Page 1803 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1272 PART 11: Special Problems in Critical Care

recommended for preanesthetic screening of subjects without a history trigger anaphylaxis through IgE-mediated mechanism as well as via
of a previous reaction. 49 direct mast cell degranulation.)
The antibiotics most commonly implicated in reactions during this Mast cell and basophil degranulation are the primary events in
period are β-lactam antibiotics and vancomycin. Rapid vancomycin anaphylaxis. Anaphylaxis commonly involves an immunologic mecha-
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administration may result in life-threatening, non-IgE-mediated ana- nism in which IgE is synthesized in response to allergen exposure and
phylaxis. 51-53 These nonimmunologic reactions to vancomycin can be becomes fixed to high affinity receptors for IgE (FcERI receptors)
reduced or eliminated by administering this drug as a dilute solution, on the surface membranes of mast cells and basophils. Aggregation
dissolved in at least 200 mL, and infused over at least a 2-hour period. of receptor-bound IgE molecules occurs on reexposure to the aller-
IgE-mediated anaphylaxis to vancomycin is much less common. gen and results in cell activation and mediator release. 71-73 IgE also
Dextran and hydroxyethyl starch (HES), large-molecular-weight contributes to the intensity of anaphylaxis by enhancing the expres-
polysaccharides, may be used as a nonblood, high oncotic fluid replace- sion of FcERI on mast cells and basophils. 71-73 Other immunologic
ment during surgery. These agents are infrequently associated with mechanisms that do not involve IgE can cause anaphylaxis. IgG-
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adverse reactions and anaphylaxis. Estimates of reaction rates are mediated anaphylaxis has been reported due to high-molecular-weight
0.008% to 0.08% for dextran and 0.08% for HES. 54 iron dextran and the infusion of chimeric, humanized, or human
Intravenous drugs used for anesthetic induction can cause periopera- therapeutic mAbs, such as infliximab. 75,76 Complement-mediated
tive anaphylaxis. Barbiturates, especially thiopental, have been reported anaphylaxis occurs in association with hemodialysis, the use of
to cause anaphylaxis. Most of the adverse reactions with barbiturates, oversulfated chondroitin sulfate (OSCS)–contaminated heparin, prot-
particularly thiopental, are caused by specific IgE antibody, though this amine neutralization of heparin, and the administration of liposomal
agent can also cause direct mast cell degranulation. 46,55-57 Propofol, a drugs and polyethylene glycols. OSCS-contaminated heparin trig-
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nonbarbiturate induction agent, has also been reported to cause peri- gers anaphylaxis through activation of the complement system as well
operative anaphylaxis through both an IgE-mediated mechanism and as via activation of the contact system. This results in the formation
direct histamine release. 58-60 of anaphylatoxins C3a and C5a and kinin. 77,78 Direct activation of the
Opiates used in the perioperative period are a common cause of flush- innate immune system might also produce anaphylactic events. In
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ing and urticaria following intravenous administration. Anaphylaxis to addition, as noted previously, nonimmune activation of mast cells and
these agents, in contrast, is very rare. 61,62 Cutaneous flushing and hives basophils occurs. 16,80,81 A trigger can lead to anaphylaxis through more
often occur after intravenous morphine administration, but with rare than one mechanism; for example, radiocontrast media can rarely
exceptions, the amount of histamine release does not result in hypoten- trigger anaphylaxis through an immunologic IgE-dependent mecha-
sion or bronchospasm. Reducing the rate of opioid administration nism as well as through direct mast cell activation. 81,82 Regardless of
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usually limits the severity of these reactions. Fentanyl does not directly the underlying mechanisms, mast cells and basophils may play an
stimulate histamine release by way of the mast-cell opioid receptor. important role in initiating and amplifying the acute allergic response.
