Low Dose Dexmedetomidine and Delirium After Cardiac Surgery
Condition: Cardiac Surgical Procedures
MeSH terms: Delirium
Study type: Interventional
Phase: Phase 4

Summary: 
      Delirium after cardiac surgery can occur in up to 50% of the patients and has been shown to
      be significantly associated with increased morbidity and mortality. Advanced age is a
      significant risk factor of delirium.

      Numerous studies have shown that sedation with high doses of Dexmedetomidine in the ICU
      reduces the incidence of postoperative delirium. On the other hand animal studies have shown
      neuroprotective effects of Dexmedetomidine by means of stimulating alpha2A-adrenoceptors.

      It is not clear whether the administration of a low dose Dexmedetomidine in cardiac surgery
      would have any neuroprotective effects by stimulating the alpha 2A-receptors and as such
      would decrease the incidence of postoperative delirium.
    

Detailed description: 
      Postoperative delirium (PD) is a common problem in cardiac surgical patients. Its incidence
      varies among studies and can reach up to 50% of the patients. PD is associated with increased
      morbidity and mortality. Its occurrence is the resultant between the predisposing factors and
      the precipitating factors. Age seems to be a significant predisposing factor. In this regard
      the pathophysiology of PD is not yet fully understood. There are several hypothetical
      mechanisms for the development of PD. The first hypothesis is cerebral ischemia and BBB
      breakdown. The second hypothesis is neuro-inflammation. Peripheral pro-inflammatory mediators
      especially released during surgery would interact with the brain. Otherwise there is the
      problem of sleep deprivation/fragmentation in patients admitted to the hospital.

      Dexmedetomidine is a potent and more selective alpha2-adrenergic receptor than clonidine.
      Studies have demonstrated that it has neuroprotective and anti-inflammatory actions.

      Numerous studies including trials in cardiac surgery have shown a decreased incidence of
      delirium when Dexmedetomidine was used as sedative in the ICU compared with other sedatives
      acting on the GABA receptors. However, in these studies high doses of Dexmedetomidine were
      used for periods up to 24h. Dexmedetomidine was started in the ICU and was not compared in a
      double-blind fashion with placebo. In a recent randomized double-blind placebo-controlled
      trial a very low dose of Dexmedetomidine decreased the occurrence of PD when compared to
      placebo. However this study was performed in non-cardiac patients. Moreover the patients were
      included after their arrival in the ICU, which means that those patients who were intubated
      at their arrival in the ICU were not included. And again the study medication was only
      started after arrival in the ICU.

      The aim of this study is to elucidate whether the administration of Dexmedetomidine at a low
      dose would decrease the incidence of PD in elderly patients undergoing cardiac surgery. The
      hypothesis is that Dexmedetomidine at low doses, by only stimulating the alpha2A
      adrenoceptors,would have neuroprotective affects ans as such decrease the incidence of PD.
      Dexmedetomidine would also have anti-inflammatory effects and effects on the quality of
      sleep. Both mechanisms would play a role in the pathophysiology of PD.
    

Intervention name(s): Dexmedetomidine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Dexmedetomidine will be started at 5mL/h while the patient is still in the operating room. The patient will be transferred to the intensive care unit with a sedative regimen based on propofol.; A continuous infusion of NaCL 0.9% will be started at 5mL/h while the patient is still in the operating room. The patient will be transferred to the intensive care unit with a sedative regimen based on propofol.
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment