Elsevier

The Lancet

Volume 375, Issue 9713, 6–12 February 2010, Pages 475-480
The Lancet

Articles
A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial

https://doi.org/10.1016/S0140-6736(09)62072-9Get rights and content

Summary

Background

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.

Methods

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 ClinicalTrials.gov, number NCT00466492.

Findings

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).

Interpretation

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.

Funding

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.

Introduction

…But what I see these days are paralyzed, sedated patients, lying without motion, appearing to be dead, except for the monitors that tell me otherwise…

Thomas Petty1

These lines were written in an editorial linked to a follow-up study of mechanically ventilated patients, in which Kollef and colleagues2 reported that continuous infusion of sedatives lengthened the duration of ventilation compared with bolus doses of sedatives. In 2000, Kress and colleagues3 showed that daily interruption of sedative infusions until patients were awake reduced the duration of mechanical ventilation. One major disadvantage of sedation for critically ill patients is that clinicians are unable to assess the patient's mental status; Kress and colleagues also recorded fewer CT scans of the brain in patients who were woken up daily than in the control group in which infusions were interrupted at the clinicians' discretion.

In a further study of daily sedative interruption, Kress and colleagues4 showed that daily interruption kept post-traumatic stress disorder to a minimum, although, at the follow-up interview, few patients recalled being woken up daily. Real memories of the intensive care stay have been shown to reduce the severity of post-traumatic stress disorder.5 Also the risk of several well known complications—ventilator-associated pneumonia, haemorrhage in the upper gastrointestinal tract, bacteraemia, barotraumas, venous thromboembolic disease, cholestasis, and sinusitis requiring surgical intervention—is reduced by daily interruption of sedation.6

Despite these findings, standard practice is to sedate critically ill patients needing intubation and mechanical ventilation.7, 8, 9 A natural development for sedation strategies would be to try to keep the amount and duration of sedation to a minimum, with the expectation that this strategy could further reduce the duration of mechanical ventilation.10 In the general intensive care unit in the Department of Anesthesia and Intensive Care Medicine at Odense University Hospital, Denmark, we have used the standard treatment of no sedation for intubated patients receiving mechanical ventilation since June, 1999. Patients receive intravenous morphine as bolus doses but no infusion of sedatives or analgesics. To our knowledge, this strategy has not been used in other departments or described in published reports. We undertook a prospective randomised study to establish whether no sedation versus sedation with daily interruption reduced the duration of mechanical ventilation.

Section snippets

Participants

We studied critically ill adult patients undergoing mechanical ventilation. Patients in Odense University Hospital, Denmark, were admitted to an 18-bed multidisciplinary, closed intensive care unit from both medical and surgical departments. The intensive care unit has at least two physicians present (one intensive care specialist and one specialist trainee) at all times. The patient to nurse ratio is 1:1, which allows the nurse to manage several tasks in addition to patient care (eg, renal

Results

428 patients were assessed for eligibility during April, 2007–December, 2008, of whom 140 were enrolled and randomly assigned to treatment (figure 1). Overall, a higher proportion of men (n=76 patients, 67%) than women (n=37, 33%) were included in the study, and the ratio of men to women was higher in the intervention group than in the control group (table 1). 27 patients were excluded from the statistical analysis because mechanical ventilation was stopped within 48 h (figure 1). An extra

Discussion

Findings from our study show that in critically ill patients receiving mechanical ventilation, a protocol of no sedation significantly increased the number of days without ventilation in a 28-day period compared with daily interruption of sedation. Use of no sedation was also associated with a significant reduction in the length of stay in the intensive care unit and in hospital. No difference in complications such as accidental removal of the endotracheal tube, ventilator-associated pneumonia,

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