Recommendations
Urgent
For patients in cardiorespiratory arrest, start CPR according to your local advanced life support guideline and call for help.[74][92][93][94]
Do not give intramuscular adrenaline (epinephrine) if cardiac arrest has occurred, as circulation to the muscle, and therefore distribution, is inadequate.[32]
This topic does not cover the detailed management of patients in cardiorespiratory arrest. Some patients who suffer a cardiorespiratory arrest following anaphylaxis and who regain spontaneous circulation may need ongoing critical care input.
Following discussion with a senior clinician and the critical care team, you may be able to continue the management of other patients in the resuscitation area of the emergency department as per below.
If a patient has cardiorespiratory function, call for help immediately so that you can position the patient, remove the trigger, and give intramuscular adrenaline at the same time.[32]
In practice, if you need to give adrenaline, call for senior assistance immediately in case the patient deteriorates.
Position the patient comfortably. Keep the patient in a supine or semi-recumbent position during treatment.[32] If the patient:[32][59]
Feels faint: do not sit or stand them up as this can cause cardiac arrest
Has predominant airway/breathing problems: place them in a semi-recumbent position, or sitting up with elevated legs, as this may make breathing easier
Has predominant circulation problems: lie them flat with/without legs up
Is unconscious and breathing: position on their side (recovery position)
Is pregnant: lie them on their left side or with the bed in a head-down position
In practice, this is only necessary in an obviously gravid uterus well into the pregnancy.
Avoid sudden changes in posture.[32]
Remove the trigger if possible.[32]
Stop any drug that may be the cause of the anaphylaxis (e.g., drug infusion, blood products).
Remove the stinger after a bee sting. Early removal is more important than the method of removal.
Do not try to make the patient vomit.
Give intramuscular adrenaline into the anterolateral aspect of the middle third of the thigh, stretching the skin, using a needle at a 90° angle to the skin and that is long enough to reach the muscle.[32][96]
25 mm (blue 23G or orange 25G) needle is suitable for all ages
16 mm (orange 25G) needle is appropriate for preterm or small infants
38 mm (green 21G) needle may be needed in some adults.
While there are no absolute contraindications to giving adrenaline for anaphylaxis, both underlying comorbidity and concomitant medications may complicate the treatment of anaphylaxis in older people and people with cardiovascular disease. Seek advice as early as possible in these patients, but do not delay giving adrenaline in order to do so.[63]
Repeat the intramuscular dose of adrenaline if there is no improvement after 5 minutes.[32] Establish the airway and follow basic or advanced life support principles.[32]
Give high-concentration oxygen at a high flow of >10 L/minute with a mask and oxygen reservoir.[32]
The Resuscitation Council (UK) and the British Thoracic Society recommend a target oxygen saturation of >94% to 98%.[32][98]
However, evidence suggests that liberal use of supplemental oxygen (target SpO 2 >96%) in acutely ill adults is associated with higher mortality than more conservative oxygen therapy.[99]
A lower target SpO 2 of 88% to 92% is appropriate if the patient is at risk of hypercapnic respiratory failure.[98]
Establish intravenous access and give a rapid intravenous fluid bolus (over less than 15 minutes) with a non-glucose-containing crystalloid that has a sodium concentration of 130 to 154 mmol/L (130 to 154 mEq/L), early in the presence of hypotension, shock, or if there is a poor response to an initial dose of intramuscular adrenaline:[32][100][101]
Adults: 500 to 1000 mL
Children: 10 mL/kg.
Consider the following:
If respiratory or cardiovascular symptoms persist despite two doses of intramuscular adrenaline (refractory anaphylaxis), seek urgent expert help to allow for a low-dose, intravenous adrenaline infusion to be started. Intravenous adrenaline should only be administered by a specialist with experience in the use and titration of vasopressors in their normal clinical practice.[32]
If there is marked stridor, give nebulised adrenaline in addition to intramuscular adrenaline.[32][56][59]
If the patient is wheezing on auscultation or signs of bronchoconstriction are present, give a nebulised short-acting beta-2 agonist such as salbutamol.[32][54][59]
Monitor vital signs early.[32]
In all critically ill patients, as soon as possible attach a:[32]
Pulse oximeter
ECG monitor
Non-invasive blood pressure monitor.
