Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01887184 |
| Other study ID # |
UW 07-212 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
January 2009 |
| Est. completion date |
April 2010 |
Study information
| Verified date |
May 2024 |
| Source |
The University of Hong Kong |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
