Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

anaphylaxis

1st line – cardiopulmonary assessment and supportive measures

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INITIAL
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anaphylaxis
1st line – 

cardiopulmonary assessment and supportive measures

Airway patency must be maintained. Airways can close within minutes when surrounding tissues swell. Supplemental oxygen should be considered for all patients with anaphylaxis regardless of their respiratory status, and must be administered to any patient with respiratory or cardiovascular compromise and to those who do not respond to initial treatment with adrenaline (epinephrine).[2]​ Early prophylactic intubation or even cricothyrotomy may be necessary, especially if there is inspiratory stridor.[2]​ Prophylactic intubation is much superior to rescue cricothyrotomy. Any subjective findings (feeling of swelling or tightness in the throat or oropharynx) or objective findings (stridor, hoarseness, visualised glottic or tongue oedema, cyanosis) warrant preparation for emergency airway management.

Cardiovascular collapse should be treated with aggressive volume resuscitation (isotonic solutions such as 0.9% normal saline or Ringer's lactate) and vasopressor infusion. This necessitates immediate transfer to an accident and emergency (A&E) department or critical care setting as soon as possible.

Unless precluded by shortness of breath or vomiting, the patient should be placed in a supine position with legs elevated (shock or Trendelenburg position).[49]​ This will augment venous return, and thereby increase preload and enhance cardiac output.

Regardless of severity of reaction, all patients with a diagnosis of anaphylaxis should be kept under observation until signs and symptoms have fully resolved, and may require extended observation or admission.[2][28]​​

Plus – adrenaline (epinephrine)

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INITIAL
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anaphylaxis
Plus – 

adrenaline (epinephrine)

Treatment recommended for ALL patients in selected patient group

All patients with signs of a systemic reaction, especially hypotension, airway swelling, or difficulty breathing, should receive immediate intramuscular adrenaline in the anterolateral thigh.[42][43][44][45][46]​ 

The dose may be repeated every 5 to 15 minutes as needed.​[1]​​[3]​ Administration in the anterolateral thigh is superior to intramuscular administration in the deltoid or a subcutaneous injection.[50][51] 

Intravenous adrenaline is administered to patients in cardiopulmonary arrest, and to profoundly hypotensive patients who have not responded to intravenous fluids and several doses of intramuscular adrenaline.[2][52]​ Continuous infusion of adrenaline, titrated to effect, is reserved for experienced practitioners. No intravenous dose regimen is universally recognised.

A prescription for two adrenaline auto-injectors must be given after any episode of anaphylaxis.[2][3][5][28][53]​​​ The patient or carer should carry both at all times and be familiar with their use.[53]​[24]​

Primary options

adrenaline (epinephrine): 0.3 to 0.5 mg (1:1000 solution) intramuscularly every 5-15 minutes; consult specialist for guidance on intravenous dose

Consider – corticosteroid

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INITIAL
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anaphylaxis
Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

Corticosteroids, if used, should not replace adrenaline (epinephrine) as the first-line of treatment for anaphylaxis, and may be prescribed as adjunctive therapy after administration of adrenaline.[2]

Corticosteroids may decrease the risk of symptoms associated with anaphylaxis including urticaria; however, the data supporting the use of corticosteroids are limited due to difficulties in performing controlled studies.[55][56]

Guidelines published in 2020 advise against administering corticosteroids to prevent biphasic anaphylaxis. This is based on limited evidence suggesting that there is no clear benefit in terms of risk reduction.[2]

Corticosteroid treatment works in a delayed fashion to decrease vascular permeability and blunt the immune response to the inciting antigen.

Primary options

methylprednisolone sodium succinate: 1-2 mg/kg intravenously every 6 hours

OR

prednisolone: 1 mg/kg orally once daily, maximum 50 mg/day

Consider – H1 antagonist + H2 antagonist

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INITIAL
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anaphylaxis
Consider – 

H1 antagonist + H2 antagonist

Additional treatment recommended for SOME patients in selected patient group

Use of H1 and H2 antagonists is limited to relief of itching, hives, and rhinorrhoea. Their use should never delay or replace the use of intramuscular adrenaline.[57][58]

H1 antagonists (antihistamines) antagonise the effects of histamine release at cellular receptors, decreasing itching, erythema, and rash. In general, non-sedating H1 antagonists (e.g., cetirizine) should be used in preference to sedating H1 antagonists.[59]

H2 antagonists (e.g., cimetidine) can be used to further potentiate the antihistamine effect, although evidence of benefit is very limited.

