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Allergic and anaphylactic reactions are the result of mast cell- and basophil-derived mediators being release by the body secondary to a triggering mechanism. These may be IgE-mediated or non IgE-mediated processes.
In a case series of 164 anaphylaxis fatalities, the median time between onset of symptoms and respiratory / cardiac arrest:
Therefore, immediate assessment and resuscitation (including epinephrine if appropriate) should be employed in any patient with signs of allergy/anaphylaxis.
Identifying anaphylaxis is key to providing the life-saving treatment often required in this disease process. It also reduces the overreliance on adjunctive medications (antihistamines, steroids) which are not in favor of lifesaving medications (epinephrine). A multidisciplinary group of experts has created criteria to define the diagnosis of anaphylaxis. Using these criteria a retrospective cohort study found a sensitivity of 92 percent, specificity of 82 percent, positive-predictive value of 69 percent, and negative-predictive value of 98 percent.
Signs and symptoms common to anaphylaxis are:
In some cases it may be difficult to tell if a patient is experiencing anaphylaxis or one of the many similar presenting disease processes (asthma, vasovagal syncope, sepsis, benign flushing, carcinoid syndrome, etc.). To further elucidate the diagnosis for long term follow up, serum markers collected soon after the onset of the episode may be beneficial.
Both mast cells and basophils produce tryptase, with mast cells releasing more than 500x that of basophils. When a mast cell is activated, they degranulate, releasing tryptase and histamine into the extracellular space. This tryptase is specific to the mast cells and can give a good indication of their activity. If warranted, serum tryptase should be measured between 15 min and 3 hours after a suspected anaphylaxis episode. A baseline level should also be drawn 24 hours after the event. Even if a tryptase is negative, it should not supplant the clinical diagnosis of anaphylaxis and treatment with epinephrine should not be avoided. In unclear cases, continuing with anaphylaxis treatment is often appropriate.
Tryptase levels are more likely to be elevated in insect stings, medication reactions and episodes involving hypotension.
Except in extreme circumstances, all patients diagnosed with anaphylaxis should receive epinephrine. Epinephrine acts through alpha-1, beta-1 and beta-2 adrenergic agonist effects to increase vasoconstriction, inotropy, chronotropy bronchodilitation and decrease release of substances from mast cells and basophils. In addition to these effects, patients may also experience anxiety, dizziness, palpitations, tremor and other responses to the catecholamine surge.
Intramuscular injection in the lateral thigh is the preferred route of admiration as it consistently increases plasma and tissue concentrations in a rapid manner. This can be repeated every 5 to 15 minutes although it is rare that a patient will require more than one dose. Subcutaneous injection may provide suboptimal levels of epinephrine so care must be made in obese patients to penetrate the adipose layer into muscle. If a patient does not respond to epinephrine the provider should consider this a sign of poor perfusion to the muscular layers that requires a more aggressive fluid resuscitation. In addition, these patients may benefit from intravenous infusion of epinephrine.
Early administration of epinephrine has been shown to decrease mortality for anaphylaxis patients and decrease the likelihood of biphasic reactions. Therefore, immediate administration is key to the care of these patients and should not be delayed.
Anaphylaxis increases vascular permeability which may result in massive shifts of fluids from the intravascular to extravascular space (up to 35 percent within minutes). Placement of two large bore IVs (or other venous access) is necessary to deliver large volumes of fluid to maintain adequate perfusion. Any patient with orthostasis, hypotension, or incomplete response to intramuscular epinephrine should be started on IV fluids (normal saline) immediately with titration to adequate perfusion. Volumes up to 100 ml/kg may be required.
If possible patients showing signs of poor perfusion should be placed in a Trendelenburg position (recumbent position with the lower extremities elevated) to maximize venous return to the heart.
If patients continue to show poor perfusion despite IM epinephrine and IV fluids, consideration should be given to start a SLOW IV infusion of epinephrine.
H1 antihistamines, such as cetirizine or diphenhydramine are effective at reducing itching and urticaria, however, they have shown NO effect on upper or lower airway obstruction, hypotension or shock and do NOT improve outcomes in anaphylaxis. They should NOT be used instead of epinephrine as the primary treatment of anaphylaxis. In addition, these medications have onsets of action of 30 to 40 minutes which is likely too long for the acute interventions needed for anaphylaxis.
H1 antihistamines may be used for symptomatic relief of itching and urticarial reactions which may be present both with and without anaphylaxis.
Bronchodilators such as albuterol may be used as an adjunctive medication in addition to epinephrine if there are signs of bronchospasm. Bronchodilators should not replace epinephrine in the treatment of anaphylaxis as they do not affect upper airway swelling, mucosal edema or the vascular effects of the disease.
1 to 23 percent of all anaphylactic reactions with have a biphasic phase (a uniphasic response, followed by and asymptomatic period (> 1 hr) and then return of symptoms without any further antigen exposure). Although rare, “clinically important events” and fatalities may occur in the second phase. Most studies have shown that the second phase is usually less severe than the initial phase and most commonly involves urticarial.
Biphasic reactions up to 72 hours have been reported although the average time of return of symptoms was 10 hours.
Risk factors for a biphasic reaction include:
Post-anaphylactic observation periods are controversial and variable between guidelines. Patients with biphasic risk factors should be observed longer for which we suggest a minimum of 12 hours. Guidelines for low risk patients vary between 2 and 6 hours. We suggest a minimum of 2 hours.
Patients with anaphylaxis, who are resistant to epinephrine or taking beta-blockers, may be treated with glucagon. Glucagon’s inotropic and chronotropic effects are not mediated through beta-receptors and therefore may provide cardiovascular support if epinephrine alone is not effective. Glucagon increases the likelihood of vomiting so patients receiving it should be also treated with an anti-emetic and monitored closely, especially if they have a suppressed mental status.
Patients with allergic reactions or anaphylaxis are at greater risk of anaphylaxis in the future. Up to 23 percent of patients with anaphylaxis may have a biphasic reaction. Because of this, home discharge care is vitally important for these patients. We suggest that all patients should receive:
There is no evidence (including a systematic review) that H2 antihistamines have any effect on anaphylaxis OR urticaria. They may provide some additional relief of itch along with H1 antihistamines. They do not impact upper or lower airway edema or hypotension and should not replace epinephrine as the primary treatment of anaphylaxis.
Although commonly used, there is no evidence (including a Cochrane review) that steroids affect the initial signs and symptoms of anaphylaxis OR prevent biphasic reactions. Glucocorticoids onset of action is several hours which is too late to affect the initial symptoms of anaphylaxis. In addition, mast cells are relatively resistant to their pharmacologic effect. A single study of 103 patients showed a trend that those patients falling into the uniphasic reaction had more steroids (55% vs. 35%) and at higher doses (63 mg vs. 31 mg) than biphasic patients. However, this trend was not statistically significant AND other studies have found no evidence that steroids decrease the incidence of biphasic reactions.