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Association between Adrenal Insufficiency and Ventilator Weaning

With regard to our recent article (1), Dr. Dimopoulou points out that hydrocortisone supplementation may increase weaning success not only by providing hemodynamic stability but also by suppressing cytokine concentrations, especially tumor necrosis factor- and interleukin-6. This point is certainly valid; however, as we mentioned in our study, multiple factors are involved in the success of ventilator weaning in the intensive care unit. That is why, although corticosteroid supplementation has shown benefits in patients with septic shock in recent studies (2), the actual mechanisms underlying such effects remain inconclusive.

In our study, severity of illness (APACHE III) and percentage of patients with sepsis did not show differences between the corticosteroid and the placebo groups. Therefore, it is difficult to conclude that the cytokine levels were different between the two groups. Although we agree that alteration of the cytokine milieu by hydrocortisone in critical illness might plausibly contribute to weaning success, this point requires further investigation.

It is true that our observation may have a significant therapeutic impact, regardless of the complexity of weaning mechanisms. Recently, studies also suggest that activation of the hypothalamic–pituitary–adrenal axis is an important protective response during critical illness. Untreated adrenal insufficiency may lead to hemodynamic instability and poor outcome (3). The interest of this new approach was confirmed by the demonstration that a single intravenous administration of 50 mg of hydrocortisone improved dose–response relationships of mean arterial pressure to norepinephrine and phenylephrine in patients with septic shock (4), particularly in those with relative adrenal insufficiency. These findings support our speculation that hydrocortisone supplementation increases weaning success by improving hemodynamic stability.

Regarding other possible confounding variables that were not included in our analysis, but might affect the association between adrenal insufficiency and ventilator weaning, we agree that additional study is warranted to better define the actual effects of hydrocortisone supplementation on these critically ill patients. Perhaps, the balance between steroids and inflammatory mediators (such as cytokines) can be determined with a randomized placebo-controlled trial of physiologic stress–dose corticosteroids in critically ill patients with adrenal insufficiency.

Horng-Chyuan Lin and Chung-Jen Huang

Chang Gung Memorial Hospital Chang Gung University, Taoyuan, Taiwan

FOOTNOTES

Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Huang C-J, Lin H-C. Association between adrenal insufficiency and ventilator weaning. Am J Respir Crit Care Med 2006;173:276–280.[Abstract/Free Full Text]
2. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862–871.[Abstract/Free Full Text]
3. Cohan P, Wang C, McArthur DL, Cook SW, Dusick JR, Armin B, Swerdloff R, Vespa P, Muizelaar JP, Cryer HG, et al. Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 2005;33:2358–2366.[CrossRef][Medline]
4. Bellissant E, Annane D. Effect of hydrocortisone on phenylephrine: mean arterial pressure dose–response relationship in septic shock. Clin Pharmacol Ther 2000;68:293–303.[CrossRef][Medline]

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