Critical Illness and Mechanical Ventilation Clinical Trial
Official title:
Early Goal-Directed Sedation Compared With Standard Care in Mechanically Ventilated Critically Ill Patients: a Prospective Multicentre Randomised Controlled Trial
The Use of sedative drugs in intensive care is widespread. A cohort study conducted in
Australia and New Zealand in 2010 revealed a high prevalence of deep sedation within the
first 48 hours of mechanical ventilation which was independently linked to prolonged
ventilation, hospital and 180 days mortality. Clinical practice is moving towards the use of
lighter levels of sedation. Recent RCTs in Europe (JAMA 2012) and previous RCTs (JAMA 2009)
supports growing evidence that dexmedetomidine facilitates rousable sedation, shortens
ventilation time and attenuates delirium when compared to midazolam and propofol.
The investigators confirmed in a pilot study the feasibility, efficacy and safety of a
process of care known as Early Goal Directed Sedation (EGDS) that delivers:
1. Early randomization after intubation or arrival in the ICU (intubated).
2. Early Adequate analgesia after randomization.
3. Goal directed sedation titrated to achieve light sedation.
4. Dexmedetomidine based algorithm as the primary sedative agent with avoidance of
benzodiazepines.
The aim of this study is to assess the effectiveness of Early Goal Directed Sedation when
compared to standard care sedation in critically ill patients.
The study hypothesis is that Early Goal-Directed Sedation (EGDS), compared to standard care
sedation, reduces 90-day all-cause mortality in critically ill patients who require
mechanical ventilation.
This is a large-scale study into the effectiveness of a novel approach for sedation in
ventilated critically ill patients. The primary aim of this study is to determine whether
Early Goal Directed Sedation therapy, compared to standard care sedation, reduces 90-day
mortality in critically ill patients ventilated > 24 hrs.
The study will be a randomized, unblinded, controlled trial conducted in approximately 35-50
intensive care units (ICUs) and will recruit 4000 mechanically ventilated patients (life
support) who are expected to remain on the ventilator > 24 hours AND require immediate
ongoing sedative medication for comfort, safety, and to facilitate the delivery of life
support measures, including mechanical ventilation.
Patients with primary brain injury or prolonged weakness are excluded. Participants will be
randomized into one of 2 study groups. All patients will receive adequate analgesia at
randomization at the discretion of treating clinician. All randomized patients will have
Light sedation as the default target unless otherwise clinically indicated. The intervention
group will receive EGDS with dexmedetomidine as the primary sedative agent to achieve light
sedation, with the addition of propofol as required. The use of benzodiazepines in the
intervention group is not allowed, with the exception of specific, defined circumstances.
The control group will have sedation according to usual practice as chosen by the treating
clinician. The use of dexmedetomidine is not allowed, with the exception of specific, defined
circumstances.
Deidentified data will be collected and will include; Baseline demographic information; Doses
of all sedative, analgesic and other related medications; Pain, sedation and delirium scores
and major treatments such as ventilation time, tracheostomy and dialysis. Patients surviving
to hospital discharge will be contacted by phone to determine independent survival status at
90 days and again at 180 days plus Health Related Quality of Life and cognitive function
assessment.
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