Page 1412 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 102: Critical Illness–Related Corticosteroid Insufficiency 985

cortisol production for up to 48 hours, prompting the suggestion of Adrenal Pathophysiology Study in which 245 of 340 (72%) critically ill
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steroid supplementation during this period. In the Annane study, patients with liver disease were diagnosed with adrenal insufficiency (the
72 patients received etomidate within 3 hours prior to randomization of hepatoadrenal Syndrome). These data suggest that adrenal dysfunction
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whom 68 were nonresponders; in this group of nonresponders the mor- and CIRCI are common in critically ill patients with end-stage liver
tality was 54% in those treated with corticosteroids as compared to 75% disease and that treatment with corticosteroids may improve outcome.
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in those who received placebo. In the CORTICUS study, 96 patients HELLP Syndrome: The acronym HELLP describes a variant of severe
received etomidate a median of 14.5 hours prior to randomization.
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In this study, etomidate was identified as an independent risk factor preeclampsia characterized by hemolysis, elevated liver enzymes, right
upper quadrant pain, and thrombocytopenia. The development of HELLP
for death, with this risk being unaffected by treatment with glucocor-
ticoids. These data suggest that critically ill patients who have received syndrome places the pregnant patient at increased risk for morbidity
and death. The HELLP syndrome usually develops suddenly during
an intubating dose of etomidate should probably be treated (within
6 hours) with stress doses of hydrocortisone for 24 hours (200 mg on day pregnancy (27-37 weeks’ gestation) or in the immediate puerperium.
The HELLP syndrome occurs in up to 20% of pregnancies complicated
1,100 mg on day 2). by severe preeclampsia. The development of a SIRS-like condition with
■ ADDITIONAL INDICATIONS FOR CORTICOSTEROIDS increased levels of proinflammatory cytokines in patients with HELLP
led to the consideration of the use of corticosteroids to treat this dis-
RCTs have demonstrated the benefit of corticosteroids in patients with ease. A number of retrospective cohort studies have been published,
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severe community-acquired pneumonia, during weaning from mechan- which suggested improved maternal and fetal outcome with the use
ical ventilation, in patients undergoing cardiac surgery, and in patients of corticosteroids. In addition, four small RCTs have been conducted,
with the HELLP syndrome. In addition, observational studies suggest which randomized participants to standard therapy or dexamethasone.
that stress doses of corticosteroids may have a role in the management A meta-analysis of these RCTs demonstrated no significant difference in
of critically ill patients with liver disease and those with pancreatitis. 77,78 maternal mortality or morbidity or fetal outcome, however hospital stay
was significantly shorter in the women allocated to dexamethasone.
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Cardiac Surgery: Corticosteroids have been demonstrated to downregu- Furthermore, taken together most of the studies demonstrate that corti-
late activation of the proinflammatory cascade following cardiopulmo- costeroids produce a significant improvement in the hematologic abnor-
nary bypass (CPB). The clinical benefits of corticosteroids (similar to malities associated with the HELLP syndrome together with a more rapid
that of sepsis and ARDS) may however be dose dependent. A number improvement of the clinical features such as mean arterial pressure and
of studies noted an increase in the shunt fraction, greater hemodynamic urine output. Most of the studies to date used dexamethasone in a dose
instability, and a delay in extubation in patients undergoing CABG of 10 mg (equivalent to 200 mg hydrocortisone) every 12 hours for 24 to
following the use of high-dose methylprednisolone. 79-81 However, Kilger 36 hours. In should be noted that the placenta has a high concentration of
and colleagues reported that the perioperative use of physiologic stress the enzyme 11β-hydroxysteroid dehydrogenase (11 β-HSD) type 2, which
doses of hydrocortisone (100 mg before induction, 10 mg/h for 24 hours converts cortisol to the inactive metabolite cortisone and prednisolone to
followed by a taper) improved the outcome of a high-risk group of prednisone. Inactivation of the synthetic corticosteroid dexamethasone
