression). The delayed the adrenaline → the worse the outcome.[1][2][1]

SAQ — Refractory anaphylaxis and the beta-blocked patient

10 minutes · 10 marks

A 60-year-old man on metoprolol for ischaemic heart disease develops anaphylaxis after a CT contrast injection. He has widespread urticaria, stridor, and hypotension (BP 70/40) despite two doses of IM adrenaline (0.5 mg) and 1 L of crystalloid. The registrar asks what to do next.

[1]

SAQ — Perioperative anaphylaxis and neuromuscular blocking agents

10 minutes · 10 marks

A 45-year-old woman undergoing induction for elective caesarean section receives thiopentone, suxamethonium, and prophylactic co-amoxiclav. Within 2 minutes she develops profound hypotension (BP 50/30), bronchospasm with peak airway pressures rising to 50 cmH2O, and widespread flushing. Outline the immediate management and the subsequent investigation.

[1]

Red flags

Clinical pearls

Clinical pearl

The IM adrenaline 0.5 mg (the 1:1000) in the anterolateral thigh — the FIRST, the EARLY, the ENOUGH. The #1 cause of the anaphylaxis death is the DELAYED adrenaline. The 0.5 mg (the 500 mcg) — the 0.5 mL of the 1:1000. The IM (the NOT the subcutaneous — the slower absorption; the NOT the IV — the risk of the VF). The anterolateral thigh (the vastus lateralis — the superior absorption; the NOT the gluteal — the slower and the less reliable). The repeat every 5 minutes (the up to the 2 doses before the IV). The NOT the wait for the skin rash; the NOT the wait for the IV access; the NOT the use the antihistamine as the substitute. The dose is the generous — the anaphylaxis does NOT respond to the subtherapeutic adrenaline.[3][9]
The POSITIONING saves the lives — the supine + the legs elevated. The anaphylaxis → the massive vasodilation + the capillary leak → the venous pooling in the legs → the empty IVC → the reduced preload → the cardiac arrest. The documented deaths from the patient sitting up on the chair or the toilet during the anaphylaxis (the empty-IVC cardiac arrest). The lie flat with the legs raised. The exception: the severe respiratory distress (the may need the upright with the caution); the vomiting (the recovery position); the pregnant (the left lateral tilt).[9]
The antihistamine + the corticosteroid are the ADJUNCTS — the NOT the first-line. The antihistamine (the H1 — the chlorphenamine; the H2 — the famotidine) treats the ONLY the skin (the urticaria, the pruritus) — the NOT the bronchospasm or the hypotension. The corticosteroid (the hydrocortisone 200 mg IV) takes the 4-6 hours to work — the too slow for the acute; the may reduce the biphasic (the evidence weak). The adrenaline is the ONLY the life-saving drug. The NO antihistamine-as-substitute.[9][10]
The tryptase — the THREE samples; the peak the 1-2 hours; the negative does NOT exclude. The acute (the ASAP), the 1-2 h (the peak), the 24 h (the baseline). The threshold: the peak above (1.2 × the baseline + 2 mcg/L). The limitation: the food anaphylaxis may have the NORMAL tryptase (the sensitivity the 60-90 per cent). The NOT the delay the treatment for the sample; the draw it the around the adrenaline. The elevated baseline (the above 20 mcg/L) → the mastocytosis — the refer.[12][13]
The biphasic — the 5-20 per cent; the observation the 6-12 h (the low-risk) the 12-24 h (the high-risk). The recurrence the 4-24 hours after the resolution WITHOUT the re-exposure. The risk factors: the delayed adrenaline, the severe initial (the grade 3), the 2+ doses of the adrenaline, the prior biphasic, the beta-blocker, the asthma. The NOT the early discharge in the high-risk. The corticosteroid + the antihistamine — the prevention (the evidence weak) — the NOT the substitute for the observation.[7]
The beta-blocked patient — the adrenaline ineffective → the GLUCAGON. The beta-blocker blocks the beta-receptor → the adrenaline's beta-effects (the inotropy, the chronotropy, the bronchodilation) the blunted. The glucagon (1-5 mg IV over 5 min, then the 5-15 mcg/min) bypasses the receptor — the glucagon receptor → the adenylate cyclase → the cAMP → the positive inotropy + the chronotropy. The emesis is the common (the have the antiemetic; the airway protected). The NOT the atropine for the bronchospasm (the only for the bradycardia).[7]
The methylene blue — the NO-mediated refractory vasoplegia. The severe anaphylaxis → the overproduction of the NO → the refractory vasoplegia (the unresponsive to the alpha-agonists). The methylene blue (1-2 mg/kg IV over 20 min) inhibits the soluble guanylate cyclase → the blocks the NO-cGMP pathway → the restores the vascular tone. The caution: the SSRI (the serotonin syndrome), the MAOI, the G6PD deficiency (the haemolysis), the pregnancy. The interferes with the pulse oximetry (the falsely low SpO2 — the co-oximetry). The evidence the case reports and the series.[11]