Key Recommendations
After initial treatment
Give a non-sedating oral antihistamine (e.g., cetirizine) after initial resuscitation in preference to chlorphenamine, which causes sedation, especially in patients with persisting skin symptoms (urticaria and/or angio-oedema).[32]
Do not use corticosteroids routinely to treat anaphylaxis.[32]
Consider giving corticosteroids after initial resuscitation for refractory reactions or ongoing asthma or shock. Do not give corticosteroids preferentially to adrenaline.[32]
Biphasic reactions
If adrenaline has been administered, monitor patients for a return of symptoms for a minimum of 6 to 24 hours, depending on the severity of the reaction and other factors.[32][52][59]
Before discharge, give patients clear instructions to return to hospital if symptoms return.
Advise patients to eat some food at least 1 hour prior to discharge to reduce the risk of subsequent symptoms after leaving hospital.[32]
Postural hypotension has been reported after both anaphylaxis and milder allergic reactions. Ask patients to stand up and assess them for dizziness. Measure blood pressure if appropriate.[32]
Discharge
After emergency treatment for suspected anaphylaxis, offer the patient (or their parent and/or carer):[52]
An appropriate adrenaline auto-injector as an interim measure before their specialist allergy service appointment
A prescription for a further two adrenaline auto-injectors.
Follow-up
All patients who have had an anaphylactic reaction should be seen in a specialist allergy clinic for long-term management, education, adrenaline auto-injector training, and possible immunotherapy.[32][59]
If cardiorespiratory arrest occurs, start CPR according to your local advanced life support guideline and call for help.[74][92][93][94]
Note that you should not give intramuscular adrenaline (epinephrine) after cardiac arrest has occurred as circulation to the muscle, and therefore distribution, is inadequate.[32]
Detailed management of patients in cardiorespiratory arrest is not covered in this topic. Patients who suffer a cardiorespiratory arrest following anaphylaxis who regain spontaneous circulation may need ongoing critical care input.
Following discussion with a senior clinician and the critical care team, you may be able to continue the management of others in the resuscitation area of the emergency department as per below.
Anaphylaxis is a medical emergency but has varied presentations. Treat the greatest threat to life first, but be aware that positioning the patient, removing the trigger, and giving adrenaline (epinephrine) take seconds, while establishing an airway may take longer and require specialist expertise.
The order of steps presented here is designed for a single responder; however, several rescuers should undertake multiple actions simultaneously.
Call for help
If a patient with anaphylaxis has cardiorespiratory function, call for help immediately so that you can position the patient, remove the trigger, and give intramuscular adrenaline at the same time.[32]
The Resuscitation Council (UK) recommends calling for help immediately, whereas the European Academy for Allergy and Clinical Immunology recommends giving adrenaline before calling for help.[32][59]
In practice, if you need to give adrenaline, call for senior assistance in case the patient deteriorates. In most hospital situations you will be able to ask someone to call for help while you administer adrenaline.
Position the patient
Position the patient comfortably. Keep the patient in a supine or semi-recumbent position during treatment.[32] If the patient:[32][59]
Feels faint: do not sit or stand them up as this can cause cardiac arrest
Has predominant airway/breathing problems: place them in a semi-recumbent position, or sitting up with elevated legs, as this may make breathing easier
Has predominant circulation problems: lie them flat with/without legs up
Is unconscious and breathing: position on their side (recovery position)
Is pregnant: lie them on their left side or with the bed in a head-down position
In practice, this is only necessary in an obviously gravid uterus well into pregnancy.
Avoid sudden changes in posture.[32]
Changes in the patient’s posture from supine to standing or sitting upright have been associated with cardiovascular collapse and death during anaphylaxis; it also further reduces venous return to the heart which can lead to a further reduction in cardiac output and can compromise myocardial perfusion.[32]
Remove the trigger
Attempt to remove the trigger, but do not delay treatment if this is not possible.[32]
Stop any drug that may be the cause of the anaphylaxis (e.g., drug infusion, blood products).
Remove the stinger after a bee sting. Early removal is more important than the method of removal.
Do not try to make the patient vomit.
Give adrenaline (epinephrine)
Give intramuscular adrenaline into the anterolateral aspect of the middle third of the thigh, using a needle long enough to reach the muscle.[32]
25 mm (blue 23G or orange 25G) needle is best and suitable for all ages
16 mm (orange 25G) needle is appropriate for preterm or small infants
38 mm (green 21G) needle may be needed in some adults.