Primary options

cetirizine: 10 mg intravenously/orally as a single dose

and

cimetidine: 4 mg/kg intravenously as a single dose

Consider – nebulised salbutamol

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INITIAL
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anaphylaxis
Consider – 

nebulised salbutamol

Additional treatment recommended for SOME patients in selected patient group

Persistent respiratory symptoms after administration of adrenaline (epinephrine) may benefit from inhaled beta-2 agonists.[4]​​

Primary options

salbutamol inhaled: 2.5 to 5 mg nebulised every 20 minutes for 3 doses, followed by 2.5 to 10 mg nebulised every 1-4 hours when required

Consider – stinger removal

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INITIAL
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anaphylaxis
Consider – 

stinger removal

Additional treatment recommended for SOME patients in selected patient group

Retained stingers should be removed because they may still contain venom. Traditional teaching suggests that squeezing the stinger (e.g., tweezers) can inject more venom into the patient. The stinger can be removed by gently scraping the stinger with the edge of a plastic ID card (driver's licence or similar object). Time to removal is more important than method in minimising the amount of venom injected.[60]

Consider – analgesia

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INITIAL
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anaphylaxis
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

Analgesia with paracetamol or a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen or naproxen can decrease swelling and pain at the site of the bite or sting.[24][32]​​

These medications can be tapered by the patient according to their symptoms. Patients should take NSAIDs at the lowest effective dose for the shortest treatment duration.

Caution should be used with NSAIDs in patients treated with aspirin or anticoagulants, or with sensitivity to these medications, or with risk factors for ulcers, gastrointestinal bleeding, or thromboembolic disease.

Primary options

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

Plus – glucagon

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INITIAL
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anaphylaxis
|
unresponsive to adrenaline (epinephrine)
Plus – 

glucagon

Treatment recommended for ALL patients in selected patient group

Patients treated with beta-blockers may be refractory to treatment with beta-agonists.

Glucagon works by bypassing the adrenergic receptors and directly activating cyclic adenosine monophosphate intracellularly. However, the resulting tachycardia can be detrimental in patients with severe coronary artery disease.[1]

Give to patients not responding to beta-agonist treatment.

Often causes nausea and vomiting, which may further prompt the need for definitive airway control. Anti-emetics may be required.

Primary options

glucagon: 1-5 mg intravenously initially, followed by 5-15 micrograms/minute infusion, titrate according to response

More
ACUTE

local reaction

1st line – supportive care

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ACUTE
|
local reaction
1st line – 

supportive care

Local pain and swelling at the site of the bite or sting can be reduced with cold compress application.[32]​ The compress should have a cloth barrier between the ice and skin to prevent local tissue damage. Applying the cold compress on and off at 15-minute intervals is a common regimen.

The wound should be cleaned with soap and water, and tetanus status should be addressed.

Surgical consultation may be needed for severe or progressive local reactions at the site of suspected brown recluse spider bites.

Fire ant pustules should be left intact. If opened, these lesions can serve as a portal for secondary infection. They should be kept clean and covered.[22][23]

All skin wounds should be assessed for tetanus prophylaxis. Tetanus-prone wounds (deep/dirty/necrotic/severe recluse spider envenomation) should receive tetanus prophylaxis if the last immunisation was >5 years ago.[61]​ Non-tetanus-prone wounds (e.g., stings/black widow spider bite) should trigger treatment if last immunisation was >10 years ago.

Consider – stinger removal

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ACUTE
|
local reaction
Consider – 

stinger removal

Additional treatment recommended for SOME patients in selected patient group

Retained stingers should be removed, as they may still contain venom. Traditional teaching suggests that squeezing the stinger (e.g., tweezers) can inject more venom into the patient. The stinger can be removed by gently scraping the stinger with the edge of a plastic ID card (driver's licence or similar object). Time to removal is more important than method in minimising the amount of venom injected.[60]

Consider – corticosteroid

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ACUTE
|
local reaction
Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

Guidelines vary regarding recommendations for the use of corticosteroids in sting allergy. In practice, many clinicians use oral corticosteroids for large local reactions; however, there is a lack of strong evidence to support the efficacy of this treatment.[32]​ In severe cases of insect sting reaction there may be a role for a short course of oral corticosteroids.[32]

Corticosteroid treatment works in a delayed fashion to decrease vascular permeability and blunt the immune response to the inciting antigen.

