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

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).

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.

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.

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.

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