Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

Abstract

B alance between infl ammation and antiinfl ammation is essential for survival during severe infections. Initially, studies performed during the late 1980s and 1990s using high doses of corticosteroids for short periods of time in severe sepsis and septic shock did not improve survival; even more, it increased the risk of dying. [1][2][3][4] More recently, a new concept of "relative" adrenal insuffi ciency in sepsis or critical illness-related corticosteroid insuffi ciency has been coined, and there has been a renewed interest in adrenal function during sepsis. Research studies using smaller doses of corticosteroids for longer period of time (5-7 days) were tested. 5,6 In 2002, Annane et al 7 performed a randomized controlled trial using hydrocortisone and fl udrocortisone in patients with severe sepsis. They found that patients with less than expected response to adrenocorticotropic hormone (ACTH) stimulation test had better survival when corticosteroid therapy was used. A subsequent study (Corticosteroid Therapy of Septic Shock ) failed to demonstrate improvement in survival; however, patients were not treated with fl udrocortisone as in the Annane study. 6 All these studies have used total serum cortisol levels to evaluate adrenal function, even though it is well known that only the unbound or free cortisol is biologically active. Free or unbound serum cortisol may be higher than expected during sepsis because of decrease in cortisol-binding globulin (CBG) and albumin. Eighty Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean Ϯ SD age was 56.6 Ϯ 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplifi ed Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P , .0001). The correlation between free serum cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P , .0001). The mean Ϯ SD free serum cortisol level was 2.27 Ϯ 1.64 m g/dL. The mean Ϯ SD salivary cortisol level was 2.60 Ϯ 2.69 m g/dL. The mean Ϯ SD total serum cortisol level was 21.56 Ϯ 8.71 m g/dL. The mean Ϯ SD CBG level ...

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

“…In addition, the correlation between salivary cortisol and total serum cortisol levels was very good (80%). Unbound plasma cortisol can be calculated using total serum cortisol and CBG measurements [21,22]. See Digital Supplement 3 for evidence profile.…”

Evaluating stress in natural populations of vertebrates: total CORT is not good enough

“…Tissue CORT levels match the level and timing of the free plasma CORT. In a separate study, Estrada‐Y‐Martin & Orlander () demonstrate that tissue CORT levels mimic free CORT levels in the plasma and that both are approximately 10% of plasma total CORT. Together, these studies indicate that total hormone is not what is available to tissues but that free hormone, not bound by CBG, is the biologically active fraction.…”

An exploratory study of the patients' sleep patterns and inflammatory response following cardiopulmonary bypass (CPB)

“…High correlations between salivary and serum cortisol levels have been found in both human and animal subjects (Rao et al . , Estrada‐Y‐Martin & Orlander ). Salivary cortisol was measured using high‐sensitivity enzyme‐linked immunoassay [ELISA] (No.…”