The perioperative anaphylaxis — the NMBAs the #1 trigger; the skin hidden under the drapes. The triad: the sudden hypotension + the high airway pressures (the bronchospasm) + the tachycardia (or the paradoxical bradycardia). The skin signs the often absent (the under the drapes — the ask the surgeon). The NMBAs (the rocuronium the most common) — the 60-70 per cent. The antibiotics — the 15-20 per cent (the teicoplanin increasingly). The chlorhexidine — the 5-8 per cent (the under-recognised).[8]
The Bezold-Jarisch reflex — the paradoxical bradycardia in the profound anaphylaxis. The massive vasodilation + the capillary leak → the empty ventricle → the vigorous contraction of the underfilled ventricle → the vagal afferent (the Bezold-Jarisch) → the bradycardia. The atropine-resistant if the hypovolaemia uncorrected — the FLUIDS + the adrenaline the first; the atropine for the symptomatic bradycardia. The bradycardia in the anaphylaxis is the OMINOUS (the pre-arrest) — the NOT the reassuring.[10]
The "iodine allergy" is the myth — the contrast reaction is NOT the iodine. The radiocontrast reaction — the non-IgE (the direct mast cell activation) — the reaction to the contrast molecule, NOT the iodine. The seafood/shellfish allergy is the IgE to the tropomyosin — the NOT the iodine. The NO the cross-reactivity between the seafood and the contrast. The premedication (the corticosteroid + the antihistamine) for the prior reactors; the low-osmolar contrast for the lower risk.[5]
The hereditary angioedema (the C1-inhibitor deficiency) — the bradykinin, NOT the histamine. The angioedema WITHOUT the urticaria (the NOT the histamine — the bradykinin-mediated), the family history, the low C4, the NOT the bronchospasm, the NOT the hypotension. The NOT the response to the adrenaline (the bradykinin — the NOT the histamine). The treatment: the C1-inhibitor concentrate (the berinert) or the bradykinin B2 antagonist (the icatibant). The laryngeal angioedema → the early intubation. The NOT the anaphylaxis — the different mediator, the different treatment.[5]
The scombroid poisoning — the histamine from the spoiled fish. The tuna, the mahi-mahi, the skipjack — the bacterial decarboxylation of the histidine → the histamine. The minutes after the ingestion: the flush, the urticaria, the diarrhoea, the wheeze, the headache. The NOT the IgE — the histamine intoxication. The multiple diners affected (the clue). The treatment: the antihistamine (the H1 + the H2). The adrenaline only if the severe. The NOT the recurrent (the eliminate the source).[5]
The systemic mastocytosis — the baseline tryptase above 20 mcg/L. The recurrent unexplained anaphylaxis, the urticaria pigmentosa (the reddish-brown macules), the Darier sign (the urtication on the rubbing), the bone and the GI symptoms. The trigger may be the trivial (the wasp sting, the temperature change, the alcohol). The baseline tryptase above 20 mcg/L → the KIT D816V mutation + the bone marrow biopsy. The refer to the haematology/allergy. The carry the 2 adrenaline auto-injectors.[12]
The sugammadex reverses the NMBA — NOT the anaphylaxis. The sugammadex encapsulates the rocuronium/vecuronium → the reversal of the neuromuscular blockade. The sugammadex does NOT reverse the IgE-mediated anaphylaxis (the allergic cascade continues). The sugammadex ITSELF can cause the anaphylaxis (the rare — the 1 in 3000). The continue the adrenaline, the fluids, the standard protocol — the NOT the rely on the sugammadex.[8]
The vancomycin "Red Man Syndrome" — the rate-dependent, the NOT the true allergy. The rapid infusion → the direct mast cell degranulation (the non-IgE) → the flush, the hypotension, the rash (the upper body — the neck, the face). The rate-dependent — the slow the infusion (the over the 60 min; the 1 g over the 60 min) → the resolves. The NOT the anaphylaxis (the no bronchospasm, the no true IgE). The antihistamine (the pre-treatment) helps. The test dose the unreliable.[8]
The IV adrenaline BOLUS — the ONLY in the cardiac arrest. The IV bolus of the adrenaline in the beating-heart anaphylaxis → the risk of the VF, the hypertension, the intracranial haemorrhage, the myocardial ischaemia. The IV adrenaline infusion (the 10 mcg/mL; the 0.05 mcg/kg/min; the titrate) — the NOT the bolus. The exception: the cardiac arrest — the 1 mg IV (the 10 mL of the 1:10,000) the standard the ACLS dose.[9][10]
The latex allergy + the spina bifida + the multiple surgeries. The latex (the Hevea proteins) — the IgE. The high-risk groups: the spina bifida (the 30-60 per cent — the multiple catheters/surgeries; the neural tube defect), the multiple surgical procedures, the healthcare workers, the rubber-industry workers. The latex-fruit syndrome (the banana, the kiwi, the avocado, the chestnut — the cross-reactive proteins). The latex-free environment — the prevention.[5]
The food + the cofactor — the cofactor-augmented anaphylaxis. The cofactors lower the threshold: the NSAID, the alcohol, the exercise, the menstruation, the intercurrent infection, the sleep deprivation, the stress. The food-dependent exercise-induced anaphylaxis (the FDEIA) — the food (the wheat, the shellfish, the celery, the peach) + the exercise within the 4-6 hours → the anaphylaxis; the food OR the exercise alone → the no reaction. The identify the cofactor — the avoid both.[14]