Injection technique:[32]
Stretch the skin and give the injection with the needle at a 90° angle to the skin.
While there are no absolute contraindications to giving adrenaline for anaphylaxis, both underlying comorbidity and concomitant medications may complicate the treatment of anaphylaxis in older people and people with cardiovascular disease. Seek cardiology advice as early as possible in these patients, but do not delay giving adrenaline in order to do so.[63]
Practical tip
Seek advice from a cardiologist as soon as you become aware that a patient has cardiovascular disease (CVD) but do not delay giving adrenaline in life-threatening anaphylaxis when adrenaline is required.
Treatment is complex because:
CVD limits cardiac reserve, which might compound hypotension
Patients with CVD may be on beta-blockers, which may counteract the effects of adrenaline by limiting heart rate, compromising cardiac output, and opposing its bronchodilatory properties. This may result in failure to reverse anaphylaxis
Hypotension, tachycardia, and adrenaline may cause myocardial ischaemia by reducing perfusion during diastole
The alpha-1 agonist action of adrenaline can lead to severe hypertension/hypertensive crisis.
The cardiologist may advise giving glucagon to treat an anaphylactic reaction in a patient taking a beta-blocker.[102]
Repeat the intramuscular dose of adrenaline if there is no improvement after 5 minutes.[32]
Refractory anaphylaxis
If the patient’s respiratory or cardiovascular symptoms do not improve after two doses of intramuscular adrenaline (refractory anaphylaxis) seek urgent expert help to allow for a low-dose, intravenous adrenaline infusion to be started by a specialist.[32] Give an initial rapid fluid bolus and maintenance fluid therapy with adrenaline therapy.[32]
Intravenous adrenaline boluses are not recommended unless the patient is in cardiac arrest (but they may be used by specialists experienced in the use and titration of vasopressors in their normal clinical practice, while the adrenaline infusion is set up).[32]
Continue to repeat intramuscular adrenaline after every 5 minutes until the infusion has been started.[32]
Intravenous adrenaline should only be administered by a specialist with experience in the use and titration of vasopressors in their normal clinical practice (e.g., anaesthetists, emergency physicians, intensive care doctors, or, in the case of children, paediatric anaesthetists, paediatric emergency physicians, paediatric intensivists).[32]
Many healthcare providers have given intravenous adrenaline as part of cardiac arrest resuscitation, but this is insufficient experience to safely use intravenous adrenaline to treat anaphylaxis.[32]
Be aware that patients on beta-blockers may be less responsive to adrenaline.[32][59]
The low-dose intravenous adrenaline infusion should be continued and titrated as symptoms improve.[32]
Evidence: Adrenaline contraindications
Due to an absence of evidence, and ethical and moral issues in conducting future randomised controlled trials in this area, determining evidence-based contraindications for adrenaline in anaphylaxis is difficult, but failure or delay in giving adrenaline to patients with anaphylaxis may increase the likelihood of death.[9]
A Cochrane review of the benefits and harms of adrenaline in the treatment of anaphylaxis conducted in 2008 and a search rerun in 2010 found no randomised controlled trials that met the inclusion criteria.[103]
Nevertheless, four key sources support the benefits of intramuscular adrenaline over its risks when used for anaphylaxis, and intramuscular adrenaline is recommended with no absolute contraindications by:
The Resuscitation Council (UK)[32]
The European Academy of Allergy and Clinical Immunology[104]
The World Allergy Organization[51]
A practice parameter from the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. This includes patients with cardiovascular disease or acute coronary syndrome.[9] Assess the risk-to-benefit ratio with care in such patients, but this assessment usually favours administration of adrenaline.[9]
The World Allergy Organization suggests the category of people who are particularly vulnerable to adverse effects includes those:[51]
At the extremes of age
With hypertension, peripheral vascular disease, ischaemic heart disease, or untreated hyperthyroidism
Taking beta-blockers (which exaggerate the effects of adrenaline by permitting unopposed alpha-adrenergic vasoconstrictor effects, potentially causing hypertension, and block the beta-adrenergic effects of adrenaline that are potentially beneficial in anaphylaxis in opening the airways).
NOTE: Intramuscular adrenaline is not recommended in patients with cardiorespiratory arrest but this is not a contraindication per se – rather, the lack of circulation to muscle associated with cardiac arrest means that intramuscular adrenaline may not be absorbed, and hence may be ineffective.
