Adjunct Anesthesia Medication, Colonoscopy
Conditions
Keywords
Fentanyl, Midazolam, Sedation, Patient tolerance, Duration of colonoscopy
Brief summary
To access the efficacy of adding diphenhydramine as adjunct to improve sedation and to reduce the amount of standard sedatives used during colonoscopy in patients on chronic opioids.
Detailed description
Specific Aims: The primary aim of our study is to determine if addition of Diphenhydramine to Fentanyl and Midazolam will decrease the dose of Fentanyl and Midazolam used during colonoscopy in individuals on chronic opioids. Secondarily we will be looking at quality of sedation, duration of colonoscopy, time to reach cecum and adverse effects (hypoxia defined as O2 saturation less than 89% lasting for more than 30 seconds, hypotension defined as systolic BP less than 90 mmhg and use of reversal agents i.e Naloxone or Flumazenil). Day of Procedure: After consent is obtained the medical records of the patients will be reviewed and demographic information, co-morbidities, current medication will be extracted and recorded. On the day of colonoscopy Alcohol use disorder inventory (AUDIT) will be used to screen for alcohol abuse. AUDIT was developed by World Health Organization and has been validated over a period of 2 decades. It consist of 10 questions, each question is scored 0-4 on the basis of subjects alcohol use. It takes about 2-4 minutes to complete. A score 10 or greater is highly specific or alcohol use. Subjects will be checked in and prepared according to routine protocols of the VA medical center. Participants will be randomly assigned to receive either 50 mg of diphenhydramine or 10 ml of 0.9% sodium chloride. On the day of colonoscopy randomization will be performed by an independent investigator who is a pharmacist at VA medical center using the website http://www.randomization.com. She will also prepare and dispense medication. Each endoscopy team will consist of an attending gastroenterologist, gastroenterology fellow and two nurses. Medications will be administered by one of the nurses under the direct supervision of the physician. At the start of procedure baseline vitals will be recorded as per our unit's policy. Research medication will be administered 3 minutes prior to administration of other medications. Neither the patient nor the medical staff including the endoscopist will be aware of the contents of the vial. Conscious sedation will be achieved using a combination of intravenous midazolam and fentanyl as standard sedative. Rarely, additional diphenhydramine will be given, on the basis of the judgment of the endoscopist. During the procedure vital signs including oxygen saturation will be monitored at 3-5 minute interval. Procedure related complications, including hypotension, desaturation and cardiac arrhythmia will be managed according to our endoscopy unit policy and protocols. Following the procedure, the nurse and the fellow or the attending will individually rate the quality if sedation on a ten-point Likert scale. Qualitative assessment will also be made (Under-sedated, adequately sedated, or over-sedated). Recovery time will be recorded. Day Following the Colonoscopy Twenty-four hour discharge a follow up call will be made and the patients will be asked to evaluate the level of sedation on a 10-point scale (1, inadequate; 10 completely without discomfort); pain (1, no pain; 10 severe pain), and amnesia (10, no memory of the procedure; 1 complete memory).