Primary options

prednisolone: 1 mg/kg orally once daily, maximum 50 mg/day

Consider – H1 antagonist + H2 antagonist

Back
ACUTE
|
local reaction
Consider – 

H1 antagonist + H2 antagonist

Additional treatment recommended for SOME patients in selected patient group

Use of H1 and H2 antagonists is limited to relief of itching, hives, and rhinorrhoea.[57][58]

H1 antagonists (antihistamines) antagonise the effects of histamine release at cellular receptors, decreasing itching, erythema, and rash. In general, non-sedating H1 antagonists (e.g., cetirizine) should be used in preference to sedating H1 antagonists.[59]

H2 antagonists (e.g., cimetidine) can be used to further potentiate the antihistamine effect, although evidence of benefit is very limited.

Primary options

cetirizine: 10 mg intravenously/orally as a single dose

and

cimetidine: 4 mg/kg intravenously as a single dose

Consider – analgesia

Back
ACUTE
|
local reaction
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

Analgesia with paracetamol or a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen or naproxen can decrease swelling and pain at the site of the bite or sting.[24][32]​​

These medications can be tapered by the patient according to their symptoms. Patients should take at the lowest effective dose for the shortest treatment duration.

Caution should be used in patients taking aspirin or anticoagulants, or with sensitivity to these medications, or with risk factors for ulcers, gastrointestinal bleeding, or thromboembolic disease.

Primary options

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

naproxen: 250-500 mg orally twice daily when required, maximum 1250 mg/day

Consider – additional analgesia

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ACUTE
|
local reaction
|
black widow spider bites
Consider – 

additional analgesia

Additional treatment recommended for SOME patients in selected patient group

Opioids (e.g., oxycodone, morphine) may be needed for more severe bites or patients with low pain tolerance.[37]

Primary options

oxycodone: 5-15 mg orally (immediate-release) every 4-6 hours when required, adjust dose according to response

OR

morphine sulfate: 10-30 mg orally (immediate-release) every 4 hours when required; 2.5 to 10 mg intravenously/intramuscularly/subcutaneously every 2-6 hours when required; adjust dose according to response

Consider – benzodiazepine

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ACUTE
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local reaction
|
black widow spider bites
Consider – 

benzodiazepine

Additional treatment recommended for SOME patients in selected patient group

Moderate or severe envenomation can cause severe pain and muscle spasms in the affected limb or in a generalised fashion. Severe muscle spasms may be relieved with benzodiazepines.[37]

Primary options

diazepam: 2-10 mg orally three to four times daily

Consider – beta-blocker

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ACUTE
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local reaction
|
black widow spider bites
Consider – 

beta-blocker

Additional treatment recommended for SOME patients in selected patient group

Tachycardia and hypertension may occur but usually resolve as pain is addressed. In patients who may not tolerate these effects, beta-blockers may be a reasonable treatment.

These spikes in blood pressure and heart rate tend to be transient. They often resolve spontaneously or after treatment of the pain or anxiety associated with the bite or sting.

Intravenous medications allow for tighter control and decrease the chance of inadvertently exceeding targets with longer-acting medications. Accidentally exceeding targets can cause blood pressure or heart rate to fall to dangerously low levels.

Primary options

labetalol: 20 mg intravenously initially, followed by 40-80 mg every 10 minutes when required according to response, maximum 300 mg total dose

Consider – antivenom

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ACUTE
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local reaction
|
black widow spider bites
Consider – 

antivenom

Additional treatment recommended for SOME patients in selected patient group

There are several black widow spider antivenoms on the market.[62][63]​​ Although fatalities from bites are exceedingly rare, treatment with antivenom may reduce the pain and duration of symptoms slightly. Indications vary by species, geographical location, and specific symptoms, but may include continued or severe pain despite aggressive opioid analgesia; autonomic instability (uncontrolled hypertension); respiratory difficulties; pregnancy; persistent symptoms despite supportive care.[37][66]​​ The modest benefits of treatment must, however, be weighed against the safety of antivenom treatment.[64] Although rare, reactions to antivenom include serum sickness (which manifests as fever, joint pain, and rash) and life-threatening anaphylaxis.[37]

In countries other than the US, antivenom is used more often and seems to have a good safety profile.[26][68]

Consider – additional analgesia

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ACUTE
|
local reaction
|
recluse spider bites
Consider – 

additional analgesia

Additional treatment recommended for SOME patients in selected patient group

Opioids (e.g., oxycodone, morphine) may be needed for more severe bites or patients with low pain tolerance.