The key facts

WHY the IM adrenaline is the first-line — the ONLY drug that treats ALL three

The adrenaline is the ONLY medication that treats ALL three the life-threatening pathologies of the anaphylaxis simultaneously: (1) the alpha-1 → the vasoconstriction → the reverses the vasodilation and the reduces the angioedema; (2) the beta-1 → the positive inotropy + the chronotropy → the supports the cardiac output; (3) the beta-2 → the bronchodilation → the reverses the bronchospasm. Additionally: the beta-2 → the stabilises the mast cell membranes → the reduces the further mediator release. The NO other drug does all of this. The antihistamines treat the ONLY the skin. The corticosteroids take the hours. The fluids treat the hypovolaemia. The adrenaline — the early, the IM, the enough.[9]

Additional red flags

[1]

The quick-reference — the management at a glance

The anaphylaxis — the first 30 minutes (the rapid reference)

The RECOGNISE — the NIAID/FAAN criteria (the skin + the respiratory/reduced-BP/GI; the 2+ systems after the allergen; the reduced BP after the known allergen).
The CALL FOR HELP — the senior, the ICU, the anaesthetist.
The IM ADRENALINE 0.5 mg (the 1:1000) in the anterolateral thigh — the FIRST, the EARLY, the ENOUGH. The repeat every 5 min.
The POSITION — the supine + the legs elevated (the NEVER the sit/stand). The pregnant — the left lateral. The vomiting — the recovery. The respiratory distress — the upright with the caution.
The OXYGEN 15 L/min via the non-rebreather. The target the SpO2 above 92 per cent.
The IV FLUIDS 20 mL/kg crystalloid rapidly. The repeat if the hypotension. The massive capillary leak → the 2-3 L in the first hour.
The ASSESS at the 5 min — the improving → the observe; the refractory → the IV adrenaline infusion 0.05 mcg/kg/min, the titrate.
The ADJUNCTS — the H1 (the chlorphenamine 10 mg IV), the H2 (the famotidine), the hydrocortisone 200 mg IV (the adjuncts — the NOT the first-line).
The BETA-BLOCKED — the glucagon 1-5 mg IV then the infusion.
The SAMPLES — the tryptase the acute + the 1-2 h + the 24 h. The save the serum.
The OBSERVE — the 6-12 h (the low-risk) the 12-24 h (the high-risk). The biphasic the 5-20 per cent.
The DISCHARGE — the 2 adrenaline auto-injectors + the action plan + the referral to the allergy clinic.

[1]

The summary

The anaphylaxis — the severe, the life-threatening, the systemic hypersensitivity. The clinical diagnosis (the NIAID/FAAN: the skin + the respiratory/reduced-BP/GI; the 2+ systems after the allergen; the reduced BP after the known allergen). The management the ABCDE: the IM adrenaline 0.5 mg (the FIRST-LINE), the 100 per cent O2, the IV fluids (the 20 mL/kg), the positioning (the supine + the legs elevated — the NEVER the sit/stand). The IV adrenaline infusion for the refractory (the 0.05 mcg/kg/min). The glucagon for the beta-blocked. The methylene blue for the NO-mediated refractory vasoplegia. The antihistamine + the corticosteroid — the adjuncts ONLY. The tryptase — the serial (the acute + the 1-2 h + the 24 h); the negative does NOT exclude. The observation — the 6-12 h (the low-risk) the 12-24 h (the high-risk); the biphasic the 5-20 per cent. The differential — the vasovagal, the anxiety, the asthma, the carcinoid, the mastocytosis, the scombroid, the hereditary angioedema. The outcome — the prompt the IM adrenaline → the low mortality; the delayed → the death.[3][5][9][14]

References

[1]Cardona V, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - IV - A quality appraisal with the AGREE II instrument World Allergy Organ J, 2022.PMID 36091188
[2]Turner PJ, et al. Prevalence of anaphylaxis among adults admitted to critical care for severe asthma exacerbation Emerg Med J, 2018.PMID 30093380
[3]Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium J Allergy Clin Immunol, 2006.PMID 16461139
[4]Campbell RL, Li JT, Nicklas RA, et al. Evaluation of national institute of allergy and infectious diseases/food allergy and anaphylaxis network criteria for the diagnosis of anaphylaxis in emergency department patients J Allergy Clin Immunol, 2012.PMID 22051698
[5]Cardona V, Ansotegui IJ, Ebisawa M, et al. World allergy organization anaphylaxis guidance 2020 World Allergy Organ J, 2020.PMID 33204386
[6]Brown SGA. Clinical features and severity grading of anaphylaxis J Allergy Clin Immunol, 2004.PMID 15316518
[7]Dribin TE, Camargo CA, Fritea L, et al. Persistent, refractory, and biphasic anaphylaxis: A multidisciplinary Delphi study J Allergy Clin Immunol, 2020.PMID 32853640
[8]Garvey LH, Dewachter P, Hepner DL, et al. Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations Br J Anaesth, 2019.PMID 31130272
[9]Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions--guidelines for healthcare providers Resuscitation, 2008.PMID 18358585
[10]Soar J. Emergency treatment of anaphylaxis in adults: concise guidance Clin Med (Lond), 2009.PMID 19435130
[11]Da Silva PS, Waisman DR. Methylene Blue to Treat Refractory Latex-Induced Anaphylactic Shock: A Case Report A A Pract, 2018.PMID 28937421
[12]Stone SF, Bosco A, Brown SGA. Mediators released during human anaphylaxis Curr Allergy Asthma Rep, 2012.PMID 22086296
[13]Francis A, Fatovich DM, Doshi R, et al. Serum mast cell tryptase measurements: Sensitivity and specificity for a diagnosis of anaphylaxis in emergency department patients with shock or hypoxaemia Emerg Med Australas, 2018.PMID 29094472
[14]Wang J, Scurlock AM, Young MC, et al. Anaphylaxis in Practice: A Guide to the 2023 Practice Parameter Update J Allergy Clin Immunol Pract, 2024.PMID 38944199
[15]Simons FE, Ardusso LR, Bilo MB, et al. 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines World Allergy Organ J, 2015.PMID 26525001

Overview & definition

[1]

The clinical — the WAO criteria

The WAO 2020 criteria for the diagnosis of the anaphylaxis (any ONE of the three):[1]

The acute onset (minutes-hours) of the skin/mucosal (the urticaria, the angioedema, the flushed) + at least ONE of: the respiratory (the wheeze, the stridor, the dyspnoea), the cardiovascular (the hypotension, the collapse), the end-organ (the GI, the dizziness).[1]
The TWO OR MORE of the following after the exposure to a likely allergen: the skin/mucosal, the respiratory, the cardiovascular, the GI (the vomiting, the diarrhoea, the cramping).[1]
The hypotension after the exposure to a known allergen (the adult SBP below 90 or the 30% drop from the baseline).[1]

The NIAID/FAAN diagnostic criteria — the foundational 2006 consensus

The respiratory compromise (the dyspnoea, the wheeze, the stridor, the hypoxaemia, the reduced PEF).
The reduced BP or the associated symptoms of the end-organ dysfunction (the collapse, the syncope, the incontinence).
The severe GI symptoms (the crampy abdominal pain, the repetitive vomiting), especially after a food allergen. [1]

The skin/mucosal (the urticaria, the flush, the angioedema, the pruritus).
The respiratory compromise (the wheeze, the stridor, the hypoxaemia).
The reduced BP or the associated symptoms (the collapse, the syncope, the dizziness).
The persistent GI symptoms (the vomiting, the cramping, the diarrhoea). [1]

