Sedation Using Intranasal Dexmedetomidine in Upper Gastrointestinal Endoscopy
Condition: Gastrointestinal Disease
MeSH terms: Gastrointestinal Diseases; Digestive System Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      Upper gastrointestinal endoscopy, like many other diagnostic and therapeutic procedures, may
      be associated with discomfort. Although upper endoscopy is usually of shorter duration and
      better tolerated by patients, most trials investigating the influence of analgesia and
      sedation have been performed on patients undergoing this procedure. Some patients may
      tolerate colonoscopy without sedation, but various techniques are used to limit discomfort
      and pain. Selection and dosing of sedatives depends on the patient's emotional state, the
      intensity of pain during examination, foreseeable technical difficulties, the endoscopist's
      experience, the presence or absence of anesthesia personnel, and hospital-specific
      procedures.

      Conscious sedation is a popular technique for colonoscopy and upper gastrointestinal
      endoscopy. The combination of an opioid and a benzodiazepine is known to provide good
      analgesic and sedative conditions during endoscopy. This combination of opioid and
      benzodiazepine, however, also increases the risk of respiratory depression. Therefore,
      pharmacologic agents which may provide adequate sedation without respiratory depression are
      of great interest to clinicians.

      Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative and analgesic
      effects. Compared with clonidine, it is more selective for the α 2 adrenoceptor and acts as a
      full agonist in most pharmacologic test models. Potentially desirable properties include
      decreased requirements for other anesthetics and analgesics, a diminished sympathetic
      response to stress and the potential for cardioprotective effects against myocardial
      ischemia. When compared with conventional sedatives such as opioids or benzodiazepines, its
      lack of respiration depression is a distinct advantage. Previous studies using
      dexmedetomidine for sedation has been promising with maintenance of respiratory function.
      Patients are readily arousable. With intravenous slow bolus administration, there is a
      minimal increase in blood pressure initially, followed by a slight decrease in blood
      pressure. Lower dose ranges, avoidance of rapid bolus injection, and a slow rate of
      administration tend to decrease these circulatory side effects. Many clinical studies have
      shown that it can be well and safely used intravenously, intramuscularly and transdermally.
      Although not an officially technique, there are also reports of intranasal administration
      resulting in fairly predictable onset in both adults and children.
    

Detailed description: 
      Aims:

      This study aims to evaluate sedative effects using intranasal dexmedetomidine in upper
      gastrointestinal endoscopy. The investigators aim to evaluate the efficacy, side effects and
      acceptability of sedation using intranasal dexmedetomidine by patients and endoscopist for
      upper gastrointestinal endoscopy.

      Methods:

      Double blind randomized prospective study.

      Sample size:

      We are planning to detect not less than 30% decrease of rescue propofol consumption when
      using intranasal dexmedetomidine. Assuming the average propofol consumption for the upper
      gastrointestinal endoscopy to be 40mg with SD=15mg, the required sample size with 80% power
      of test is 25 per group at the 0.05 level of significance.

      They will be randomly allocated to one of the following study groups:

      Group D: Intranasal dexmedetomidine 1.5mcg/kg; Group P: Intranasal saline (placebo)

      In addition, rescue sedation will be provided by a patient-controlled sedation using
      propofol/ alfentanil in both groups. Patient-controlled sedation (PCS) has been shown to
      provide safe and effective sedation for the individual patient by allowing the patient to
      decide whether he or she requires sedation and to determine the amount required. PCS has been
      used for various procedures performed under local and regional anesthesia. PCS with propofol
      and alfentanil has been used for sedation of patients during endoscopy.

      Process Written consent will be signed. No sedative premedication will be prescribed. The
      patients will be fasted for 6 hours before the procedure. Then patients will be sent to the
      endoscopy room about 1 hour before the procedure. A nasal catheter is positioned to deliver
      oxygen if oxygen is needed. Vital signs including heart rate, blood pressure, SpO2 and
      respiratory rate will be recorded. After obtaining baseline hemodynamic data (NIBP, HR) and
      respiratory data (SpO2, RR), the patients will be asked to evaluate their baseline levels of
      anxiety using a numerical rating scale.

      The intranasal study drugs will be administrated according to a code on a piece of folded
      paper drawn randomly from a box. The patients will be randomly allocated to one of the two
      treatment groups and sedation will be performed 1 hour before the procedure as follows:

      P) Placebo (0.015ml/kg); D) Intranasal dexmedetomidine 0.015ml/kg

      Before study drug administration, patients gently blow their noses. After baseline testing,
      an investigator who is blind to the study medication will administers the study drug to each
      naris and the patient remains in a semi-recumbent position with the head of the bed elevated
      at a 20-40 angle.

      After which, measurements including HR, NiBP, SpO2, RR will be recorded every 5 minutes while
      Numerical Rating Scale of anxiety every 15 minutes. Sedation is evaluated by investigator
      using Observer Assessment of Alertness/ Sedation (OAA/S]) scale every 15 minutes. Both the
      investigators and the subjects are blinded to the study medications. The patient will be
      shown 2 cards of picture about 1 hour after the study drug administration.

