Potential treatment plan for anaphylaxis: therapeutic protocol and pharmacologic intervention.

Therapy is divided into initial and secondary treatment. Therapy must be individualized, and the following is provided as a potential guide when these life-threatening events occur:


Drug or blood infusions should be immediately stopped. From a practical perspective, this may not always be possible. Limiting antigen administration may prevent further recruitment of activated mast cells and basophils.

Profound ventilation perfusion abnormalities producing hypoxemia can occur with anaphylactic reactions. Always administer 100% oxygen along with airway support as needed. Patients may not initially be intubated but may required endotracheal intubation if severe cardiopulmonary collapse occurs. Arterial blood gases should be drawn and followed during resuscitation. Patients not intubated who develop laryngeal edema may require tracheostomy.

These drugs interfere with the body's compensatory response to shock and cardiovascular dysfunction. Inhalational anesthetic drugs are not the bronchodilators of choice in treating bronchospasm following anaphylaxis, especially during hypotension.

Hypovolemia rapidly ensues during anaphylactic shock with up to 40 percent loss of intravascular fluid into the interstitial space during reactions, as demonstrated by hemoconcentration. Therefore, volume expansion is extremely important in conjunction with epinephrine in correcting the acute hypotension. Initially, in an adult, 25-50 ml/kg of lactated Ringer's solution, normal saline, or colloid solutions should be administered, keeping in mind that additional volume may be necessary with persistent hypotension. Refractory hypotension following volume and epinephrine administration requires additional hemodynamic monitoring including transesophageal echocardiography to acutely determine the underlying mechanism of ventricular dysfunction and it can be an extremely useful tool in patients who develop acute cardiovascular collapse. Fulminant non-cardiogenic pulmonary edema with loss of intravascular volume can occur following anaphylaxis. This condition requires intravascular volume repletion with careful hemodynamic monitoring until the capillary defect improves. Colloid volume expansion has not been proven to be more effective than crystalloid volume expansion for treating anaphylactic shock.

Epinephrine is the drug of choice when resuscitating patients during anaphylactic shock. Alpha1-adrenergic effects produce vasoconstriction of both vascular capacitance and arterial resistance vessels to reverse hypotension; beta2 receptor stimulation bronchodilates and inhibits mediator release by increasing cyclic AMP in mast cells and basophils. The route of epinephrine administration and the dose depends upon the patient's condition. Rapid and timely intervention with common sense must be used when treating anaphylaxis. Furthermore, during anesthesia patients may have altered sympathoadrenergic responses to acute anaphylactic shock while patients during spinal or epidural anesthesia may be partially "sympathectomized", requiring even larger doses of catecholamines. This is also a consideration regarding patients who are receiving beta-adrenergic blocking agents.

In hypotensive patients, 5-10 mcg IV boluses of epinephrine (0.05-0.1 ml of 1:10,000 epinephrine) should be titrated for restoring blood pressure. Additional volume and incremental doses of epinephrine should be administered until hypotension is corrected. Although an epinephrine infusion represents an ideal method of administering epinephrine, it is usually impossible to infuse the drug through peripheral intravenous access during acute volume resuscitation. With cardiovascular collapse, full intravenous cardiopulmonary resuscitative doses of epinephrine, 0.25 to 0.5 mg (5-10 mcg/kg), should be administered and repeated until hemodynamic stability occurs. Higher doses may be required in the patient who is "sympathectomized" following spinal or epidural anesthesia. Patients with laryngeal edema without hypotension should receive subcutaneous epinephrine. Epinephrine should not be administered intravenously to patients with normal blood pressures. If IV access is not available, then epinephrine can be administered down the endotracheal tube. The cardiovascular system is the major target organ in anaphylaxis and shock must be aggressively treated.


Since H1 receptors mediate many of the adverse effects of histamine, the intravenous administration of 0.5 to 1 mg/kg of an H1 antagonist such as diphenhydramine may be useful in treating acute anaphylaxis. Antihistamines do not inhibit anaphylactic reactions or inhibit histamine release but compete with histamine at receptor sites. H1 antagonists are indicated in all forms of anaphylaxis. The H1 antagonists presently available for parenteral administration may have anti-dopaminergic effects and should be given slowly to prevent precipitous hypotension in potentially hypovolemic patients. The indication for administering an H2 antagonist once anaphylaxis has occurred remains unclear.

