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

Abstract

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.

Trial registration: ANZCTR.org.au , ACTRN12616001200471, Registered on 22 January 2016.

Keywords: Allostasis; Critical illness; Multiple organ failure; Sedatives.

Conflict of interest statement

Ethics approval and consent to participate

Following ethics committee and local hospital governance approval was provided; written informed consent was obtained from each patient or the patient’s legally authorised surrogate prior to conduct of study-specific procedures.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

CONSORT diagram. Of the screened patients, 2 (3.9%) did not meet inclusion criteria, 33 (64.7%) met exclusion criteria and 4 (7.8%) were excluded based on medical decision

Fig. 2

Physiological markers of stress. Median and interquartile range for each time point. a Temperature. b Heart rate. c Mean arterial pressure

Fig. 3

Cardiac profile. Median and interquartile range for each time point. Normal range is represented by the shaded area. a Troponin I, b β-Natriuretic peptide

Fig. 4

Metabolic profile. Median and interquartile range for each time point. Normal range is represented by the shaded area. a total cholesterol, b HDL cholesterol, c Triglycerides, d lactate, e ketones, f base excess. * upper limit for individuals at low cardiovascular risk. $ upper limit for individuals at high cardiovascular risk

Fig. 5

Hormone profile. Median and interquartile range for each time point. Normal range is represented by the shaded area. a Adrenaline. b Noradrenaline. c FT3. d Aldosterone

Fig. 6

Correlation of administered noradrenaline dose (mcg/min) and plasma noradrenaline level (pmolL−1)

Fig. 7

Richmond Agitation Sedation Scale (RASS) scores in the first 48 h. In the first 48 h, a total of 59 RASS scores were performed. Most of the scores were in the light sedation range (55%)