Allostasis and sedation practices in intensive care evaluation: an observational pilot study

BACKGROUND: A dysregulated stress response has been implicated in the pathogenesis of critical illness. Sedative agents utilised in the critically unwell patient may impact upon the stress response with a downstream negative effect on multiple organ systems. This study was designed to assess the feasibility of investigating components of the stress response as a sub-study of the current SPICE-III study (NCT01728558). METHODS: This pilot observational cohort study was conducted in a single intensive care unit in Queensland, Australia. Enrolled patients were over 18 years who had been commenced on mechanical ventilation requiring sedation for less than 12 h but expected to remain ventilated for > 24 h. Blood samples were taken at 12 h intervals over a 5-day period commencing at the time of enrolment, and subsequently tested for various markers of key efferent limbs of the stress axis. RESULTS: The 12 patients recruited closely mirrored the population within the pilot study used to design SPICE-III. Eighty-nine percent (107/120) of all planned blood samples were obtained and drawn within 0 h (0-0.3) of the planned sampling time point. Time from eligibility to enrolment was a median (IQR) 1.4 h (0.36-9.19), and time from eligibility to the first blood sample was 4.79 h (2.0-10.61). Physiological, hormonal, metabolic and cardiac biomarkers were consistent with an elevated stress response at baseline which mostly normalised over the 5-day study period. Plasma noradrenaline levels correlated with the dose of norepinephrine used. CONCLUSIONS: A larger sub-study of the SPICE-III study is feasible. The study has demonstrated a predictable trend of variation of the components of the blood panel during the evolution of critical illness and supports multiple sampling time points for the follow-up study