Some 30% of patients presenting for surgery have an 'allergy', yet the overwhelming majority are non-anaphylactic and indeed mostly non-allergic full-stop
The incidence of bona fide perioperative anaphylaxis is 0.01% (1 in 10,000 anaesthetics)
This appears to be somewhat consistent at an international level; the incidence of perioperative anaphylaxis in China is 1 in 11,000
(BJA, 2022)
A composite scoring system used in the JESPA study (BJA, 2023) found the incidence in Japan to be 1 in 5,000
This makes perioperative anaphylaxis marginally more common than the European incidence of all-cause anaphylaxis (1.5 - 7.9 per 100,000 person years)
The Resus Council themselves note that, as anaphylaxis is a clinical diagnosis, "a precise definition is not important for treatment"
This may be an unimpressive thing to say in a viva, so you could instead borrow one of the following definitions:
A serious systemic hypersensitivity reaction that is usually rapid in onset and may cause death
An acute, life-threatening type 1 hypersensitivity reaction
I.e. anaphylaxis is rapid-onset immune-mediated badness which requires emergent treatment
Anaphylaxis is a type 1 hypersensitivity reaction cause by antigens binding to IgE immunoglobulins
Initial exposure to an allergen can cause sensitisation and generation of IgE
Exposure may be to compounds with molecularly similarity to drugs used in the perioperative period e.g. pholcodine and NMBAs
(BJA, 2021)
Upon repeat exposure, IgE binds to high-affinity Fc receptors on mast cells (and basophils), causing them to degranulate
IgE antibodies also bind to low-affinity Fc receptors on lymphocytes, eosinophils and platelets
Mast cells release anaphylatoxins; histamine, prostaglandins, serotonin, tryptase and leukotrienes
These mediators are responsible for the physiological effects of anaphylaxis: vasodilation, increase capillary permeability and smooth muscle constriction
It's worth noting that adrenaline, by preventing mast cell degranulation via the β2-adrenoreceptor is the treatment
for anaphylaxis, not merely a vasoactive agent aiming to reverse the offending vasoplegia
Antibiotics (47%)
Beta-lactam antibiotics are overall responsible for the largest number of antibiotic-associated anaphylaxes
This includes cephalosporins; cefazolin was the most frequently causative antibiotic in the JESPA study
Teicoplanin is 17x more likely to cause anaphylaxis than alternatives, but is given much less frequently
There is a tragic irony to the fact that patients with spurious penicillin allergies are often given teicoplanin perioperatively i.e. a significantly
more anaphylactogenic drug
Neuromuscular blocking agents (33%)
The quaternary ammonium group is an antigen found in many drugs, foods, cosmetics and hair products, as well as NMBA
As such, prior exposure to NMBAs is not a prerequisite for NMBA-induced anaphylaxis
Rocuronium is the most common source of NMBA-anaphylaxis (NAP 6; incidence 8 in 100,000), although suxamethonium may also be implicated
Atracurium and mivacurium may cause non-anaphylaxis allergic reactions by causing direct release of histamine from mast cells
Other drugs
Chlorhexidine (9%)
Patent blue dye (5%)
Sodium thiopental
Colloids
Latex
Changes in policy have reduce incidence of latex anaphylaxis
There is an increased risk of latex allergy in healthcare workers, those undergoing repeated surgeries and those with tropical fruit allergy (kiwi, avocado, banana)
NB tracheal tubes do not contain latex and therefore do not increase risk
The exact reaction to latex depends on the route of exposure, previous exposure and predisposition (e.g. atopic individuals, food allergies)
Type 1 hypersensitivity reactions are most severe but least frequent, and there may be cross-reactivity with latex proteins in fruits e.g. banana, chestnut, avocado
Contact dermatitis due to cutaneous exposure, which is a T-cell mediated delayed hypersensitivity reaction
Non-immune mediated dermatitis is the commonest reaction, leading to itching, irritation and blistering
Opioids
Anaphylaxis to opioids is very rare
Morphine, diamorphine and codeine can cause direct mast cell degranulation and histamine release, without IgE antibodies
This means they can induced positive skin prick results in normal controls
