Page 1804 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 128: Anaphylactic and Anaphylactoid Reactions 1273

TABLE 128-3 Anaphylactic Mediators and the Resultant Pathophysiologic Activities Pathway activation during anaphylaxis
Mediator Pathophysiologic Event Clinical Correlate
Histamine and products Smooth muscle spasm, mucus Wheeze, urticaria,
of arachidonic acid secretion, vasodilatation, increased angioedema, flush, itch, Clotting Factor Contact
system
XII
metabolism (leukot- vascular permeability, activation diarrhea and abdominal pain,
rienes, thromboxane, of nociceptive neurons, platelet hypotension, rhinorrhea, and Kallikrein
prostaglandins, and adherence, eosinophil activation, bronchorrhea
platelet-activating factor) eosinophil chemotaxis Plasmin
Neutral proteases: Cleavage of complement May recruit complement by Mast
cell
tryptase, chymase, components, chemoattractants cleaving C3, may ameliorate Trypsin
carboxypeptidase, for eosinophils and neutrophils, symptoms by invoking a Complement
cathepsin G further activation and degranu- hypertensive response through
lation of mast cells, cleavage of the conversion of angiotensin FIGURE 128-1. Pathways activated during anaphylaxis.
neuropeptides, conversion of I to angiotensin II and by inac-
angiotensin I to angiotensin II tivating neuropeptides. Also, In addition, many of these mediators are capable of activating
can magnify response due to
further mast cell activation other inflammatory pathways (Fig. 128-1). Mast cell kininogenase
and basophil kallikrein can activate the kinin system. Tryptase also
Proteoglycans: Anticoagulation, inhibition of Can prevent intravascular has kallikrein activity and can activate the complement cascade and
heparin, chondroitin complement, binding phospholipase coagulation and the cleave fibrinogen. Platelet-activating factor induces clotting and dis-
sulphate A2, chemoattractant for eosinophils, recruitment of complement. seminated intravascular coagulation. In addition, chemotactic agents,
inhibition of cytokine function, Also can recruit kinins increasing by recruiting eosinophils and other cells, have the capacity to prolong
activation of kinin pathway the severity of the reaction and intensify reactions. Heparin can inhibit clotting, plasmin, and
Chemoattractants: Calls forth cells to the site May be partly responsible for kallikrein. It also modulates the effects of tryptase and has anticom-
chemokines, eosinophil recrudescence of symptoms in plementary activity. Chymase is capable of converting angiotensin I
chemotactic factors late phase reaction or extension into angiotensin II and therefore theoretically could enhance the
and protraction of reaction compensatory response to hypotension. Cells, especially eosinophils,
Nitric oxide Smooth muscle relaxation Perhaps relief of broncho- called forth to the site by chemotactic agents originally released from
causing vasodilatation of peripheral spasm, but most important mast cells and basophils, can be responsible for protracted episodes
vascular bed, bronchodilatation, effect appears to be the of anaphylaxis and for a recrudescence in symptoms after an initial
and coronary artery vasodilatation. production of hypotension improvement (late-phase response).
In addition, nitric oxide causes and shock Nitric oxide (NO), synthesized from L-arginine by nitric oxide
increased vascular permeability synthase, has an important role in the pathophysiological changes
93
Tumor necrosis Production of platelet- activating Vascular permeability and associated with anaphylaxis. NO production can be increased in
factor-α activates factor vasodilatation. Also since it is anaphylaxis. This has been demonstrated in a rabbit model of anaphy-
NFK-β synthesized and released “late,” laxis and human anaphylactic events. 93,94 NO can play a dual role in
has been incriminated in anaphylaxis. While it prevents mast cell mediator release and dilates
production of late phase bronchial smooth muscle, it simultaneously can cause vasodilation and
reactions enhance vascular permeability. Nitric oxide synthase inhibitor attenu-
Interleukins 2, 6, 10 These are usually found later in the Unknown ates hypotension and hemoconcentration and decreases venous return
but does not improve cardiac depression. In animals pretreated with a
course of an event than histamine NO synthase inhibitor, the cardiac output falls significantly, although
and tryptase, and persist longer. venous return is increased. However, the role of NO during anaphy-
The effects they cause have not laxis has been questioned as well. In one study, there was no correla-
been determined. IL-10 may be tion between nitric oxide level, plasma histamine and serum tryptase
active in recovery from events levels. There was also no correlation between nitric oxide levels and
Tumor necrosis factor Unknown Elevated levels have been urticaria or erythema, and the levels were not higher in patients with
receptor-1 associated with more bronchospasm and hypotension. 95
profound hypotension The hemodynamic abnormalities during anaphylaxis result from
the loss of intravascular fluid and vasodilation and are often followed
by vasoconstriction and then myocardial depression. Up to 50%
TABLE 128-4 Recruitment of Other Inflammatory Cascades During Anaphylaxis
of vascular volume can be lost into the extravascular space within
Mediator Pathophysiologic Event Clinical Correlate 10 minutes secondary to increased vascular permeability. 96,97 The intra-
Activation of the contact Vasodilatation and Hypotension and vascular fluid loss triggers compensatory mechanisms (Fig. 128-2)
system (kinins) vasopermeability angioedema which includes the endogenous production of various vasoconstric-
Activation of the complement C3a/C5a can cause Possible urticaria/ tors, for example, epinephrine, norepinephrine, angiotensin, and
endothelin-1.
61,98-100
system vasopermeability angioedema The early fall in arterial pressure (vasodilation) may lead to a brief and
Activation of the clotting system Intravascular coagulation Disseminated intravascular temporary increase in cardiac output due to left ventricular unloading or
(Factor XI, plasmin) coagulation an increase in cardiac contractility (effects of epinephrine, norepinephrine,
and histamine). Subsequently, the loss of plasma volume, the decrease in
the heart and other systemic vasculature. Their stimulation leads to venous return, and the pooling of blood in the splanchnic circulation will
inhibition of norepinephrine release. Blockade of the H receptor would decrease cardiac output, causing shock. Transient pulmonary hyperten-
3
be potentially beneficial by correcting hypotension through restoration sion and increased pulmonary vascular resistance has been observed
of the release of norepinephrine. 92 in animal models of anaphylaxis. The high albumin concentration in

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