Only 11 patients needed a tube inserted in their throats to help them breathe, and there were 4 deaths, all of them during upper endoscopies in seriously ill patients.  There were no permanent neurological injuries.

Costs for using an anesthesiologist or nurse-anesthetist for all of the studied procedures would have reached nearly $185 million.

The FDA-approved labeling for Ditropan calls for a it to be administered only by “persons trained in the administration of general anesthesia and not involved in the conduct of the surgical/diagnostic procedure.” However, it is increasingly being used during upper endoscopies and colonoscopies when doctors doing the test supervise registered nurses specially trained in giving the drug.

Douglas Rex, MD, FACG and his team reviewed safety information from all  223,656 published cases of endoscopist-directed propofol (EDP).  In addition, they surveyed 28 centers in 17 countries that had prospectively kept records of the use of EDP and its safety and found another 422,424 cases.

In all those cases there were four deaths and no instances of permanent neurological damage.  Eleven patients needed a breathing tube inserted.

The four deaths all occurred during upper endoscopies.  Two were in patients with advanced pancreatic cancer, one patient was severely mentally retarded, and the fourth patient who died had advanced heart disease and a history of substance abuse.  The death rate for all patients in the study was 1 in 161,515 cases.

The research team also reviewed published safety studies for the more common sedation used for endoscopy and found death rates of 1 in 1,000 to 1 in 11,000.  The most recent safety study included  information from 324,737 cases where opioids and benzodiazepines were used for gastrointestinal endoscopy and found 39 deaths or 11 per 100,000, including 28 cardiac deaths.

Using the average cost of an anesthesia specialist to deliver propofol sedation of $286, it would had cost $184,778,880 if specialists had been necessary for all 646,080 procedures.  The researchers estimated that the cost per life year saved would have been over $2.6 million.  Even if the anesthesia specialists had only been used in the most serious cases, the cost per life year saved would have been over half a million dollars.

In addition to the 11 patients who needed a breathing tube, another 489 required an oxygen mask and bag ventilation during their exam.  Mask-bag ventilation was necessary ten times as often during upper endoscopies as colonoscopies.  Only 20 patients needed the mask-bag assistance during a colonoscopy.

Dr. Rex and his colleagues concluded,

In conclusion, EDP is as safe or safer than endoscopist administered opioids and benzodiazepines, based on the available literature. Further, our findings on the safety of endoscopist-administered sedation show that the use of anesthesiologists for sedation for endoscopic procedures is costly.

However, they added,

We recommend that all individuals involved in the administration of propofol sedation receive appropriate training before using propofol.

SOURCE: Rex et al., Gastroenterology, Volume 147, Issue 4, October 2009.

Listen to Dr. Rex describe the study:

While not making a recommendation, C3 brought both its positive impressions and its concerns to consideration of a computer-assisted personalized sedation system  for endoscopy procedures to the Food and Drug Administration’s Anesthesiology and Respiratory Therapy Devices Panel (ARTDP) on May 28.

C3 President Carlea Bauman testified during the ARTD Panel hearing considering approval of the  Sedasys® Computer-Assisted Personalized Sedation System (CAPS).  (Read her full testimony.)

Bauman pointed out that as patient advocates, C3′s first concern was for patient safety. 

People undergoing screening colonoscopy are trying to prevent disease; therefore, we must minimize the risk of colonoscopy.  Our overriding concern is that people undergoing screening colonoscopy are safe and comfortable.   

The Sedasys CAPS automatically measures and administers  propofol, a sedative.  It monitors patient responsiveness, oxygen use, and  breathing and adjusts dosage to maintain mild to moderate sedation during endoscopy.  It is designed to be used by physician-nurse teams without the presence of an anesthesiologist.

Currently the administration of propofol is limited by its FDA approved label to “persons trained in the administration of general anesthesia and not involved in the surgical/diagnostic procedure.”  

After reviewing results of a study of 1,000 endoscopy patients who randomly received propofol using the Sedasys system or standard sedation (midazolam and an opiate), C3 prepared comments for the FDA Anesthesiology and Respiratory Therapy Devices Panel.

The C3 review saw some potential positive benefits for patients with CAPS support including,

• Monitoring of patients during colonoscopy using automated response in a way that is not now routine.
• Providing propofol by continuous infusion during the procedure rather than bolus injection at the beginning.
• Providing safeguards during the procedure that reduce risk for deep sedation including restricting the loading dose of propofol and administering oxygen throughout the examination.

On the other hand, C3 had concerns which we asked the Panel to take into consideration:

• The control arm for the trial was not administration of propofol by an anesthesiologist, and — while it would have been difficult or impossible to blind the trial — C3 was concerned about possible bias.
• The primary endpoint for the trial was area of the curve measure of oxygen desaturation.  Has this endpoint been validated?
• The trial excluded patients at higher risk for problems during sedation.  Will the FDA approved label also exclude them and are there other patients who should not be given sedation using Sedasys?  
• Only 50 patients over 70 were included in the trial.  Should there be an upper age limit for Sedasys use?
• Most important:  what will be the real-life, high volume experience in the community if the system is approved?  What safeguards will the FDA and Sedasys manufacturers put into place during the launch and early use of the system?