Propofol vs Propofol + Benzo/Opiates in High Risk Group

Obesity Clinical Trial

Official title:

Incidence of Sedation Related Complications With Propofol Alone Versus Propofol With Benzodiazepines and Opiates in a High Risk Group Undergoing Advanced Endoscopic Procedures: A Randomized Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01315158
• Other study ID #: 10-1133
• Status: Terminated
• Phase: N/A
• First received: March 11, 2011
• Last updated: August 15, 2014
• Start date: January 2011
• Est. completion date: July 2014

Study information

• Verified date: August 2014
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This will be a randomized controlled trial that compares the rates of sedation related complications in high risk patients (ASA greater or equal to 3, BMI greater or equal to 30, those at risk for OSA) undergoing advanced endoscopy procedures with propofol alone compared to propofol in combination with benzodiazepines and opioids.

Description:

The use of propofol (2,6-di-isopropofol) for sedation during endoscopic procedures has increased in recent years primarily because of its favorable pharmacokinetic profile compared with traditional endoscopic sedation with benzodiazepines and opioids. Propofol has a rapid onset of action (30-45 sec) and short duration of effect (4-8 min). There also are data to support the safe use of propofol for advanced endoscopic procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS).

There is limited information on the incidence of sedation related complications during advanced endoscopy. Prior studies were limited by controlled patient populations at low risk of developing sedation related cardiopulmonary complications. In a recent study, we defined the frequency of sedation related adverse events including the rate of airway modifications (AMs) with propofol use during advanced endoscopy. From a total of 799 patients, AMs were required in 14.4% of patients, hypoxemia in 12.8%, hypotension in 0.5% and premature termination in 0.6% of the patients. In addition, body mass index (BMI), male sex and American Society of Anesthesiologists (ASA) class of 3 or higher were independent predictors of AMs. Similarly, Wehrmann and Riphaus identified ASA class of 3 or higher, total propofol dose, history of alcohol use and having an emergency endoscopy as independent factors for sedation related complications in patients undergoing advanced procedures.

Given the alarming rates of obesity in the United States, it is believed that the prevalence of obstructive sleep apnea (OSA) may be 10% or higher and in obese adults these numbers could be as high as 25%. Using a previously validated screening tool for OSA [STOP-BANG (SB)], we reported a prevalence rate of patients at risk for OSA of 43.3% in patients undergoing advanced endoscopy procedures. Patients at risk for OSA with a positive SB score (score ≥ 3 of 8) had a higher rate of AMs (20% vs. 6.1%, adjusted relative risk 1.7) and frequency of hypoxemia (12% vs. 5.2%, adjusted relative risk 1.63) compared to those at low risk for OSA. Thus, based on the available data, it appears that ASA class 3 or higher, high BMI, and patients at risk for OSA are factors that place patients undergoing advanced endoscopy procedures at high risk for sedation related complications including airway modifications.

The optimal method for achieving deep sedation in this high risk group of patients is unclear. Propofol may accentuate airway collapse as patients become unresponsive to verbal stimulation (deep sedation). Recent studies suggest that propofol with midazolam and/or opioids may be synergistic in action and therefore the combined application of these drugs may permit smaller doses of each to be used and potentially lead to a reduction in risk of complications and in the dose of propofol needed while retaining the individual advantages of each compound. There is limited data evaluating the synergistic effect of propofol with midazolam and opioids in patients undergoing advanced endoscopy procedures. Ong and colleagues in a randomized controlled trial compared patient sedation and tolerance during ERCP using propofol alone or midazolam, ketamine and pentazocine (sedato-analgesic cocktail) for induction along with propofol for maintenance. Patient tolerance as assessed by visual analog scales by endoscopist and anesthetist were higher in the combination group. Paspatis et al reported higher dosage of intravenous propofol required in patients being sedated with propofol alone compared with that required in patients receiving oral dose of midazolam with propofol for ERCP procedures. In addition, the patients' anxiety levels before the procedure were lower in the combination group. The mean percentage decline in the oxygen saturation during the procedure was significantly greater in propofol alone group. However, these studies excluded patients deemed to be at a high risk for sedation related complications. Patients with ASA class 3 or higher were excluded, the mean BMI was less than 25, and included only patients at average risk for complications associated with sedation.

