Anaesthesia 2023 doi:10.1111/anae.16206
Guidelines
Emergency treatment of peri-operative anaphylaxis:
Resuscitation Council UK algorithm for anaesthetists
A. Dodd,1 P. J. Turner,2 J. Soar,3 L. Savic4 and representing the UK Perioperative
Allergy Network
1 Consultant, Department of Anaesthesia, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
2 Reader, Department of Paediatric Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial
College, London, UK
3 Consultant, Department of Anaesthesia and Intensive Care Medicine, Southmead Hospital, North Bristol NHS Trust,
Bristol, UK
4 Consultant, Department of Anaesthesia, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Summary
Peri-operative anaphylaxis is a rare but potentially catastrophic event which must be considered whenever
unexpected and significant cardiovascular or respiratory compromise occurs during anaesthesia. The
Resuscitation Council UK algorithm for peri-operative anaphylaxis highlights the importance of early
intravenous adrenaline and fluid resuscitation and provides guidance on the treatment of refractory anaphylaxis
and immediate follow-up. This algorithm is endorsed by the Royal College of Anaesthetists, Association of
Anaesthetists, British Society of Allergy and Clinical Immunology and Clinical Immunology Professional
Network of the British Society for Immunology. This document was produced by the Perioperative Allergy
Network steering committee in collaboration with the Resuscitation Council UK.
.................................................................................................................................................................
Correspondence to: A. Dodd
Email:
Accepted: 18 November 2023
Keywords: intravenous adrenaline; perioperative Allergy Network; peri-operative anaphylaxis; Resucscitation Council UK
Twitter/X: @jas_soar; @LouiseSavic
Key recommendations 3 Adrenaline must be supported by intravenous
1 Consider anaphylaxis whenever unexpected and crystalloid fluid. Administer rapid, large-volume fluid
significant cardiovascular or respiratory compromise boluses (adults and children aged > 12 y, 500–1000 ml;
occurs. children aged < 12 y, up to 20 ml.kg-1). Multiple fluid
2 First-line treatment of peri-operative anaphylaxis is boluses may be required.
intravenous adrenaline (epinephrine). An initial dose of 4 If signs of anaphylaxis persist despite adrenaline
50 lg (0.5 ml of 1 mg.10 ml -1
[1:10,000]) strength is boluses, start an adrenaline infusion. A low-dose
recommended in adults and children aged > 12 y adrenaline infusion, given via a peripheral venous line, is
(some patients may respond to smaller doses (10– an effective alternative if central venous access is
50 lg) titrated to effect). unavailable.
.................................................................................................................................................................
Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit
commercial exploitation.
© 2023 Association of Anaesthetists. 1
, 13652044, 0, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.16206 by All India Institute Of Medical Sciences (Aiims), Jodhpur, Wiley Online Library on [13/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthesia 2023 Dodd et al. | Treatment of peri-operative anaphylaxis
5 Start cardiopulmonary resuscitation if systolic blood of potential triggers for anaphylaxis, with an average of
pressure is < 50 mmHg despite initial adrenaline and eight drugs administered, but this can be as many as 20 [7].
intravenous fluid. These include induction and maintenance drugs;
6 Antihistamines and corticosteroids are not useful in the analgesics; antibiotics and anti-emetics. In the UK, almost
immediate treatment of anaphylaxis. Do not prioritise half of general anaesthetics include the use of a
these over adrenaline and fluid resuscitation. neuromuscular blocking drug [7]. The majority of patients
are also exposed to chlorhexidine and many are also
What other guideline statements are exposed to latex. Other potential triggers include
available on this topic? radiocontrast and other dyes; surgical materials such as
The Resuscitation Council UK (RCUK) published an updated glues and cements; and intravenous colloid fluids [8]. In the
guideline in 2021 for the emergency treatment of 6th National Audit Project of the Royal College of
anaphylaxis by healthcare providers in hospital and Anaesthetists (NAP6) the most common causes
community settings [1]. Recommendations for the of anaphylaxis were antibiotics (47%); neuromuscular
management and investigation of peri-operative blocking drugs (33%); chlorhexidine (9%) and patent blue
anaphylaxis have been published by the International dye (3%) [7].
