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1278 PART 11: Special Problems in Critical Care

thigh) than when it is administered either subcutaneously or intra-
TABLE 128-10 Medications Used in the Treatment of Anaphylaxis
muscularly in the deltoid muscle of the arm. There are no outcome
Drugs Dose and Route data comparing directly the subcutaneous and intramuscular routes
Epinephrine 0.3-0.5 mL (1:1000) IM in adult in anaphylaxis but some studies in healthy volunteers have shown
higher peak plasma epinephrine concentrations after intramuscular
0.1 mg/kg (1:1000) or 0.1-0.3 mL IM in children
injection. Epinephrine may be repeated every 5 to 15 minutes, as nec-
Antihistamines essary. Intravenous epinephrine administration may be considered in
Diphenhydramine 25-50 mg IM or IV in adult patients that are poorly responsive to intramuscular or subcutaneous
epinephrine, and/or are showing signs of hypotension and organ dys-
12.5-25 mg PO or IM or IV in children
function. No established dosage or regimen for intravenous epineph-
Ranitidine 1 mg/kg IV rine in anaphylaxis is recognized. The initial infusion of intravenous
Aerosolized β-agonist (albuterol) 0.25-0.5 mL in 1.5-2 mL saline epinephrine must be very slow, titrated to response, and always under
close hemodynamic monitoring. The usual starting dose is 1 to 4 µg/
Hydrocortisone 100-1000 mg IV or IM in adult
min titrated to a maximum of 10 µg/min. A dosage of 0.1 to 1 µg/kg/
10-100 mg IV in children min is recommended for children. Because of the risk of potentially
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Volume expanders lethal arrhythmias, cardiac ischemia, and severe hypertension, intra-
Crystalloids (normal saline or Ringer 1-2 L boluses in adults, 30 mL/kg in first hour venous epinephrine should only be used in profoundly hypotensive
lactate) in children patients or patients in cardio/respiratory arrest who have failed to
respond to intravenous volume replacement and several injected
Colloids (hydroxyethyl starch) 500 mL rapidly infused followed by slow infusion doses of epinephrine.
in adults
Vasopressors Volume Replacement: Effective therapy during anaphylaxis consists of
rapid replacement of intravascular volume. Acute anaphylactic reac-
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Dopamine 2-20 µg/kg/min IV
tion occurring in the setting of anesthesia induction is associated with
Drugs used in patients taking rapid loss of intravascular fluid into the interstitial space, up to 40% of
β-blockers intravascular volume. Rapid fluid loss and successful treatment with
150
Atropine sulfate 0.3-0.5 mg IV fluid replacement have been documented in the case of anaphylactic
reaction observed incidentally by transesophageal echocardiography.
151
Glucagon Initial dose of 1-5 mg IV followed by infusion
of 5-15 µg/min Patients should receive either intravenous crystalloid solutions or colloid
volume expanders. Normal saline is generally the preferred crystalloid
in distributive shock (eg, anaphylactic shock) because it stays in the
intravascular space longer than dextrose and contains no lactate which
may potentially exacerbate metabolic acidosis. Large volumes of fluid
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caused laryngospasm or angioedema, an upper airway obstruction are often required, especially in patients taking a β-adrenergic blocking
is imminent and a secure airway must be obtained. This could be agent. One to 2 L of normal saline should be given as boluses in the first
accomplished by endotracheal intubation under direct or video few minutes of treatment (eg, 1 L every 30 minutes). Adults receiving
laryngoscopy. Although intubation is usually feasible, severe edema colloid solution should receive 500 mL rapidly, followed by slow infu-
of the tongue, larynx, or vocal cords may preclude oropharyngeal or sion. Those patients with cardiac or renal disease must be monitored
nasopharyngeal intubation. Under these circumstances, an emer- carefully for fluid overload, but keeping in mind that fluid repletion is
gency surgical airway, cricothyroidotomy, or tracheotomy may be key in the treatment of anaphylaxis.
4. Establishment of large-bore intravenous access for rapid administra- ■ SECONDARY TREATMENT
necessary.
tion of intravenous fluids and medications. If above measures fail, additional treatment with antihistamines,
■ PRIMARY TREATMENT vasopressors, corticosteroids may be added. These should be
considered adjuvant and not equivalent substitutes to epinephrine
Increased vascular permeability with intravascular volume depletion treatment.
and systemic vasodilation occur in all patients with anaphylactic reac-
tions. Hence, the administration of intravenous fluid and epinephrine H and H Antihistamines: Histamine is one of the major mediators of
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are both cornerstones of any successful treatment of anaphylaxis. the acute manifestations of anaphylactic reactions. It is responsible for a
wide variety of cutaneous and cardiovascular manifestations. Histamine
Epinephrine: The initial drug of choice is epinephrine. Epinephrine release is mediated by both H and H receptors, and both of these
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should be administered as soon as the diagnosis of anaphylaxis is receptors must be blocked for optimal blunting of histamine action.
suspected. 141-147 It is useful for several reasons. The α -adrenergic No clinical evidence indicates that administration of antihistamines
1
effects increase peripheral vascular tone, counteracting the vasodi- is effective in treating anaphylaxis once mediators have been released.
lation caused by inflammatory mediators. The β -adrenergic effect Therefore, administration of antihistamines is only as a secondary treat-
1
increases cardiac output through positive inotropic and chronotropic ment in acute reactions. Adverse cardiopulmonary responses can be
effects. The β -adrenergic effects inhibit bronchoconstriction and prevented when patients are pretreated with H -and H -receptor block-
2
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1
the release of mediators from stimulated mast cells or basophils by ers. Diphenhydramine, an H antagonist, may be given IM or by slow
152
1
upregulating the production of intracellular C-AMP. Epinephrine intravenous infusion in a dose of 25 to 50 mg in adults, and 1 mg/kg up
148
is commercially available in several dilutions, for which it is always to 50 mg in children. Oral diphenhydramine as well as other oral first or
better to think in terms of milligrams (intramuscular) or micrograms second generation H antihistamines can also be used. An H antagonist
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(intravenous) to be administered. The standard adult dose of epi- added to the H antagonist may be helpful in the management of anaphy-
1
nephrine is 0.2 to 0.5 mg (0.2-0.5 mL of a dilution 1/1000) to be given laxis. 153-157 Parenteral ranitidine can be considered in a dose of 1 mg/kg
subcutaneously or intramuscularly. The dose in a child is 0.01 mg/kg, in adults, and 12.5 to 50 mg in children and cimetidine in a dose of 4 mg/
maximum 0.3 mg dosage. The time to highest blood concentration kg. In spite of anecdotal evidence, a recent Cochrane review did not find
(Cmax), when studied in asymptomatic subjects, is shorter when any conclusive evidence supporting the role of antihistamines and sug-
injection is given intramuscularly in the vastus lateralis muscle (lateral gested further randomized clinical trials. 158
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