Prevention of Adrenal Crisis in Stress: Serum cortisol during elective surgery, acute trauma surgery and during 'stress dose cover' hydrocortisone replacement in adrenal insufficiency

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 26-40-Glucocorticoid Actions & Disease
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-39
Angela E Taylor*1, Niki Karavitaki2, Mark Foster3, Sibylle Meier2, Donna M O'Neil1, John Komninos2, Dimitra A Vassiliadi1, Christopher J Mowatt1, Janet M Lord1, John A. H. Wass2 and Wiebke Arlt1
1University of Birmingham, Birmingham, United Kingdom, 2Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, United Kingdom, 3University Hospital Birmingham, Birmingham, United Kingdom
Patients with adrenal insufficiency (AI) require adjustment of hydrocortisone (HC) dose replacement to avoid life-threatening adrenal crisis during illness, surgery and trauma. However, studies assessing the optimal perioperative HC cover in patients with AI are lacking and suggested doses have been selected on empirical rather than rational grounds, with huge variability in choice of doses and administration modes in routine practice. 

The aim of this study was to compare cortisol levels achieved by currently recommended HC doses to those achieved under real life stress conditions such as elective surgery and acute trauma.

To this end, we firstly studied patients undergoing elective surgery (n=23) or surgery after acute trauma (n=25) in comparison to healthy controls (n=86).  Severity of the operation was graded as either minor (day case procedure, minimal blood loss, <1h duration) or major (complex surgery, significant expected blood loss).  Secondly, we investigated a group of ten patients with chronic autoimmune adrenal failure on four study days: 50mg HC orally every 6hrs, 50mg HC im every 6hrs, 50mg iv injection every 6hrs, and 200mg HC per continuous iv infusion.  Serum samples were collected over a 24hr period and analyzed by liquid chromatography/tandem mass spectrometry.

Results demonstrated that cortisol levels peaked in both minor and major elective surgery between 2 and 4 hours after induction of anaesthesia (minor, median(range) 431(249-570)nmol/L, major 611(165-1379)nmol/L). Cmax values for trauma surgery patients were 433(337-585)nmol/L for minor and 363(203-1504)nmol/L for major surgery. All these values were significantly lower than Cmax observed after HC administration via any administration mode with median values ranging from 836-1440nmol/L. However, cortisol levels decreased to Cmin 277(64-398), 289(148-458), 173(118-375)nmol/L after administration of HC via oral, im or iv injection, respectively, which is below the required range.  

By contrast, continuous infusion of HC yielded steady state cortisol concentrations after one hour, with Cmax 836(661-1073) and Cmin(388-617nmol/L). These data indicate that an HC dose of 200mg per 24hr will only be required in AI patients undergoing major surgery or severe inflammatory stress. Furthermore, the pharmacokinetic results for the different modes of HC administration clearly indicate that steroid stress dose cover in these situations should be administered by continuous i.v. infusion.

Nothing to Disclose: AET, NK, MF, SM, DMO, JK, DAV, CJM, JML, JAHW, WA

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