Criterion 3. The reduced BP after the exposure to a KNOWN allergen for that patient:

The adults — SBP below 90 mmHg (or the 30 per cent drop from the baseline).
The infants and the children — SBP below 70 mmHg (1 month-1 yr), below 70 + (2 × age) (1-10 yr), below 90 (11-17 yr).[3]

The NIAID/FAAN 2006 vs the WAO 2020 — the diagnostic criteria

Feature	The NIAID/FAAN 2006	The WAO 2020
Criterion 1	Skin/mucosa + (respiratory OR reduced BP/end-organ OR severe GI)	Skin/mucosa + (respiratory OR cardiovascular OR end-organ/GI)
Criterion 2	2+ systems after a LIKELY allergen	2+ systems after a LIKELY allergen
Criterion 3	Reduced BP after a KNOWN allergen	Reduced BP after a KNOWN allergen
The GI	Criterion 1 (severe) + Criterion 2	A standalone system
The paediatric BP	Explicit age-based thresholds	Adult thresholds adapted
The clinical use	The foundational criteria — still widely cited	The current international standard

[1]

The severity grading — the Brown 3-grade system

The Brown SGA 2004 three-grade severity grading — the practical bedside and the research tool.[6]

Grade 1 (mild): the skin and the subcutaneous tissue only (the urticaria, the flush, the angioedema) — WITHOUT the respiratory, the cardiovascular, or the severe GI.
Grade 2 (moderate): the grade 1 features PLUS the mild-to-moderate respiratory (the wheeze, the dyspnoea), the cardiovascular (the tachycardia, the mild hypotension), OR the GI.
Grade 3 (severe): the hypoxaemia (the cyanosis, the SpO2 below 92 per cent), the hypotension (the collapse, the syncope), and/or the neurological compromise (the confusion, the collapse, the incontinence). The highest risk of the biphasic and the death.[6]

The grade 3 reaction → the longer the observation (the 12-24 h); the grade 1 may be observed the 6 h if the rapid response. The grade predicts the biphasic and the adrenaline requirement. [1]

The pathophysiology

The triggers — the allergens and the agents

The common anaphylaxis triggers — the community vs the perioperative

Trigger	The mechanism	The community (the ED)	The perioperative (the theatre/ICU)	The notes
The drugs — beta-lactams (penicillins, cephalosporins)	IgE	The #1 drug trigger	15-20 per cent of perioperative	The penicillin-cephalosporin cross-reactivity the low (1-2 per cent with the modern side chains)
The drugs — NMBAs (rocuronium, suxamethonium, vecuronium)	IgE to the quaternary ammonium	Rare	The #1 perioperative trigger (60-70 per cent)	The cross-reactivity between the NMBAs the 60-70 per cent. The sugammadex reverses the NMBA — NOT the anaphylaxis
The drugs — NSAIDs (aspirin, ibuprofen, diclofenac)	Non-IgE (the COX-1 inhibition → the leukotriene)	Common	—	The class effect within the strong COX-1 inhibitors; the COX-2 selective (the celecoxib) usually tolerated
The drugs — radiocontrast media (the iodinated)	Non-IgE (the direct mast cell activation)	Common (the radiology)	—	The "iodine allergy" is the myth — the reaction is to the contrast molecule, NOT the iodine. The premedication (the steroid + the antihistamine) for the prior reactors
The drugs — vancomycin	Non-IgE (the direct degranulation — the Red Man Syndrome)	—	Common	The rate-dependent — slow the infusion (the NOT the anaphylaxis if the infusion slowed resolves it)
The foods (the peanut, the tree nut, the shellfish, the milk, the egg, the sesame)	IgE	The #1 cause in the children	—	The peanut and the tree nut — the most likely to be the severe and the fatal
The insect stings (the bee, the wasp, the hornet, the fire ant)	IgE to the venom	Common (the adults)	—	The beekeeper and the prior large local reaction — the higher risk
The latex	IgE (the Hevea proteins)	Decreasing (the healthcare workers, the spina bifida)	The decreasing — the latex-free theatre	The type I (anaphylaxis); NOT the type IV (the contact dermatitis)
The chlorhexidine	IgE	Under-recognised	5-8 per cent perioperative (the skin prep, the central line, the urinary catheter lubricant)	The ubiquitous — the test if the unexplained perioperative reaction
The Patent Blue / the dyes	IgE	Rare	2-4 per cent (the lymph node mapping — the breast, the melanoma)	The falsely low SpO2 for 1-2 min
The exercise / the cold / the co-factors	Non-IgE / the cofactor-augmented	The exercise-induced (the food + the exercise), the cold-induced	—	The cofactors (the NSAID, the alcohol, the exercise, the menstruation, the intercurrent infection) lower the threshold
The idiopathic	Unknown	20 per cent	5-10 per cent	The work-up (the tryptase, the skin testing, the component testing) — the referral to the allergy clinic

[1]