Evidence: Adrenaline timing
Guidelines consistently recommend giving adrenaline early.[51][59]
A Cochrane systematic review found that delayed adrenaline was associated with death.[103] This was based on five studies of anaphylaxis fatalities.[17][54][105][106][107]
The European Academy of Allergy and Clinical Immunology guideline recommends giving adrenaline early.[59] This is based on evidence from case series in which prompt adrenaline reduced the risk of death from anaphylaxis.
The World Allergy Organization guideline recommends prompt adrenaline administration in the initial treatment of anaphylaxis.[51] This is based on:
Four observational studies of patients with anaphylaxis[108][109][110][111]
Three randomised controlled clinical pharmacology studies in patients at risk for anaphylaxis but not experiencing it at the time of the investigation[63][112][113]
Twelve retrospective studies, including epidemiologic studies[63][103][112][113][114][115][116][117][118][119][120][121]
Evidence: Adrenaline route of administration
Guidelines consistently recommend giving adrenaline intramuscularly for the initial management of anaphylaxis.[51][59]
Adrenaline has a vasodilator effect in skeletal muscle, which is well-vascularised. After intramuscular injection into the vastus lateralis (mid-anterolateral thigh), rapid absorption allows adrenaline to reach the central circulation rapidly, so the intramuscular route is preferred over the subcutaneous route.[59]
The Resuscitation Council (UK) guideline does not recommend subcutaneous or inhaled routes for adrenaline.[32] This is because evidence from randomised controlled trials in adults and children shows they are less effective.[122][123][124]
A literature review from 2003 reported fatal cardiac arrhythmias and myocardial infarction associated with intravenous adrenaline, usually when it was given too rapidly, inadequately diluted, or in an excessive dose (based on fatality reports and expert opinion).[63]
Intravenous adrenaline should only be administered to patients with anaphylaxis by a specialist with experience in the use and titration of vasopressors in their normal clinical practice (e.g., anaesthetists, emergency physicians, intensive care doctors, or, in the case of children, paediatric anaesthetists, paediatric emergency physicians, paediatric intensivists).[32]
Practical tip
An important differential diagnosis is bradykinin-mediated angio-oedema (BMA).[95] This is usually due to hereditary C1-esterase inhibitor deficiency and can be triggered by ACE inhibitors. Facial and perioral swelling can be life-threatening, but patients with BMA tend not to have urticaria or haemodynamic instability and do not respond to adrenaline.
These patients require a C1-esterase inhibitor concentrate, icatibant (a bradykinin B2 receptor antagonist), or fresh frozen plasma. Seek urgent expert help if you suspect BMA. See Differentials.
Establish the airway
Be aware of the potential for impending airway difficulties. If there is airway obstruction at presentation, basic manoeuvres to maintain the airway may be required immediately. Seek help from an anaesthetist early if you are worried about maintaining the airway.[32]
Follow basic or advanced life support principles.[32] Give high concentration oxygen at a high flow of >10 L/minute with a mask and oxygen reservoir.[32]
The Resuscitation Council (UK) and the British Thoracic Society recommend a target oxygen saturation of >94% to 98%.[32][98]
However, evidence suggests that liberal use of supplemental oxygen (target SpO 2 >96%) in acutely ill adults is associated with higher mortality than more conservative oxygen therapy.[99]
A lower target SpO 2 of 88% to 92% is appropriate if the patient is at risk of hypercapnic respiratory failure.[98]
If there is marked stridor, give nebulised adrenaline in addition to intramuscular adrenaline.[32][56][59]
Ensure oxygen levels are maintained if a patient needs a nebulised bronchodilator such as adrenaline.[32][98]
Nebulisers should be driven by piped oxygen or from an oxygen cylinder fitted with a high-flow regulator capable of delivering a flow rate of >6 L/minute.[32][98]
Change the patient back to their usual oxygen mask or cannulae when nebuliser therapy is complete.[32][98]
In some countries a specific nebulised adrenaline formulation is available. However, this is not available in the UK, and the solution in the parenteral ampoules is used to give the nebulised dose. Consult local protocols.