Primary options

oxycodone: 5-15 mg orally (immediate-release) every 4-6 hours when required, adjust dose according to response

OR

morphine sulfate: 10-30 mg orally (immediate-release) every 4 hours when required; 2.5 to 10 mg intravenously/intramuscularly/subcutaneously every 2-6 hours when required; adjust dose according to response

Consider – dapsone

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ACUTE
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local reaction
|
recluse spider bites
Consider – 

dapsone

Additional treatment recommended for SOME patients in selected patient group

Despite their reputation, only a small proportion of recluse spider bites become necrotic.[27][Figure caption and citation for the preceding image starts]: Lesions from reported brown recluse (Loxoscelesspecies) envenomationCourtesy of Theodore Freeman [Citation ends].com.bmj.content.model.Caption@602e1918[Figure caption and citation for the preceding image starts]: Lesions from reported brown recluse (Loxosceles species) envenomationCourtesy of Theodore Freeman [Citation ends].com.bmj.content.model.Caption@7725e9fb

Dapsone treatment has been used to prevent or slow the development of necrosis, and has effects on reducing pain in necrotic lesions but it should not be used routinely.[37]​ No controlled trials have been conducted in humans. Data in animal models have been contradictory.[25]​​

Patients should be screened for glucose-6-phosphate dehydrogenase deficiency. Dapsone can cause a severe haemolytic anaemia in these patients. Screening is usually available within 1 day, and it is not necessary to start dapsone treatment immediately for it to be beneficial.

Primary options

dapsone: consult specialist for guidance on dose

Consider – surgical debridement + empirical antibiotics

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ACUTE
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local reaction
|
recluse spider bites
Consider – 

surgical debridement + empirical antibiotics

Additional treatment recommended for SOME patients in selected patient group

Continued necrosis may need surgical debridement and subsequent skin grafting for full healing, although this is a rare occurrence.[37]​ Necrotic tissue presents a prime substrate for secondary infection. Patients should be taught appropriate wound care and to be aware of signs of infection (e.g., fever, pus formation).

Antibiotic treatment is often begun empirically, because the diagnosis of spider bite is often not clear, and infections are the top other consideration on the differential diagnosis list. Antibiotic coverage should be appropriate for cellulitis in line with local susceptibility patterns for community-acquired MRSA.

Consider – antivenom

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ACUTE
|
local reaction
|
recluse spider bites
Consider – 

antivenom

Additional treatment recommended for SOME patients in selected patient group

Antivenoms for recluse spider bites are available in some South American countries, but not in the US. Some animal studies suggest efficacy at limiting necrosis, but there have not been any good clinical studies.[62]

ONGOING

secondary infection

1st line – antibiotics

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ONGOING
|
secondary infection
1st line – 

antibiotics

Antibiotics should only be prescribed if there are symptoms and signs of infection.[37][67]​​​ Antibiotics should be directed at common skin pathogens (staphylococcal and streptococcal species) and directed by local resistance patterns.

Treatment for 7 to 10 days' duration is usually adequate.

Non-beta-lactam antibiotics are suggested in patients with a severe allergy to penicillin.

Black widow spider bites do not become necrotic; antibiotics are not needed unless signs of secondary infection develop over the next few days.

Primary options

cefalexin: 250-500 mg orally every 6 hours

OR

flucloxacillin: 250 mg orally every 6 hours

OR

dicloxacillin: 250 mg orally every 6 hours

OR

nafcillin: 1-2 g intravenously every 4 hours

OR

cefazolin: 1-2 g intravenously every 8 hours

Secondary options

clindamycin: 300-450 mg orally every 6 hours

OR

linezolid: 600 mg intravenously every 12 hours

OR

vancomycin: 15 mg/kg intravenously every 12 hours

OR

daptomycin: 4 mg/kg intravenously once daily

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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