      An intravenous cannula will be inserted then. The degree of the cannulation pain will be
      assessed as using NRSpaincannulation. The intravenous cannula is connected to a 50 mL syringe
      patient-controlled analgesia pump containing 200 mg (20 mL) propofol and 0.5 mg (1 mL)
      alfentanil, which will be provided as the rescue sedative medications. The drugs are
      delivered in response to pressure on a hand-held button. Each bolus dose of 0.5 mL delivered
      contained 4.8 mg propofol and 12 μg alfentanil. No loading dose was used and the lock out
      time was set at zero. Despite the zero lock out time, a few seconds were required for the
      pump to deliver the preset bolus. The PCA pump was programmed to deliver a bolus dose of 0.5
      ml at 200 ml/h on patient's demand and the pump took 9 s to deliver the bolus, during which
      time it would not respond to a further demand. Thus, the effective lockout time was 9s.
      Patients are instructed in the use of the hand-held button before upper endoscopy.

      After the cannulation, local anesthetic spray will be administered to the oropharynx or
      rectum. 10 minutes after the local anesthesia, patient may start to push the button. When the
      first dose of propofol and alfentanil is infused, patient will be asked whether there is any
      pain of infusion, and the degree of the pain will be assessed as Numerical Rating Scale of
      pain due to infusion.

      The procedure will be started once the patients feel that they are relaxed. Vital signs
      including NIBP, SpO2, HR, RR, and OAA/S will be monitored throughout the sedation and
      procedure process every 5 minutes. If the patient becomes totally unresponsive or any adverse
      event occurs, the procedure will be stopped. If the SpO2 falls to below 90% for more than 10
      seconds, the endoscope will be removed and the patient's vital signs observed, and O2
      administered as required by the attending anesthesiologist until the patient becomes
      responsive again. Once the patient starts responding to command, the procedure will continue.
      Duration of unresponsiveness would be recorded. The time of start of procedure and duration
      of procedure and the frequencies of interruption due to patient events will be noted. The PCS
      propofol and alfentanil will be terminated and disconnected from the patient when the
      endoscopist indicates that the operative procedure is completed, and the dose consumption
      recorded. The endoscopist will determine the operating conditions by evaluating the ease of
      insertion and the patient's lack of motion and ability to obey commands, using
      NRSsatisfactionendoscopist.

      The patients will be transferred to the recovery room for monitoring for 30 minutes. The
      vital signs (blood pressure, pulse, RR and SpO2, and OAA/S) will be continued every 5 min.
      When the patients are fully recovered, they will be asked if there is any pain and discomfort
      and their severity will be assessed as NRSpain and NRSdiscomfort during the procedure.
      Discomfort is defined as 'a feeling of uneasiness that interfered with the patient's ability
      to relax'. They will also be asked if they remember any of the following events: the pictures
      shown to them, the insertion of the endoscope, the discomfort and pain during the
      examination.

      Discharge criteria will be assessed as postanaesthesia discharge score hourly. When the
      patients are fully recovered, defined as an OAA/S score of 5 and the postanaesthesia score is
      more than 9, they are fit for discharge. Satisfaction evaluation of sedation will be graded
      by the patients on NRS in satisfaction patient. They will be questioned on whether they think
      that they have received an adequate amount of sedation, too little or too much, whether they
      are relaxed and whether they will undergo the same procedure again.

      Data Collection

        1. Demographic data

        2. Type of endoscopy

        3. Duration of sedation

        4. Duration of procedure

        5. Duration of recovery area

        6. Duration from the end of procedure to become fully awake

        7. Duration at general ward before discharge

        8. Pain severity (NRS of pain) of cannulation, when being infused of propofol and
           alfentanil, during the examination

        9. Vital signs before and during the sedation, during the procedure and Postoperatively
           (HR, NIBP, SpO2, RR)

       10. OAA/S before and after administration, during and after procedure

       11. NRSpain and NRSdiscomfort after administration, during and after procedure

       12. Time when OAA/S is 4

       13. Tries and goods of propofol and alfentanil during the procedure

       14. Propofol and alfentanil consumption

       15. NRSsatisfactionendoscopist

       16. NRSsatisfactionpatient

       17. Adverse events and severity intraoperatively and postoperatively including oversedation,
           respiratory depression, hypotension, paradoxical reaction, dizziness, nausea and
           vomiting, bradycardia. The severity of adverse event are graded as follows:

      Mild: no treatment Moderate: require treatment Severe: refractory to treatment

      Data Analysis Student t test, Mann-Whitney U test and Chi-square test are applied on the
      analysis.

      Study Duration: 18 months. Provide some data on current case load of upper endoscopies in
      Queen Mary Hospital.
    

Intervention name(s): Dexmedetomidine
Intervention type(s): Drug
Intervention description(s): Dexmedetomidine 1.5mcg/kg was given intranassaly
Other intervention name(s): Dexmedetomidine (Hospira)
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment