Anesthesia: Essays and Researches

: 2012  |  Volume : 6  |  Issue : 2  |  Page : 115--123

Anaphyllaxis management: Current concepts

Shrikant Mali1, Rajesh Jambure2,  
1 MDS Oral and Maxillofacial Surgery, Lecturer, Kanchanwadi, Aurangabad, Maharashtra, India
2 Associate Professor CSMSS Dental College, Kanchanwadi, Aurangabad, Maharashtra, India

Correspondence Address:
Shrikant Mali
Flat no. 1 Varun Corner, Osmanpura, Aurangabad, Maharashtra


Anaphylactic shock is medical emergency characterized by circulatory collapse resulted from severe acute allergic reactions, namely anaphylaxis and anaphylactoid reaction. Anaphylaxis is an acute, systemic, IgE-mediated, and immediate hypersensitivity reaction caused by the release of mediators by mast cells and basophils after exposure to antigens. The pathophysiology involves activated mast cells and basophils releasing preformed, granule-associated mediators, and newly formed lipid mediators, as well as generating cytokines and chemokines. These cause vasodilatation, increased capillary permeability, and smooth muscle contraction, and attract new cells to the area. Positive feedback mechanisms amplify the reaction, although conversely reactions can self-limit. Anaphylaxis is a clinical diagnosis with a combinations of symptoms and signs that include weakness, dizziness, flushing, angioedema, urticaria of the skin, congestion, and sneezing. More severe symptoms include bronchial constriction, hypotension, vascular collapse associated with angioedema and urticaria, gastrointestinal distress, cardiovascular arrhythmias, and arrest. Prompt administration of epinephrine is critical for the success in the treatment of acute anaphylaxis.

How to cite this article:
Mali S, Jambure R. Anaphyllaxis management: Current concepts.Anesth Essays Res 2012;6:115-123

How to cite this URL:
Mali S, Jambure R. Anaphyllaxis management: Current concepts. Anesth Essays Res [serial online] 2012 [cited 2021 Apr 13 ];6:115-123
Available from:

Full Text


The term anaphylaxis literally meaning "against protection" was introduced by Richet and Portier in 1902. The World Allergy Organisation (WAO) has suggested that the term allergic anaphylaxis is used to describe immunological reactions involving IgE, IgG, or immune complexes. In IgE-mediated allergic anaphylaxis there is a systemic release of mediators by mast cells and basophils. Where nonimmunological mechanisms are involved, the WAO paper suggests that the term nonallergic anaphylaxis is used. It represents the most catastrophic of the immediate-type generalized hypersensitivity reactions. Anaphylaxis following exposure to a trigger presents in a dynamic continuum from mild to severe, gradual in onset to fulminant, and may involve multiple organ systems or cause isolated shock or wheeze. It presents unheralded in otherwise healthy people and mandates prompt clinical diagnosis based on pattern recognition and probability, in the absence of any immediate confirmatory test.

Anaphylaxis is a medical emergency that requires immediate attention as respiratory distress and, in case of anaphylactic shock, vascular collapse may occur within minutes after exposure to the allergic substances. Fatality from anaphylactic shock, though uncommon, may occur most commonly from cardiovascular collapse and airway obstruction if medical attention is delayed.

Potentially any substance is able to cause anaphylaxis; however, the most common causes of IgE-mediated anaphylaxis are insect stings, medications, latex, peanuts and tree nuts, shellfish and fish, milk, eggs, and wheat. Shock could also arise in severe anaphylactoid reaction that is clinically indistinguishable from anaphylaxis, but are not IgE-mediated and is seen in response to opiates, nonsteroidal anti-inflammatory drugs, and radiocontrast agents. Anaphylaxis generally occurs on reexposure to a specific antigen and requires the release of proinflammatory mediators, but it can also occur on first exposure, because there is cross-reactivity among many commercial products and drugs.

Immune-mediated allergic reactions are classified, according to their mechanism, on the basis of the Gell and Coombs classification. Whereas anaphylaxis is a Type I immunoglobulin (Ig)E-mediated hypersensitivity reaction involving mast cells and basophils, contact dermatitis is a Type IV T-lymphocyte cell-mediated delayedtype hypersensitivity reaction. Other immune-mediated reactions include Type II reactions in which IgG, IgM, and complement mediate cytotoxicity and Type III reactions in which immune-complex formation and deposition leads to tissue damage. Anaphylactoid reactions occur through a direct nonimmune-mediated release of mediators from mast cells and/or basophils or result from direct complement activation, but they present with clinical symptoms similar to those of anaphylaxis. [1],[2],[3],[4],[5],[6]

Anaphylaxis is highly likely when any one of the following three three criteria are fulfilled [1],[2],[3],[5],[6],[7]

Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg., generalized hives, pruritus or flushing, swollen lips-tongue-uvula) and at least one of the following:

Respiratory compromise (eg., dyspnoea, wheeze-bronchospasm, stridor, reduced PEF, hypoxaemia).Reduced BP or associated symptoms of end-organ dysfunction (eg., hypotonia [collapse], syncope, incontinence).Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):

Involvement of the skin-mucosal tissue (eg., generalized hives, itch-flush, swollen lips-tongue-uvula).Respiratory compromise (eg., dyspnoea, wheeze-bronchospasm, stridor, reduced PEF, hypoxaemia).Reduced BP or associated symptoms (eg., hypotonia [collapse], syncope, incontinence).Persistent gastrointestinal symptoms (eg., crampy abdominal pain, vomiting).Reduced BP after exposure to known allergen for that patient (minutes to several hours):Infants and children: Low systolic BP (age specific) or greater than 30% decrease in systolic BP.Adults: Systolic BP of less than 90 mmHg or greater than 30% decrease from that person's baseline.

