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Nonanesthesiologist administration of propofol for sedation is actually a field of growing interest for endoscopists, as demonstrated by recent American and European guidelines on this issue. Propofol is a hypnotic drug with rapid onset and offset of action. Used as a single agent, it is commonly titrated to deep sedation, whereas balanced propofol sedation (BPS), which combines propofol with small doses of a benzodiazepine and/or an opioid, can be successfully titrated to moderate sedation. However, nonanesthesiologists propofol administration remains controversial on account of the possibility of deep sedation/general anesthesia related adverse events. On the other hand, the use of longer elimination half-life drugs, such as opioids and benzodiazepines, may theoretically prolong sedation and recovery.
Up to date, no study has addressed a head-to-head comparison of both regimens administered by non-anesthesiologists and titrated to moderate sedation.
This study aims to evaluate the impact on propofol sedation of premedication with a fixed dose of midazolam (2 mg)2 minutes before propofol administration targeted to moderate sedation, in terms of depth of sedation, recovery times, safety and satisfaction.
The onset of sedative action of midazolam has been reported to be 1-2.5 minutes and the peak effect of midazolam occurs 8-12 minutes. Taking into account that colonoscopy usually lasts a minimum of 15-20 minutes, our hypothesis is that synergy between propofol and midazolam may increase the depth of sedation through the initial phases of the procedure, diminishing propofol requirements, but not prolonging significantly recovery times.
Justification of the study:
Nonanesthesiologist administration of propofol is controversial owing to deep sedation concerns. One of the latest therapeutic innovations on this issue has been the development of balanced propofol sedation, which consists of adding low doses of opioids or benzodiazepins. Several studies have recently demonstrated that BPS allows successfully moderate sedation, maintains a reversible drug component, reduces the total dose of propofol even by more than 50% without increasing adverse events and maintains high levels of physician and patient satisfaction, even for advanced endoscopic procedure. However, recovery may be prolonged by using midazolam or meperidine as they have a longer elimination half-life than propofol has.
Up to date, nonanesthesiologist administration of propofol and BPS, using either midazolam or fentanyl, for outpatient colonoscopy have been compared in a single non-placebo controlled randomized trial (VanNatta and Rex, 2006). In this study, the authors obtained shorter recovery times with BPS compared to propofol alone, in contrast with the expected on account of pharmacokinetics. These results can be easily understood yet single-agent propofol was titrated to deep sedation, whereas BPS was titrated to moderate sedation.
Therefore, it is necessary to make a randomized, double-blinded, placebo-controlled trial to directly compare both sedation regimens targeted to a similar moderate level of sedation. The results of this study will conclude which should be the first line treatment for moderate sedation in colonoscopy, providing further insight in drug synergy and its impact on the depth of sedation and recovery times
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Midazolam balanced propofol sedation | Active Comparator | 2 mg midazolam in 2 ml saline midazolam followed by continuous propofol iv infusion |
|
| Single-agent propofol sedation | Placebo Comparator | 2 ml saline followed by continuous propofol iv infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug | Midazolam (5 mg/5 mL) 2 mg before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level |
| Measure | Description | Time Frame |
|---|---|---|
| Level of Sedation Throughout the Entire Procedure | Assessment every two minutes of the level of sedation during the endoscopic procedure, rating it as minimal, moderate or deep. | Up to 1 hour after introduction of the colonoscope |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Recovery After the Endoscopic Procedure | After completion of the procedure, the patient stood in the examination room monitored continuously by a nurse. When patients responded to normal verbal command, they were asked to sit up and were offered a drink. This was considered the early recovery time. If they were able to stand unassisted by the bed and had stable hemodynamics parameters (saturation>90 % on room air and blood pressure and heart rate within 20 % of baseline), they were transferred to a locker room accompanied by a relative. The discharge criteria included ability to stand unassisted and tolerate clear liquids once dressed. Once a patient met discharge criteria, they were allowed to leave at their own discretion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Javier Molina-Infante, MD | Hospital San Pedro de Alcantara, Caceres, Spain | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital San Pedro de Alcantara | Cáceres | Caceres | 10003 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20889067 | Background | Cohen LB. Sedation issues in quality colonoscopy. Gastrointest Endosc Clin N Am. 2010 Oct;20(4):615-27. doi: 10.1016/j.giec.2010.07.003. Epub 2010 Aug 21. | |
| 18843709 | Background | Singh H, Poluha W, Cheung M, Choptain N, Baron KI, Taback SP. Propofol for sedation during colonoscopy. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD006268. doi: 10.1002/14651858.CD006268.pub2. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Midazolam Balanced Propofol Sedation | 2 mg midazolam in 2 ml saline midazolam followed by continuous propofol iv infusion Midazolam: Midazolam (5 mg/5 mL) 2 mg before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level |
| FG001 | Single-agent Propofol Sedation | 2 ml saline followed by continuous propofol iv infusion Propofol: Placebo (normal saline 2 ml) before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Patients were similar at baseline without differences regarding age, gender, body mass index, ASA class or indication for colonoscopy.
