Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose Associated 90-day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE-III).

Shehabi, Yahya; Serpa Neto, Ary; Bellomo, Rinaldo; Howe, Belinda D; Arabi, Yaseen M; Bailey, Michael; Bass, Frances E; Bin Kadiman, Suhaini; McArthur, Colin J; Reade, Michael C; Seppelt, Ian M; Takala, Jukka; Wise, Matt P; Webb, Steve A (2023). Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose Associated 90-day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE-III). American journal of respiratory and critical care medicine, 207(7), pp. 876-886. American Thoracic Society 10.1164/rccm.202206-1208OC

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RATIONALE

Sedation Practice in Intensive Care Evaluation (SPICE-III) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation.

OBJECTIVES

to quantify the association of different infusion rates of dexmedetomidine or propofol, given in combination, with mortality and if this is modified by age.

METHODS AND MEASUREMENTS

We included 1177 patients randomized in SPICE-III to receive dexmedetomidine and given supplemental propofol, stratified by age (>65 or ≤65 years). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine, while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression, adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality.

MAIN RESULTS

Younger patients 598/1177(50.8%) received a significantly higher dose of both sedatives compared with older patients, to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 mcg/kg/h) was associated with reduced adjusted mortality in younger, but not older patients. This was consistent with multivariable regression modelling [hazard ratio: 0.59(95% Confidence Interval 0.43-0.78),P<0.0001], adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality [HR:1.30(95%CI 1.03-1.65), P=0.029].

CONCLUSION

In patients ≤ 65 years sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registration available at www.

CLINICALTRIALS

gov, ID: NCT01728558.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
UniBE Contributor:	Takala, Jukka
ISSN:	1535-4970
Publisher:	American Thoracic Society
Language:	English
Submitter:	Pubmed Import
Date Deposited:	11 Oct 2022 13:12
Last Modified:	01 Apr 2023 00:12
Publisher DOI:	10.1164/rccm.202206-1208OC
PubMed ID:	36215171
Uncontrolled Keywords:	Mechanical ventilation; Sedative effect, Age groups, Intensive Care, Respiratory
URI:	https://boris.unibe.ch/id/eprint/173641