Give a nebulised short-acting beta-2 agonist such as salbutamol to relieve symptoms of bronchoconstriction or if there is wheezing on auscultation.[32][54][59]
Ensure oxygen levels are maintained if a patient needs a nebulised bronchodilator such as salbutamol.[32][98]
Nebulisers should be driven by piped oxygen or from an oxygen cylinder fitted with a high-flow regulator capable of delivering a flow rate of >6 L/minute.[32][98]
Change the patient back to their usual oxygen mask or cannulae when nebuliser therapy is complete.[32][98]
If the patient has persistent signs of bronchoconstriction (whether or not the patient has pre-existing asthma), see our Acute asthma exacerbation topics for information on further bronchodilator therapy.
Practical tip
Patients with asthma who have anaphylaxis
If the patient has signs of anaphylaxis in addition to wheeze, coughing, and shortness of breath, give adrenaline before administering an asthma reliever.[104][125] Such additional signs include:[51]
Hypotension
Itching
Urticaria
Angio-oedema
Abdominal pain.
This is because the asthma reliever will only address respiratory symptoms; adrenaline addresses many of the pathological mechanisms occurring during anaphylaxis.
Fluids
Establish intravenous access as soon as possible.[32]
If you cannot obtain intravenous access, attempt intraosseous access if you are trained to do so.[32]
Give a rapid intravenous fluid bolus (over less than 15 minutes), early in the presence of hypotension or shock, or if there is a poor response to an initial dose of intramuscular adrenaline, with a non-glucose-containing crystalloid that has a sodium concentration in the range of 130 to 154 mmol/L (130 to 154 mEq/L) to counteract fluid shifts associated with vasodilation and/or leaky capillaries:[32][100]
Adults: 500 to 1000 mL
Children: 10 mL/kg.
Check local protocols for specific recommendations on fluid choice. There is debate, based on conflicting evidence, on whether there is a benefit in using normal saline or balanced crystalloid in critically ill patients.
Practical tip
Be aware that large volumes of normal saline as the sole fluid for resuscitation may lead to hyperchloraemic acidosis.
Also note that use of lactate-containing fluid in a patient with impaired liver metabolism may lead to a spuriously elevated lactate level, so results need to be interpreted with other markers of volume status.
Evidence: Choice of fluids
Evidence from two large randomised controlled trials (RCTs) suggests there is no difference between normal saline and a balanced crystalloid for critically ill patients in mortality at 90 days, although results from two meta-analyses including these RCTs point to a possible small benefit of balanced solutions compared with normal saline.
There has been extensive debate over the choice between normal saline (an unbalanced crystalloid) versus a balanced crystalloid (such as Hartmann’s solution [also known as Ringer’s lactate] or Plasma-Lyte®). Clinical practice varies widely, so you should check local protocols.
In 2021 to 2022 two large double blind RCTs were published assessing intravenous fluid resuscitation in intensive care unit [ICU] patients with a balanced crystalloid solution (Plasma-Lyte) versus normal saline. The Plasma-Lyte 148 versus Saline (PLUS) trial (53 ICUs in Australia and New Zealand; N= 5037) and the Balanced Solutions in Intensive Care Study (BaSICS) trial (75 ICUs in Brazil; N=11,052).[126][127]
In the PLUS study 45.2% of patients were admitted to ICU directly from surgery (emergency or elective), 42.3% had sepsis and 79.0% were receiving mechanical ventilation at the time of randomisation.
In BaSICS almost half the patients (48.4%) were admitted to ICU after elective surgery and around 68.0% had some form of fluid resuscitation before being randomised.
Both found no difference in 90-day mortality overall or in pre-specified subgroups for patients with acute kidney injury (AKI), sepsis or post-surgery. They also found no difference in the risk of AKI.
In BaSICS, for patients with traumatic brain injury, there was a small decrease in 90-day mortality with normal saline - however, the overall number of patients was small (<5% of total included in the study) so there is some uncertainty about this result. Patients with traumatic brain injury were excluded from PLUS as the authors felt these patients should be receiving saline or a solution of similar tonicity.
One meta-analysis of 13 RCTs (including PLUS and BaSICS) confirmed no overall difference, although the authors did highlight a non-significant trend towards a benefit of balanced solutions for risk of death.[128]
One subsequent individual patient data meta-analysis included six RCTs of which only PLUS and BaSICS were assessed as being at low risk of bias. There was no statistically significant difference in in-hospital mortality (OR 0·96, 95% CI 0·91 to 1·02). However, the authors argued that using a Bayesian analysis there was a high probability that balanced solutions reduced in-hospital mortality, although they acknowledged that the absolute risk reduction was small.[129]
A pre-specified subgroup analysis of patients with traumatic brain injury (N=1961) found that balanced solutions increased the risk of in-hospital mortality compared with normal saline (OR 1·42, 95% CI 1·10 to 1·82).
