Goal Directed Propofol Sedation With Magnesium Sulphate Versus Dexmedetomidine for ERCP Procedure
Condition: Lack of Drug Action
Study type: Interventional
Phase: Phase 3

Summary: 
      Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive longer endoscopic
      procedure. It is performed in remote locations under a continuum of anesthetic depth, ranging
      from conscious to deep sedation leading to general anesthesia.

      Propofol sedation for (ERCP) procedures is the most popular current technique that has
      generated controversy in the medical field. Propofol can be safely administered because of
      its shorter half-life which results in a shorter recovery time than conventional sedation
      (opioid and/or benzodiazepine) that makes it widely used for sedation in many
      gastrointestinal procedures including ERCP. However, because of its narrow therapeutic
      window, the level of conscious sedation can easily go deeper from moderately deep sedation to
      near general anesthesia. Therefore, propofol as a sole agent can cause oversedation and
      apnea. Depth of sedation could be estimated better when target effect concentration of
      propofol is titrated by using bispectral index monitoring device(BIS).Targeting BIS within a
      specific range ensures additional safety during the procedure. Scores between 60-80 have been
      recommended for sedation. Propofol requirement can be reduced with addition of adjuvants (eg.
      Ketamine, Magnesium sulfate and Dexmedetomidine). Most adjuncts have analgesic properties
      with opioid and anesthetic sparing effects, without clinically significant respiratory
      depression.

      Dexmedetomidine, is a selective alpha 2 agonist; it has sedative, amnestic, and analgesic
      properties. It is a useful addition to a propofol/remifentanil anesthetic combination as it
      reduced their requirements intraoperatively and can help supplement analgesia
      postoperatively. Its combination with propofol was proved to provide satisfactory anesthesia
      for upper gastrointestinal (GI)) endoscopy in obstructive sleep apnea patients .

      Magnesium can also act as an adjuvant in analgesia due to its properties as calcium channel
      blocker and N-methyl-D-aspartate antagonists .It was suggested to be a near ideal intravenous
      (IV) adjunct to propofol/ remifentanil based total anesthesia in gynaecology patients .

      Hypothesis of this study is that Magnesium sulfate can have a propofol sparing effect during
      ERCP procedures guided by BIS monitoring as efficient as dexmedetomidine but with less cost
      and complications together with more patient and doctor satisfaction in addition to better
      patient outcome.
    

Detailed description: 
      After Theodor Bilharz Research Institute (TBRI) Ethics Committee approval, sixty patients
      scheduled for ERCP procedures will be informed about the study and written consents will be
      obtained.

      Patients will be allocated into two groups, thirty patients each, Magnesium (M) and
      Dexmedetomidine (D). Group (M) will receive 40 mg.kg-1 of magnesium sulphate bolus followed
      by IV infusion of 10 mg.kg-1.h-1. Group (D) will receive dexmedetomidine bolus (1μg.kg-1)
      followed by infusion of 0.5μg.kg-1h-1 all through the procedure.

      Randomization of the patients will be established by computer generated random number table
      utilizing sealed envelope technique.

      On arrival to the ERCP suit, two IV cannulae will be inserted in both hands of each patient
      in both groups. One for isotonic saline infusion and propofol administration and the other
      will be preserved for the study drug administration. IV fluid will be started at a rate of
      8-12 ml.kg-1.h-1 continued throughout the procedure. All patients will be premedicated with
      intravenous pantoprazole 40mg and ondansetron 8mg.

      Routine monitoring of ECG, pulse oximetry, non-invasive blood pressure will be established
      before induction of sedation. BIS three electrodes sensor will be applied over the patient's
      forehead using fronto-temporal montage for the monitoring of level of sedation . The baseline
      variables will be recorded and documented as well as continuous monitoring and documentation
      every 5 min for the first 30 min and every 10 min till the end of procedure. Supplemental
      oxygen will be administered with nasal prongs at 3 l.min-1. The total duration of the
      procedure, defined as the time taken from insertion of the endoscope to its removal, will
      also be documented.

      Each study drug will be loaded in 50 ml syringes (for both bolus and infusion) & labeled as
      "study drug bolus" and "study drug infusion". The identity of the constituted drug in the
      syringe is not revealed to the anesthetist handling the patients and the observer recording
      the post procedure variables. Depending upon the body weight, each patient will receive a
      bolus of the study drug, diluted up to 50 ml with saline (direct IV)followed by infusion of
      the same drug in another 50 ml using a syringe pump. Each bolus will be given and the rate of
      drug infusion will be adjusted by the anesthesia resident not involved in the study.

      The study drugs IV infusions will be administered using injector pumps with unidentified
      screen to assure that the observer remains blinded.

      For each patient, bolus dose of the each study drug will be administered slowly over 10 min,
      after mouth gag insertion and patient positioning (either lateral or prone position) followed
      by induction with propofol in a dose of 0.5-1.5 mgkg-1, targeting BIS between 60-70.Once the
      target BIS is attained, the infusion of the study drug is started with the pre-adjusted rate
      (discussed before) along with the propofol maintenance infusion starting at a rate of 3
      mg/kg/hr to be adjusted to maintain a BIS value between 60-70.At the end of the procedure,
      propofol and study drug infusions will be stopped. BIS values will be allowed equilibrating
      above 80. Patients oropharynx will be thoroughly suctioned and patients will be turned supine
      with head up tilt (15 degrees), to allow for complete recovery with eye opening on command,
      ability to handle secretions, follow simple commands, hemodynamic stability, maintaining O2
      saturation at room air >95% and attainment of BIS value >90 as end points
    

Intervention name(s): Dexmedetomidine; Magnesium Sulphate
Intervention type(s): Drug; Drug
Intervention description(s): added to propofol sedation; added to propofol sedation
Other intervention name(s): Precedex
Intervention MeSH terms: Magnesium Sulfate; Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Group M: the Drug consisted of 2 ampoules each one containing 2500 mg magnesium sulphate (Egypt Otsuka pharma.Co)in 50 ml syringe .(i.e. 100 mg/ml). Loading dose was 40mg/kg, given over 10min and maintenance dose was 10mg/kg/h.
Group D: the Drug consisted of 2ml containing 200μg Dexmedetomidine (precedex®; united pharmaceutical group company, USA) diluted up to 50ml with normal saline (4μg/ml). Loading dose was 1μg/kg; given over 10min. The maintenance dose was 0.5 μg / kg / h.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Other
Keywords: Endoscopic retrograde cholangiopancreatography; sedation; dexmedetomidine; propofol; Magnesium sulphate; Bispectral index monitoring