Current Topics of Interest to CRNAs

May 15, 2009

Mr. Neel Patel

Biomedical Engineer, Anesthesiology and Respiratory Devices Branch

Executive Secretary, Anesthesiology and Respiratory Therapy Devices Panel

Food and Drug Administration

Rockville, MD 20850 neel.patel@fda.hhs.gov

ATTN: Docket No. FDA-2009-N-0664

Dear Mr. Patel –

On behalf of the 40,000 members of the American Association of Nurse Anesthetists

(AANA), I am pleased to present testimony before the Anesthesiology and Respiratory

Therapy Devices Panel of the Medical Devices Advisory Committee of the Food and

Drug Administration (FDA), for its hearing Thu., May 28, 2009, regarding the

SEDASYS™ Computer Assisted Personalized Sedation System (74 FR 19230,

4/28/2009).

The AANA is the professional association representing over 90 percent of the Certified

Registered Nurse Anesthetists (CRNAs) and student nurse anesthetists in the United

States. CRNAs are prepared to the master’s or doctoral level, and must be certified by

the autonomous National Board for Certification and Recertification of Nurse

Anesthetists in order to practice, and must be recertified every two years. As advanced

practice nurses, CRNAs administer about 30 million anesthetics given to patients each

year in the United States. Our services include administering the anesthetic, monitoring

and interpreting the patient’s vital signs, and managing the patient throughout the

surgery, as well as managing acute and chronic pain. CRNAs work in every setting in

which anesthesia is delivered, including hospital surgical suites and obstetrical delivery

rooms, ambulatory surgical centers (ASCs), pain management units, and the offices of

dentists, podiatrists, and general and specialty surgeons.

Our primary professional objective is anesthesia patient safety. In the absence of

substantial professional literature available to discuss the SEDASYS™ device, our

testimony speaks to the conditions under which the device may be used, if the agency

chooses to approve it. We will ask why and how the agency anticipates approving a

device that allows non-anesthesia professionals (individuals other than CRNAs or

physician anesthesiologists) to administer propofol (Diprivan) in direct conflict with the

FDA-approved labeling for this potentially dangerous drug. Further, we will raise our

concern with determining how non-anesthesia professionals using the device will be

trained and certified to rescue patients in the event of a cardiorespiratory emergency.

I. Why the SEDASYS™ Device Should Only Be Used by Anesthesia Professionals

We understand that the SEDASYS™ device is intended to enable non-anesthesia

professionals to administer propofol. Little has been published publicly about the

controlled and standardized environments appropriate for a device awaiting pre-market

approval by the agency. As we have described above, propofol is administered in a wide

spectrum of offices, facilities and settings in which rescue situations can arise.

We note that the FDA-approved labeling of the drug which SEDASYS™ is intended to

administer, propofol, directs that under all circumstances it must be administered by

persons with expertise in general anesthesia. Since we assume a device administering

propofol would require the intervention of a healthcare professional to set-up and

program the device before its use on a patient, the healthcare professional performing

those tasks should be subject to the same warnings and requirements that FDA has

established for propofol for unassisted injection. As such, should the panel recommend

the agency approve the SEDASYS device, the panel should restrict this device to use

only by anesthesia professionals, who are expert in general anesthesia and in patient

rescue.

II. Properties of Propofol, as Described by FDA, Require that Persons

Administering It be Expert in General Anesthesia; Any Device Administering

Propofol Should be Subject to the Same Constraints in the Interest of Patient Safety

and so as Not to Weaken the Existing Warnings for Propofol Administration

The current FDA-approved, bolded warning on propofol (FDA-Approved Label for

Several attributes of propofol justify this warning. Many of these attributes are published

on the FDA Draft Final Printed Labeling for generic propofol (FDA, Application

#075392, Gensia Sicor Pharmaceuticals, Approval Date 9/19/2000). Others relate to the

literature, education and professional experience of CRNAs and anesthesiologists.

