아나필락틱 쇽 / anaphylaxis / shock

BOX 2. Drugs Used in the Treatment of Anaphylaxis

Epinephrine19

• 0.02–0.04 mg/kg via endotracheal tube
• 0.2–0.5 mg (total dose) SC or IM
• 0.01–0.1 mg/kg IV
• 0.05 mcg/kg/min CRI

Antihistamines20

• Famotidine: 0.5–1 mg/kg IV
• Ranitidine: 0.5–2.5 mg/kg IV
• Diphenhydramine: 1–4 mg/kg IM (dogs); 0.5 to 2 mg/kg IM (cats)

Glucocorticoids21

• Dexamethasone-SP: 0.1–0.5 mg/kg IV
• Prednisone: 0.5–1.0 mg/kg PO

Bronchodilators16

• Albuterol: 1 to 2 puffs via inhaler; can be administered up to every 15 minutes as a 90-g/puff inhaler, up to 3 doses10
• Aminophylline: 5–10 mg/kg IM or slow IV

Vasopressors16

• Norepinephrine: 0.01–1 mcg/kg/min IV CRI
• Dopamine: 5–10 mcg/kg/min IV CRI
• Vasopressin: 0.5–1.25 mU/kg/min IV CRI

Anticholinergic16

• Atropine: 0.02–0.04 mg/kg IV

Epinephrine

As an α- and β-agonist, epinephrine is essential in the treatment of anaphylaxis. It has the following effects:

• α-adrenergic effects. Vasoconstriction, which increases vascular resistance and thus blood pressure and coronary perfusion, and decreased edema, which leads to relief of upper airway obstruction
• β1-adrenergic effects. Positive inotropic and chronotropic activity, leading to increased cardiac output
• β2-adrenergic effects. Bronchodilation, leading to increased tissue oxygenation; also, the rate of adenosine triphosphate hydrolysis into adenosine monophosphate increases, which results in inhibition of histamine and cytokine release from mast cells and basophils, truncating the type 1 hypersensitivity reaction

In total, epinephrine works to accelerate heart rate, increase cardiac contractions, decrease mast cell degranulation, and improve oxygenation through bronchodilation.19 Potential adverse reactions include ventricular arrhythmias; hypertension; tachycardia; and transient, mild effects, including pallor, tremors, and dizziness (in humans).2

Epinephrine may be administered via the endotracheal tube; via SC, IM, or IV routes; or as a continuous-rate infusion (CRI). Current recommendations state that an initial dose of epinephrine may be administered IM. This can be repeated every 5 to 15 minutes.19 For the fastest and most profound effect, IV administration is recommended. If shock has developed, IV administration of epinephrine (bolus dose) followed by a CRI that can be titrated to effect is recommended.2,19 If IV epinephrine boluses appear to have little to no effect, a CRI may be started.20 Studies have shown that SC administration may provide a very delayed effect and is not recommended.

Antihistamines

While pretreatment with antihistamines is widely practiced to prevent the onset of anaphylaxis, studies show that their use during anaphylaxis may not relieve serious clinical signs. However, they may be administered in an effort to downregulate the release of more mediators during treatment.20

Both H1 and H2 antihistamines act as inverse agonists, not competitive antagonists. Inverse agonists differ from competitive antagonists in that when they bind to the receptor, they induce an opposite response instead of simply not causing receptor activation. H1 antihistamines have a higher affinity for H1R and may act to stabilize the receptors. H1 antihistamines are most effective in treating localized allergic reactions and include diphenhydramine, chlorpheniramine, and cyproheptadine. H1 antihistamines cross the blood–brain barrier; therefore, they may cause central nervous system depression.

H2 antihistamines include famotidine, ranitidine, and cimetidine. Studies have shown that use of H1 and H2 antihistamines together relieved cutaneous symptoms of anaphylaxis more effectively.20 However, these drugs should never be substituted for epinephrine during anaphylaxis. They should be used as ancillary treatments to help reduce some of the cutaneous and gastrointestinal signs.

Glucocorticoids

Glucocorticoids do not relieve initial clinical signs but may be used in long-term management of anaphylaxis. Clinical improvement is typically seen up to 4 to 6 hours after administration. Glucocorticoids act to inhibit the inflammatory responses of the late-phase eosinophil response and inhibit the arachidonic cascade.4

Bronchodilators

Albuterol, an inhaled β-adrenergic agonist, may be used to treat respiratory signs and to relieve bronchospasm. However, it does not replace the need for epinephrine because it has minimal α-adrenergic effect. Aminophylline, a phosphodiesterase inhibitor, may be useful for increasing amounts of cyclic adenosine monophosphate, which in turn increases the release of endogenous epinephrine and thus furthers the inhibition of mediator release.16 Aminophylline also directly relaxes smooth muscles in the bronchi and pulmonary vasculature.

Fluid Therapy

Fluid therapy is useful in treating patients with hypotension. Severe decrease in blood volume secondary to permeability changes and vasodilation secondary to histamine and cytokine release make aggressive fluid therapy necessary. Fluid therapy helps prevent cardiovascular collapse by increasing vascular volume.14,16 Basic guidelines for fluid therapy are as follows:16

• Crystalloids: 10- to 20-mL/kg boluses over 5 to 15 minutes; this can be repeated up to 90 mL/kg (dogs) or 60 mL/kg (cats)
• Colloids: 5-mL/kg bolus; this can be repeated up to 20 mL/kg

Volume resuscitation should be tailored to the patient’s clinical response. Improvement in perfusion parameters (mentation, mucous membrane color, capillary refill time), rectal temperature, heart rate, blood pressure, and lactate measurements can help determine whether resuscitation is adequate.

Oxygen

When patients with respiratory or hemodynamic compromise are treated, high-flow oxygen should be administered via facemask, nasal cannula, or endotracheal tube.14,16

Treatment of Severe Anaphylaxis

In some cases, a more aggressive approach may be needed for treatment of anaphylaxis. Patients with severe hypotension and/or bradycardia that is unresponsive to epinephrine and fluid resuscitation should be treated symptomatically with vasopressors and/or anticholinergics.

Vasopressors

Use of vasopressors should be considered when epinephrine and fluid resuscitation fail to improve blood pressure. Vasopressors act to increase myocardial contractility and cause vasoconstriction.2,16 These effects may help to counteract the vasodilation and myocardial dysfunction that occur during an anaphylactic reaction.

Anticholinergics

For patients with persistent bradycardia in which epinephrine does not aid in the treatment of bronchospasm, anticholinergics may be administered.2,16

Monitoring

Patients experiencing anaphylactic shock should be hospitalized for an observational period of 48 to 72 hours.16 Organs involved in the initial reaction may quickly deteriorate and should be monitored closely. These organ systems can experience a secondary or biphasic response.

Summary

Anaphylaxis is a severe condition that requires rapid emergency treatment. Because of the lack of definitive diagnostic criteria, it may be difficult to diagnose and is often overlooked. Rapid patient history and assessment are key in diagnosing and treating anaphylaxis.