Current concept

Corticosteroid Insufficiency in Acutely ill Patients

Mark S. Cooper, M.D., and Paul M. Stewart, M.D.

NEJM Volume 348:727-734 February 20, 2003 Number 8 By Ri 93-04-05

Questions
How to make a diagnosis of adrenal insufficiency in patient under stress? Treatment?

Hypothesis
The normal range of cortisol level (plasma, morning: 6 ~ 30 g/dl) But it should be adjust in patient with stress.

Knowledge
Fight or Fright The need of corticosteroid increases in patient with stress

Whats known or unknown

The s/s of adrenal insufficiency are usually nonspecific. Adrenal crisis can cause fetal outcome. The role of using corticosteroid in pt with infection is still unclear. If the diagnosis of adrenal insufficiency is established, how long should corticosteroid be used?

The HypothalamicPituitaryAdrenal Axis in Acute illness

The Hypothalamic-Pituitary-Adrenal Axis A diurnal pattern cortisol secretion corticotropin (pituitary gland) hypothalamic corticotropin-releasing hormone Negative feedback

The HypothalamicPituitaryAdrenal Axis in Acute illness

Stress: severe infection, trauma, burns, illness, surgery cortisol Roughly proportional to the severity. Diurnal variation: vanished. Stimulation of the hypothalamicpituitary adrenal axis: elevated levels of circulating cytokines and other factors.

The HypothalamicPituitaryAdrenal Axis in Acute illness

During severe illness, many factors can impair the normal corticosteroid response.

Head injury; CNS depressants Pituitary infarction

Ketoconazole

Extensive destruction by tumor or infection

Adrenal hemorrhage in septicemia or coagulopathy

High level of inflammatory cytokines in sepsis pt directly inhibit adrenal cortisol synthesis

The HypothalamicPituitaryAdrenal Axis in Acute illness

The metabolism of cortisol: Liver, can be enhanced by drugs such as rifampin or phenytoin Excessive inflammatory cytokines during sepsis: systemic or tissue-specific resistance to cortisol The need of corticosteroid increases in patient with stress

The HypothalamicPituitaryAdrenal Axis in Acute illness

Develop during an illness Transient Functional adrenal insufficiency -- no obvious structral defects in HPA axis Relative adrenal insufficiency -- insufficient to control the inflammatory response

Diagnosis of Corticosteroid Insufficiency during Acute illness

Corticosteroid insufficiency associated with acute illness -- difficult to discern clinically, but there are some features that suggest the diagnosis.

Features suggesting corticosteroid insufficiency

common in patients with acute severe illness.

Easy been masked by fluid replacement, especially in ICU

Relatively uncommon

Diagnosis of Corticosteroid Insufficiency during Acute illness

It still remains extremely difficult to recognize adrenal insufficiency in the ICU. Important diagnostic clues Hemodynamic instability despite adequate fluid resuscitation Ongoing evidence of inflammation without an obvious source that does not respond to empirical treatment.

Laboratory Investigations
What an appropriate response should be in a critically ill patient. Assessment of corticosteroid sufficiency based on: randomly measured cortisol levels or the corticotropin stimulation test.

Laboratory Investigations
Randomly measured cortisol levels More useful would be the identification of a minimal threshold level and a maximal threshold level. 15 g/dl (10 g/dl to 34 g/dl) best identifies persons with clinical features of corticosteroid insufficiency or who would benefit from corticosteroid replacement

Laboratory Investigations
Corticotropin stimulation test IV or IM 250 g of Cosyntropin

Check plasma cortisol levels 0, 30, ( 60 ) mins after administration

Laboratory Investigations
Corticotropin stimulation test Prognostic implications -- < 9 g /dl increased risk of death.

Laboratory Investigations
The authors opinion > 34 g /dl: unlike. <15 g /dl: likely.

Methylprednisolone 2 mg/kg/day

Laboratory Investigations
When to recheck ? Development of new clinical features Deterioration in clinical condition

Treatment of Acute Adrenal Insufficiency

Critically ill patients with established hypoadrenalism: IV or IM Hydrocortisone (solu-cortef) 50 mg q6h. Patients in shock: 5 percent dextrose in normal saline should be given IV initially.

Treatment of Acute Adrenal Insufficiency

(in septic shock) Evidence-based support the use of supplemental corticosteroid in septic shock pt, esp. in ICU. 3 randomized, controlled trials of hydro-cortisone replacement in patients with septic shock Improvements in hemodynamics Reduction in the need for vasopressor therapy.

Treatment of Acute Adrenal Insufficiency

(in septic shock)

In the largest randomized, placebo-controlled trial, treatment of 300 medical and surgical patients with 200 mg of hydrocortisone per day and 50 g of fludrocortisone once daily for 7 days significantly reduced mortality and the duration of vasopressor therapy.

Treatment of Acute Adrenal Insufficiency

(in septic shock)

Supplemental corticosteroid treatment in septic shock pt should be initiated ASAP.

Treatment of Acute Adrenal Insufficiency

(in other critical illness)

It may be beneficial in patients with other critical illnesses such as trauma, burns, and medical and surgical conditions. But no evidence now

Conclusions
Diagnose corticosteroid insufficiency in patients with critical illnesses: still difficult. Recent trials confirmed corticosteroid replacement in septic shock pt have substantial benefits.

Conclusions
Treatment with physiologic levels of corticosteroid appears to carry few risks. low threshold to testing of the hypothalamic pituitaryadrenal axis and corticosteroidreplacement therapy in acutely ill patients.

Prospect
Further studies are needed to clarify specific situations: in which corticosteroid replacement is beneficial optimal dose optimal duration

Take Home Message

Supplemental corticosteroid treatment in septic shock pt should be initiated ASAP.

Thanks for your attention !!