Efficacy of Dexmedetomidine Versus Clonidine to Control Delirium in Patients Undergoing CABG
Condition: Delirium on Emergence
MeSH terms: Delirium; Emergence Delirium
Study type: Interventional

Summary: 
      This prospective, randomised, double blinded, controlled clinical trial will be conducted in
      147 patients between 60 yr and 70 yr , ASA physical status II and III, undergoing CABG.
      Patients will be randomly allocated to either dexmedetomidine or clonidine (control) groups
      .Upon arrival to ICU, in the dexmedetomidine group, patients will receive an infusion of
      0.5-0.7 μg/kg/h then 1.4 μg/kg/h if Richmond assessment sedation score from +1 to +4

      Taking into consideration if the heart rate less than 60 per minute or persistent hypotension
      reduce infusion rate by 0.2 μg/kg/h.

      Once the patient will be extubated, wean the infusion by 0.1μg/kg/h till reaching 0.2μg/kg/h.
      Slow the weaning rate if evidence of withdrawal reactions as agitation or hypertension occur.
      In clonidine group, the patients will receive 0.5μg/kg then 0.1-0.2 μg/kg/h.Primary end point
      of the study is the incidence of delirium.The secondary endpoints will be the the duration of
      extubation, the length of ICU stay, need for inotropic support or vasopressors, hospital stay
      , mean arterial blood pressure and heart rate , hospital mortality rate , all additional
      sedatives including overall doses of morphine and haloperidol the incidence of adverse events
      as bradycardia
    

Detailed description: 
      After Ethics committee approval, and a written informed consent will be taken from every
      patient, . Patients with a history of mental illness, severe dementia, delirium or undergoing
      emergency procedures will be excluded.

      Anesthesia management will be standardized to minimize any effect of anesthetic type on
      neurological outcomes. Premedication with midazolam will be limited to a maximum of 0.05
      mg/kg.

      Anesthesia will be induced with 12 μg/kg fentanyl, 5-7mg/kg thiopental sodium, and 0.15 mg/kg
      pancuronium and maintained with 1% to 2.0% isoflurane. The heart rate and blood pressure will
      be maintained within 20% of the baseline values. Anticoagulation will be achieved with
      heparin to maintain an activated clotting time above 480 s.The CPB circuit will be primed
      with 1.8 l lactated Ringer's solution and 50 ml of 20% mannitol. Management of CPB will
      include systemic temperature drift to 32 C, targeted mean perfusion pressure between 60 and
      80 mmHg, and pump flow rates of 2.2 l/min/m2 . Myocardial protection will be achieved with
      antegrade cold blood cardioplegia. A 32-μ m filter (Avecor Affinity, USA)will be used in the
      arterial perfusion line. Before separation from CPB, patients will be rewarmed to 36 to 37C.
      After separation from CPB, heparin will be neutralized with protamine sulfate, 1 mg/100 U
      heparin, to reach an activated clotting time within 10% of baseline.All patients will be
      transferred to ICU after surgery. Patients will be randomly allocated to either
      dexmedetomidine or clonidine (control) groups according to a computer-generated randomization
      code, with allocation ratio 1:1 .Opaque sealed envelopes will be done according to the
      randomization schedule and opened by a physician not involved in the study . Upon arrival to
      ICU, in the dexmedetomidine group, patients will receive an infusion of 0.5-0.7 μg/kg/h then
      1.4 μg/kg/h if Richmond assessment sedation score from +1 to +4

      +4 Combative ,+3 Very agitated ,+2 Agitated,+1 Restless, 0 Alert and calm, -1 Drowsy , -2
      Light sedation, -3 Moderate sedation, -4 Deep sedation, -5 Unarrousable A four millilitres
      vial of dexmedetomidine ( 100 micrograms per ml)will be drawn up and diluted in 46 ml of
      normal saline.The infusion of dexmedetomidine will be continued for a maximum period of 24 h.
      Taking into consideration if the heart rate less than 60 per minute or persistent hypotension
      reduce infusion rate by 0.2 μg/kg/h.Dexmedetomidine infusion will not be discontinued before
      extubation. Once the patient will be extubated, wean the infusion by 0.1μg/kg/h till reaching
      0.2μg/kg/h. Slow the weaning rate if evidence of withdrawal reactions as agitation or
      hypertension occur. In clonidine group, the patients will receive 0.5μg/kg then 0.1-0.2
      μg/kg/h.

      Five ampoules of clonidine(750 μg) was drawn up and diluted in 45ml of normal saline.

      Opioids were titrated to reach pain score 3 out of 10. Pain will be assessed using a standard
      10-cm visual analog scale (0, no pain; 10, worst and unbearable pain). Patients received 2 mg
      morphine as rescue analgesic.

      Primary end point of the study is the incidence of delirium, which is defined as a disturbed
      level of consciousness that develops over a period of hours or days and fluctuates over time.

      Delirium will be assessed preoperatively (baseline)and postoperatively, in ICU every 2 hours
      using the confusion assessment method (CAM) for ICU.(7) When patients are discharged from ICU
      to the ward, delirium will be assessed using CAM every 8 hours for the next 5 days. The
      CAM-ICU is used for both ventilated and extubated patients. It included a fourstep algorithm
      : (1) an acute onset of changes or fluctuations in the course of mental status,
      (2)inattention, (3) disorganized thinking, and (4) an altered level of consciousness.
      Patients are delirious if both (1) and (2) were found inanition to either feature (3)or (4).
      Patients are stated either CAM positive (delirium present) or CAM negative (delirium absent).
      Incidence of delirium was confirmed by the psychiatry consultant. The onset and duration of
      delirium will be also recorded. The CAM-ICU and CAM testers were involved in the study . IV
      haloperidol(2.5-5 mg PRN), will be used as a first-line treatment in delirious patients, a
      regular dose 1 mg ads until symptoms resolve.

      The secondary endpoints will be the the duration of extubation, the length of ICU stay, need
      for inotropic support or vasopressors, hospital stay , mean arterial blood pressure and heart
      rate , hospital mortality rate , all additional sedatives including overall doses of morphine
      and haloperidol, finally the incidence of adverse events as bradycardia, heart block , the
      need for pacemaker , nausea and vomiting will be recorded as well.
    

Intervention name(s): Dexmedetomidine; Clonidine
Intervention type(s): Drug; Drug
Intervention description(s): an infusion of 0.5-0.7 μg/kg/h then 1.4 μg/kg/h if Richmond assessment sedation score from +1 to +4 ,if the heart rate less than 60 per minute or persistent hypotension reduce infusion rate by 0.2 μg/kg/h.; an infusion of 0.5μg/kg then 0.1-0.2 μg/kg/h if Richmond assessment sedation score from +1 to +4.
Other intervention name(s): demedetomidine hydrochloride; clonidine hydrochloride
Intervention MeSH terms: Clonidine; Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention
Keywords: dexmedetomidine, clonidine, postoperative, CABG