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Failure of Sedasys: Destiny or Poor Design?

Goudra, Basavana MD, FRCA, FCARCSI; Singh, Preet Mohinder MD, DNB

doi: 10.1213/ANE.0000000000001643
The Open Mind: The Open Mind

Published ahead of print November 17, 2016.

From the *Department of Anesthesiology and Critical Care Medicine, Hospital of the University of Pennsylvania and Perleman School of Medicine, Philadelphia, Pennsylvania; and Department of Anesthesia, All India Institute of Medical Sciences, New Delhi, India.

Published ahead of print November 17, 2016.

Accepted for publication August 24, 2016.

Funding: None.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Basavana Goudra, MD, Department of Anesthesiology and Critical Care Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104. Address e-mail to goudrab@uphs.upenn.edu.

Ethicon, Inc, announced on March 10, 2016, that it is pulling Sedasys, the computer-assisted personalized sedation system (CAPS) used by a handful of facilities in the United States to administer mild to moderate sedation during gastrointestinal (GI) endoscopic procedures.1 Although outpatientsurgery.net called it a surprise move, many of those following the device are not so surprised. Nevertheless, a significant number of anesthesia scholars were optimistic about the device performance and clinical impact. We had published 2 articles in connection with this device before it was released in the United States.2,3 We feel that it is an appropriate time to examine the possible reasons for the device’s failure to make an impact with gastroenterologists who were the targeted end users. It is also hoped that the failure of Sedasys will not discourage other CAPS device manufacturers, but serve as a learning opportunity for the future.

For a technology to succeed, it is important to introduce it at the most appropriate time and even then its success can be mere coincidence. For instance, were it not for propofol, laryngeal mask airway might not have been as popular. Similarly, had it not been for total intravenous anesthesia, propofol might have stayed mainly as an induction agent. In other words, there should be a need for such a device/drug/technology, and the proposed solution should be able to fill the void. For the following 3 reasons, Sedasys was destined to fail.

The first issue is that, although propofol might be a perfectly acceptable choice for closed loop general anesthesia, it is a poor selection for a CAPS. The sedative anesthetic has a pharmacological variability of >300%.4 Addition of fentanyl increases the variability to 400%.5 By including the patient in the loop, the device manufacturers tried to overcome this variability. However, the machine was only programmed to decrease the sedation depth (propofol dose) but not to increase it. If the patient were to become “light” during a procedure, the Sedasys system was incapable of stepping up the depth of the sedation. The initial dose of propofol and any increases in propofol dosing required the clinician’s intervention. This feature may have increased the safety; however, it was also a major limitation. The main component of the device was its bedside monitoring unit (BMU), and the automated responsiveness monitor (ARM) was its core. The ARM assessed the responsiveness of the patient by testing his/her ability to squeeze a handheld switch in response to an auditory or vibrational stimulus. In addition, the BMU monitored oxygen saturation, blood pressure, and the electrocardiogram.6 As we stated in our earlier publication, the highly restrictive strategy adopted by the manufacturers to obtain Food and Drug Administration (FDA) approval was counterproductive.2 The regulatory approval for mild to moderate sedation was a significant constraint. The FDA labeling clearly states that propofol should be administered only by persons skilled in the medical management of critically ill patients and trained in cardiovascular resuscitation and airway management.

Given this limitation, it would have been difficult to achieve consistent mild to moderate sedation with a drug of such wide variability. The Sedasys protocol itself involved administration of fentanyl (25–100 μg), a wait of 3 minutes, followed by the administration of about 0.4 mg/kg of body weight of propofol, again over 3 minutes. As we had discussed elsewhere,2 a total of 6 minutes would elapse and an infusion at variable rates follows. Most diagnostic upper GI endoscopic procedures are completed in 5 to 10 minutes.7 As a result, in the context of a diagnostic upper GI endoscopy, efficiency was not its strength. However, it is acknowledged that the efficiency of an operating suite or a procedure room is not solely dependent on the sedation-related time savings.8 In fact, it is only a minor component of the whole process. More importantly, one should not forget that investigators have successfully administered propofol-remifentanil in a CAPS mode in research settings.9,10

The second reason is that both the patients and the endoscopists have begun to expect deep general anesthesia in the guise of moderate sedation. In a prospective study involving patients undergoing colonoscopy, we demonstrated that the majority of patients were experiencing either general anesthesia or deep general anesthesia.11 As measured using the SedLine brain function monitor (Masimo Corporation, Irvine, CA) the depth of anesthesia was often deeper than that provided during major surgery. Frequently, patients were experiencing burst suppression on the electroencephalogram, an indication of deep general anesthesia. Despite demonstrated increase in the incidence of events like cardiac arrest during GI endoscopy using propofol (compared with general anesthesia),12,13 the popularity of deep propofol sedation/general anesthesia is on the increase. With the FDA reluctant to approve anything beyond moderate sedation and patients continuing to expect deep sedation, the device cannot plausibly satisfy both groups. Consequently, it is difficult to see how a successful CAPS device capable of providing deep sedation while still keeping the patient in the loop can be ever designed.

The third factor was the perception that the Sedasys was an effort to replace anesthesia services in the area of GI endoscopy. Rebecca Twersky, MD, a respected anesthesiologist from SUNY Downstate Medical Center, in an interview with Washington Post, stated that Sedasys is an example of disruptive innovation.14 It is true that the use of anesthetic providers increases the cost of GI endoscopy. In fact, it was estimated that from 2003 to 2009, the cost of using anesthesia services for low-risk patients during GI endoscopies increased steadily to >$1.1 billion per year at the national level. Rightfully, efforts have been made to cut the sedation-related costs of endoscopy and colonoscopy. Nevertheless, reducing the number of anesthetic providers, who deliver critical service in GI endoscopy, was not the appropriate strategy. It is true that nonanesthesia practitioners have provided safe propofol sedation even for advanced endoscopic procedures in research settings.15 Notably, the practice was associated with significantly reduced patient and endoscopist satisfaction. With recent seismic shift in patients’ expectations from the hospital and its caregivers, quality of care is increasingly measured by both outcome and patient satisfaction. Considering that propofol sedation is difficult to regulate and patients expect deep sedation with all its unintended consequences, the majority of gastroenterologists are ill-equipped to shoulder this additional responsibility. As a consequence, further refinement in technology and drug development is needed. More importantly, a device intended for use by providers skilled in airway management is much more likely to succeed.

Before examining anesthesia provider-administered propofol sedation through the prism of cost alone, it is important to discuss other implications. The success of any national screening program like colonoscopy depends on its uptake. Without public participation, such programs are doomed to fail. Fear of discomfort might keep away many of these patients. Considering that the incidence of colonic cancer is demonstrably less since the advent of screening colonoscopy, an argument can be made for propofol deep sedation/general anesthesia. It is noteworthy that both patients and endoscopists (at least in the United States) prefer deep sedation/general anesthesia and that appropriate knowledge and airway skills are mandatory for its safe conduct. Even in relation to cost, the savings in terms of cancer treatment might offset any propofol administration-related expenses. The burden of dealing with cancer in the family, both financial and psychological, cannot be ignored. The increased efficiency that can be achieved with propofol sedation adds another dimension.

Although Sedasys as a device may be finished, the idea lives on. As it was rightly pointed out by Hemmerling and Terrasini,16 computer-assisted personalized sedation is not science fiction any more. Nevertheless, for future device developers to succeed in the area of CAPS, it is important to learn what we can from Ethicon, Inc. The manufacturers of Sedasys could have waited to gather extensive and unequivocal data to support the clinical usefulness. Nonfunded studies could have gained more approval. This is highlighted by the fact that a PubMed search yields only 1 prospective clinical trial, despite being approved by the FDA in 2013 and the device has existed for nearly 7 years. Future closed loop sedation system manufacturers should be cautioned that selling an “expensive” idea without clinical evidence may not be easy. At least in the United States, where the patients wish to feel nothing and the endoscopists would like no patient movement, the idea of mild to moderate sedation is dead on arrival. Instead, a device that can provide deep sedation is more likely to succeed. Inevitably, it would necessitate the services of an anesthesia provider to manage inevitable and undesirable adverse events. Sadly, restricting CAPS to moderate sedation decreases patient and gastroenterologist satisfaction. Inevitably, to err too much on the side of caution is a compromise on the quality of sedation. In conclusion, further research is needed in the area of both drug and device to avoid a fate similar to that of Sedasys.

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DISCLOSURES

Name: Basavana Goudra, MD, FRCA, FCARCSI.

Contribution: This author helped prepare and edit the manuscript.

Name: Preet Mohinder Singh, MD, DNB.

Contribution: This author helped edit the manuscript.

This manuscript was handled by: Maxime Cannesson, MD, PhD.

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