Skin prick testing is not appropriate; drug provocation testing should used instead
Synthetic opioids (fentanyl, remifentanil alfentanil) do not induce histamine release
Skin prick and intradermal testing is therefore appropriate
Angioedema of the face, lips and oropharynx that may precipitate airway obstruction
May necessitate intubation in the un-intubated patient
Wheezing and bronchospasm (18%)
A more common presenting feature in asthmatics or the obese/overweight patient
Rising airway pressures and difficult ventilation
Absent capnograph trace (30%)
Pulmonary oedema may compound hypoxia
Hypotension is the most common presenting complaint (46%)
All cases experience hypotension at some point (NAP6)
Hypotension is often refractory and may lead to circulatory collapse
15% experience cardiac arrest
Tachycardia is often present too
(No overt signs)
Flushing, wheals or urticaria are an uncommon presenting symptom, are often a late sign and their absence does not exclude anaphylaxis
Differential diagnosis
Anaphylactoid or angiodeomatous reaction
Bronchospasm
Massive PE
High regional block
Haemorrhage
Myocardial infarction
Sepsis
Malignant hyperpyrexia
Tension pneumothorax
Immediate management
Should one be faced with a viva question on anaphylaxis, simply recite the opening gambit for any clinical emergency:
Anaphylaxis is an anaesthetic emergency and I would seek senior anaesthetic support as well as making a rapid but thorough assessment of the patient
One should then stop injecting or infusing the responsible agent and reach for the theatre action card, if available
The subsequent ABC approach should be familiar:
Maintain and, if necessary, secure the airway via endotracheal intubation
Administer 100% oxygen and ensure adequate ventilation (which may be tricky in the face of overwhelming bronchospasm)
Administer adrenaline, either 500μg IM (0.5ml 1:1,000) or 50μg IV (0.5ml of 1:10,000)
Paediatric dosing of adrenaline is 10μg/kg IV (0.1ml/kg 1:10,000 IV)
Repeat IV dose every 1 minute until circulation restored
Start an adrenaline infusion after three boluses [NB this differs from the 'infusion after two IM doses' recommended by the Resus Council]
Administer IV crystalloid bolus 20ml/kg to increase circulating volume
Passive leg raise to increase central blood volume
Start CPR if SBP ≤50mmHg
Early management
Consider adjunctive therapy:
Anti-histamines e.g. chlorphenamine 10mg IV
Steroids e.g. hydrocortisone 200mg IV
Bronchodilators such as aminophylline, magnesium or salbutamol
Bicarbonate if profound acidosis e.g. 50 - 100ml 8.4% NaHCO3
Additional vasopressors e.g. noradrenaline
Take blood for serum tryptase at 0, 1 - 2 and 24hrs
Discuss with senior anaesthetist and surgeon need to continue with surgery
Admit to ICU and consider leaving intubated if airway concerns, with an appropriate check for cuff leak prior to extubation
Use of a clinical scoring system to predict whether a true anaphylaxis is occurring
(BJA, 2022) is of debateable use in my opinion
Subsequent management
Document events in patient notes and document allergy on drug chart
Inform patient of events and answer any questions
Write a letter to the GP informing them of the events
Inform the MHRA e.g. complete yellow card (in back of BNF)
Complete a critical incident form
Referral to immunology for allergen testing as per local/national guidelines
Mast cell tryptase
This is a neutral serine protease released from both mast cells and basophils
It is spontaneously released in pro-enzyme forms in a constitutive fashion and is a relatively stable molecule with a t1/2 of 2hrs
Hence, multiple measurements are needed to show a rise and then fall in suspected anaphylaxis
It may be raised outwith anaphylaxis in mastocytosis, AML and myelodysplastic syndromes
Mortality from perioperative anaphylaxis is fairly low;
The overall rate in NAP6 was 0.0003%
If the patient had life-threatening anaphylaxis, the rate was 3.8%
This is similar to the pre-NAP6 literature, which reported a rate of 1 - 4%, although higher than the 2% of an American patient cohort
(BJA, 2021)
Most cardiac arrests in NAP6 were PEA
Risk factors for fatal anaphylaxis
Age >66yrs
Obesity
Existing coronary artery disease or, indeed, virtually any major medical comorbidity
Taking a beta-blocker or ACE-inhibtor, presumably by exacerbating hypotension or making it refractory