ECE2015 Guided Posters Adrenal (8 abstracts)
Prevention of adrenal crisis in stress (The PACS Study): serum cortisol during elective surgery, acute trauma and sepsis in comparison to ‘stress dose' hydrocortisone administration in adrenal insufficiency
Angela Taylor 1 , Niki Karavitaki 2 , David Smith 3 , Irina Bancos 1 , Mark Foster 4 , Sibylle Meier 2 , Donna O’Neil 1 , John Komninos 2 , Dimitra Vassiliadi 1 , Christopher Mowatt 1 , Janet Lord 4 , John Wass 2 & Wiebke Arlt 1
1Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingahm, UK; 2Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK; 3School of Mathematics, University of Birmingham, Birmingham, UK; 4NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UK.
Patients with adrenal insufficiency require increased hydrocortisone (HC) replacement doses during surgery, trauma and infection to avoid life-threatening adrenal crisis. However, currently administered HC doses are chosen empirically rather than on rational grounds, with huge variability in administration modes, total dose and dosing intervals. To conclusively determine serum cortisol levels observed under stress conditions, we firstly collected blood samples from healthy controls (n=86), soldiers under combat stress (n=105) and patients undergoing elective surgery with general anaesthesia (n=22), acute major trauma (n=85), and severe sepsis (n=100). Secondly, we undertook frequent sampling over a period of 24 h in ten patients with primary adrenal insufficiency who omitted their regular replacement and received HC 200 mg/24 h in four different administration modes: 50 mg every 6 h orally or per i.m. or i.v. bolus injection or 200 mg/24 h as continuous i.v. infusion (IV-C). All analyses were carried out by liquid chromatography/tandem mass spectrometry. Serum cortisol concentrations were highest in patients with sepsis (median 973, range 77–7717 nmol/l), followed by elective surgery with general anaesthesia (617, 269–1379), combat stress (441, 69–789), acute trauma (235, 23–1257), and healthy controls (197, 67–752 nmol/l). Initial peak concentrations after HC exceeded stress levels, but serum cortisol decreased to under the median of controls several hours before repeat administration of oral, i.v., and i.m. bolus. By contrast, HC IV-C maintained steady state cortisol levels above the median of stressed controls throughout. Linear pharmacokinetic modelling combined with mixed effects regression calculated the optimal dose and administration mode as an initial bolus of 50–100 mg HC i.v., followed by continuous i.v. infusion of 200 mg/24 h. Continuous i.v. rather than bolus administration of HC will avoid dangerous intermittent trough levels and thus represents the recommended administration mode for patients with adrenal insufficiency exposed to pathological stress due to trauma, sepsis, or surgery.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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