Causes of anaphylaxis

Drug-induced anaphylaxi

Penicillin is the most common cause of drug induced anaphylaxis. True allergic cross-reactivity to cephalosporins occurs in under 4%, and is largely with the first-generation cephalosporins. Aspirin and nonsteroidal anti-inflammatory drugs (NSAID) are the next most common cause of drug-induced anaphylaxis. Reactions appear to be medication specific as there is no clinical cross reactivity with structurally unrelated NSAIDs. Valid tests for IgE-mediated reactions are unavailable for most drugs or biologics, with the exception of penicillins. Low-molecular-weight medications induce an IgE mediated reaction only after combining with a carrier protein to produce a complete multivalent antigen.

Penicillin spontaneously degrades to major and minor antigenic determinants, both of which should be included in skin testing for penicillin hypersensitivity. The negative predictive value of penicillin skin testing with both major and minor determinants (for immediate-type reactions) is between 97% and 99% (depending on the reagents used), and the positive predictive value is at least 50%. Patients with a history of penicillin allergy who have negative penicillin skin test responses can safely receive cephalosporins.

Patients who need to receive cephalosporins and who have a history of penicillin allergy and positive penicillin skin test responses can (1) receive an alternate (nonbeta lactam) antibiotic; (2) receive a cephalosporin through graded challenge; or (3) receive a cephalosporin through rapid desensitization. Aztreonam does not crossreact with other beta lactams, except ceftazidime, with which it shares a common R group side chain. [2],[3],[4],[5],[6],[8],[9],[10],[11],[12],[13]

Anaesthesia-related anaphylaxis

Neuromuscular blocking drugs (muscle relaxants), latex, antibiotics and induction agents cause most anaphylaxis cases, but opioids, col loids, blood products, radiocontrast dye, isosulphan or methylene blue, methylmethacrylate, chlorhexidine, and protamine may be responsible.

The incidence ranges from 1:3,500 to 1:20,000 cases, with up to 4% of reactions fatal. Muscle relaxants lead to 60% of general anesthesia reactions, with suxamethonium in the highest-risk group. [3],[4],[5],[6],[8],[9],[10],[11],[12],[13],[14],[15]

Latex-induced anaphylaxis

The highest-risk group for latex allergy includes health care workers, children with spina bifida and genitourinary abnormalities because of number of operations they undergo, and occupational exposure. Reactions follow direct contact, parenteral contamination or aerosol transmission. Patients at known risk must be treated in a latex-free environment with glass syringes and nonlatex containing gloves, stethoscope, breathing-system, BP cuff, intravenous tubing, and administration ports. [1],[2],[3],[4],[5],[6],[8],[9],[10],[11],[12],[13]

Various causes of anaphylaxis are [1],[3],[4],[5],[6],[8],[9],[10],[11],[12],[13],[15]

IgE-dependent mechanisms

Drugs, chemicals, and biologic agents:

Penicillins, cephalosporins, sulphonamides, muscle relaxants, vaccines, insulin, thiamine, protamine, gamma globulin, antivenoms, formaldehyde, ethylene oxide, chlorhexidine, semen. Foods: Peanuts, tree nuts, shellfish, fin fish, milk, egg, fruits, vegetables, flour. Hymenopteran sting venom, insect saliva, other venoms: Bees, wasps, ants, hornets, ticks, triatomid bugs, snakes, scorpions, jelly fish. Latex. Environmental: Pollen, horse dander, hydatid cyst rupture.Non-IgE-dependent mechanisms

Physical factors: Exercise, cold, and heat. Medications and biologic agents: Opiates, aspirin and NSAIDs, ACEI, vancomycin, radiocontrast media, N-acetylcysteine, fluorescein. Food additives: Metabisulphite, tartrazine.Idiopathic.


Mast cells and basophils release inflammatory mediators following binding of multivalent allergen that cross-links surface, high-affinity IgE Fc receptors (FcERI), or from cell membrane perturbation. This coupled with mobilization of Ca++ in the endoplasmic reticulum leads to the release of preformed granule-associated mediators by exocytosis, or the de novo synthesis of lipid mediators based on arachidonic acid metabolism, and the activation of genes for various cytokines and chemokines.

The preformed mediators include histamine, proteases such as tryptase, chymase, and carboxypeptidase A, and proteoglycans such as heparin and chondroitin sulfate E. Newly synthesized lipid mediators include prostaglandin D2 and thromboxane A2 via the cyclo-oxygenase pathway, and the leucotrienes LTC4, LTD4, and LTE4 via the lipoxygenase pathway. Cytokines released include TNF-α, various interleukins such as IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, and IL-16 and GM-CSF. Finally important chemokines include the platelet-activating factor (PAF), neutrophil chemotactic factor, and eosinophil chemotactic factor, plus macrophage inflammatory protein I. PAF actually has many pro-inflammatory properties that can lead to bronchoconstriction, vascular permeability, and hypotension, and its concentration may relate to the severity of some anaphylactic reactions.

These mediators induce vasodilatation, increase capillary permeability and glandular secretion, cause smooth muscle spasm particularly bronchoconstriction and attract new cells to the area such as eosinophils, leucocytes, and platelets.

Positive feedback mechanisms amplify and perpetuate the reaction recruiting further effector cells to release increasing amounts of mediators in a "mast cell - leucocyte cytokine cascade" effect.

Anaphylaxis often produces signs and symptoms within minutes of exposure to an offending stimulus but some reactions may develop later (e.g., greater than 30 min after exposure). Late phase or "biphasic" reactions, which occur 1 to 72 h (most within 10 h) after the initial attack, have also been reported. Protracted, severe anaphylaxis may last up to 32 h despite aggressive treatment. Increased vascular permeability, a characteristic feature of anaphylaxis, allows transfer of as much as 35% of the intravascular fluid into the extravascular space within 10 min. As a result, hemodynamic collapse may occur rapidly with little or no cutaneous or respiratory manifestations. [1],[3],[4],[5],[6],[10]

Clinical features of anaphylaxis

Anaphylaxis is characteristically a disease of fit patients and is rarely seen or described in critically ill or shocked patients, other than asthmatics. The speed of onset relates to the mechanism of exposure, and the severity of the reaction. Parenteral antigen exposure may cause life-threatening anaphylaxis within minutes, whereas symptoms can be delayed for some hours following oral or topical exposure. [1],[2],[3],[4],[5],[6],[10],[15]

Cutaneous and generalized allergic reactions

A premonitory aura, tingling or warm sensation, anxiety, and feeling of impending doom precede generalized erythema, urticaria with pruritus, and angioedema of the neck, face, lips and tongue. Rhinorrhoea, conjunctival injection, and tearing are seen. Eighty to ninety five percent of patients with anaphylaxis have cutaneous features, which assist the prompt, early diagnosis. However, alerting cutaneous features may be absent because of prehospital treatment or their spontaneous resolution, be subtle clinically and missed, or the onset of other life-threatening systemic complications such as laryngeal oedema or shock may precede them.

Systemic reactions

The hallmark of anaphylaxis is the precipitate onset of multisystem dysfunction with respiratory, cardiovascular, gastrointestinal, and or neurological system involvement.

Respiratory manifestations

Throat tightness and cough can precede mild to critical respiratory distress due to oropharyngeal or laryngeal oedema with dyspnoea, hoarseness, stridor even aphonia, or related to bronchospasm with tachypnoea and wheeze. Hypoxia with oxygen saturation less than 92% on pulse oximetry and central cyanosis indicate severe anaphylaxis and the need for immediate treatment.

Nasal itching, congestion, rhinorrhea, sneezing;

Throat itching and tightness, dysphonia, hoarseness, stridor, dry staccato cough;

Lower airways: Increased respiratory rate, shortness of breath, chest tightness, deep cough, wheezing/bronchospasm, decreased peak expiratory flow.

Cyanosis, respiratory arrest

Cardiovascular and neurological manifestations

Light-headedness, sweating, incontinence, syncope, or coma may precede or accompany cardiovascular collapse with tachycardia, hypotension, and cardiac arrhythmias, again heralding severe anaphylaxis. These arrhythmias can appear as benign supraventricular rhythms, particularly in children, but may progress to an impalpable pulse requiring external cardiac massage. Aura of impending doom, uneasiness (in infants and children, sudden behavioral change, eg., irritability, cessation of play, clinging to parent); throbbing headache (pre-epinephrine), altered mental status, dizziness, confusion, tunnel vision.

Gastrointestinal manifestations

Difficult or painful swallowing, nausea, vomiting, diarrhea and abdominal cramps may be associated with a severe reaction, although they are frequently overshadowed by more immediately life-threatening features.

Abdominal pain, nausea, vomiting (stringy mucus), diarrhea, and dysphagia.

Skin, subcutaneous tissue, and mucosa

Flushing, itching, urticaria (hives), angioedema, morbilliform rash, pilor erection;

Periorbital itching, erythema and edema, conjunctival erythema, tearing;

Itching of lips, tongue, palate, and external auditory canals; and swelling of lips, tongue, and uvula;

Itching of genitalia, palms, and soles.


Metallic taste in the mouth

Cramps and bleeding due to uterine contractions in females

Premonitory aura, anxiety, feeling of impending doom, pallor

Pelvic cramps.

Differential diagnosis of anaphylaxis

It is not practical to differentiate between anaphylactic and anaphylactoid reactions, because both respond to the same treatment in the acute stage. However, if anaphylactic shock is present, it must be differentiated from other causes of cardiovascular collapse. As in anaphylactic shock, hypotension, pallor, bradycardia, weakness, nausea, vomiting, and diaphoresis also present in vasovagal reactions, making it the most common condition that mimic anaphylaxis. However, urticaria, pruritus, angioedema, tachycardia, and bronchospasm are not present in vasovagal reactions. Besides warm phase of septic shock may also mimic anaphylactic shock as hypotension resulted from peripheral vasodilation. However, the progressive onset, fever and other signs of infection may be present. Other conditions such as seizure disorders, myocardial infarction, and arrhythmias may infrequently present initially with similarities to anaphylaxis, but are readily distinguished clinically. [1],[3],[4],[5],[6],[8],[13],[15]

Respiratory and neurological

The protean manifestations of anaphylaxis have a potentially vast differential diagnosis, although the rapidity of onset, accompanying cutaneous features, and the relationship to a likely or known potential trigger suggests the true diagnosis in most cases. Differential diagnoses to be considered in the wheezy or short of breath patient include bronchial asthma, cardiogenic pulmonary oedema, foreign body inhalation, irritant chemical exposure, and tension pneumothorax, which are distinguished by their history, co-morbidity and associated presenting features. In patients presenting with light-headedness and syncope, consider an anxiety or vasovagal reaction from a history of exaggerated fear of an impending reaction, or in the context of a painful procedure such as an injection or local anesthetic anesthetic infiltration with collapse. Bradycardia, sweating and pallor without urticaria, erythema or itch, associated with a brief prodrome and rapid response to the recumbent position favor the vasovagal reaction over anaphylactic shock.

Shock and or flushing

Other types of distributive shock such as septicaemia, spinal denervation, epidural or spinal block, hypovolaemic shock from hemorrhage or fluid loss, cardiogenic shock from primary myocardial dysfunction, and obstructive shock from cardiac tamponade or tension pneumothorax should all be apparent from the history and examination.

Cutaneous and respiratory features other than tachypnoea are absent in these nonanaphylactic causes of shock. In patients with flushing consider scombroid poisoning following spoiled-fish ingestion, carcinoid syndrome, alcohol, and systemic mastocytosis that require a careful history and investigation to differentiate.

Facial oedema

Finally bacterial or viral infections usually have fever and or pain, and traumatic or anticoagulant-related bleeding cause recognizable bruising. Angioedema in the absence of urticaria can be caused by actual or functional C1 esterase inhibitor deficiency. This may be hereditary autosomal dominant, with a positive family history, an absence of pruritus, prominent abdominal symptoms and a history of recurrent attacks related to minor stress27. Alternatively, C1 esterase inhibitor deficiency may be acquired in lymphoproliferative and some connective tissue disorders. A rapid, inexpensive screening test for serum C4 should be performed, and if low, be followed by the more specific C1 esterase inhibitor assay to confirm the diagnosis. Management is with C1 esterase inhibitor concentrate in a serious attack, or with fresh frozen plasma in its absence.

Common diagnostic dilemmas [1],[3],[4],[5],[6],[8]

Acute asthmaSyncopeAnxiety/panic attackAcute generalized urticariaaAspiration of a foreign bodyCardiovascular (myocardialinfarctiona, pulmonary embolusNeurologic events (seizure, cerebrovascular event)ShockHypovolemicCardiogenicDistributivedSepticFlush syndromesPeri-menopauseCarcinoid syndromeAutonomic epilepsyMedullary carcinoma of the thyroidExcess endogenous histamineMastocytosis/clonal mast cell disorderseBasophilic leukemiaPostprandial syndromesScombroidosisbPollen-food allergy syndromecMonosodium glutamateSulfitesFood poisoningCardiacMyocardial infarction, cardiac arrest, arrhythmiasNeurologicAutonomic epilepsy, cerebrovascular accidentPsychogenicPanic attack, hyperventilationMiscellaneousVasovagal reaction, hereditary angioedemaTreatment


A patient with anaphylaxis may have the reaction in hospital on a ward, in the operating theatre, the radiology department, even in outpatients. Initially stop any potential causative agent such as an intravenous drug or infusion and manage the patient in a monitored resuscitation area in the emergency department, or bring equipment including at least a pulse oximeter, non-invasive blood pressure device and ECG monitor to them.

Obtain a brief history of possible allergen exposure and perform a rapid assessment of the extent and severity of the reaction including vital signs, and looking particularly for upper airway swelling, bronchospasm or circulatory shock. Administer oxygen, adrenaline and fluids with the patient supine as the mainstay of treatment to stabilize the cardiorespiratory status. Antihistamines and steroids play no role until this has been achieved, and even then their value is debatable.

 Initial Treatment of Anaphylaxis

Stop delivery of any potential causative agent.

Call for help.

Give adrenaline 0.01 mg/kg i.m. into lateral thigh, to maximum 0.5 mg (0.5 mL of 1:1000 adrenaline). May be repeated every 5-15 minutes.

Lay supine (or elevate legs) for shock.

Give high-flow oxygen.

Insert large-bore i.v. cannula (14-g or 16-g) and give crystalloid fluid bolus of 10-20 mL/kg. [1],[3],[4],[5],[6]

 Failure to Respond, or Deteriorating Rapidly

Start adrenaline infusion 1 mL (1 mg) of 1:1000 adrenaline in 100 mL normal saline at 30-100 mL/hr (5-15 μg/min) titrated to response.

Must be on ECG monitor.

Give faster in cardiopulmonary collapse/arrest.

Consider assisted ventilation and endotracheal intubation.

If the patient is in extremis and endotracheal intubation is impossible, perform a surgical airway via a cricothyroidotomy. [1],[3],[4],[5],[6]

 Positioning of Patient

Patients who become hypotensive should remain recumbent until the cardiovascular system has been stabilized and they are completely asymptomatic. Deaths have occurred if the patient assumes the upright sitting position prematurely. Patients with anaphylaxis should not suddenly sit, stand, or be placed in the upright position. Instead, they should be placed on the back with their lower extremities elevated or, if they are experiencing respiratory distress or vomiting, they should be placed in a position of comfort with their lower extremities elevated. This accomplishes 2 therapeutic goals: 1) preservation of fluid in the circulation (the central vascular compartment), an important step in managing distributive shock; and 2) prevention of the empty vena cava/empty ventricle syndrome, which can occur within seconds when patients with anaphylaxis suddenly assume or are placed in an upright position. Patients with this syndrome are at high risk for sudden death. They are unlikely to respond to epinephrine regardless of route of administration, because it does not reach the heart and therefore cannot be circulated throughout the body.

Elevate the head and torso if respiratory distress is prominent or worsened. The signs of impending airway obstruction are worsening stridor or hoarseness, or rapidly progressive respiratory failure with tachypnoea and wheeze.

Cyanosis and exhaustion indicate imminent respiratory arrest, but sedative or muscle relaxant drugs should never be given unless the physician is trained in the management of the difficult airway. [3],[4],[5],[6]

Oxygen and airway patency

Give oxygen by face mask to all patients aiming for an oxygen saturation above 92%. Call for urgent experienced anesthetic assistance, if there are Supplemental oxygen should be administered by face mask or by oropharyngeal airway at a flow rate of 6-8 L/min to all patients with respiratory distress and those receiving repeated doses of epinephrine.

Bag valve masks of less than 700 ml are discouraged in adults in the absence of an endotracheal tube since ventilated volume will not overcome 150-200 ml of anatomic dead space to provide effective tidal volume. (Bag valve masks may be used in children provided the reservoir volume of the device is sufficient). [1],[2],[3],[4],[5],[6],[8],[15],[16]

 Drug of Choice

Adrenaline dose and route

It has beneficial α-, β1- and β2-adrenergic effects that counteract the profound vasodilatation, mucosal oedema and bronchospasm. Another crucial role of adrenaline is via β2-adrenergic receptors triggering a rise in intracellular cyclic AMP that inhibits further mast cell and basophil mediator release, thereby attenuating the severity of the reaction when given early. [1],[2],[3],[4],[5],[6],[8],[16],[17],[18],[19],[20],[21]

At alpha-1 adrenergic receptor

Increases vasoconstriction and increases vascular resistance (in most body organ systems)c

Increases blood pressure

Decreases mucosal edema in the airways

At beta-1 adrenergic receptor

Increases cardiac contraction force

Increases heart rate

At beta-2 adrenergic receptor

Decreases mediator release

Increases bronchodilation

Significant effects

Increases blood pressure and prevents and relieves hypotension and shock; decreases upper airway obstruction, for example for example, in larynx; decreases urticaria and angioedema; decreases wheezing.

Epinephrine has a vasodilator effect in skeletal muscle; skeletal muscle is well vascularized; after intramuscular injection into the vastus lateralis (mid-anterolateral thigh), absorption is rapid and epinephrine reaches the central circulation rapidly; rapid absorption is important in anaphylaxis, in which the median times to cardiorespiratory arrest are reported as 5 min (iatrogenic, eg., injected medication), 15 min (stinging insect venom), and 30 min (food).

Intramuscular adrenaline

Intramuscular adrenaline is superior to subcutaneous, and should be given into the vastus lateralis muscle in the thigh rather than the arm deltoid muscle.

Intramuscular adrenaline is rapidly bioavailable, with peak concentrations occurring within 10 min of administration, and has a much better safety profile and long-lasting action than intravenous adrenaline.

It is used when anaphylaxis is treated early, progressing slowly, if venous access is difficult or delayed or in the unmonitored patient. The dose of adrenaline is 0.01 mg/kg up to a maximum of 0.5 mg intramuscularly, repeated every 5 to 15 min as necessary. Give this as 0.01 mL/kg of 1:1000 aqueous adrenaline up to a maximum of 0.5 mL into the upper outer thigh.

If all limbs have been used for immunizations, epinephrine must still be administered to the patient intramuscularly. Epinephrine can be administered into a muscle close to the site where the immunization agent was administered. A minimum distance of 2.5 cm (or 1 inch) must be maintained between the injection sites of the immunization agent and the epinephrine drug.

Safe and practical intramuscular adrenaline doses in children are 0.3 mg (0.3 mL of 1:1000 aqueous adrenaline) for children aged 6-12 years, 0.15 mg (0.15 mL of 1:1000 aqueous adrenaline) for ages 6 months to 6 years, and 0.1 mg (0.1 mL of 1:1000 aqueous adrenaline) for children aged less than 6 months. [1],[2],[3],[4],[5],[6],[8],[15],[18],[19],[20],[21]

Adrenaline IM dose - adults

0.5 mg IM (= 500 micrograms = 0.5 mL of 1:1000) adrenaline.

Intravenous adrenaline

Because of the risk of potentially lethal arrhythmias, epinephrine should be administered intravenously only in profoundly hypotensive patients or patients in cardio/respiratory arrest who have failed to respond to intravenous.

Volume replacement and several injected doses of epinephrine

This route is used only when there is rapidly progressive vascular collapse with shock, imminent airway obstruction, or critical bronchospasm, and should be given by practitioners with regular experience in its use. Administer the intravenous adrenaline slowly to the patient on an ECG monitor with extreme care, suitably diluted and titrated to response to avoid potentially lethal complications such as cardiac arrhythmias, myocardial ischaemia, and cerebrovascular accident.

A prospective study demonstrated the efficacy of a 1:100 000 solution of epinephrine (0.1 mg [1 mL of 1:1000] in 100 mL saline) intravenously by infusion pump at an initial rate of 30-100 mL/h (5-15 mg/min), titrated up or down depending on clinical response or epinephrine side effects (toxicity).

The initial dose of adrenaline intravenously is just 0.75-1.5 μg/kg (ie. 50-100 μg) over up to 5 min depending on the rapidity and severity of the patient's decline. This dose may be repeated according to response. Intravenous adrenaline is best delivered as an infusion of adrenaline 1 mg in 100 mL normal saline (10 μg/mL) started at 30-100 mL/hr, that is 5-15 μg/min titrated to response. Continue the infusion for anything up to 60 min after the resolution of all symptoms and signs of anaphylaxis, then wean over the next 30 min and stop, watching closely for any recurrence.

An epinephrine infusion may be prepared by adding 1 mg (1 mL) of 1:1000 dilution of epinephrine to 250 mL of D5W to yield a concentration of 4.0 μg/mL. This 1:250 000 solution is infused at a rate of 1 mg/min (15 drops/min using a microdrop apparatus [60 drops/min 51 mL 5 60 mL/h]), titrated to desired hemodynamic response, increasing to a maximum of 10.0 mg/min for adults and adolescents. A dosage of 0.01 mg/ kg (0.1 mL/kg of a 1:10 000 solution up to 10 mg/min; maximum dose, 0.3 mg) is recommended for children.

Alternative pediatric dosage by the "Rule of 6" is, as follows: 0.6 X body weight (in kg) of mg diluted to total 100 mL saline; then 1 mL/h delivers 0.1 mg/kg/min.

If repeated adrenaline doses are needed, start an IV adrenaline infusion.

The prefilled 10 mL syringe of 1:10 000 adrenaline contains 100 micrograms/mL. A dose of 50 micrograms is 0.5 mL, which is the smallest dose that can be given accurately.

Do not give the undiluted 1:1000 adrenaline concentration IV. [1],[2],[3],[4],[5],[6],[8],[15],[18],[19],[20],[21]

Adverse effects of adrenaline

Transient pharmacologic effects after a recommended dose of adrenaline by any route of administration include pallor, tremor, anxiety, palpitations, dizziness, and headache. These symptoms indicate that a therapeutic dose has been given. Serious adverse effects such as ventricular arrhythmias, hypertensive crisis, and pulmonary edema potentially occur after an overdose of epinephrine by any route of administration. Typically, they are reported after intravenous dosing; for example, overly rapid intravenous infusion, bolus administration, and dosing error because of intravenous infusion or intravenous injection of the 1:1000 (1 mg/mL) solution appropriate for intramuscular injection, instead of the dilute solutions appropriate for intravenous administration (1:10 000 [0.1 mg/mL] or 1:100 000 [0.01 mg/mL]). [3],[4],[5],[6],[8]

Fluid replacement

When anaphylactic shock fails to respond to the initial epinephrine, persisted hypotension patient should receive intravenous fluid challenge. Caution should be taken to avoid overzealous fluid administration as pulmonary edema may develop.

Insert a large-bore intravenous cannula as soon as possible in patients showing signs of shock. Administer an initial fluid bolus of 10-20 mL/kg normal saline, up to 50 mL/kg total to counter the massive intravascular fluid shifts and peripheral vasodilatation that occurs in minutes with anaphylactic shock.

Of available crystalloid solutions, saline is generally preferred in distributive shock (eg., anaphylactic shock) because it stays in the intravascular space longer than dextrose and contains no lactate that may potentially exacerbate metabolic acidosis. Large volumes of fluid are often required, especially in patients taking a beta-adrenergic blocking agent. One to 2 L of normal saline may need to be administered to adults at a rate of 5-10 mL/kg in the first 5 min. Children should receive up to 30 mL/kg in the first hour. Adults receiving colloid solution should receive 500 mL rapidly, followed by slow infusion. Caution for volume overload is advised if the patient has a history of congestive heart failure. [1],[2],[3],[4],[5],[6],[8],[17],[19]

Second-line agents





Vasopressors such as noradrenaline, metaraminol, phenylephrine, and vasopressin have anecdotally treated hypotension resistant to initial adrenaline and fluid therapy.

Vasopressors, such as dopamine (400 mg in 500 mL of 5% dextrose) administered at 2-20 mg/kg/min and titrated to maintain systolic blood pressure greater than 90 mm Hg should be administered if epinephrine injections and volume expansion fail to alleviate hypotension. Dopamine will usually increase blood pressure while maintaining or enhancing blood flow to the renal and splanchnic circulation.

