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Title: 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).
Austin Authors: 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
Affiliation: St John of God Health Care Inc, Intensive Care , Subiaco , Australia
Monash University Faculty of Medicine Nursing and Health Sciences, ANZIC-RC, Prahran, Victoria, Australia
Intensive Care
Monash University, ANZIC-RC, Prahran, Victoria, Australia
ANZIC-RC, School of Public Health and Preventive Medicine , Melbourne, Victoria, Australia
Monash University, School of Clinical Sciences , Clayton, Victoria, Australia
Monash Health, Intensive Care Services, Clayton, Victoria, Australia
University of New South Wales - Kensington Campus, Intensive Care - School of Clinical Medicine , Sydney, New South Wales, Australia
Royal North Shore Hospital, Intensive Care , St Leonards, New South Wales, Australia
University of Queensland, Burns, Trauma and Critical Care Research Centre, Brisbane, Queensland, Australia
Australian Defence Force, Joint Health Command, Brisbane, Queensland, Australia
University of Sydney Nepean Clinical School Intensive Care Medicine, Kingswood, New South Wales, Australia
University of Western Australia, Perth, Australia
Royal Perth Hospital, Perth, Australia
King Saud bin Abdulaziz Medical City for Science and Technology, Intensive Care Medicine, Riyadh, Saudi Arabia..
National Heart Institute University of Technology Malaysia Cardiovascular Engineering Centre, Johor Bahru, Johor, Malaysia..
Auckland City Hospital, Intensive Care, Auckland, New Zealand..
Inselspital University Hospital Bern, Bern, Switzerland..
University Hospital of Wales, Adult Critical Care, Cardiff, United Kingdom of Great Britain and Northern Ireland..
Issue Date: 1-Apr-2023
Date: 2022
Publication information: American Journal of Respiratory and Critical Care Medicine 2023; 207(7)
Abstract: 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. to quantify the association of different infusion rates of dexmedetomidine or propofol, given in combination, with mortality and if this is modified by age. 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. 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]. 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. gov, ID: NCT01728558.
DOI: 10.1164/rccm.202206-1208OC
ORCID: 0000-0001-5735-6241
Journal: American journal of respiratory and critical care medicine
PubMed URL: 36215171
Type: Journal Article
Subjects: Mechanical ventilation; Sedative effect, Age groups, Intensive Care, Respiratory
Appears in Collections:Journal articles

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