Catecholamine infusions are life saving therapeutic modalities when treating anaphylaxis with persistent hypotension. The catecholamines used clinically to treat different forms of shock including anaphylaxis include dopamine, dobutamine, epinephrine, norepinephrine and isoproterenol. The currently available catecholamines have different effects on alpha, ß1, and ß2-adrenergic receptors and variable effects on heart rate, rhythm, systemic vascular resistance, and pulmonary vascular resistance. Patients during anaphylactic shock are vasodilated with low systemic vascular resistance, necessitating therapy with catecholamines that have alpha-adrenergic effects. Epinephrine stimulates alpha, ß1, and ß2 receptors and is often the mainstay therapy for anaphylaxis and for patients who have had cardiac surgery. Dopamine, a precursor of norepinephrine, undergoes biosynthetic transformation to norepinephrine when administered in high doses, and by virtue of its ability to stimulate renal dopaminergic receptors, dopamine also increases renal perfusion. Patients with heart failure or in shock can have neurotransmitter depletion and be less responsive to indirect-acting catecholamines, such as dopamine. Norepinephrine at doses as high as 1 µg/kg per minute has been administered to cardiac surgical patients to maintain systemic arterial blood pressure without evidence of renal dysfunction. Dobutamine, a synthetic catecholamine, stimulates primarily ß1 receptors. Isoproterenol, a ß1, ß2 selective drug produces tachydysrhythmias as well as systemic vasodilatation and is used primarily in right ventricular failure for pulmonary hypertension and/or in status asthmaticus. Catecholamine administration also stimulates ß1-adrenergic receptors resulting in increase in heart rate. The first-line catecholamines that should be used to treat anaphylactic shock include epinephrine and norepinephrine.

Epinephrine infusions may be useful in patients with persistent hypotension or bronchospasm after initial resuscitation. Epinephrine infusions should be started at 4 to 8 mcg/min (0.05-0.1 mcg/kg/min) and titrated to correct hypotension. Norepinephrine infusions may be required in patients with refractory hypotension due to decreased systemic vascular resistance. It may be started at 4 to 8 µg/min (0.05-0.1 mcg/kg/min) and adjusted to correct hypotension. Isoproterenol infusions can be used in patients with refractory bronchospasm, pulmonary hypertension, or right ventricular dysfunction. The usual starting dose is 0.5 to 1 mcg/min. Isoproterenol has profound beta2adrenergic effects that can produce systemic vasodilatation; therefore, it must be used cautiously in hypotensive or hypovolemic patients.

Aminophylline, a phosphodiesterase inhibitor is a weak bronchodilator that also increases right and left ventricular contractility and decreases pulmonary vascular resistance. Aminophylline may be useful in patients with persistent bronchospasm and hemodynamic stability; however, the newer cyclic AMP specific phosphodiesterase inhibitors (e.g., milrinone) have increasing importance in treating right ventricular failure and pulmonary hypertension. An intravenous loading dose of 5 to 6 mg/kg of aminophylline given over 20 minutes should be followed by an infusion of 0.5-0.9 mg/kg/hr.

Indications for corticosteroid administration during anaphylaxis are not well defined. Experimental evidence suggests that they will decrease arachidonic acid metabolites by inducing synthesis of nuclear regulatory proteins to inhibit phospholipid membrane breakdown. In addition, they may alter the activation and migration of other inflammatory cells (i.e., polymorphonuclear leukocytes) following an acute reaction. Corticosteroids may require 12 to 24 hours to work and, despite their unproved usefulness in treating acute reactions, they often administered as adjuncts to therapy when refractory bronchospasm or refractory shock occurs following resuscitative therapy. Although the exact corticosteroid dose and preparation are unclear, investigators have recommended 0.25 to 1 g of hydrocortisone in IgEmediated reactions. Alternately, 1 to 2 g of methylprednisolone (30 to 35 mg/kg) may be useful in reactions thought to be complementmediated such as catastrophic pulmonary vasoconstriction following protamine transfusion reactions. Administering corticosteroids after an anaphylactic reaction may also be important in attenuating the late phase reactions reported to occur 12 to 24 hours after anaphylaxis.

Acidosis rapidly develops in patients with persistent hypotension. This diminishes the effect of epinephrine on the heart and systemic vasculature. Therefore, with refractory hypotension or acidemia, sodium bicarbonate, 0.5 to 1 mEq/kg, should be given and repeated every 5 minutes or as dictated by arterial blood gases.

Because profound laryngeal edema may be the sequela of anaphylactic reactions, the airway should be evaluated before extubation of the trachea. Persistent facial edema suggests airway edema. The tracheas of these patients should remain intubated until the edema subsides. The development of a significant air leak after endotracheal tube cuff deflation before extubation of the trachea is useful in assessing airway patency. If there is any question of airway edema, then direct laryngoscopy should be performed before extubation of the trachea.


Bronchospasm refractory to therapy should be treated with inhaled ß2-adrenergic agents (albuterol or terbutaline) administered by metered dose inhaler to the patient, or through an endotracheal tube in the critically ill patient. For refractory bronchospasm and/or status asthmaticus, urgent cardiopulmonary support may have a role.


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