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
OF THE ANTIGEN.
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.
MAINTAIN THE AIRWAY
WITH 100% OXYGEN
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.
SEDATIVES, HYPNOTICS, OR ANESTHETIC DRUGS
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
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
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
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.
EVALUATE THE AIRWAY
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.
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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