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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    ABSTRACT: The power of a study can be established with estimation of total effective sample size (Ntotal). In this study, the impact of the length of mechanical ventilation (LoMV) distribution shape in intensive care on the estimated Ntotal is investigated. This study provides an overview on the study design involving LoMV, the resulting potential limitations, and the criteria for a 'successful' design. Data from mechanical ventilated patients in a single-center intensive care unit were used in this study. The Ntotal was estimated using two methods: 1) Model-based Altman's nomogram (a standard); and 2) Monte-Carlo simulation. Using Monte-Carlo simulation, a patient selection criteria is imposed to estimate Ntotal from 'realistic' patient cohorts. The Altman nomogram shows that the Ntotal to detect a 25% change in LoMV (∆LoMV) at power of 0.8 is ≥1000 patients. For the Monte-Carlo simulation, a Ntotal ≥260 patients is needed to detect similar changes. It is important to consider the LoMV distribution shape and variability, particularly relative to target patient groups who might benefit from the intervention. Assessment of ∆LoMV in response to treatment should be carefully considered to avoid an under-powered studies. The Monte-Carlo simulation combined with objective patient selection provides better design of such studies.
    IFAC Symposium on Biological and Medical Systems, Berlin; 09/2015
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    • "Although sedation is an important component of the management of critically ill patients requiring mechanical ventilation, oversedation is associated with increased length on mechanical ventilation [1], delirium [2], and higher mortality [3]. Strategies to decrease sedation burden such as sedation protocols [4] [5], daily interruption of sedatives infusion [6] [7], and " no sedation " [8] have been shown to be effective in reducing time on mechanical ventilation. However, these benefits might come at the expense of increased psychological distress because lightly sedated patients may have greater recall of events of their intensive care unit (ICU) stay [9]. "
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    ABSTRACT: Strategies aiming light sedation are associated with decreased length on mechanical ventilation. However, awake or easily arousable patients may be prone to greater prevalence of posttraumatic stress disorder (PTSD). These systematic review and meta-analysis aimed to evaluate the safety of light sedation strategies regarding the prevalence of PTSD. We searched MEDLINE, Scopus, and Web of Science from inception to November 2014 for randomized controlled trials that evaluated light sedation strategies and addressed PTSD prevalence in the follow-up as a specific outcome. Because not all trials performed the same comparisons, we performed a network meta-analysis to evaluate indirect comparisons. Five studies fulfilled our inclusion criteria and were included in the meta-analysis. Two studies compared daily sedation interruption with usual care (92 patients), 2 studies compared a light sedation protocol with daily sedation interruption (47 patients), and 1 study compared light and deep sedation (102 patients). Compared with usual sedation care/deep sedation, neither daily interruption of sedation (odds ratio = 0.66; 95% confidence interval, 0.22-1.98) nor a light sedation protocol (odds ratio = 0.90, 95% confidence interval, 0.27-3.05) was associated with increased risks on long-term PTSD prevalence. Light sedation strategies seem to be safe in terms of PTSD prevalence. However, the small number of included trials and patients may not be sufficient to drive strong statements. Copyright © 2015. Published by Elsevier Inc.
    Journal of critical care 07/2015; DOI:10.1016/j.jcrc.2015.07.023 · 2.00 Impact Factor
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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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    ABSTRACT: There is a change in paradigm in intensive care units with trends towards lighter sedation. Light or no sedation protocols are, however, a radical change for clinical practice and can cause challenges for the patients. Undergoing mechanical ventilation when conscious can be a distressing experience for the patients. Receiving a tracheostomy increases patient comfort, but some patients still undergo prolonged endotracheal intubation during mechanical ventilation. The experience of being conscious during endotracheal intubation and mechanical ventilation in the intensive care unit has not previously been described. The aim of the study was to explore adult intensive care unit patients' experience of being conscious during endotracheal intubation and mechanical ventilation. Data collection was performed through semi-structured interviews and four patients were enrolled. Data were collected at two multidisciplinary intensive care units in Denmark. Data were analysed using Ricoeur's theory of interpretation, using the method described by Dreyer and Pedersen. The scientific tradition was phenomenological-hermeneutic. During the analysis, three themes emerged: (1) The tube in the throat. (2) To be conscious but feeling doped. (3) When passing of time is dragging on. The findings shed a light over the experience of being conscious during endotracheal intubation and mechanical ventilation in the intensive care unit. A no-sedation protocol may cause problems for the patients both of a physical and an existential character, but despite this, patients seem positive towards being conscious. The study suggests that clinical nursing practice may have to be further developed to accommodate the patients' needs, e.g. communicating and participating as well as optimizing nursing interventions towards thirst, pain and tube management. Furthermore, the intensive care unit setting may need revision, providing space for the patient and sensory meaningful inputs in the technologically intense environment. © 2015 British Association of Critical Care Nurses.
    Nursing in Critical Care 07/2015; DOI:10.1111/nicc.12200 · 0.65 Impact Factor
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