Propofol vs Propofol + Benzo/Opiates in High Risk Group

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.

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