It has been shown that a dose of dopamine > 10 mg/kg/min is usually required to produce peripheral vasoconstriction which would be required to maintain systolic blood pressure. [1],[2],[3],[4],[5],[6],[8],[15],[17],[19]

H1-antihistamines and H2-antihistamines

These are used for symptomatic relief of skin symptoms such as urticaria, mild angioedema and pruritus. Diphenhydramine, an H1 antagonist, may be given IM or by slow intravenous infusion in a dose of 25 to 50 mg in adults, and 1 mg/kg up to 50 mg in children.

Parenteral ranitidine can be considered in a dose of 1 mg/kg in adults, and 12.5 to 50 mg in children. The side effects of sedation, confusion, and vasodilatation can be troublesome, particularly if given parenterally. The combination of an H2-antihistamine with an H1-antihistamine is better at attenuating the cutaneous manifestations of a generalized allergic reaction than an H1-antagonist given alone. A nonsedating H1-antihistamine should be selected especially on discharge, if the patient wishes to continue working, or driving a vehicle. [1],[2],[3],[4],[5],[6],[8],[15],[17],[19],[20],[21]

Inject chlorphenamine slowly intravenously or intramuscularly can also be given.

The dose of chlorphenamine depends on age:

>12 years and adults: 10 mg IM or IV slowly

>6-12 years: 5 mg IM or IV slowly

>6 months to 6 years: 2.5 mg IM or IV slowly

<6 months: 250 micrograms/kg IM or IV slowly


These are not life saving drugs. These are given empirically.

Prednisone 1 mg/kg up to 50 mg orally or hydrocortisone 1.5-3 mg/kg IV particularly in patients with airway involvement and bronchospasm, based empirically on their important role in asthma.

Steroids are of course fundamental to the management of recurrent idiopathic anaphylaxis. Dose of hydrocortisone for adults and children depends on age:

>12 years and adults: 200 mg IM or IV slowly

>6-12 years: 100 mg IM or IV slowly

>6 months to 6 years: 50 mg IM or IV slowly

<6 months: 25 mg IM or IV slowly. [1],[2],[3],[4],[5],[6],[8],[15],[17],[19],[20],[21]


Greater severity of anaphylaxis observed in patients receiving b-blockers might relate, in part, to a blunted response to epinephrine administered to treat anaphylaxis. Adrenaline administered to a patient taking a β-blocker can produce unopposed α-adrenergic and reflex vagotonic effects, possibly leading to hypertension and the risk of cerebral hemorrhage. In patients receiving b-blockers, increased propensity not only for bronchospasm, but also decreased cardiac contractility with perpetuation of hypotension and bradycardia might exist. For these reasons, b-blocker-related anaphylaxis may be more likely to be refractory to management.

Patients taking b-blockers may be more likely to experience severe anaphylactic reactions characterized by paradoxical bradycardia, profound hypotension, and severe bronchospasm. Patients taking β-blockers have more severe or treatment-refractory anaphylaxis, and anecdotally glucagon is reported to have been successful when other more well-recognized treatments have failed. Glucagon has direct chronotropic, inotropic and vasoactive effects that are independent of catecholamine receptors. Additionally, glucagon also promotes endogenous release of catecholamines.

Glucagon raises cyclic AMP via a nonadrenergic mechanism, given as 1-5 mg intravenously, followed by an infusion at 5-15 μg/min titrated to response. Note that it may cause nausea and vomiting. Glucagon may reverse refractory bronchospasm and hypotension during anaphylaxis in patients on β- blockers by activating adenyl cyclase directly and bypassing the β -adrenergic receptor. The recommended dosage for glucagon is 1 to 5 mg (20-30 mg/kg [max. 1 mg] in children) administered intravenously over 5 min and followed by an infusion, 5-15 mg/min, titrated to clinical response. Protection of the airway is important since glucagon may cause emesis and risk aspiration in severely drowsy or obtunded patients. Placement in the lateral recumbent position may be sufficient airway protection for many of these patients. [1],[3],[4],[5],[6],[8],[15]

Interventions for cardiopulmonary arrest occurring during anaphylaxis [3],[4],[19]

Cardiopulmonary resuscitation and advanced cardiac life support measures.High-dose epinephrine IV (ie, rapid progression to high dose). A common sequence is 1 to 3 mg (1:10 000 dilution) IV slowly administered over 3 min, 3 to 5 mg IVover 3 min, and then 4-10 mg/min infusion. For children, the recommended initial resuscitation dosage is 0.01 mg/kg (0.1 ml/kg of a 1:10 000 solution up to 10 mg/min rate of infusion), repeated every 3 to 5 min for ongoing arrest. Higher subsequent dosages (0.1-0.2 mg/kg; 0.1 mL/kg of a 1:1000 solution) may be considered for unresponsive asystole or pulseless electrical activity (PEA).Rapid volume expansion.Atropine if asystole or pulseless electrical activity (PEA) is present.Prolonged resuscitation is encouraged, if necessary, since a successful outcome is more likely in anaphylaxis.Transport to emergency department or intensive care, as setting dictates.


Patient with anaphylactic shock not completely respond to initial treatment should be admitted to an intensive unit for further care. For those responds initially, post-treatment observation in the emergency department for a period of time is necessary because of the potential for a second phase of reaction. Most of these reactions occur within 1-8 h, but second phase reactions may occur 38 h later.