The differential diagnosis — the mimics of the anaphylaxis

The anaphylaxis vs the mimics — the distinguishing features

Condition	The key distinguishing features	The trap
The vasovagal syncope	The pallor (NOT the flush/urticaria), the bradycardia (NOT the tachycardia), the nausea, the rapid resolution on the supine, the precipitant (the pain, the sight of blood). The NO urticaria, the NO bronchospasm, the normal tryptase	The over-diagnosis of the vasovagal in the young — the bradycardia can occur in the anaphylaxis too (the Bezold-Jarisch reflex from the empty ventricle)
The anxiety / the panic attack	The dyspnoea WITHOUT the wheeze/hypoxaemia, the tingling fingers (the hyperventilation → the respiratory alkalosis), the NO urticaria, the NO hypotension, the normal tryptase	The genuine anaphylaxis dismissed as the panic — the fatal error
The asthma	The isolated bronchospasm — the NO urticaria, the NO hypotension, the NO GI, the history of the asthma	The anaphylaxis may present as the isolated bronchospasm. The severe asthma after a food/drug → the anaphylaxis until proven otherwise
The carcinoid syndrome	The flush (NOT the urticaria), the diarrhoea, the right-heart valvular disease, the wheeze — the elevated 24-h urinary 5-HIAA, the NOT the tryptase	The flush in the carcinoid is the prolonged and the patchy — the anaphylaxis flush is the acute and the generalised
The systemic mastocytosis	The recurrent unexplained anaphylaxis, the urticaria pigmentosa, the Darier sign, the baseline tryptase elevated (above 20 mcg/L), the KIT D816V mutation	The trigger may be trivial (the wasp sting, the temperature change). The baseline tryptase above 20 → the mastocytosis
The scombroid poisoning	The histamine from the spoiled fish (the tuna, the mahi-mahi) — the flush, the urticaria, the diarrhoea, the wheeze, the minutes after the ingestion. The NOT IgE — the histamine intoxication. The response to the antihistamine (the adrenaline NOT the first-line unless the severe)	The multiple diners affected — the clue
The hereditary angioedema (the C1-inhibitor deficiency)	The angioedema WITHOUT the urticaria (the bradykinin — NOT the histamine), the family history, the low C4, the NOT the bronchospasm, the NOT the hypotension. The NOT the response to the adrenaline — the C1-inhibitor concentrate or the icatibant	The laryngeal angioedema → the intubation. The bradykinin-mediated
The shock from the other cause (the septic, the cardiogenic, the hypovolaemic)	The NO urticaria, the NO bronchospasm, the appropriate history	The anaphylaxis can be the isolated shock (the Criterion 3) — the skin may be absent

[1]

The practical rule: the acute unexplained bronchospasm + the hypotension within the minutes of a drug/food/sting → the anaphylaxis until proven otherwise.[9]

The management — the ABCDE

[1]

1. The IM adrenaline 0.5 mg (the FIRST-LINE).[1][2]

The 0.5 mg (0.5 mL of the 1:1000) IM in the anterolateral thigh. The repeat every 5 minutes if no response (up to 2 doses before the IV).[1]
The alpha-1 (the vasoconstriction — the BP, the oedema reduction), the beta-1 (the increased the inotropy and the chronotropy), the beta-2 (the bronchodilation).[1]

2. The airway + the breathing.[1][1]

The 100% O2 (the high-flow, the non-rebreather). The early intubation if the airway oedema (the laryngeal — the rapidly progressive; the intubate before the impossible).[1]
The nebulised adrenaline (5 mg) for the upper airway oedema (the laryngeal).[1]

3. The circulation.[1][1]

The IV fluid (the 20 mL/kg crystalloid rapidly — the vasodilation + the capillary leak → the relative the hypovolaemia).[2]
The vasopressor (the noradrenaline) if the refractory. The IV adrenaline infusion (the 0.05-0.1 mcg/kg/min — for the refractory to the IM).[1]

4. The adjuncts.[1][1]

The antihistamine (the chlorphenamine 10 mg IV — the H1; the H2 — the famotidine; the secondary — NOT the first-line).[1]
The corticosteroid (the hydrocortisone 200 mg IV — the prevent the biphasic; the delayed onset 4-6 h).[1]
The bronchodilator (the salbutamol nebulised — the bronchospasm refractory to the adrenaline).[1]
The glucagon (1-2 mg IV) for the beta-blocked patient (the adrenaline ineffective; the glucagon bypasses the receptor).[1]

5. The positioning.[1]

The supine + the legs raised (the cardiovascular collapse — the venous return).[1]
The sitting up (the respiratory distress — the easier the breathing).[1]
The left lateral (the pregnant — the vena cava).[1]

The diagnosis — the tryptase

The biphasic reaction

Refractory anaphylaxis — the escalation beyond the standard therapy

The refractory anaphylaxis — the rescue agents

Agent	The dose	The mechanism	The indication
The IV adrenaline infusion	0.05-0.5 mcg/kg/min, the titrate to the MAP above 65	The alpha-1 + the beta-1 + the beta-2	The first escalation after the 2 doses IM + the fluids
The IV noradrenaline	0.05-0.5 mcg/kg/min	The alpha-1 predominant (the vasoconstriction)	The vasoplegia refractory to the adrenaline
The vasopressin	0.01-0.04 U/min	The V1 receptor — the independent pathway (NOT the alpha)	The second vasopressor — the catecholamine-resistant vasoplegia
The methylene blue	1-2 mg/kg IV over 20 min (the repeat in 30-60 min if the partial response)	The inhibits the soluble guanylate cyclase → the blocks the NO-cGMP-mediated vasoplegia	The NO-mediated refractory vasoplegia (the case reports and the series). The caution: the SSRI interaction (the serotonin syndrome), the MAOI. The NOT in the G6PD deficiency (the haemolysis). The interferes with the pulse oximetry (the falsely low SpO2)[11]
The glucagon	1-5 mg IV over 5 min, then the 5-15 mcg/min infusion	The activates the adenylate cyclase via the glucagon receptor (the bypasses the beta-receptor) → the cAMP → the positive inotropy + the chronotropy	The beta-blocked patient (the adrenaline ineffective). The emesis is the common (the have the antiemetic and the airway protected)[7]
The atropine	0.5-1 mg IV	The muscarinic antagonist	The severe bradycardia from the Bezold-Jarisch reflex (the profound vasodilation + the empty ventricle → the vagal reflex)
The VA-ECMO	—	The mechanical circulatory support	The last resort — the refractory cardiovascular collapse or the cardiac arrest (the bridge to the recovery)

The refractory anaphylaxis — the escalation protocol

The ASSESS at 5 minutes after the second IM adrenaline + the 20 mL/kg fluid — the BP, the wheeze, the skin, the mental state. The refractory = the persistent hypotension/wheeze.
The IV adrenaline infusion — the 1 mg in the 100 mL 0.9 per cent saline (the 10 mcg/mL), the start the 0.05 mcg/kg/min, the titrate the every 2-5 min to the MAP above 65. The NOT the IV bolus (the risk of the VF, the intracranial haemorrhage) unless the cardiac arrest.
The second vasopressor (the noradrenaline) if the adrenaline infusion inadequate — the central access when the safe.
The methylene blue 1-2 mg/kg IV over 20 min — the NO-mediated vasoplegia. The monitor the SpO2 (the falsely low — the co-oximetry if the available).
The glucagon 1-5 mg IV over 5 min then the infusion — the beta-blocked (the check the medication history the early).
The vasopressin 0.01-0.04 U/min — the catecholamine-resistant.
The VA-ECMO — the refractory collapse. The call the early.