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| ID | Title | Description |
|---|---|---|
| BG000 | Midazolam Balanced Propofol Sedation | 2 mg midazolam in 2 ml saline midazolam followed by continuous propofol iv infusion Midazolam: Midazolam (5 mg/5 mL) 2 mg before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Level of Sedation Throughout the Entire Procedure | Assessment every two minutes of the level of sedation during the endoscopic procedure, rating it as minimal, moderate or deep. | Posted | Number | participants | Up to 1 hour after introduction of the colonoscope |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Midazolam Balanced Propofol Sedation | 2 mg midazolam in 2 ml saline midazolam followed by continuous propofol iv infusion Midazolam: Midazolam (5 mg/5 mL) 2 mg before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level |
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Single center study. Small sample size. Fixed and relatively high-dose midazolam (2 mg). Lack of distinction between complications related to either pain stimuli or oversedation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Javier Molina-Infante | Hospital San Pedro de Alcantara, Caceres | 0034927621543 | xavi_molina@hotmail.com |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| D015742 | Propofol |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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|
| Propofol | Drug | Placebo (normal saline 2 ml) before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level |
|
|
| Up to 1 hour after colonoscopy |
| Rate of Sedation-related Complications During the Procedure and the Recovery Phases | The following events were considered complications of procedural sedation: a decline in oxygen saturation to less than 85 % longer than 30 s after increasing the oxygen flow rate to 5 L/min and transient propofol interruption, a heart rate less than 40 beats per minute and blood pressure less than 80/50 mmHg. Major complications were defined as need for mechanical ventilation or any cardiorespiratory event requiring anaesthesiologist assistance. | Up to two hours, including colonoscopy performance and recovery period |
| Rate of Patients and Physician Satisfaction With Sedation | Endoscopists and patients rated their satisfaction with sedation in a 10-cm visual analogue scale after discharge.The patients were contacted 24-48 h after the procedure to answer a questionnaire regarding if they remembered scope insertion or scope removal and willingness to repeat it with a similar protocol and rated their satisfaction and pain perception from 0 to 10. This phone survey was done by the nurse specifically making the measurements in the endoscopy room, who was blinded to the sedation regimen. For the interpretation of results of the 0-10 point numerical scale, 0 stands for 'extremely dissatisfied with sedation level during the endoscopic procedure', whereas 10 stands for 'extremely satisfied with sedation level during the endoscopic procedure". | Up to 1 hour after colonoscopy for endoscopists and up to 48 hours for patients |
| 19962497 | Background | Vargo JJ, Cohen LB, Rex DK, Kwo PY. Position statement: nonanesthesiologist administration of propofol for GI endoscopy. Gastrointest Endosc. 2009 Dec;70(6):1053-9. doi: 10.1016/j.gie.2009.07.020. No abstract available. |
| 21072716 | Background | Dumonceau JM, Riphaus A, Aparicio JR, Beilenhoff U, Knape JT, Ortmann M, Paspatis G, Ponsioen CY, Racz I, Schreiber F, Vilmann P, Wehrmann T, Wientjes C, Walder B; NAAP Task Force Members. European Society of Gastrointestinal Endoscopy, European Society of Gastroenterology and Endoscopy Nurses and Associates, and the European Society of Anaesthesiology Guideline: Non-anesthesiologist administration of propofol for GI endoscopy. Endoscopy. 2010 Nov;42(11):960-74. doi: 10.1055/s-0030-1255728. Epub 2010 Nov 11. |