Previous evidence has been mixed.
One 2015 double-blind, cluster randomised, double-crossover trial conducted in four ICUs in New Zealand (N=2278), the 0.9% Saline vs Plasma-Lyte for ICU fluid Therapy (SPLIT) trial, found no difference for in-hospital mortality, AKI, or use of renal-replacement therapy.[130]
However, one 2018 US multicentre unblinded cluster-randomised trial - the isotonic Solutions and Major Adverse Renal events Trial (SMART), among 15,802 critically ill adults receiving ICU care - found possible small benefits from balanced crystalloid (Ringer’s lactate or Plasma-Lyte) compared with normal saline. The 30-day outcomes showed a non-significant reduced mortality in the balanced crystalloid group versus the normal saline group (10.3% vs 11.1%; OR 0.90, 95.% CI 0.80 to 1.01) and a major adverse kidney event rate of 14.3% versus 15.4% respectively (OR 0.91, 95% CI 0.84 to 0.99).[42]
One 2019 Cochrane review included 21 RCTs (N=20,213) assessing balanced crystalloids versus normal saline for resuscitation or maintenance in a critical care setting.[131]
The three largest RCTs in the Cochrane review (including SMART and SPLIT) all examined fluid resuscitation in adults and made up 94.2% of participants (N=19,054).
There was no difference in in‐hospital mortality (OR 0.91, 95% CI 0.83 to 1.01; high quality evidence as assessed by GRADE), acute renal injury (OR 0.92, 95% CI 0.84 to 1.00; GRADE low), or organ system dysfunction (OR 0.80, 95% CI 0.40 to 1.61; GRADE very low).
Repeat fluid boluses if necessary.[32] Large amounts of fluid may be needed.
Use a non-glucose-containing crystalloid in preference to 0.9% sodium chloride to reduce the risk of hyperchloraemic acidosis.
Decrease or stop the fluid infusion if signs of fluid overload develop.
Practical tip
Differentiating fluid overload from signs and symptoms of anaphylaxis:
Shortness of breath, peripheral oedema, raised jugulovenous pressure, a third heart sound, and inspiratory crackles in the lungs on auscultation indicate cardiac failure, but many of these symptoms and signs overlap with those of anaphylaxis
Newly raised jugulovenous pressure, new respiratory crackles, peripheral oedema, and chest x-ray may help identify fluid overload more specifically.
Seek expert help to improve tissue perfusion with inotropes or vasopressors if needed.
Monitoring
Monitor vital signs early.[32] In all critically ill patients, as soon as possible, attach a:
Pulse oximeter
ECG monitor
Non-invasive blood pressure monitor.
Be aware of biphasic reactions. See our Biphasic reactions section under Further management below.
In patients with refractory anaphylaxis, monitor for adrenaline side effects: tachycardia, arrhythmia, hypertension. If present, the infusion rate should be reduced (or stopped if side effects are severe).[32]
Other drugs
Consider giving intravenous atropine if the patient becomes bradycardic.[32][102] Consult a cardiologist or senior clinician with experience in administering this drug.[32][74][109]
Consider giving an intravenous glucagon infusion if the patient is on a beta-blocker and is not responding to adrenaline infusion and adequate fluid resuscitation.[102] Consult a cardiologist or senior clinician with experience in administering this drug.[32]
After initial treatment
Give a non-sedating oral antihistamine (e.g., cetirizine) once the patient has been stabilised, in preference to chlorphenamine which causes sedation, especially in patients with persisting skin symptoms (urticaria and/or angio-oedema).[32]
Do not delay administration of adrenaline and intravenous fluids to give antihistamines. Antihistamines do not treat respiratory or cardiovascular symptoms of anaphylaxis.[32]
Do not use corticosteroids routinely to treat anaphylaxis.[32]
There is little evidence that corticosteroids help shorten protracted symptoms or prevent biphasic reactions. Emerging data suggest that early use of corticosteroids in anaphylaxis is associated with an increased risk of intensive care admissions, even after adjusting for severity of presenting symptoms.[32]
Consider giving corticosteroids after initial resuscitation for refractory reactions or ongoing asthma or shock. Do not give corticosteroids preferentially to adrenaline.[32]
Evidence: Antihistamines
Guidelines recommend antihistamines as adjuvant treatment only to relieve itching, flushing, urticaria, angio-oedema, and nasal and eye symptoms after initial resuscitation.