The significance of synergistic sedation in patients undergoing advanced endoscopy procedures in the high risk patients is unclear. The overall risk of sedation related complications is thought to be higher compared to standard endoscopy due to longer procedure times and the need for relatively deeper levels of sedation.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 108
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ability to provide informed consent

• Age greater than or equal to 18 years

• Presence of at least 1 of the following criteria:

1. ASA class 3 or higher

2. BMI of 30 or greater

3. At risk for OSA (score of 3 or greater on the STOP-BANG screening tool)

Exclusion Criteria:

• drug allergy to Propofol, Benzodiazepines, or Opioids

• patients who received Benzodiazepines or Opioids within 24 hours of the procedure

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Obesity
• Sleep Apnea, Obstructive

Intervention

Drug:
• Propofol Alone
Recommended Propofol doses before considering crossover: Induction: 2-2.5 mg/kg Maintenance: 0.1-0.2 mg/kg/min
• Propofol+Benzo/Opioids
Recommended Versed: a. Prior to intubation patient is < 50 kg = 1 mg Versed patient is 50-75 kg = 1.5 mg Versed patient is > 75 kg = 2 mg Versed Recommended Fentanyl Prior to intubation = 0.5 ug/kg Total procedural dose = 1 ug/kg

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (24)

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Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990 Aug;10(4):244-51. — View Citation

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Coté GA, Hovis CE, Hovis RM, Waldbaum L, Early DS, Edmundowicz SA, Azar RR, Mullady DK, Jonnalagadda SS. A screening instrument for sleep apnea predicts airway maneuvers in patients undergoing advanced endoscopic procedures. Clin Gastroenterol Hepatol. 2010 Aug;8(8):660-665.e1. doi: 10.1016/j.cgh.2010.05.015. Epub 2010 May 23. — View Citation

Coté GA, Hovis RM, Ansstas MA, Waldbaum L, Azar RR, Early DS, Edmundowicz SA, Mullady DK, Jonnalagadda SS. Incidence of sedation-related complications with propofol use during advanced endoscopic procedures. Clin Gastroenterol Hepatol. 2010 Feb;8(2):137-42. doi: 10.1016/j.cgh.2009.07.008. Epub 2009 Jul 14. — View Citation

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Ong WC, Santosh D, Lakhtakia S, Reddy DN. A randomized controlled trial on use of propofol alone versus propofol with midazolam, ketamine, and pentazocine "sedato-analgesic cocktail" for sedation during ERCP. Endoscopy. 2007 Sep;39(9):807-12. — View Citation

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. — View Citation

Paspatis GA, Manolaraki MM, Vardas E, Theodoropoulou A, Chlouverakis G. Deep sedation for endoscopic retrograde cholangiopancreatography: intravenous propofol alone versus intravenous propofol with oral midazolam premedication. Endoscopy. 2008 Apr;40(4):308-13. Epub 2007 Dec 5. — View Citation

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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. Review. — View Citation

Rex DK, Heuss LT, Walker JA, Qi R. Trained registered nurses/endoscopy teams can administer propofol safely for endoscopy. Gastroenterology. 2005 Nov;129(5):1384-91. — View Citation

Riphaus A, Stergiou N, Wehrmann T. Sedation with propofol for routine ERCP in high-risk octogenarians: a randomized, controlled study. Am J Gastroenterol. 2005 Sep;100(9):1957-63. — View Citation

Seifert H, Schmitt TH, Gültekin T, Caspary WF, Wehrmann T. Sedation with propofol plus midazolam versus propofol alone for interventional endoscopic procedures: a prospective, randomized study. Aliment Pharmacol Ther. 2000 Sep;14(9):1207-14. — View Citation

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Tohda G, Higashi S, Wakahara S, Morikawa M, Sakumoto H, Kane T. Propofol sedation during endoscopic procedures: safe and effective administration by registered nurses supervised by endoscopists. Endoscopy. 2006 Apr;38(4):360-7. — View Citation

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. — View Citation

Vargo JJ, Zuccaro G Jr, Dumot JA, Shermock KM, Morrow JB, Conwell DL, Trolli PA, Maurer WG. Gastroenterologist-administered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective, randomized trial. Gastroenterology. 2002 Jul;123(1):8-16. — View Citation

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* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of airway maneuvers	In high risk patients (meeting at least of 1 of 3 criteria: ASA = 3, BMI = 30, those at risk for OSA) undergoing advanced endoscopy procedures, compare the frequency of AMs when sedated with propofol alone versus propofol in combination with benzodiazepines and opioids.	one day (during procedure)	No
Secondary	Frequency of other sedation related complications	We will compare the frequency of other sedation related complications such as hypotension, hypoxemia and need for termination of the procedure between the two groups	one day (during procedure)	No
Secondary	Compare propofol doses between the two groups	The dose of propofol used between the two groups will be compared	one day (during procedure)	No
Secondary	Predictors of sedation related complications		one year	No
Secondary	Patient tolerance as assessed by the patient, endoscopist and CRNAs will be compared between the two groups	The frequency of symptoms of nausea and vomiting in the two groups of patients will be recorded. Patient tolerance of the procedure will be assessed independently by the endoscopist and CRNA using a 100-mm visual analog scale (VAS, 0=unmanageable, 100=excellent). The patient will also score the level of tolerance using the same VAS at a routine follow-up phone call made 24-48 hours after the procedure.	24-48 hours	No
Secondary	Frequency of symptoms of nausea and vomiting will be compared between the two groups	The frequency of symptoms of nausea and vomiting in the two groups of patients will be recorded. This will be recorded during the follow-up phone call made 24-48 hours after the procedure.	24-48 hours	No