SPICE III RCT

Sedation Practices in Intensive Care Evaluation: SPICE III: A Prospective Multicentre Randomised Controlled Trial of Early Goal-Directed Sedation Compared with Standard Care in Mechanically Ventilated Patients in Intensive Care

A prospective, un-blinded, randomised controlled trial of Early Goal-Directed Sedation (EGDS) compared with standard care. The study will recruit patients who are intubated and ventilated in a participating ICU, are expected to remain intubated the day after enrolment and need immediate and ongoing sedation.

Over the last decade clinical practice has changed somewhat towards the use of lighter levels of sedation whenever clinically safe, better management of pain, and 'recognition of delirium as occurring commonly in patients with a critical illness.' A number of studies suggest that the centrally mediated alpha­2 agonist sedative dexmedetomidine facilitates rousable sedation, shortens ventilation time, and attenuates the occurrence of delirium, and may therefore be advantageous compared to other sedatives. Whether these potential advantages are associated with improvement in patient­centred outcomes, such as long­term mortality and cognitive function, is unknown.

The primary aim of this study is to determine whether Early Goal-Directed Sedation, compared to standard care sedation, reduces 90-day mortality in critically ill patients who are expected to require mechanical ventilation for longer than 24 hours.

The study will compare a strategy of early titrated light sedation (early goal directed sedation) to standard sedation practices in critically ill patients ventilated for >24 hours. The primary aim of this study is to determine whether Early Goal­Directed Sedation, compared to standard care sedation, reduces 90­day mortality in critically ill patients who are expected to require mechanical ventilation for longer than 24 hours. The study is an international multi­centre trial which in total will recruit 4000 patients.

FAQ

Inclusion Criteria?

Subject has been intubated and is receiving mechanical ventilation, the treating clinician expects that the patient will remain intubated until the day after tomorrow (unlikely to be extubated the following day) and the patient requires immediate ongoing sedative medication for comfort, safety, and to facilitate the delivery of life support measures.

Exclusion Criteria?

• Age less than 18 years
• Patient is pregnant and/or lactating
• Has been intubated (excluding time spent intubated within an operating theatre or transport) for greater than 12 hours in an intensive care unit?
• Proven or suspected acute primary brain lesions such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury
• Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness?
• Admission as a consequence of a suspected or proven drug overdose or burns
• Administration of ongoing neuromuscular blockade
• Mean arterial blood (MAP) pressure that is less than 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomization
• Heart rate less than 55 beats per minute unless the patient is being treated with a betablocker or a high-grade atrio­ ventricular block in the absence of a functioning pacemaker
• Known sensitivity to any of the study medications or the constituents of propofol (egg, soya, or peanut protein)
• Acute fulminant hepatic failure?
• Patient has been receiving full-time residential nursing care
• Death is deemed to be imminent or inevitable during this admission and either the attending physician, patient, or substitute decision-maker is not committed to active treatment