Propofol is preferred for anesthesia care for many procedures, including certain

gastrointestinal diagnostic procedures, because of the comparatively rapid dissipation of

its sedative effects. Patients wake up from propofol quickly, compared with other drugs

used for sedation. However, unlike many other pharmaceuticals used for sedation or

induction, there is no agent that reverses the effects of propofol. Beyond a certain dose,

propofol stops a patient’s breathing, with each patient responding somewhat differently to

a given dosing pattern. If breathing is halted, the patient transitions from sedation into a

general anesthetic state. The healthcare provider must ventilate the patient, and

understand and manage the physiological changes that can occur during a general

anesthetic state. Under many gastrointestinal procedures for which sedation is used, the

patient lies prone. If an airway emergency occurs, the patient must be placed in the

supine position to immediately secure an adequate airway.

The issue, therefore, is not whether a healthcare provider may adequately administer

propofol with the assistance of a device such as the SEDASYS™. The question is

whether a healthcare provider, untrained in general anesthesia, can adequately address the

known complications of propofol administration to ensure patient safety were such a

device to administer a dose of propofol leading to these complications, by human error in

programming or otherwise.

Such experiential factors are buttressed by the FDA’s own labeling, worth excerpting at

some length here (FDA, Application #075392), and by the literature:

The anesthesia literature since the FDA’s 2000 approval of generic propofol further

describes propofol’s properties. Though propofol has well understood sedative properties,

Drs. Frolich, Price, Robinson et al more recently found that “subjects rated both pain

intensity and unpleasantness higher when sedated with propofol…. This effect was

unexpected and may be explained by a difference of subjective pain experience by a patient

and the perceived level of analgesia by a healthcare provider in sedated patients. This

finding calls further attention to the need for adequate analgesia in patients sedated with

propofol.” (Frolich M, Price D, et al. The effect of propofol on thermal pain perception.

Anesth Analg 2005;100:481-6). Propofol does not possess analgesic properties.

Therefore, anesthesia professionals understand the patient’s need for medication that will

control pain during procedures. The addition of opiate medications provides analgesia and

when used concomitantly with propofol has the potential to cause apnea. Anesthesia

professionals recognize this possible outcome and are fully prepared to manage apnea,

should it occur.

In reviewing literature associated with emergency medicine, Drs. Wilbur and Zed

buttressed findings of the FDA approved labeling of propofol in stating that while

propofol provided “markedly shorter induction and recovery times than

midazolam…(a)pneic episodes (>30 seconds) occurred in 23% of propofol recipients,

28% of thiopental recipients, and 7% of etomidate and midazolam recipients…. Propofol

is a cardiovascular depressant that causes dose-related blood pressure reductions…. In

the 6 DCC (direct current cardioversion, parenthetical added) studies reviewed, 21

(23.3%) of 90 patients who received propofol experienced apnea episodes longer than 30

seconds.” (Wilbur K, Zed P. Is propofol an optional agent for procedural sedation and

rapid sequence intubation in the emergency department. Can J Emerg Med 2001;3:1

which references Can J Anaesth 1988;35:479-83, Anaesthesia 1990;45:872-5, J

Cardiothor Vasc Anesth 1991;5:566-8, Acta Anaesthesiol Scan 1991;35:609-15, Anesth

Analg 1993;77:690-4; Crit Care Med 1993;23:1509-13).

The anesthesia literature underscores age and body mass index as factors in appropriate

propofol dosage. (Niiyama Y, Omote K, et al. Effects of gender, age and body mass

index on sedation level during infusion of propofol by target-controlled infusion. J

Anesth 2002;96:A63)

Given the propofol-related literature, it is clear that training in the administration of

general anesthesia and in managing propofol’s known properties (e.g., physiological

responses and the possible complications that can occur from administration) are required

to assure patient safety. The professionals who have such training are CRNAs and

anesthesiologists. Any device designed to control the administration of propofol to a

patient will require operation by a healthcare professional. Those healthcare

professionals should be limited to those with training in general anesthesia and patient

rescue.

III. Prior to Consideration of SEDASYS™ for Approval, Professional

Organizations Have Widely Recommended That FDA Maintain Current Warnings

on Propofol Constraining Its Use to Anesthesia Professionals Only

Recognizing the powerful attributes of propofol, several professional organizations have

issued policy statements speaking directly to the safety concerns associated with the drug

which the SEDASYS™ device is intended to administer. These organizations include

societies of healthcare professionals, and nongovernmental standardsetting bodies

authorized to accredit or certify various types of healthcare facilities where procedures

requiring sedation are provided.