Prolonged observation in a monitored setting period is ideal but not practical. So it may be appropriate to discharge asymptomatic patient after 4-8 h of observation for those with less severe reactions. These patients must be told returning to emergency department immediately if any symptom recurs and their family should also be informed of the discharge least four to six hours after apparent full recovery, up to 10 h or longer. [1],[2],[3],[4],[5],[6],[8],[15],[17],[20],[21]

Summary of treatment protocol

Prepare for anaphylaxis assessment and management of anaphylaxis in healthcare settings. Have a posted, written emergency protocol and rehearse it regularly. As soon as the clinical diagnosis of anaphylaxis is made, discontinue exposure to the trigger, if possible; for example, discontinue an intravenously administered diagnostic or therapeutic agent. Assess the patient rapidly (circulation, airway, breathing, mental status, and skin). Simultaneously and promptly: Call for help; inject epinephrine (adrenaline) by the intramuscular route in the midanterolateral aspect of the thigh; and place the patient on the back or in a position of comfort with the lower extremities elevated. When indicated at any time during the anaphylactic episode, administer supplemental oxygen, give intravenous fluid resuscitation, and initiate cardiopulmonary resuscitation with continuous chest compressions. At frequent and regular intervals, monitor the patient's blood pressure, cardiac rate and function, respiratory status and oxygenation and obtain electrocardiograms; start continuous noninvasive monitoring, if possible.

Patients with anaphylaxis refractory to the above measures, for example, those requiring intubation and mechanical ventilation and those requiring intravenous epinephrine or another vasopressor should, if possible, be transferred to a healthcare facility where additional support is available. Ideally, this includes specialists in emergency medicine, critical care medicine and/or anesthesiology, trained and experienced nurses and technicians, and appropriate medications, supplies, and equipment. Advise patients that they need follow-up visits with a physician, preferably an allergy/immunology specialist, to confirm their specific anaphylaxis trigger(s), prevent recurrences by avoiding specific trigger(s), and receive immunomodulation, if relevant.


1Brown AF. Current management of anaphylaxis. Emergencias 2009;21:213-23.
2Muraro A, Roberts G, Clark A, Eigenmann PA, Halken S, Lack G, et al. The management of anaphylaxis in childhood: Position paper of the European academy of allergology and clinical immunology. Allergy 2007;62:857-71.
3Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 Update. J Allergy Clin Immunol 2010;126:477-80.
4Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 Update. J Allergy Clin Immunol 2010;126:e1-e42.
5Phoon LY, Chong CF, Wang TL. Recognition and Management of Anaphylactic Shock. Ann Disaster Med 2004;2 Suppl 2:S61-8.
6Simons R, Estelle F, Ardusso RF, Beatrice M, El-Gamal YM, Ledford DK, et al. World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis. WAO J 2011;4:13-37.
7Hepner DL, Castells MC. Anaphylaxis during the perioperative period. Anesth Analg 2003;97:1381-95.
8Arroabarren E, Lasa EM, Olaciregui I, Sarasqueta3 C, Mun˜ oz JA, Pe× rez-Yarza EG. Improving anaphylaxis management in a pediatric emergency department. Pediatr Allergy Immunol 2011;22:708-14.
9Estelle F, Simons R. Anaphylaxis: Recent advances in assessment and treatment. J Allergy Clin Immunol 2009;124:625-36.
10Laxenaire MC, Mertes PM and Groupe d'Etudes des Reactions Anaphylactoides Peranesthesiques. Anaphylaxis during anaesthesia: Results of a two-year survey in France. Br J Anaesth 2001;87:549-58.
11Lobera T, Audicana MT, Pozo MD, Blasco A, Fernández E, Cañada P, et al. Study of Hypersensitivity Reactions and Anaphylaxis During Anesthesia in Spain. J Investig Allergol Clin Immunol 2008;18:350-6.
12Anaphyllaxis and anaphyllactoid reactions. Available from: [Last accessed on 2011 Dec 04].
13Ewan PW, Dugu´e2 P P, Mirakian R, Dixon TA, Harper JN, Nasser SM. BSACI guidelines for the investigation of suspected anaphylaxis during general anaesthesia. Clin Exp Allergy 2010;40:15-31.
14Ebo DG, Fisher MM, Hagendorens MM, Bridts CH, Stevens WJ. Anaphylaxis during anaesthesia: Diagnostic approach. Allergy 2007;62:471-87.
15Suspected anaphylactoid reactions with general anaesthesia. Available from: [Last cited on 2011 Dec 04].
16Claudius C, Garvey LH, Viby-Mogensen J. The undesirable effects of neuromuscular blocking drugs. Anaesthesia 2009;64(Suppl. 1):10-21.
17Emergency treatment of anaphylactic reactions Guidelines for healthcare providers. Available from: [Last cited on 2011 Dec 04].
18Protocol for Management of Suspected Anaphylactic Shock. Communicable disease control. Available from: [Last cited on 2011 Dec 04].
19Protocol for the management of immunization-related anaphylaxis in non-hospital settings. Available from: [Last cited on 2011 Dec 04].
20The diagnosis and management of anaphylaxis: An updated practice parameter. J Allergy Clin Immunol 2005;115 (3 Suppl):S483-523.
21Available from: Anaphyllaxis guide lines. [Last cited on 2011 Dec 04].