TREATING SEPSIS

Step MN – Metabolic and Neuroendocrine Control

Sepsis is a multisystem disease modulated by the neuroendocrine response. The early response (the Ebb phase) is characterized by reduced metabolism and vasoconstriction. This is followed by a hypermetabolic phase, characterized by vasodilation, fluid sequestration, hyper-adrenergic activity, protein catabolism, hyperlactemia (not necessarily due to anerobic metabolism), and dysregulation of fat and lipoprotein metabolism. Hyperglycemia is inevitable and there is good evidence that control of blood sugar improves outcome in critical illness (1), due to a reduction in infectious complications.

Prolonged critical illness is characterized by derangement of the entire neuroendocrine response. There is dysfunction of the somatrophic and the hypothalmo-pituitary axis, sick euthyroid syndrome and loss of central endocrine control (2;3) . A relative adrenal insufficiency frequently manifests – the patient remains pressor dependent in spite of apparent source control (cortisol is required to facilitate the activity of norepinephrine and epinephrine at sympathetic nerve terminals).The diagnosis is made by ACTH stimulation test (4) (a 2 hour “bump” of less than 5mg/dl or a cortisol level of <20mg/dl is diagnostic) and the treatment is hydrocortisone. It is controversial whether other hormones should be replaced with similar physiologic doses (5).

References

(1)   Van den BG, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M et al. Intensive insulin therapy in the surgical intensive care unit. N Engl J Med 2001; 345(19):1359-1367.

(2)   Van den Berghe GH. Acute and prolonged critical illness are two distinct neuroendocrine paradigms. Verh K Acad Geneeskd Belg 1998; 60(6):487-518.

(3)   Van den Berghe GH. The neuroendocrine stress response and modern intensive care: the concept revisited. Burns 1999; 25(1):7-16.

(4)   Rivers EP, Gaspari M, Saad GA, Mlynarek M, Fath J, Horst HM et al. Adrenal insufficiency in high-risk surgical ICU patients. Chest 2001; 119(3):889-896.

(5)   Ligtenberg JJ, Girbes AR, Beentjes JA, Tulleken JE, van der Werf TS, Zijlstra JG. Hormones in the critically ill patient: to intervene or not to intervene? Intensive Care Med 2001; 27(10):1567-1577.page28.htm

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