Page 1409 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

982 PART 8: Renal and Metabolic Disorders

CRITICAL ILLNESS–RELATED TABLE 102-1 Causes of Adrenal Insufficiency
CORTICOSTEROID INSUFFICIENCY Reversible dysfunction of the hypothalamic-pituitary adrenal axis
There has recently been a great deal of interest regarding the assessment Sepsis/systemic inflammatory response syndrome
of “adrenal function” and the indications for corticosteroid therapy Drugs
in critically ill patients. While the use of high-dose corticosteroid Corticosteroids (secondary AI)
(10,000 to 40,000 mg of hydrocortisone equivalent over 24 hours) in Ketoconazole (primary AI)
patients with severe sepsis and ARDS failed to improve outcome and Etomidate (primary AI)
was associated with increased complications, 27,28 an extended course of Megesterol acetate (secondary AI)
“stress-dose” corticosteroids (200-350 mg hydrocortisone equivalent/ Rifampin (increased cortisol metabolism)
day for up to 21 days) has been demonstrated to increase ventilator- and Phenytoin (increased cortisol metabolism)
hospital-free days and improve short-term survival in select groups of Metyrapone (primary AI)
ICU patients. 29-32 These patients typically have an exaggerated proin- Mitotane (primary AI)
flammatory response and are considered to be “relatively” corticosteroid Hypothermia (primary AI)
insufficient. Primary adrenal insufficiency
Until recently the exaggerated proinflammatory response that char- Autoimmune adrenalitis
acterizes patients with systemic inflammation has focused on suppres- HIV infection
sion of the HPA axis and “adrenal failure.” However, experimental and HIV
clinical data suggest that corticosteroid tissue resistance may also play Drugs
an important role. This complex syndrome is referred to as critical Cytomegalovirus infection
illness–related corticosteroid insufficiency (CIRCI). CIRCI is defined as Metastatic carcinoma
2,33
inadequate corticosteroid activity for the severity of the patient’s illness. lung
CIRCI manifests with insufficient corticosteroid mediated downregula- breast
kidney
tion of inflammatory transcription factors. Systemic fungal infections
■ TISSUE CORTICOSTEROID RESISTANCE DURING CRITICAL ILLNESS Histoplasmosis
Tissue corticosteroid resistance is a well-known manifestation of Cryptococcus
Blastomycosis
chronic inflammatory diseases such as chronic obstructive pulmo- Tuberculosis
nary disease (COPD), severe asthma, systematic lupus erythematosus Acute hemorrhage/infarction
(SLE), ulcerative colitis, and rheumatoid arthritis. Emerging data disseminated intravascular coagulation
suggest that corticosteroid tissue resistance may develop in patients meningococcemia
with acute inflammatory diseases such as sepsis and acute lung anticoagulation
injury (ALI). 2,34 In a sheep model of ALI induced by Escherichia coli antiphospholipid syndrome
endotoxin, Liu et al demonstrated decreased nuclear GRα-binding heparin induced thrombocytopenia (HIT)
capacity and increased expression of phospholipase A2 (PLA2) despite trauma
increased serum cortisol levels. These authors demonstrated similar Secondary adrenal insufficiency
35
findings in the liver cytosol following a burn injury in rats, which were Chronic steroid use
partially reversed by TNF-α and IL-1β neutralizing antibodies. In an Pituitary or metastatic tumor
36
ex vivo model, Meduri and colleagues compared the cytoplasmic to Pituitary surgery or radiation
nuclear density of the GR complex in patients with ARDS who were Empty-sella syndrome
survivors and nonsurvivors. These authors demonstrated a markedly Craniopharyngioma
34
reduced nuclear density of the GR complex in nonsurvivors while the Sarcoidosis, histiocytosis
cytoplasmic density was similar between survivors and nonsurvivors. Postpartum pituitary necrosis
This experiment provides further evidence that the nuclear GC-GR HIV infection
activity may be impaired in critically ill patients despite adequate cyto- Head trauma
plasmic (serum) levels of cortisol.
■ HPA AXIS FAILURE IN ACUTE ILLNESS CLINICAL MANIFESTATIONS OF CIRCI

HPA axis failure appears to be a common problem in patients with sys- Patients with chronic adrenal insufficiency (Addison disease) usually
temic inflammation. Patients at risk for developing tissue glucocorticoid present with a history of weakness, weight loss, anorexia, and lethargy
resistance are similarly at risk for HPA axis failure. The incidence of with some patients complaining of nausea, vomiting, abdominal pain,
HPA axis failure varies widely depending on the criteria used to make and diarrhea. Clinical signs include orthostatic hypotension and hyper-
the diagnosis and the patient population studied. The overall incidence pigmentation (primary adrenal insufficiency). Laboratory testing may
of “adrenal insufficiency” in critically ill patients approximates 20%, demonstrate hyponatremia, hyperkalemia, hypoglycemia, and a normo-
with an incidence as high as 60% in patients with severe sepsis and sep- cytic anemia. This presentation contrasts with the features of CIRCI. The
tic shock. The mechanisms leading to inadequate cortisol production clinical manifestations CIRCI are consequent upon an exaggerated pro-
37
during critical illness are complex and poorly understood, and likely inflammatory immune response. Hypotension refractory to fluids and
include decreased production of CRH, ACTH, and cortisol. A subset of requiring vasopressors is a common manifestation of CIRCI. 17,38 CIRCI
2
patients may suffer structural damage to the adrenal gland from either should therefore be considered in all ICU patients requiring vasopressor
hemorrhage or infarction and this may result in long-term adrenal support as well as those with severe progressive ARDS. Patients usually
2
dysfunction. In addition, a number of drugs are associated with adrenal have a hyperdynamic circulation which may compound the hyper-
failure. However, reversible HPA dysfunction is increasingly being recog- dynamic profile of the patient with sepsis/systemic inflammation.
38
nized in critically ill patients with systemic inflammation associated with However, the systemic vascular resistance, cardiac output, and pul-
the sepsis, ALI, liver disease, and following cardiopulmonary bypass monary capillary wedge pressure can be low, normal, or high. The
39
(see Table 102-1). variability in hemodynamics reflects the combination of CIRCI and

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