Clonidine for sedation in the critically ill: a systematic review and meta-analysis.
BACKGROUND
This systematic review and meta-analysis investigates the efficacy and safety of clonidine as a sedative in critically ill patients requiring invasive mechanical ventilation.


METHODS
We performed a comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane trial registry. We identified RCTs that compared clonidine to any non-clonidine regimen in critically ill patients, excluding neonates, requiring mechanical ventilation. The GRADE method was used to assess certainty of evidence.


RESULTS
We included eight RCTs (n = 642 patients). In seven of the trials clonidine was used for adjunctive rather than stand-alone sedation. There was no difference in the duration of mechanical ventilation (mean difference (MD) 0.05 days, 95% confidence interval (CI) = -0.65 to 0.75, I2= 86%, moderate certainty), ICU mortality (relative risk (RR) 0.98, 95% CI = 0.51 to 1.90, I2= 0%, low certainty), or ICU length of stay (MD 0.04 days, 95% CI = -0.46 to 0.53, I2= 16%, moderate certainty), with clonidine. There was a significant reduction in the total dose of narcotics (standard mean difference (SMD) -0.26, 95% CI = -0.50 to -0.02, I2= 0%, moderate certainty) with clonidine use. Clonidine was associated with increased incidence of clinically significant hypotension (RR 3.11, 95% CI = 1.64 to 5.87, I2= 0%, moderate certainty).


CONCLUSIONS
Until further RCTs are performed, data remains insufficient to support the routine use of clonidine as a sedative in the mechanically ventilated population. Clonidine may act as a narcotic-sparing agent, albeit with an increased risk of clinically significant hypotension.
Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Jing Gennie
JG
Wang
Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON, Canada.
Emilie
E
Belley-Coté
Department of Pharmacy, Mount Sinai Hospital, Toronto, ON, Canada.|Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Lisa
L
Burry
Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON, Canada.|Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
Mark
M
Duffett
Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.|Hamilton Health Sciences, Hamilton, ON, Canada.
Timothy
T
Karachi
Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.|St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
Dan
D
Perri
Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.|Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON, Canada.
Waleed
W
Alhazzani
Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON, Canada.
Frederick
F
D'Aragon
Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Anesthesia, University of Toronto, Toronto, ON, Canada.|Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
Hannah
H
Wunsch
Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada. bram.rochwerg@gmail.com.|Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON, Canada. bram.rochwerg@gmail.com.
Bram
B
Rochwerg
D003000:Clonidine / Q000494:pharmacology* / Q000627:therapeutic use; D016638:Critical Illness / Q000628:therapy*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology* / Q000627:therapeutic use; D007022:Hypotension / Q000209:etiology; D007362:Intensive Care Units / Q000458:organization & administration; D007902:Length of Stay; D012121:Respiration, Artificial / Q000379:methods
D006993:Hypnotics and Sedatives; D003000:Clonidine
Clonidine; Delirium; Mechanical ventilation; Sedation; Systematic review; Weaning