Interventions
DRUGDiphenhydramine
DRUGPlacebo
Sponsors
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged 18-64 years undergoing screening, surveillance, diagnostic and therapeutic colonoscopy * Patient on chronic opioids defined as at least 5 mg of morphine or its equivalent at least 3 days per week for more than 3 months
Exclusion criteria
* Inability to execute informed consent * Allergy to Diphenhydramine, fentanyl or midazolam * Known or suspected pregnancy * Endoscopic procedure without sedation * Patient scheduled to have other endoscopic procedures on the same day * Prior alimentary tract surgery * Severe cardiopulmonary disease (ASA IV) * Monoamine Oxidase Inhibitors (MOI) use within 2 weeks of procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dosage of Fentanyl | From induction (first dose of sedative) to end of procedure | Moderate sedation (using the American Society of Anesthesiologists definition of maintaining purposeful response to verbal or tactile stimulation, adequate ventilation requiring no airway protection, and maintenance of cardiovascular function) was then achieved using incremental doses of the combination of intravenous midazolam (1 mg) and fentanyl (25 μg) given every 2 to 3 minutes. To minimize any crossover, additional diphenhydramine was not permitted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Procedure | Time from induction (first dose of sedative) to discharge | Induction period (time from first dose of fentanyl to scope insertion), procedural time (time from scope insertion to scope out), and recovery time (time from scope out to discharge) were recorded by the nursing staff in their standard documentation. |
| Number of Participants With Adverse Events | From induction (first dose of sedative) to discharge | Following adverse events will be recorded: (1)Hypoxia defined as O2 saturation less than 89% lasting for more than 30 seconds, (2)hypotension defined as systolic BP less than 90 mmhg and (3)use of reversal agents i.e Naloxone or Flumazenil |
| Quality of Sedation | During the colonoscopy and 24 hours after discharge | Quality of sedation will be accessed by the nurse and the physician at the end of procedure. Name: 10 point visual analogue scale Minimum score: 1 (worse) Maximum score: 10 (better) |
| Dosage of Midazolam | From induction (first dose of sedative) to end of procedure | Moderate sedation (using the American Society of Anesthesiologists definition of maintaining purposeful response to verbal or tactile stimulation, adequate ventilation requiring no airway protection, and maintenance of cardiovascular function) was then achieved using incremental doses of the combination of intravenous midazolam (1 mg) and fentanyl (25 μg) given every 2 to 3 minutes. To minimize any crossover, additional diphenhydramine was not permitted. |
| 24 Hour Follow up Amnesia Score | At about 24 after the procedure | Patient were also asked to rate amnesia on a 10 point scale 24 after discharge. minimum= 0 (worse) maximum =10 (better) |
| 24 Hour Follow up Pain Score | About 24 hours after the procedure | At 24 hr follow up patients were asked to rate the level of pain during the procedure using 10 point scale. 10 point visual analogue scale minimum= 0 (better) maximum =10 (worse) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diphenhydramine Diphenhydramine 50 mg IV 3 minutes prior to administration of other sedatives | 61 |
| Placebo 0.9% sodium chloride 10 ml IV 3 minuted prior to administration of other sedatives | 58 |
| Total | 119 |
Baseline characteristics
| Characteristic | Diphenhydramine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 9.3 | 60.1 years STANDARD_DEVIATION 9.7 | 60.37 years STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized Race Others | 16 Participants | 12 Participants | 28 Participants |
| Race/Ethnicity, Customized Race White | 45 Participants | 46 Participants | 91 Participants |
| Region of Enrollment United States | 61 participants | 58 participants | 119 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 57 Participants | 56 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 58 |
| other Total, other adverse events | 17 / 61 | 25 / 58 |
| serious Total, serious adverse events | 0 / 61 | 0 / 58 |
Outcome results
Primary
Dosage of Fentanyl
Moderate sedation (using the American Society of Anesthesiologists definition of maintaining purposeful response to verbal or tactile stimulation, adequate ventilation requiring no airway protection, and maintenance of cardiovascular function) was then achieved using incremental doses of the combination of intravenous midazolam (1 mg) and fentanyl (25 μg) given every 2 to 3 minutes. To minimize any crossover, additional diphenhydramine was not permitted.
Time frame: From induction (first dose of sedative) to end of procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diphenhydramine | Dosage of Fentanyl | 125.4 (μg) | Standard Deviation 56.2 |
| Placebo | Dosage of Fentanyl | 126.9 (μg) | Standard Deviation 53.5 |
Secondary
24 Hour Follow up Amnesia Score
Patient were also asked to rate amnesia on a 10 point scale 24 after discharge. minimum= 0 (worse) maximum =10 (better)
Time frame: At about 24 after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diphenhydramine | 24 Hour Follow up Amnesia Score | 7.8 score on a 10 point point scale | Standard Deviation 3.4 |
| Placebo | 24 Hour Follow up Amnesia Score | 6.5 score on a 10 point point scale | Standard Deviation 3.8 |
Secondary
24 Hour Follow up Pain Score
At 24 hr follow up patients were asked to rate the level of pain during the procedure using 10 point scale. 10 point visual analogue scale minimum= 0 (better) maximum =10 (worse)
Time frame: About 24 hours after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diphenhydramine | 24 Hour Follow up Pain Score | 2.0 score on a scale | Standard Deviation 2.17 |
| Placebo | 24 Hour Follow up Pain Score | 3.09 score on a scale | Standard Deviation 3.95 |
Secondary
Dosage of Midazolam
Moderate sedation (using the American Society of Anesthesiologists definition of maintaining purposeful response to verbal or tactile stimulation, adequate ventilation requiring no airway protection, and maintenance of cardiovascular function) was then achieved using incremental doses of the combination of intravenous midazolam (1 mg) and fentanyl (25 μg) given every 2 to 3 minutes. To minimize any crossover, additional diphenhydramine was not permitted.
Time frame: From induction (first dose of sedative) to end of procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diphenhydramine | Dosage of Midazolam | 4.9 mg | Standard Deviation 2.1 |
| Placebo | Dosage of Midazolam | 5.0 mg | Standard Deviation 1.9 |
Secondary
Duration of Procedure
Induction period (time from first dose of fentanyl to scope insertion), procedural time (time from scope insertion to scope out), and recovery time (time from scope out to discharge) were recorded by the nursing staff in their standard documentation.
Time frame: Time from induction (first dose of sedative) to discharge
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diphenhydramine | Duration of Procedure | Procedure time | 34.8 minutes | Standard Deviation 19.5 |
| Diphenhydramine | Duration of Procedure | Recovery | 34.4 minutes | Standard Deviation 9.2 |
| Diphenhydramine | Duration of Procedure | Induction | 6.4 minutes | Standard Deviation 3.2 |
| Placebo | Duration of Procedure | Procedure time | 34.7 minutes | Standard Deviation 17.8 |
| Placebo | Duration of Procedure | Recovery | 32.4 minutes | Standard Deviation 5.9 |
| Placebo | Duration of Procedure | Induction | 6.3 minutes | Standard Deviation 2.8 |
Secondary
Number of Participants With Adverse Events
Following adverse events will be recorded: (1)Hypoxia defined as O2 saturation less than 89% lasting for more than 30 seconds, (2)hypotension defined as systolic BP less than 90 mmhg and (3)use of reversal agents i.e Naloxone or Flumazenil
Time frame: From induction (first dose of sedative) to discharge
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diphenhydramine | Number of Participants With Adverse Events | Hypotension | 12 Participants |
| Diphenhydramine | Number of Participants With Adverse Events | Arrhythmia | 0 Participants |
| Diphenhydramine | Number of Participants With Adverse Events | Desaturation | 0 Participants |
| Diphenhydramine | Number of Participants With Adverse Events | Reversal agent use | 0 Participants |
| Diphenhydramine | Number of Participants With Adverse Events | Hypertension | 5 Participants |
| Diphenhydramine | Number of Participants With Adverse Events | Tachypnea | 0 Participants |
| Diphenhydramine | Number of Participants With Adverse Events | Apnea | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Tachypnea | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Hypotension | 22 Participants |
| Placebo | Number of Participants With Adverse Events | Hypertension | 3 Participants |
| Placebo | Number of Participants With Adverse Events | Desaturation | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Apnea | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Arrhythmia | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Reversal agent use | 0 Participants |
Secondary
Quality of Sedation
Quality of sedation will be accessed by the nurse and the physician at the end of procedure. Name: 10 point visual analogue scale Minimum score: 1 (worse) Maximum score: 10 (better)
Time frame: During the colonoscopy and 24 hours after discharge
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diphenhydramine | Quality of Sedation | Physician rating | 6.2 score on a scale | Standard Deviation 1.1 |
| Diphenhydramine | Quality of Sedation | Nurse rating | 5.6 score on a scale | Standard Deviation 1.5 |
| Placebo | Quality of Sedation | Physician rating | 5.3 score on a scale | Standard Deviation 1.2 |
| Placebo | Quality of Sedation | Nurse rating | 5.1 score on a scale | Standard Deviation 1.4 |