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59 JULY/AUGUST 2017 ■ TVPJOURNAL.COM CONTINUING EDUCATION 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