Suspected Perioperative Allergic Reactions group [2] and During anaphylaxis degranulation of mast cells and
the European Academy of Allergy and Clinical Immunology basophils leads to the activation of multiple inflammatory
[3]. pathways [9]. This results in tissue oedema and smooth
muscle contraction in the airways (causing high airway
Why was this algorithm developed? pressures, bronchospasm and wheeze); fluid extravasation,
This algorithm was developed by the RCUK and leading to tissue oedema, hypovolaemia, and a profound
Perioperative Allergy Network to provide specific guidance reduction in venous tone; depressed myocardial function,
on the treatment of anaphylaxis in the peri-operative setting which can lead to cardiogenic shock and arrhythmias; and
where anaesthetists are providing patient care. fluid leakage into the bowel, as well as smooth muscle
contraction, which can result in abdominal and pelvic
How and why does this statement differ cramps.
from existing guidelines? Peri-operative anaphylaxis is a clinical diagnosis. It can
The RCUK guideline for the emergency treatment of be particularly difficult to make a diagnosis in the peri-
anaphylaxis [1] is a generic guideline for healthcare operative setting because typical presenting features of an
providers and recommends intramuscular adrenaline for allergic reaction (such as urticaria and other skin signs) are
the immediate treatment of suspected anaphylaxis. absent in around one-third of reactions. There is a wide
However, the intramuscular route is less appropriate in the range of differential diagnoses, including exaggerated
peri-operative setting, where patients typically present with physiological responses to induction agents; airway
more severe and rapid onset reactions, are very closely manipulation; and surgical interventions. Peri-operative
monitored, have intravenous access and are under the anaphylaxis occurs most frequently following induction of
direct care of an anaesthetist. The peri-operative anaesthesia, with symptom onset typically within minutes
anaphylaxis algorithm emphasises the importance of using of exposure to the culprit drug. Time to cardiac arrest
early intravenous adrenaline in small doses, titrated to following intravenous exposure is faster than other routes of
effect, before establishing a low-dose intravenous exposure to a triggering drug, with onset typically within 5–
adrenaline infusion if needed. The algorithm is aligned with 10 min [7].
the treatment detailed in the Quick Reference Handbook of The modified Ring and Messmer Scale (Table 1)
the Association of Anaesthetists [4]. characterises the phenotypes of peri-operative allergic
reactions and severity grading [10]. Grades 1 and 2
Background describe non-life-threatening reactions with skin and or
Peri-operative anaphylaxis during anaesthesia is a moderate organ involvement. Grade 3 and 4 reactions
potentially catastrophic event with a quoted incidence demonstrate life-threatening organ involvement, fulfilling
ranging from 1:353 to 1:18,600 anaesthetics and an the criteria for severe anaphylaxis. Grade 3 peri-operative
estimated mortality of around 1–4% [5]. This is higher than anaphylaxis typically presents with sudden onset, life-
the mortality reported for anaphylaxis in other settings [6]. threatening hypotension [6, 11], with or without tachycardia
During anaesthesia, patients are exposed to a large number or bradycardia [7]. Bronchospasm as a presenting sign is
2 © 2023 Association of Anaesthetists.
Guidelines
Emergency treatment of peri-operative anaphylaxis:
Resuscitation Council UK algorithm for anaesthetists
A. Dodd,1 P. J. Turner,2 J. Soar,3 L. Savic4 and representing the UK Perioperative
Allergy Network
1 Consultant, Department of Anaesthesia, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
2 Reader, Department of Paediatric Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial
College, London, UK
3 Consultant, Department of Anaesthesia and Intensive Care Medicine, Southmead Hospital, North Bristol NHS Trust,
Bristol, UK
4 Consultant, Department of Anaesthesia, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Summary
Peri-operative anaphylaxis is a rare but potentially catastrophic event which must be considered whenever
unexpected and significant cardiovascular or respiratory compromise occurs during anaesthesia. The
Resuscitation Council UK algorithm for peri-operative anaphylaxis highlights the importance of early
intravenous adrenaline and fluid resuscitation and provides guidance on the treatment of refractory anaphylaxis
and immediate follow-up. This algorithm is endorsed by the Royal College of Anaesthetists, Association of
Anaesthetists, British Society of Allergy and Clinical Immunology and Clinical Immunology Professional
Network of the British Society for Immunology. This document was produced by the Perioperative Allergy
Network steering committee in collaboration with the Resuscitation Council UK.
.................................................................................................................................................................
Correspondence to: A. Dodd
Email:
Accepted: 18 November 2023
Keywords: intravenous adrenaline; perioperative Allergy Network; peri-operative anaphylaxis; Resucscitation Council UK
Twitter/X: @jas_soar; @LouiseSavic
Key recommendations 3 Adrenaline must be supported by intravenous
1 Consider anaphylaxis whenever unexpected and crystalloid fluid. Administer rapid, large-volume fluid
significant cardiovascular or respiratory compromise boluses (adults and children aged > 12 y, 500–1000 ml;
occurs. children aged < 12 y, up to 20 ml.kg-1). Multiple fluid
2 First-line treatment of peri-operative anaphylaxis is boluses may be required.
intravenous adrenaline (epinephrine). An initial dose of 4 If signs of anaphylaxis persist despite adrenaline
50 lg (0.5 ml of 1 mg.10 ml -1
[1:10,000]) strength is boluses, start an adrenaline infusion. A low-dose
recommended in adults and children aged > 12 y adrenaline infusion, given via a peripheral venous line, is
(some patients may respond to smaller doses (10– an effective alternative if central venous access is
50 lg) titrated to effect). unavailable.
