A protocol of no sedation for critically ill patients receiving mechanical ventilation: A randomized trial

Department of Anesthesia and Intensive Care Medicine, Odense University Hospital, University of Southern Denmark, Denmark.
The Lancet (Impact Factor: 45.22). 02/2010; 375(9713):475-80. DOI: 10.1016/S0140-6736(09)62072-9
Source: PubMed


Standard treatment of critically ill patients undergoing mechanical ventilation is continuous sedation. Daily interruption of sedation has a beneficial effect, and in the general intesive care unit of Odense University Hospital, Denmark, standard practice is a protocol of no sedation. We aimed to establish whether duration of mechanical ventilation could be reduced with a protocol of no sedation versus daily interruption of sedation.
Of 428 patients assessed for eligibility, we enrolled 140 critically ill adult patients who were undergoing mechanical ventilation and were expected to need ventilation for more than 24 h. Patients were randomly assigned in a 1:1 ratio (unblinded) to receive: no sedation (n=70 patients); or sedation (20 mg/mL propofol for 48 h, 1 mg/mL midazolam thereafter) with daily interruption until awake (n=70, control group). Both groups were treated with bolus doses of morphine (2.5 or 5 mg). The primary outcome was the number of days without mechanical ventilation in a 28-day period, and we also recorded the length of stay in the intensive care unit (from admission to 28 days) and in hospital (from admission to 90 days). Analysis was by intention to treat. This study is registered with, number NCT00466492.
27 patients died or were successfully extubated within 48 h, and, as per our study design, were excluded from the study and statistical analysis. Patients receiving no sedation had significantly more days without ventilation (n=55; mean 13.8 days, SD 11.0) than did those receiving interrupted sedation (n=58; mean 9.6 days, SD 10.0; mean difference 4.2 days, 95% CI 0.3-8.1; p=0.0191). No sedation was also associated with a shorter stay in the intensive care unit (HR 1.86, 95% CI 1.05-3.23; p=0.0316), and, for the first 30 days studied, in hospital (3.57, 1.52-9.09; p=0.0039), than was interrupted sedation. No difference was recorded in the occurrences of accidental extubations, the need for CT or MRI brain scans, or ventilator-associated pneumonia. Agitated delirium was more frequent in the intervention group than in the control group (n=11, 20%vs n=4, 7%; p=0.0400).
No sedation of critically ill patients receiving mechanical ventilation is associated with an increase in days without ventilation. A multicentre study is needed to establish whether this effect can be reproduced in other facilities.
Danish Society of Anesthesiology and Intensive Care Medicine, the Fund of Danielsen, the Fund of Kirsten Jensa la Cour, and the Fund of Holger og Ruth Hess.

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    • "Thus, small reductions in LoMV for a specific study may not be detected if it is under-powered (Whitley and Ball, 2002, Pintado et al., 2013). Table 1 shows several RCTs where only three (The Acute Respiratory Distress Syndrome Network, 2000, Mercat et al., 2008, Strøm et al., 2010) were able to show statistical significance in reducing LoMV. "
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    • "It was not until the year 2000 that sedation procedures were changed, when a study by Kress et al. (2000) showed that daily sedation breaks reduced the number of days with MV as well as the length of hospital stay. After 10 years, in 2010, it was shown that a no-sedation protocol was also associated with reduced number of days with MV and length of hospital stay in both ICU and hospital (Strøm et al., 2010), and another step was taken towards light or no-sedation of patients. Light or no-sedation protocols are a radical change for clinical practice and a challenge to both health care personnel (Everingham et al., 2014) and patients (Karlsson et al., 2012a). "
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