Treatment Algorithm And A Brief Description Of Anaphylaxis

Anaphylaxis is a generalized immunological condition of sudden onset, which develops after exposure to a foreign substance.

Pathophysiology: The mechanism may:
• Involve an IgE-mediated reaction to a foreign protein (stings, foods, streptokinase), or to a protein–hapten conjugate (antibiotics) to which the patient has previously been exposed.
• Be complement mediated (human proteins eg G -globulin, blood products).
• Be unknown (aspirin, ‘idiopathic’).
Irrespective of the mechanism, mast cells and basophils release mediators (eg histamine, prostaglandins, thromboxanes, platelet activating factors, leukotrienes) producing clinical manifestations.
Angio-oedema caused by ACE inhibitors and hereditary angio-oedema may present in a similar way
to anaphylaxis. Hereditary angio-oedema is not usually accompanied by urticaria and is treated with C1 esterase inhibitor.

Common causes: include:

• Drugs and vaccines (e.g antibiotics, streptokinase, suxamethonium, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), intravenous (IV) contrast agents).
• Hymenoptera (bee/wasp) stings.
• Foods (nuts, shellfi sh, strawberries, wheat).
• Latex.

Clinical features: The speed of onset and severity vary with the nature and amount of the stimulus, but the onset is usually in minutes/hours. A prodromal aura or a feeling of impending death may be present. Patients on B -blockers or with a history of ischemic heart disease (IHD) or asthma may have especially severe features.
Usually two or more systems are involved:
Respiratory:  Swelling of lips, tongue, pharynx, and epiglottis may lead to complete upper airway occlusion. Lower airway involvement is similar to acute severe asthma — dyspnoea, wheeze, chest tightness, hypoxia, and hypercapnia.
Skin: Pruritus, erythema, urticarial, and angio-oedema.
Cardiovascular:  Peripheral vasodilation and increased vascular permeability cause plasma leakage from the circulation, with decreased intravascular volume, hypotension, and shock. Arrhythmias, ischaemic chest pain, and electrocardiogram (ECG) changes may be present.
GI tract:  Nausea, vomiting, diarrhoea, abdominal cramps.

Treatment
• Discontinue further administration of suspected factor (eg drug). Remove stings by scraping them carefully away from skin.
• Give 100 % oxygen (O 2 ).
• Open and maintain airway. If upper airway oedema is present, get specialist senior help immediately. Emergency intubation or a surgical airway and ventilation may be required.
• In patients with shock, airway swelling, or respiratory difficulty give 0.5mg (0.5mL of 1:1000 solution) adrenaline intramuscular (IM). Repeat after 5 min if there is no improvement. In adults treated with an adrenaline autoinjector (eg EpiPen ® ) the 300mcg dose is usually sufficient, but additional doses may be required. Give only 50 % of the usual dose of adrenaline to patients taking tricyclic antidepressants, MAOIs, or B –blockers.
• In profound shock or immediately life-threatening situations, give CPR/ ALS as necessary, and consider slow IV adrenaline 1:10,000 or 1:100,000 solution. This is recommended only for experienced clinicians who can also obtain immediate IV access. Note the different strength of adrenaline required for IV use. If there is no response to adrenaline, consider glucagon 1–2mg IM/IV every 5min (especially in patients taking B -blockers).
• Give a B 2 -agonist (eg salbutamol 5mg) nebulized with O 2 for bronchospasm, possibly with the addition of nebulized ipratropium bromide 500 mcg.
• Give IV fluid if hypotension does not rapidly respond to adrenaline. Rapid infusion of 1–2 L IV 0.9% saline may be required, with further infusion according to the clinical state.
• Antihistamine H 1 blockers (e.g chlorphenamine 10–20 mg slow IV) and H 2 blockers (e.g ranitidine 50 mg IV) are commonly given. They are second line drugs that, with hydrocortisone 100–200 mg slow IV, may reduce the severity/duration of symptoms.
• Admit/observe after initial treatment: prolonged reactions and biphasic responses may occur.
•  Where identified, the patient and GP must be informed and the hospital records appropriately labelled. Medic-Alert bracelets are useful.

Notes: For the treatment algorithm given above , some details are as follows:

1. Life-threatening problems: include

• Airway: Swelling, hoarseness, stridor
• Breathing: Rapid breathing, wheeze, fatigue, cyanosis, SpO2 < 92%, confusion
• Circulation: Pale, clammy, low blood pressure, faintness, drowsy/coma

2. Adrenaline (give IM unless experienced with IV adrenaline)

IM doses of 1:1000 adrenaline (repeat after 5 min if no better)

• Adult: 500 micrograms IM (0.5 mL)

• Child more than 12 years: 500 micrograms IM (0.5 mL)

• Child 6–12 years: 300 micrograms IM (0.3 mL)

• Child less than 6 years: 150 micrograms IM (0.15 mL)

Adrenaline IV to be given only by experienced specialists 

Titrate: Adults 50 micrograms; Children 1 microgram/kg

3. IV fluid challenge:

• Adult - 500–1000 mL
• Child - crystalloid 20 mL/kg

Stop IV colloid if this might be the cause of anaphylaxis.

4. An inhaled B 2 -agonist such as salbutamol may be used as an adjunctive measure if bronchospasm is severe and does not respond rapidly to other treatment.

5. If adults are treated with an EpiPen ® the 300mcg will usually be sufficient. A second dose may be required.