.................................................................................................................................................................
Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit
commercial exploitation.
© 2023 Association of Anaesthetists. 1
, 13652044, 0, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.16206 by All India Institute Of Medical Sciences (Aiims), Jodhpur, Wiley Online Library on [13/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthesia 2023 Dodd et al. | Treatment of peri-operative anaphylaxis
5 Start cardiopulmonary resuscitation if systolic blood of potential triggers for anaphylaxis, with an average of
pressure is < 50 mmHg despite initial adrenaline and eight drugs administered, but this can be as many as 20 [7].
intravenous fluid. These include induction and maintenance drugs;
6 Antihistamines and corticosteroids are not useful in the analgesics; antibiotics and anti-emetics. In the UK, almost
immediate treatment of anaphylaxis. Do not prioritise half of general anaesthetics include the use of a
these over adrenaline and fluid resuscitation. neuromuscular blocking drug [7]. The majority of patients
are also exposed to chlorhexidine and many are also
What other guideline statements are exposed to latex. Other potential triggers include
available on this topic? radiocontrast and other dyes; surgical materials such as
The Resuscitation Council UK (RCUK) published an updated glues and cements; and intravenous colloid fluids [8]. In the
guideline in 2021 for the emergency treatment of 6th National Audit Project of the Royal College of
anaphylaxis by healthcare providers in hospital and Anaesthetists (NAP6) the most common causes
community settings [1]. Recommendations for the of anaphylaxis were antibiotics (47%); neuromuscular
management and investigation of peri-operative blocking drugs (33%); chlorhexidine (9%) and patent blue
anaphylaxis have been published by the International dye (3%) [7].
Suspected Perioperative Allergic Reactions group [2] and During anaphylaxis degranulation of mast cells and
the European Academy of Allergy and Clinical Immunology basophils leads to the activation of multiple inflammatory
[3]. pathways [9]. This results in tissue oedema and smooth
muscle contraction in the airways (causing high airway
Why was this algorithm developed? pressures, bronchospasm and wheeze); fluid extravasation,
This algorithm was developed by the RCUK and leading to tissue oedema, hypovolaemia, and a profound
Perioperative Allergy Network to provide specific guidance reduction in venous tone; depressed myocardial function,
on the treatment of anaphylaxis in the peri-operative setting which can lead to cardiogenic shock and arrhythmias; and
where anaesthetists are providing patient care. fluid leakage into the bowel, as well as smooth muscle
contraction, which can result in abdominal and pelvic
How and why does this statement differ cramps.
from existing guidelines? Peri-operative anaphylaxis is a clinical diagnosis. It can
The RCUK guideline for the emergency treatment of be particularly difficult to make a diagnosis in the peri-
anaphylaxis [1] is a generic guideline for healthcare operative setting because typical presenting features of an
providers and recommends intramuscular adrenaline for allergic reaction (such as urticaria and other skin signs) are
the immediate treatment of suspected anaphylaxis. absent in around one-third of reactions. There is a wide
However, the intramuscular route is less appropriate in the range of differential diagnoses, including exaggerated
peri-operative setting, where patients typically present with physiological responses to induction agents; airway
more severe and rapid onset reactions, are very closely manipulation; and surgical interventions. Peri-operative
monitored, have intravenous access and are under the anaphylaxis occurs most frequently following induction of
direct care of an anaesthetist. The peri-operative anaesthesia, with symptom onset typically within minutes
anaphylaxis algorithm emphasises the importance of using of exposure to the culprit drug. Time to cardiac arrest
early intravenous adrenaline in small doses, titrated to following intravenous exposure is faster than other routes of
effect, before establishing a low-dose intravenous exposure to a triggering drug, with onset typically within 5–
adrenaline infusion if needed. The algorithm is aligned with 10 min [7].
the treatment detailed in the Quick Reference Handbook of The modified Ring and Messmer Scale (Table 1)
the Association of Anaesthetists [4]. characterises the phenotypes of peri-operative allergic
reactions and severity grading [10]. Grades 1 and 2
Background describe non-life-threatening reactions with skin and or
Peri-operative anaphylaxis during anaesthesia is a moderate organ involvement. Grade 3 and 4 reactions
potentially catastrophic event with a quoted incidence demonstrate life-threatening organ involvement, fulfilling
ranging from 1:353 to 1:18,600 anaesthetics and an the criteria for severe anaphylaxis. Grade 3 peri-operative
estimated mortality of around 1–4% [5]. This is higher than anaphylaxis typically presents with sudden onset, life-
the mortality reported for anaphylaxis in other settings [6]. threatening hypotension [6, 11], with or without tachycardia
During anaesthesia, patients are exposed to a large number or bradycardia [7]. Bronchospasm as a presenting sign is
2 © 2023 Association of Anaesthetists.