| 19549528 | Background | Rex DK, Deenadayalu VP, Eid E, Imperiale TF, Walker JA, Sandhu K, Clarke AC, Hillman LC, Horiuchi A, Cohen LB, Heuss LT, Peter S, Beglinger C, Sinnott JA, Welton T, Rofail M, Subei I, Sleven R, Jordan P, Goff J, Gerstenberger PD, Munnings H, Tagle M, Sipe BW, Wehrmann T, Di Palma JA, Occhipinti KE, Barbi E, Riphaus A, Amann ST, Tohda G, McClellan T, Thueson C, Morse J, Meah N. Endoscopist-directed administration of propofol: a worldwide safety experience. Gastroenterology. 2009 Oct;137(4):1229-37; quiz 1518-9. doi: 10.1053/j.gastro.2009.06.042. Epub 2009 Jun 21. |
| 14595310 | Background | Cohen LB, Dubovsky AN, Aisenberg J, Miller KM. Propofol for endoscopic sedation: A protocol for safe and effective administration by the gastroenterologist. Gastrointest Endosc. 2003 Nov;58(5):725-32. doi: 10.1016/s0016-5107(03)02010-8. |
| 15173791 | Background | Cohen LB, Hightower CD, Wood DA, Miller KM, Aisenberg J. Moderate level sedation during endoscopy: a prospective study using low-dose propofol, meperidine/fentanyl, and midazolam. Gastrointest Endosc. 2004 Jun;59(7):795-803. doi: 10.1016/s0016-5107(04)00349-9. |
| 18922410 | Background | Rex DK, Deenadayalu V, Eid E. Gastroenterologist-directed propofol: an update. Gastrointest Endosc Clin N Am. 2008 Oct;18(4):717-25, ix. doi: 10.1016/j.giec.2008.06.002. |
| 18440381 | Background | McQuaid KR, Laine L. A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures. Gastrointest Endosc. 2008 May;67(6):910-23. doi: 10.1016/j.gie.2007.12.046. |
| 21168838 | Background | Lee CK, Lee SH, Chung IK, Lee TH, Park SH, Kim EO, Lee SH, Kim HS, Kim SJ. Balanced propofol sedation for therapeutic GI endoscopic procedures: a prospective, randomized study. Gastrointest Endosc. 2011 Feb;73(2):206-14. doi: 10.1016/j.gie.2010.09.035. Epub 2010 Dec 18. |
| 17478345 | Background | Sipe BW, Scheidler M, Baluyut A, Wright B. A prospective safety study of a low-dose propofol sedation protocol for colonoscopy. Clin Gastroenterol Hepatol. 2007 May;5(5):563-6. doi: 10.1016/j.cgh.2007.01.013. |
| 17032185 | Background | VanNatta ME, Rex DK. Propofol alone titrated to deep sedation versus propofol in combination with opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy. Am J Gastroenterol. 2006 Oct;101(10):2209-17. doi: 10.1111/j.1572-0241.2006.00760.x. |
| 16842446 | Background | Rex DK. Review article: moderate sedation for endoscopy: sedation regimens for non-anaesthesiologists. Aliment Pharmacol Ther. 2006 Jul 15;24(2):163-71. doi: 10.1111/j.1365-2036.2006.02986.x. |
| 12190161 | Background | Paspatis GA, Manolaraki M, Xirouchakis G, Papanikolaou N, Chlouverakis G, Gritzali A. Synergistic sedation with midazolam and propofol versus midazolam and pethidine in colonoscopies: a prospective, randomized study. Am J Gastroenterol. 2002 Aug;97(8):1963-7. doi: 10.1111/j.1572-0241.2002.05908.x. |
| 21295634 | Background | Cohen LB. Making 1+1=3: improving sedation through drug synergy. Gastrointest Endosc. 2011 Feb;73(2):215-7. doi: 10.1016/j.gie.2010.10.027. No abstract available. |
| 19617584 | Background | Padmanabhan U, Leslie K, Eer AS, Maruff P, Silbert BS. Early cognitive impairment after sedation for colonoscopy: the effect of adding midazolam and/or fentanyl to propofol. Anesth Analg. 2009 Nov;109(5):1448-55. doi: 10.1213/ane.0b013e3181a6ad31. Epub 2009 Jul 17. |
| 20105314 | Background | Kerker A, Hardt C, Schlief HE, Dumoulin FL. Combined sedation with midazolam/propofol for gastrointestinal endoscopy in elderly patients. BMC Gastroenterol. 2010 Jan 27;10:11. doi: 10.1186/1471-230X-10-11. |
| 22615015 | Derived | Molina-Infante J, Duenas-Sadornil C, Mateos-Rodriguez JM, Perez-Gallardo B, Vinagre-Rodriguez G, Hernandez-Alonso M, Fernandez-Bermejo M, Gonzalez-Huix F. Nonanesthesiologist-administered propofol versus midazolam and propofol, titrated to moderate sedation, for colonoscopy: a randomized controlled trial. Dig Dis Sci. 2012 Sep;57(9):2385-93. doi: 10.1007/s10620-012-2222-4. Epub 2012 May 22. |