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Intravenous protamine, an agent used to reverse heparin anticoagula- Calcium influx is the essential proximal intracellular event leading to
tion, may cause both anaphylactic and anaphylactoid reactions; the latter mast cell degranulation and is controlled by both positive and nega-
is characterized by increases in pulmonary artery pressure. Potential tive regulation through calcium channels. 71,83 Mast cells and basophils
pathophysiologic mechanisms are numerous and varied. 64-68 A case- release preformed chemical mediators of inflammation, including his-
controlled study showed that previous neutral protamine Hagedorn tamine, tryptase, carboxypeptidase A, and proteoglycans. 71,72,84-86 They
(NPH) insulin use, fish allergy, and other medication allergy are inde- also release newly generated mediators, such as leukotrienes, prosta-
pendent risk factors for anaphylaxis to protamine. It has been esti- glandins, platelet-activating factor, and cytokines, such as IL-6, IL-33,
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mated that up to 39% of cardiopulmonary bypass patients have one or and TNF-α. 71,72,84,87-90 Sphingosine-1-phosphate is now recognized as a
more of these risk factors. Latex has been reported to account for up to circulating mediator in anaphylaxis, and in addition, it acts as a signal-
17% of intraoperative anaphylaxis. 69 ing component within the mast cell. 91
The features of intraoperative anaphylaxis may differ considerably The clinical manifestations are the result of the activities of the media-
from anaphylaxis not associated with surgical procedures. While cuta- tors released from the mast cell and basophils (Table 128-3). These
neous, hypotensive and respiratory events occur in both, hypotensive mediators not only exert direct effects on the target organs, but also
cardiovascular collapse is a more predominant feature of reactions recruit other inflammatory cascades including the complement system,
during surgery. Latex-induced anaphylaxis is due to IgE-mediated the contact system, and the clotting cascade. These recruited pathways
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mechanisms. Unfortunately, no standardized skin test reagent for latex can amplify the severity of the event and change the nature of the patho-
is available in the United States. For diagnostic purposes, in vitro tests physiology (Table 128-4).
for latex-specific IgE are available, but the sensitivity of these tests may Histamine is one of the important mediators. Histamine acts on the
vary. Due to the suboptimal diagnostic utility of these tests, results must smooth muscle cells of the bronchi, coronary arteries, and the GI tract. It
be carefully correlated with the clinical history. Latex-induced anaphy- leads to smooth muscle spasm, increased vascular permeability, vasodi-
laxis may occur in a variety of situations, all involving direct contact lation, stimulation of sensory nerve endings, and myocardial depression.
with latex, usually gloves, or instruments, or with aerosolization of The clinical effects present as wheezing, hypotension, nausea, vomiting,
latex antigen adherent to the cornstarch powder of latex gloves. Thus, diarrhea, and myocardial ischemia, as well urticaria and angioedema.
latex reactions can occur during operative procedures when gloves are Histamine binds to four different receptors. Anaphylactic events are
donned. Latex reactions may occur immediately with latex contact or mostly mediated through activation of the H and H receptors.
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may be delayed from 30 to 60 minutes. Intraoperative latex anaphylaxis Vasodilation is the primary event of histamine stimulation and is medi-
may be related to the administration of drugs through a latex port prior ated through both H and H receptors. Vasodilation is the direct effect
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to surgery. of H receptor stimulation on the vascular bed, whereas H stimulation
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1
causes stimulation of endothelial cells and the production of nitric oxide
PATHOPHYSIOLOGY (NO), which in turn leads to vasodilation. Vasodilation produces flush-
ing and lowers peripheral resistance and blood pressure. Smooth muscle
The mechanisms underlying anaphylactic reactions can be broadly contraction in the bronchial tree and GI tract is mediated primarily
divided into immunologic and nonimmunologic categories (Table 128-2). through the H receptor and causes wheezing, cramping abdominal
1
Immunologic reactions can be further subdivided into IgE-mediated pain, and diarrhea. Cardiac effects and the increase in glandular secre-
and non–IgE–mediated events. There are agents that can cause anaphy- tions are mediated through both the H and H receptors. H receptors
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laxis through several mechanisms (eg, radiocontrast agents can rarely are present in presynaptic terminals of sympathetic nerves innervating

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