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patients after cardiac surgery. Similarly, corticosteroids have been dem- and betamethasone by the placenta is negligible. With our increased
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onstrated to reduce the incidence of postoperative atrial fibrillation. 83 understanding of the role of corticosteroids in SIRS, dexamethasone in a
2,33
Posttraumatic Stress Disorder: Corticosteroids are believed to play an dose of 10 mg every 12 hours appears appropriate. However, we would
important role in the posttraumatic stress disorder (PTSD) by influencing recommend treatment for at least 5 days followed by a slow taper. 2
the consolidation or retrieval of traumatic memories. Patients with PTSD
often show neuroendocrine system alterations such as increased urinary PERIOPERATIvE CORTICOSTEROIDS IN PATIENTS
norepinephrine excretion and low plasma or urinary cortisol excretion. 84,85 ON CHRONIC CORTICOSTEROIDS
Patients with low cortisol blood levels after a major motor vehicle accident
have a high risk of developing PTSD during follow-up. 86,87 The adminis- In 2001, over 34 million prescriptions were written in the Unites States
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tration of physiologic doses of hydrocortisone to critically ill patients with for the four most commonly used oral corticosteroids. Corticosteroids
sepsis and following cardiac surgery results in a significant reduction of are prescribed for patients with a wide variety of autoimmune and
PTSD symptoms after recovery as well as improvements in health-related inflammatory diseases, for patients with chronic obstructive pulmonary
quality of life. 88-90 The mechanisms by which glucocorticoids improve disease (COPD) and asthma, as well as recipients of organ transplants.
PTSD may be a direct effect of glucocorticoids on neurotransmission; Due to their chronic medical conditions, these patients frequently require
alternatively, the benefit may be due to the deceased use of catecholamines both elective and emergency surgical procedures. It is generally believed
or the suppression of inflammatory mediators. that patients taking long-term glucocorticoids require perioperative
“stress doses” of corticosteroids due to the presumed suppression of the
Liver Failure: Sepsis and end-stage liver disease have a number of patho- HPA axis. 102-105 Furthermore, it is believed that failure to provide supple-
physiologic mechanisms in common (endotoxemia, increased levels of mental perioperative corticosteroids will result in “adrenal crisis.” 102-105
proinflammatory mediators, decreased levels of HDL), and it is therefore We performed a systematic review of prospective and cohort studies
not surprising that adrenal insufficiency (and CIRCI) is common in which specifically investigated the necessity for perioperative corticoste-
patients with end-stage liver disease. 91-93 Tsai and colleagues performed a roids in patients receiving chronic corticosteroids (duration >2 weeks).
corticotrophin stimulation test in 101 patients with cirrhosis and sepsis. This study suggested that patients receiving therapeutic doses of
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In this study 51.4% of the patients were diagnosed with adrenal insuffi- corticosteroids who undergo a surgical procedure do not routinely
ciency; survival at 90 days was 15.3% in these patients compared to 63.2% require stress doses of corticosteroids so long as they continue to receive
in those patients with normal adrenal function. None of the patients their usual daily dose of corticosteroid. Adrenal function testing is not
were treated with corticosteroids. Fernandez and coauthors compared required in these patients, as the test is overly sensitive and does not
the survival of patients with cirrhosis and sepsis who underwent adrenal predict which patients will develop an adrenal crisis. However, the
function testing in which patients with adrenal insufficiency were treated anesthesiologist, surgeon, and intensivist must be aware that the patient
with hydrocortisone (Group 1) compared to a control group (Group 2) was receiving suppressive doses of corticosteroids, necessitating close
that did not undergo cosyntropin testing and were not treated with cor- perioperative hemodynamic monitoring and the use of stress doses
ticosteroids. The incidence of adrenal failure was 68% in Group 1; the of hydrocortisone in patients with volume refractory hypotension (a
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hospital survival was 64% in Group 1 as compared to 32% in Group 2 serum cortisol should be measured in these patients prior to initiating
(p = 0.003). We reported the results of the Hepatic Cortisol Research and treatment). These recommendations do not apply to patients who
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