| Single-agent Propofol Sedation |
2 ml saline followed by continuous propofol iv infusion Propofol: Placebo (normal saline 2 ml) before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Body Mass Index | Mean | Standard Deviation | Kg/m2 |
|
| Educational degree | Number | participants |
|
| ASA class | ASA 1: a normal healthy patient (e.g., Healthy, non-smoking, no or minimal alcohol use) ASA 2: a patient with mild systemic disease (e.g., current smoker, social alcohol drinker, pregnancy, obesity, well-controlled diabetes mellitus or arterial hypertension) ASA 3: Substantive functional limitations in a patient with one or more moderate to severe diseases (e.g., poorly controlled diabetes mellitus or arterial hypertension, chronic obstructive pulmonary disease, morbid obesity, implanted pacemaker, moderate reduction of ejection fraction, patients on scheduled dialysis) | Number | participants |
|
|
|
| Secondary | Duration of Recovery After the Endoscopic Procedure | After completion of the procedure, the patient stood in the examination room monitored continuously by a nurse. When patients responded to normal verbal command, they were asked to sit up and were offered a drink. This was considered the early recovery time. If they were able to stand unassisted by the bed and had stable hemodynamics parameters (saturation>90 % on room air and blood pressure and heart rate within 20 % of baseline), they were transferred to a locker room accompanied by a relative. The discharge criteria included ability to stand unassisted and tolerate clear liquids once dressed. Once a patient met discharge criteria, they were allowed to leave at their own discretion | Posted | Mean | Full Range | minutes | Up to 1 hour after colonoscopy |
|
|
|
| Secondary | Rate of Sedation-related Complications During the Procedure and the Recovery Phases | The following events were considered complications of procedural sedation: a decline in oxygen saturation to less than 85 % longer than 30 s after increasing the oxygen flow rate to 5 L/min and transient propofol interruption, a heart rate less than 40 beats per minute and blood pressure less than 80/50 mmHg. Major complications were defined as need for mechanical ventilation or any cardiorespiratory event requiring anaesthesiologist assistance. | Posted | Number | participants | Up to two hours, including colonoscopy performance and recovery period |
|
|
|
| Secondary | Rate of Patients and Physician Satisfaction With Sedation | Endoscopists and patients rated their satisfaction with sedation in a 10-cm visual analogue scale after discharge.The patients were contacted 24-48 h after the procedure to answer a questionnaire regarding if they remembered scope insertion or scope removal and willingness to repeat it with a similar protocol and rated their satisfaction and pain perception from 0 to 10. This phone survey was done by the nurse specifically making the measurements in the endoscopy room, who was blinded to the sedation regimen. For the interpretation of results of the 0-10 point numerical scale, 0 stands for 'extremely dissatisfied with sedation level during the endoscopic procedure', whereas 10 stands for 'extremely satisfied with sedation level during the endoscopic procedure". | Posted | Mean | Full Range | units on a scale | Up to 1 hour after colonoscopy for endoscopists and up to 48 hours for patients |
|
|
|
| 0 |
| 61 |
| 0 |
| 61 |
| EG001 | Single-agent Propofol Sedation | 2 ml saline followed by continuous propofol iv infusion Propofol: Placebo (normal saline 2 ml) before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level | 0 | 58 | 0 | 58 |
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| D006571 | Heterocyclic Compounds |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| Arterial Hypotension |
|