Pharmacokinetics of Dexmedetomidine During Prolonged Infusion in ICU (DEX PK)

Inclusion Criteria:

• Written informed consent obtained from the patient's legal representative according to local regulations before starting any study procedures other than pre-screening
• Patients sedated and ventilated in ICU for whom sedation is expected to be clinically required for at least 24 hours, as determined by the responsible physician
• Prescribed light to moderate sedation (target RASS = 0 to -3)

Exclusion Criteria:

• Acute severe intracranial or spinal neurological disorder due to vascular causes, infection, intracranial expansion or injury
• Uncompensated acute circulatory failure at screening (severe hypotension with mean arterial pressure(MAP) < 55 mmHg despite vasopressor and inotrope therapy)
• Heart rate (HR) < 50 beats/min for longer than 5 min between screening and starting study treatment
• Atrioventricular (AV)-conduction block II-III (unless pacemaker installed)
• Severe hepatic impairment (e.g. bilirubin > 101 μmol/L)
• Need for continuous muscle relaxation
• Any condition which would significantly interfere with the collection of study data
• Burn injuries or other conditions requiring regular anesthesia or surgery
• Use of centrally acting alpha-2 agonists or antagonists within 24 hours prior to starting the study (e.g. dexmedetomidine, clonidine, tizanidine, apraclonidine and brimonidine)
• Known allergy to dexmedetomidine or any excipients of the study treatment
• Patients who have or are expected to have treatment withdrawn or withheld due to poor prognosis
• Patients receiving sedation for therapeutic indications rather than to tolerate the ventilator (e.g. epilepsy)
• Patients unlikely to require continuous sedation during mechanical ventilation (e.g. Guillain-Barré syndrome)
• Patients who are unlikely to be weaned from mechanical ventilation; e.g. diseases/injuries primarily affecting the neuromuscular function of the respiratory apparatus such as clearly irreversible disease requiring prolonged ventilatory support (e.g. high spinal cord injury or advanced amyotrophic lateral sclerosis)