[1]

The tryptase — the mast cell degranulation marker (the expanded)

The acute sample — the ASAP (the within 30 min, the ideally before the adrenaline — but the NOT the delay the treatment).
The 1-2 hour sample — the peak.
The baseline sample — the at least 24 hours after the resolution (the serial tryptase — the most informative).

The limitations:

The sensitivity the 60-90 per cent — the food anaphylaxis may have the NORMAL tryptase (the mast cell burden lower; the food triggers the less tryptase than the drug/venom). The negative tryptase does NOT exclude the anaphylaxis.[13]
The elevated baseline (above 20 mcg/L) → the systemic mastocytosis — the refer for the KIT D816V mutation and the bone marrow biopsy.
The tryptase also elevated in the trauma, the cardiac arrest, the AMI — the NOT the specific to the anaphylaxis.

The observation period — the biphasic risk stratification

The observation — the 6-12 hours for the low-risk; the 12-24 hours for the high-risk. The decision — the balanced (the biphasic risk vs the bed-occupancy).[7][14]

The biphasic reaction — the risk stratification for the observation

The low-risk (the observe 6 h, the may discharge with the action plan)	The high-risk (the observe 12-24 h, the admit to the HDU/ICU)
The grade 1 (the skin only)	The grade 3 (the hypoxia/hypotension/neuro)
The single dose of the adrenaline with the rapid response	The 2+ doses of the adrenaline
The beta-agonist NOT required	The refractory (the IV adrenaline infusion)
The no prior biphasic history	The prior biphasic history
The no beta-blocker	The beta-blocker therapy
The no comorbidity (the asthma, the cardiovascular)	The asthma, the cardiovascular disease, the mastocytosis
The reaction the over 1 hour ago, the stable	The slow onset, the prolonged reaction
The access to the auto-injector + the carer	The social isolation, the no access to the care

[1]

The perioperative anaphylaxis — the unique ICU/theatre challenge

The perioperative anaphylaxis — the theatre protocol

The SUSPECT — the sudden hypotension + the high airway pressures + the tachycardia/bradycardia within the minutes of a drug (the induction, the antibiotic, the skin prep, the dye). The ask the surgeon to check the skin.
The STOP all the potential triggers — the most recently administered agent (the NMBA, the antibiotic, the contrast, the dye, the chlorhexidine). The NOT give more.
The CALL FOR HELP — the senior anaesthetist, the ICU team, the stop the surgery if possible.
The POSITION — the supine with the legs elevated (the Trendelenburg).
The IM adrenaline 0.5-1 mg (the 1:1000) — the IM even in the anaesthetised (the anterolateral thigh).
The IV fluids — the 20-50 mL/kg crystalloid rapidly (the massive capillary leak; the consider the colloid cautiously — the colloid itself can be the trigger).
The IV adrenaline infusion if the refractory. The vasopressin/methylene blue/glucagon as the above.
The SAMPLES — the tryptase the acute, the 1-2 h, the 24 h. The send the saved serum (the drug-specific IgE later). The refer to the allergy clinic at the 4-6 weeks for the skin testing (the NOT the earlier — the false negative in the first 4 weeks).[8]

Prognosis

SAQ — Refractory anaphylaxis and the beta-blocked patient

10 minutes · 10 marks

[1]

SAQ — Perioperative anaphylaxis and neuromuscular blocking agents

10 minutes · 10 marks

[1]

