Effect of Dexmedetomidine on Propofol Requirement During Anesthesia
Condition: Anesthesia
Study type: Interventional
Phase: Phase 4

Summary: 
      Dexmedetomidine, a selective alpha-2 agonist agent used for maintaining sedation in intensive
      care patients in receipt of mechanical ventilation, is being increasingly utilized in
      anaesthesia practice for facilitating anaesthesia depth as an adjunct to base anaesthetics
      (intravenous; propofol: inhalational; sevoflurane, desflurane). The investigators intend to
      assess the anaesthetic potential of dexmedetomidine in controlled anaesthesia settings
      empowered by the use of an objective, patient response based, safe, efficient, and patented
      closed loop anaesthesia delivery system (CLADS). CLADS functions on control of processed EEG
      response parameter captured from anaesthetized patients with the help of a BIS- monitor,
      which is continuously fed into a automated drug infusion pump. The infusion pump then
      accordingly delivers the anaesthetic drug to the patients based on pharmacodynamic
      requirements. If dexmedetomidine has anaesthesia potential then it is likely that propofol
      use delivered by CLADS can be reduced further. In addition the effect of two drugs (viz, base
      agent-propofol plus adjunct agent-dexmedetomidine) on different receptor site within the
      brain would help gain greater anaesthetic depth consistency as well as a lower incidence of
      intraoperative patient awareness. This prospective randomized two-arm study aims to assess
      effect of the use of dexmedetomidine on propofol requirements (primary objective),
      anaesthesia depth consistency, and intraoperative patient awareness (secondary objectives).
    

Detailed description: 
      After Institutional Ethics Committee approval and written informed consent, eighty
      patient-participants (40 per group) aged 20-65 years, ASA physical status I/II, of either
      sex, and undergoing major laparoscopic / robotic surgery of more than 60-minutes duration
      will be included in this single-center (Sir Ganga Ram Hospital, New Delhi-110060, India )
      prospective, double-blinded, two-arm, randomized controlled study.

      The patients will be randomly divided into two groups:

      Group-I: Pre-induction dexmedetomidine + intraoperative dexmedetomidine plus anesthesia with
      propofol delivered by CLADS (induction + maintenance) [Dexmedetomidine group] Group-II:
      Pre-induction 0.9% saline solution + intraoperative 0.9% saline solution infusion +
      anesthesia with propofol delivered by CLADS (induction + maintenance) [Non Dexmedetomidine
      group]

      Sample-size Estimation:

      The sample size estimation was estimated from the cue that the average propofol doses
      required for maintenance of anaesthesia (4.7+ 1.6 mg/kg/hr) when using manual propofol and
      remifentanil target controlled infusion18 with a 90% power employed to detect a 30% decrease
      of propofol dosage among the patients who will receive dexmedetomidine in addition to base
      anesthetic propofol; with a bilateral α risk value of 0.05, the investigators would require
      66 patients for the study. To cover up for unanticipated losses the investigators would need
      additional 20% patients. Thus the investigators would require 80-patients for the study

      Randomization, Allocation Concealment:

      The patients will be randomly allocated to one of the two groups based on a
      computer-generated random number table
      (url:stattrek.com/statistics/random-number-generator.aspx). Randomization sequence
      concealment will include opaque-sealed envelopes with alphabetic codes whose distribution
      will be in control of an independent analyst. The envelopes will be opened; patient's
      data-slip will be pasted on them, and will be sent back to the control analyst.

      Management of Anaesthesia:

      Two peripheral venous lines (18G/20G catheter) will be secured. Invasive vascular access
      (arterial line for direct continuous blood pressure assessment, central venous catheter) will
      be secured as per the requirement of surgery and/or patients morbid status. A BIS sensor
      (Covidien IIc, Mansfield, USA) for monitoring depth of anaesthesia, using the BIS monitoring
      module (Model DSC-XP, Aspect medical system, USA), will be applied over the patient's
      forehead according to manufacturer's instruction prior to induction of anaesthesia.

      The patients will be randomly allocated to one of the two groups separated by method of
      dexmedetomidine administration. The pre-induction and the infusion dose of dexmedetomidine
      will be 1-µ/kg over 10 minutes and 0.5-µ/kg/hour, respectively. Dexmedetomidine infusion will
      be stopped in case of acute haemodynamic suppression (>20% pre-induction baseline) or acute
      blood loss (>200-ml) at any point of time and it will be recorded as an event. It will be
      restarted upon normalcy of haemodynamics is achieved and also full surgical hemostasis is
      ensured.

      Anesthesia Technique:

      All the patients will be administered pre-induction fentanyl-citrate analgesia as per a
      predefined strategy (total 2-µg/kg IV: 1-µg/kg at 0 minute, 3-minutes time points].
      Pre-oxygenation will be initiated at 6-minute time point or prior to that if there is a fall
      in oxygen saturation < 94 percent. At 9-minute time point anaesthesia will be induced with
      propofol 2-mg/kg and vecuronium bromide 0.08-mg/kg for skeletal muscle relaxation to
      facilitate tracheal intubation. Ventilator settings of CMV, tracheal tube size [7.5-mm I.D
      (male), 6.5-mm I.D (female)] and breathing circuit (circle-CO2 absorber system) will be the
      standardized in all the patients. Routine monitoring (EKG, NIBP, pulse oximetery, EtCO2) will
      be applied during the procedure as per the established practice. Over and above the use of
      study drug dexmedetomidine as per group allocation, propofol administration will be
      controlled with CLADS system tuned to consistent anaesthetic depth (BIS 40-60) in all the
      patients. In addition, all the patients will receive 0.5-µg/kg/hr fentanyl infusion during
      surgery. Oxygen.-air mixture (FiO2 0.50) will be utilized for intraoperative ventilation.
      Neostigmine (50-µg/kg) and glycopyrrolate (20-µg/kg) will be administered to reverse the
      residual neuromuscular blockade (non-depolariser).
    

Intervention name(s): Propofol; Dexmedetomidine; Placebo (normal saline)
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Dexmedetomidine; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: dexmedetomidine; propofol; BIS; CLADS