Antihistamines (H1 antagonists) do not prevent or relieve upper airway obstruction, hypotension, or shock; however, histamine is released from mast cells and basophils in acute allergic inflammation, so it is logical to give antihistamines for such conditions.[132][133][134]
A Cochrane systematic review (literature search last rerun in 2010) found no randomised controlled trials examining the benefit of antihistamines in people with anaphylaxis.[135]
Nevertheless, despite an absence of evidence, the Resuscitation Council (UK), the World Allergy Organization, and the European Academy of Allergy and Clinical Immunology (EAACI) are consistent in recommending antihistamines to relieve itching, flushing, urticaria, angio-oedema, and nasal and eye symptoms associated with anaphylaxis.[32][51][59]
There is little evidence to support the initial use of H2 antagonists (e.g., ranitidine, cimetidine) in anaphylaxis and they are not recommended.[32][133]
Evidence: Corticosteroids
Guidelines differ in their recommendation for corticosteroid use after initial resuscitation in anaphylaxis.
Corticosteroids switch off transcription of activated genes encoding pro-inflammatory proteins and are thought to relieve protracted symptoms of anaphylaxis and prevent biphasic anaphylaxis (recurrence of symptoms after initial resolution despite no further exposure to the trigger).[51]
A Cochrane systematic review in 2012 found no randomised controlled trials investigating corticosteroid treatment in anaphylaxis.[136]
However, the European Academy of Allergy and Clinical Immunology (EAACI; 2014) and World Allergy Organization (WAO; 2015) anaphylaxis guidelines are consistent in recommending corticosteroids to relieve protracted symptoms and prevent biphasic reactions after the patient has been stabilised.[51][59]
More recently, evidence has emerged that corticosteroids may not improve outcomes in anaphylaxis. Two separate systematic reviews from 2017, with some overlap in trials included, reached different conclusions.[137][138]
One systematic review identified 22 human studies (19 retrospective cohort studies, one cross-sectional descriptive study, and two prospective cohort studies) evaluating the use of corticosteroids in emergency management of anaphylaxis.[137] The authors conclude that there is no compelling evidence to support or oppose the use of corticosteroids in emergency treatment of anaphylaxis. However, they also state, based on the available data, that corticosteroids appear to be beneficial and there is no evidence of adverse outcomes related to their use in emergency treatment of anaphylaxis.
The second systematic review included a total of 22 relevant case series, prospective and retrospective cohort studies, and clinical trials that looked at the association of corticosteroid treatment with biphasic anaphylaxis.[138] Substantial heterogeneity between the studies was noted and confounding was considered to be a major limitation, but 21 of the studies found no preventive association between corticosteroids and biphasic anaphylaxis. The authors do not recommend the routine use of corticosteroids in anaphylaxis because of “the potential detrimental adverse effects of corticosteroids and lack of compelling evidence demonstrating an effective role in reducing anaphylaxis severity or preventing biphasic anaphylaxis”.
The Resuscitation Council UK (2021) guidelines do not recommend using corticosteroids routinely to treat anaphylaxis, but recommend considering corticosteroids in refractory anaphylaxis or ongoing asthma or shock.[32]
When prescribing corticosteroids, clinicians should be aware of the following points:
Biphasic reactions
Be aware of the potential for a biphasic reaction in patients who have had an anaphylactic reaction. This usually occurs within 12 hours after the initial reaction.[32]
Biphasic reactions occur in approximately 5% of patients.[32] There is no reliable way of predicting who will have a biphasic reaction. They can be difficult to distinguish from sustained anaphylaxis with a transient response to adrenaline, or from progression following continued allergen absorption from food remaining in the gastrointestinal tract.[32]
The median time to biphasic symptoms (i.e., time by which 50% of biphasic reactions have occurred) is estimated to be around 12 hours.[139][140][141][142]
Monitor patients for a return of symptoms for a minimum of 2 to 12 hours depending on the severity of the reaction and other factors.[32] See Observation section below. Risk factors for biphasic reactions following anaphylaxis include:[32]
More severe initial presentation of anaphylaxis
Initial reaction requiring more than one dose of adrenaline
Delay in adrenaline administration (>30-60 minutes from symptom onset)
History of a previous biphasic reaction.
Manage patients having a biphasic reaction in the same way as you would for an initial anaphylactic reaction.[52]
Before discharge from hospital, give clear instructions to patients to return to hospital if symptoms recur.
Advise patients to eat some food at least 1 hour prior to discharge to reduce the risk of subsequent symptoms after leaving hospital.[32]
Ask patients to stand up (or to sit upright, if possible, if they have an existing disability) and assess them for dizziness. Measure blood pressure if appropriate.[32]
If a patient has received adrenaline (epinephrine), a senior clinician should decide on further treatment and how long observation is required.[32] Observation should occur in a clinical area with facilities for treating life-threatening airway, breathing, and circulation problems.[32]
Follow your local protocol for observing patients following a suspected anaphylactic reaction.
Based on the available evidence, the Resuscitation Council (UK) recommends observation to monitor for biphasic reactions as follows:[32]
For at least 2 hours after resolution of symptoms (consider fast-track discharge) if there is:
A good response (within 5-10 minutes) to a single dose of adrenaline given within 30 minutes of onset of reaction
and
Complete resolution of symptoms
and
The patient has unused adrenaline autoinjectors and has been trained how to use them
and
There is adequate supervision following discharge
For at least 6 hours after resolution of symptoms if 2 doses of intramuscular adrenaline were given or there was a previous biphasic reaction.
Some patients may be discharged after 2 hours despite needing 2 doses of intramuscular adrenaline, for example, following a supervised allergy challenge in a specialist setting.
For at least 12 hours following resolution of symptoms for patients with:
Severe reaction requiring >2 doses of adrenaline
Severe asthma or reaction involved severe respiratory compromise
The possibility of continuing absorption of the allergen (e.g., slow-release medicines)
Presentation late at night
Possible inability to respond to deterioration
Difficulty accessing emergency care.
The National Institute for Health and Care Excellence in the UK recommends observing patients after suspected anaphylaxis for 6 to 12 hours from the onset of symptoms, depending on their response to emergency treatment.[52] It also recommends that you:[52]
Beware of biphasic reactions in which symptoms may return up to 12 hours after the initial response.[32]
Follow your local protocol for prescribing adrenaline (epinephrine) auto-injectors to patients who have had a suspected anaphylactic reaction.
The UK National Institute for Health and Care Excellence (NICE) recommends providing an adrenaline auto-injector as an interim measure to cover the period before the patient’s allergy clinic appointment.[52]
Latest European and UK guidance recommends offering a prescription for a further two adrenaline auto-injectors, which the patient should carry at all times.[32][52][143][144] Also consider needle length when choosing a suitable auto-injector.[143][144] Prescribing an auto-injector with the correct needle length (see table below) is important to ensure that the adrenaline is injected intramuscularly rather than subcutaneously.
Ensure the patient or carer thoroughly understands how and when to use the specific device they have been prescribed as technique varies between devices.[143][144]
Encourage people with allergies and their carers to practise the technique of using their specific adrenaline auto-injector using a trainer device. These are available free of charge from manufacturers’ websites.
Advice for patients and carers is available from the UK Medicines and Healthcare products Regulatory Agency. Adrenaline auto-injectors: advice on use Opens in new window
Adrenaline auto-injectors available in the UK are Emerade®, EpiPen®, and Jext®.
Adrenaline auto-injector | Size | Length of needle (mm) |
|---|---|---|
Emerade® | Children | 16 |
Adults | 23 | |
EpiPen® | Children | 13 |
Adults | 16 | |
Jext® | Children | 13 |
Adults | 15 |
Refer patients to an age-appropriate specialist allergy service for accurate investigation, diagnosis, monitoring, ongoing management, patient education, and possible immunotherapy.[32][52][59]
Provide patients (or their parent and/or carer) after a first anaphylactic presentation with advice about:[52]
How to recognise an anaphylactic reaction
The importance of using an adrenaline auto-injector and calling emergency services if an anaphylactic reaction occurs
How to use the adrenaline auto-injector
Biphasic reactions
How to avoid the suspected trigger (if known)
Referral to a specialist allergy service and the referral process
Patient support groups.
At subsequent presentations check that the patient understands the points above. Written information leaflets can be helpful.
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