Red flags

Clinical pearls

Clinical pearl

The IM adrenaline 0.5 mg (the 1:1000) in the anterolateral thigh — the FIRST, the EARLY, the ENOUGH. The #1 cause of the anaphylaxis death is the DELAYED adrenaline. The 0.5 mg (the 500 mcg) — the 0.5 mL of the 1:1000. The IM (the NOT the subcutaneous — the slower absorption; the NOT the IV — the risk of the VF). The anterolateral thigh (the vastus lateralis — the superior absorption; the NOT the gluteal — the slower and the less reliable). The repeat every 5 minutes (the up to the 2 doses before the IV). The NOT the wait for the skin rash; the NOT the wait for the IV access; the NOT the use the antihistamine as the substitute. The dose is the generous — the anaphylaxis does NOT respond to the subtherapeutic adrenaline.[3][9]
The POSITIONING saves the lives — the supine + the legs elevated. The anaphylaxis → the massive vasodilation + the capillary leak → the venous pooling in the legs → the empty IVC → the reduced preload → the cardiac arrest. The documented deaths from the patient sitting up on the chair or the toilet during the anaphylaxis (the empty-IVC cardiac arrest). The lie flat with the legs raised. The exception: the severe respiratory distress (the may need the upright with the caution); the vomiting (the recovery position); the pregnant (the left lateral tilt).[9]
The antihistamine + the corticosteroid are the ADJUNCTS — the NOT the first-line. The antihistamine (the H1 — the chlorphenamine; the H2 — the famotidine) treats the ONLY the skin (the urticaria, the pruritus) — the NOT the bronchospasm or the hypotension. The corticosteroid (the hydrocortisone 200 mg IV) takes the 4-6 hours to work — the too slow for the acute; the may reduce the biphasic (the evidence weak). The adrenaline is the ONLY the life-saving drug. The NO antihistamine-as-substitute.[9][10]
The tryptase — the THREE samples; the peak the 1-2 hours; the negative does NOT exclude. The acute (the ASAP), the 1-2 h (the peak), the 24 h (the baseline). The threshold: the peak above (1.2 × the baseline + 2 mcg/L). The limitation: the food anaphylaxis may have the NORMAL tryptase (the sensitivity the 60-90 per cent). The NOT the delay the treatment for the sample; the draw it the around the adrenaline. The elevated baseline (the above 20 mcg/L) → the mastocytosis — the refer.[12][13]
The biphasic — the 5-20 per cent; the observation the 6-12 h (the low-risk) the 12-24 h (the high-risk). The recurrence the 4-24 hours after the resolution WITHOUT the re-exposure. The risk factors: the delayed adrenaline, the severe initial (the grade 3), the 2+ doses of the adrenaline, the prior biphasic, the beta-blocker, the asthma. The NOT the early discharge in the high-risk. The corticosteroid + the antihistamine — the prevention (the evidence weak) — the NOT the substitute for the observation.[7]
The beta-blocked patient — the adrenaline ineffective → the GLUCAGON. The beta-blocker blocks the beta-receptor → the adrenaline's beta-effects (the inotropy, the chronotropy, the bronchodilation) the blunted. The glucagon (1-5 mg IV over 5 min, then the 5-15 mcg/min) bypasses the receptor — the glucagon receptor → the adenylate cyclase → the cAMP → the positive inotropy + the chronotropy. The emesis is the common (the have the antiemetic; the airway protected). The NOT the atropine for the bronchospasm (the only for the bradycardia).[7]
The methylene blue — the NO-mediated refractory vasoplegia. The severe anaphylaxis → the overproduction of the NO → the refractory vasoplegia (the unresponsive to the alpha-agonists). The methylene blue (1-2 mg/kg IV over 20 min) inhibits the soluble guanylate cyclase → the blocks the NO-cGMP pathway → the restores the vascular tone. The caution: the SSRI (the serotonin syndrome), the MAOI, the G6PD deficiency (the haemolysis), the pregnancy. The interferes with the pulse oximetry (the falsely low SpO2 — the co-oximetry). The evidence the case reports and the series.[11]
The perioperative anaphylaxis — the NMBAs the #1 trigger; the skin hidden under the drapes. The triad: the sudden hypotension + the high airway pressures (the bronchospasm) + the tachycardia (or the paradoxical bradycardia). The skin signs the often absent (the under the drapes — the ask the surgeon). The NMBAs (the rocuronium the most common) — the 60-70 per cent. The antibiotics — the 15-20 per cent (the teicoplanin increasingly). The chlorhexidine — the 5-8 per cent (the under-recognised).[8]
The Bezold-Jarisch reflex — the paradoxical bradycardia in the profound anaphylaxis. The massive vasodilation + the capillary leak → the empty ventricle → the vigorous contraction of the underfilled ventricle → the vagal afferent (the Bezold-Jarisch) → the bradycardia. The atropine-resistant if the hypovolaemia uncorrected — the FLUIDS + the adrenaline the first; the atropine for the symptomatic bradycardia. The bradycardia in the anaphylaxis is the OMINOUS (the pre-arrest) — the NOT the reassuring.[10]
The "iodine allergy" is the myth — the contrast reaction is NOT the iodine. The radiocontrast reaction — the non-IgE (the direct mast cell activation) — the reaction to the contrast molecule, NOT the iodine. The seafood/shellfish allergy is the IgE to the tropomyosin — the NOT the iodine. The NO the cross-reactivity between the seafood and the contrast. The premedication (the corticosteroid + the antihistamine) for the prior reactors; the low-osmolar contrast for the lower risk.[5]
The hereditary angioedema (the C1-inhibitor deficiency) — the bradykinin, NOT the histamine. The angioedema WITHOUT the urticaria (the NOT the histamine — the bradykinin-mediated), the family history, the low C4, the NOT the bronchospasm, the NOT the hypotension. The NOT the response to the adrenaline (the bradykinin — the NOT the histamine). The treatment: the C1-inhibitor concentrate (the berinert) or the bradykinin B2 antagonist (the icatibant). The laryngeal angioedema → the early intubation. The NOT the anaphylaxis — the different mediator, the different treatment.[5]
The scombroid poisoning — the histamine from the spoiled fish. The tuna, the mahi-mahi, the skipjack — the bacterial decarboxylation of the histidine → the histamine. The minutes after the ingestion: the flush, the urticaria, the diarrhoea, the wheeze, the headache. The NOT the IgE — the histamine intoxication. The multiple diners affected (the clue). The treatment: the antihistamine (the H1 + the H2). The adrenaline only if the severe. The NOT the recurrent (the eliminate the source).[5]
The systemic mastocytosis — the baseline tryptase above 20 mcg/L. The recurrent unexplained anaphylaxis, the urticaria pigmentosa (the reddish-brown macules), the Darier sign (the urtication on the rubbing), the bone and the GI symptoms. The trigger may be the trivial (the wasp sting, the temperature change, the alcohol). The baseline tryptase above 20 mcg/L → the KIT D816V mutation + the bone marrow biopsy. The refer to the haematology/allergy. The carry the 2 adrenaline auto-injectors.[12]
The sugammadex reverses the NMBA — NOT the anaphylaxis. The sugammadex encapsulates the rocuronium/vecuronium → the reversal of the neuromuscular blockade. The sugammadex does NOT reverse the IgE-mediated anaphylaxis (the allergic cascade continues). The sugammadex ITSELF can cause the anaphylaxis (the rare — the 1 in 3000). The continue the adrenaline, the fluids, the standard protocol — the NOT the rely on the sugammadex.[8]
The vancomycin "Red Man Syndrome" — the rate-dependent, the NOT the true allergy. The rapid infusion → the direct mast cell degranulation (the non-IgE) → the flush, the hypotension, the rash (the upper body — the neck, the face). The rate-dependent — the slow the infusion (the over the 60 min; the 1 g over the 60 min) → the resolves. The NOT the anaphylaxis (the no bronchospasm, the no true IgE). The antihistamine (the pre-treatment) helps. The test dose the unreliable.[8]
The IV adrenaline BOLUS — the ONLY in the cardiac arrest. The IV bolus of the adrenaline in the beating-heart anaphylaxis → the risk of the VF, the hypertension, the intracranial haemorrhage, the myocardial ischaemia. The IV adrenaline infusion (the 10 mcg/mL; the 0.05 mcg/kg/min; the titrate) — the NOT the bolus. The exception: the cardiac arrest — the 1 mg IV (the 10 mL of the 1:10,000) the standard the ACLS dose.[9][10]
The latex allergy + the spina bifida + the multiple surgeries. The latex (the Hevea proteins) — the IgE. The high-risk groups: the spina bifida (the 30-60 per cent — the multiple catheters/surgeries; the neural tube defect), the multiple surgical procedures, the healthcare workers, the rubber-industry workers. The latex-fruit syndrome (the banana, the kiwi, the avocado, the chestnut — the cross-reactive proteins). The latex-free environment — the prevention.[5]
The food + the cofactor — the cofactor-augmented anaphylaxis. The cofactors lower the threshold: the NSAID, the alcohol, the exercise, the menstruation, the intercurrent infection, the sleep deprivation, the stress. The food-dependent exercise-induced anaphylaxis (the FDEIA) — the food (the wheat, the shellfish, the celery, the peach) + the exercise within the 4-6 hours → the anaphylaxis; the food OR the exercise alone → the no reaction. The identify the cofactor — the avoid both.[14]

