Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study

Shehabi, Yahya, Bellomo, Rinaldo, Reade, Michael C., Bailey, Michael, Bass, Frances, Howe, Belinda, McArthur, Colin, Murray, Lynne, Seppelt, Ian M., Webb, Steve and Weisbrodt, Leonie (2013) Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study. Critical Care Medicine, 41 8: 1983-1991. doi:10.1097/CCM.0b013e31828a437d

Author Shehabi, Yahya
Bellomo, Rinaldo
Reade, Michael C.
Bailey, Michael
Bass, Frances
Howe, Belinda
McArthur, Colin
Murray, Lynne
Seppelt, Ian M.
Webb, Steve
Weisbrodt, Leonie
Title Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study
Journal name Critical Care Medicine   Check publisher's open access policy
ISSN 0090-3493
Publication date 2013-08-01
Year available 2013
Sub-type Article (original research)
DOI 10.1097/CCM.0b013e31828a437d
Open Access Status Not Open Access
Volume 41
Issue 8
Start page 1983
End page 1991
Total pages 9
Place of publication Baltimore, MD, United States
Publisher Lippincott Williams & Wilkins
Language eng
Abstract Nebulized antimicrobial agents are increasingly administered for treatment of respiratory infections in mechanically ventilated (MV) patients. A structured online questionnaire assessing the indications, dosages and recent patterns of use for nebulized antimicrobial agents in MV patients was developed. The questionnaire was distributed worldwide and completed by 192 intensive care units. The most common indications for using nebulized antimicrobial agent were ventilator-associated tracheobronchitis (VAT; 58/87), ventilator-associated pneumonia (VAP; 56/87) and management of multidrug-resistant, Gram-negative (67/87) bacilli in the respiratory tract. The most common prescribed nebulized agents were colistin methanesulfonate and sulfate (36/87, 41.3% and 24/87, 27.5%), tobramycin (32/87, 36.7%) and amikacin (23/87, 26.4%). Colistin methanesulfonate, amikacin and tobramycin daily doses for VAP were significantly higher than for VAT (p < 0.05). Combination of parenteral and nebulized antibiotics occurred in 50 (86%) of 58 prescriptions for VAP and 36 (64.2%) of 56 of prescriptions for VAT. The use of nebulized antimicrobial agents in MV patients is common. There is marked heterogeneity in clinical practice, with significantly different in use between patients with VAP and VAT. Randomized controlled clinical trials and international guidance on indications, dosing and antibiotic combinations to improve clinical outcomes are urgently required.
Formatted abstract
Objective: To assess the feasibility and safety of delivering early goal-directed sedation compared with standard sedation.

Design: Pilot prospective, multicenter, randomized, controlled trial.

Setting: Six ICUs.

Patients: Critically ill adults mechanically ventilated for greater than 24 hours.

Interventions: Patients randomized to early goal-directed sedation received a dexmedetomidine-based algorithm targeted to light sedation (Richmond Agitation Sedation Score of –2 to 1). Patients randomized to standard sedation received propofol and/or midazolam-based sedation as clinically appropriate.

Measurements and Main Results: The main feasibility outcomes were time to randomization and proportion of Richmond Agitation Sedation Score assessments in the first 48 hours in the light and deep sedation range. Safety outcomes were delirium-free days, vasopressor and physical restraints use, and device removal. Randomization occurred within a median (interquartile range) of 1.1 hours (0.46–1.9) after intubation or ICU admission for out of ICU intubation. Patients in the early goal-directed sedation (n = 21) mean (SD) Acute Physiology and Chronic Health Evaluation II score was 20.2 (6.2) versus 18.6 (8.8; p = 0.53) in the standard sedation (n = 16). A significantly higher proportion of patients was lightly sedated on days 1, 2, and 3 (12/19 [63.2%], 19/21 [90.5%], and 18/20 [90%] vs 2/14 [14.3%], 8/15 [53.3%], and 9/15 [60%]; p = 0.005, 0.011, 0.036) and more Richmond Agitation Sedation Scale assessments between (–2 and 1), in the first 48 hours (203/307 [66%] versus (74/197 [38%]; p = 0.01) in the early goal-directed sedation versus standard sedation, respectively. Early goal-directed sedation patients received midazolam on 6 of 173 (3.5%) versus 4 of 114 (3.5%) standard sedation patient-days when dexmedetomidine was given. Propofol was given to 16 of 21 (76%) of early goal-directed sedation versus 16 of 16 (100%) of standard sedation patients (p = 0.04). Early goal-directed sedation patients had 101 of 175 (58%) versus 54 of 114 (47%; p = 0.27) delirium-free days and required significantly less physical restraints 1 (5%) versus 5 (31%; p = 0.03) than standard sedation patients. There were no differences in vasopressor use and self-extubation.

Conclusions: Delivery of early goal-directed sedation was feasible, appeared safe, achieved early light sedation, minimized benzodiazepines and propofol, and decreased the need for physical restraints. The findings of this pilot study justify further investigation of early goal-directed sedation.
Keyword Critical illness
Goal directed
Intensive care
Mechanical ventilation
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID G1000417
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 39 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 10 Nov 2013, 10:20:40 EST by System User on behalf of Anaesthesiology and Critical Care - RBWH