Page 1817 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1286 PART 11: Special Problems in Critical Care

FIGURE 129-9. Vasopressin-induced skin necrosis. Retiform purpura with central necrosis.
(Used with permission of Dr Vesna Petronic-Rosic.)
FIGURE 129-8. Warfarin-induced skin necrosis. Ill-defined, edematous, violaceous
plaque with central hemorrhagic vesicles. (Used with permission of Dr Keyoumars Soltani.)
and variceal hemorrhage. Uncommon adverse reactions to large-dose
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(0.2-0.4 U/min), centrally administered vasopressin include cardiac
females and the abdomen and thighs in males. Histopathology shows arrhythmias, ischemia, infarction, and bowel ischemia. When periph-
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fibrin occluding dermal and hypodermal veins, with diffuse necrosis. eral intravenous administration is used, accidental extravasation of the
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This occurs more commonly in women. Other risk factors include a drug may result in skin necrosis (Fig. 129-9) and gangrene. This CADR
large loading dose, protein C deficiency, and the presence of the factor V may occur even at small doses (0.04 U/min) or when small quantities
Leiden mutation. Treatment consists of discontinuation of warfarin and that are undetectable by the occlusion pressure monitor infiltrate the
administration of intravenous heparin. Some investigators have reported tissue. Administration through a central venous catheter is encouraged,
success with the use of protein C concentrate, prostacyclin, and factor even for small doses, to minimize the occurrence of this adverse reac-
VII. Lesions are treated as any other skin ulcer; however, when they are tion, although skin necrosis with low-dose vasopressin infusion through
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extensive, surgical debridement, grafting, or occasionally amputation may central venous route has been recently reported. Interestingly, skin
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be necessary to prevent the development of infection and sepsis. necrosis does not occur with large-dose subcutaneous administration,
■ ADVERSE REACTIONS TO ALTERNATIVE DRUGS as performed for diabetes insipidus. Mortality rate is usually high in
patients with septic shock who develop necrotic skin lesions. Treatment
Herbal remedies are classified as dietary supplements. As such, they are consists of stopping the vasopressin infusion, surgically débriding the
exempt from the stringent evaluation and regulatory processes that drugs ischemic tissue, and applying wet dressings or grafting.
have to undergo to show efficacy, safety, and quality. 30,31 It is not uncommon Diffuse ischemic skin lesions, defined as new areas of mottled or livid
for patients admitted to the ICU to have been taking herbal medicines or skin, have been found to occur in approximately 30% of patients during
supplements. Contrary to popular belief, herbal products may result in infusion of arginine-vasopressin, an alternative powerful vasopressor
clinically significant adverse reactions and herbal-drug interactions. Some agent that is increasingly used in catecholamine-resistant vasodilatory
remedies have been found to contain traditional drugs, such as aspirin, shock. Sepsis and arterial occlusive disease are predisposing factors.
paracetamol, mefenamic acid, diazepam, and triamcinolone, with cor- These lesions, often seen on the limbs and trunk but also on the tongue,
responding adverse reactions. Contaminants, such as lead, arsenic, and may lead to gangrene, necessitating debridement and amputation. 37
other heavy metals, have been found in numerous herbal remedies and are
a significant source of adverse reactions. Autoimmune thrombocytopenia ■ ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS
has been reported in a patient receiving kelp tainted with arsenic. Acute generalized exanthematous pustulosis (AGEP) is a rare, T-cell–
Similarly, interactions with traditional drugs are a significant cause of mediated drug reaction that often presents within 1 to 5 days of start-
concern in individuals taking herbal remedies concurrently with tradi- ing the culprit medication. It is typically reported in association with
tional medicines (estimated at 18% of the population). Components in antibacterial drugs (>90% of cases) including ampicillin, amoxicillin,
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herbal remedies such as St John’s wort and Kava-Kava, used for depres- quinolones, clindamycin, and sulfonamides. However, other topical and
sion and anxiety, respectively, have been shown to inhibit monoamine systemic medications, including corticosteroids, terbinafine, diltiazem,
oxidase activity. Interactions with drugs affecting the metabolism of chloroquine, and herbal remedies, have also been implicated.
neuroactive amines, such as the selective serotonin-reuptake inhibitors, AGEP is clinically characterized by the acute onset of edematous
are a potential problem. Therefore, coffee, tea, and foods containing erythema, followed by disseminated, small, nonfollicular sterile pustules
tyramine (aged cheese, soy sauce, smoked meats, bananas, and avocados) which may coalesce into bullae (Fig. 129-10). Marked edema of the
should be avoided. face, target-like lesions, blisters, and purpura may be seen, but are not
Because many of the mechanisms underlying acute hypersensitivity typical of AGEP. Mild and nonerosive mucosal involvement occurs in
reactions are unclear, a careful history and evaluation is necessary. 20% of patients. Patients have fever (T >38°C) and massive leukocytosis,
In addition, because the half-life of many of these components is not sometimes with eosinophilia, but there is no internal organ involvement.
known, they should be discontinued immediately on admission to the Histologically, AGEP is characterized by a subcorneal or intraepidermal
hospital or the critical care unit. sterile pustule and marked spongiosis with a few necrotic keratinocytes.
■ VASOPRESSIN-INDUCED SKIN NECROSIS 5% mortality rate, which is often reported, results from secondary infec-
AGEP is self-limiting and spontaneously resolves within 2 weeks. The
Vasopressin, a nonselective vasoconstrictor, is used in the treatment of tions in patients with other medical comorbidities. Treatment consists
vasodilatory septic shock, hypotension unresponsive to catecholamines, of discontinuation of the suspected drug and supportive therapy. Oral
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