The key facts

WHY the IM adrenaline is the first-line — the ONLY drug that treats ALL three

Additional red flags

The quick-reference — the management at a glance

The anaphylaxis — the first 30 minutes (the rapid reference)

The RECOGNISE — the NIAID/FAAN criteria (the skin + the respiratory/reduced-BP/GI; the 2+ systems after the allergen; the reduced BP after the known allergen).
The CALL FOR HELP — the senior, the ICU, the anaesthetist.
The IM ADRENALINE 0.5 mg (the 1:1000) in the anterolateral thigh — the FIRST, the EARLY, the ENOUGH. The repeat every 5 min.
The POSITION — the supine + the legs elevated (the NEVER the sit/stand). The pregnant — the left lateral. The vomiting — the recovery. The respiratory distress — the upright with the caution.
The OXYGEN 15 L/min via the non-rebreather. The target the SpO2 above 92 per cent.
The IV FLUIDS 20 mL/kg crystalloid rapidly. The repeat if the hypotension. The massive capillary leak → the 2-3 L in the first hour.
The ASSESS at the 5 min — the improving → the observe; the refractory → the IV adrenaline infusion 0.05 mcg/kg/min, the titrate.
The ADJUNCTS — the H1 (the chlorphenamine 10 mg IV), the H2 (the famotidine), the hydrocortisone 200 mg IV (the adjuncts — the NOT the first-line).
The BETA-BLOCKED — the glucagon 1-5 mg IV then the infusion.
The SAMPLES — the tryptase the acute + the 1-2 h + the 24 h. The save the serum.
The OBSERVE — the 6-12 h (the low-risk) the 12-24 h (the high-risk). The biphasic the 5-20 per cent.
The DISCHARGE — the 2 adrenaline auto-injectors + the action plan + the referral to the allergy clinic.

[1]

The summary

References

[1]Cardona V, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - IV - A quality appraisal with the AGREE II instrument World Allergy Organ J, 2022.PMID 36091188
[2]Turner PJ, et al. Prevalence of anaphylaxis among adults admitted to critical care for severe asthma exacerbation Emerg Med J, 2018.PMID 30093380
[3]Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium J Allergy Clin Immunol, 2006.PMID 16461139
[4]Campbell RL, Li JT, Nicklas RA, et al. Evaluation of national institute of allergy and infectious diseases/food allergy and anaphylaxis network criteria for the diagnosis of anaphylaxis in emergency department patients J Allergy Clin Immunol, 2012.PMID 22051698
[5]Cardona V, Ansotegui IJ, Ebisawa M, et al. World allergy organization anaphylaxis guidance 2020 World Allergy Organ J, 2020.PMID 33204386
[6]Brown SGA. Clinical features and severity grading of anaphylaxis J Allergy Clin Immunol, 2004.PMID 15316518
[7]Dribin TE, Camargo CA, Fritea L, et al. Persistent, refractory, and biphasic anaphylaxis: A multidisciplinary Delphi study J Allergy Clin Immunol, 2020.PMID 32853640
[8]Garvey LH, Dewachter P, Hepner DL, et al. Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations Br J Anaesth, 2019.PMID 31130272
[9]Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions--guidelines for healthcare providers Resuscitation, 2008.PMID 18358585
[10]Soar J. Emergency treatment of anaphylaxis in adults: concise guidance Clin Med (Lond), 2009.PMID 19435130
[11]Da Silva PS, Waisman DR. Methylene Blue to Treat Refractory Latex-Induced Anaphylactic Shock: A Case Report A A Pract, 2018.PMID 28937421
[12]Stone SF, Bosco A, Brown SGA. Mediators released during human anaphylaxis Curr Allergy Asthma Rep, 2012.PMID 22086296
[13]Francis A, Fatovich DM, Doshi R, et al. Serum mast cell tryptase measurements: Sensitivity and specificity for a diagnosis of anaphylaxis in emergency department patients with shock or hypoxaemia Emerg Med Australas, 2018.PMID 29094472
[14]Wang J, Scurlock AM, Young MC, et al. Anaphylaxis in Practice: A Guide to the 2023 Practice Parameter Update J Allergy Clin Immunol Pract, 2024.PMID 38944199
[15]Simons FE, Ardusso LR, Bilo MB, et al. 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines World Allergy Organ J, 2015.PMID 26525001