The AANA and the American Society of Anesthesiologists (ASA) published a Joint

Statement regarding propofol administration April 14, 2004

Subsequently, the Accreditation Association for Ambulatory Health Care (AAAHC)

endorsed the above statement “regarding the safe use of propofol and other intravenous

drugs that do not have antagonist medications.” (AAAHC statement, 5/24/2005,

4,000 ASCs and other healthcare facilities in the United States.

The American Association for the Accreditation of Ambulatory Surgical Facilities

(AAAASF) has further stipulated restrictions on the administration of propofol in its

accredited facilities. The AAAASF’s standards for ambulatory surgical facilities

(December 2007) provide as follows:

The AAAASF’s accreditation program classifies facilities based on the type of anesthesia

used in a facility for procedures. Class C facility is defined as the following:

With respect to the administration of anesthesia in these facilities, AAAASF provides as

follows:

AAAASF’s standards for surgical procedures performed in physician offices (February

2008) also provide as follows:

Similar to AAAASF’s standards for ambulatory surgical facilities, AAAASF’s

procedural standards also classify facilities based on anesthesia used for procedures and

limit administration of propofol to anesthesia professionals, as follows:

Lastly, all of the relevant facility accreditation manuals issued by The Joint Commission

(2009) for hospitals, critical access hospitals, ambulatory care, and office-based surgical

practices, require that “individuals administering moderate or deep sedation and

anesthesia are qualified and have credentials to manage and rescue patients at whatever

level of sedation or anesthesia is achieved, either intentionally or unintentionally.”

IV. Should FDA Approve the SEDASYS™ Device, How Will the Agency Assure

Clinicians Operating the Device Can Rescue Patients?

We have presumed that the SEDASYS™ device has been tested in highly controlled

environments, where procedures associated with the device’s use and the characteristics

of patients treated with the aid of such a device were subject to strict oversight and

documented procedures. Should the device be approved by FDA, it will enter the broader

market of healthcare delivery where procedures and oversight may not be nearly so strict

or controlled. Further, approval cannot be based solely on the instances in which the

device and the human systems supporting it have worked well. Rather, approval also

needs to examine and scrutinize device performance and patient safety during those times

when either the device or the procedural team surrounding the patient does not properly

perform.

One method of ensuring a margin of safety with a device that administers propofol is to

require, as does the approved propofol label, that it be operated only by a person expert in

general anesthesia, such as a CRNA or anesthesiologist, as we have recommended.

Alternatively, if the FDA authorizes pre-market approval of SEDASYS™ as the

manufacturer has requested so that it may be operated by clinicians who are not

anesthesia professionals, the agency and the manufacturer bear an exceedingly heavy

responsibility to ensure that persons operating this device possess the requisite skills and

training necessary to rescue patients in all possible scenarios (e.g. failure of the device,

error in programming the device, other health complication with the patient). It is

erroneous and dangerous to assume that using SEDASYS™ somehow renders nonanesthesia

providers qualified to administer a potentially dangerous anesthetic drug such

as propofol and ensure patient safety in the process.

Unfortunately, representatives of the developer of the device have advised health

professional governing bodies in at least one state that requiring persons operating the

device to undertake even one competency-based evaluation presented an “unnecessary

burden” on nurses and facilities. (McKenna M. Letter to Ms. Vicky Stone-Gale, Florida

Sedation Advisory Committee of the Florida Board of Nursing, on behalf of Ethicon

Endo-Surgery. Jan. 18, 2008) In its letter, the manufacturer recommended the state

adopt language that “nurses can administer anesthetic agents with a drug delivery device

approved by the U.S. Food and Drug Administration, with FDA-approved labeling that

allows such administration for moderate (conscious) sedation by nurses who are not

anesthesia providers, when used under the supervision of a physician.” Ethicon Endo-

Surgery specifically objected to language requiring that “a registered nurse must

successfully complete a criteria-based competency evaluation, which reflects the extent

of the privileges requested,” adding further that “(t)he administration of sedation by a

nurse is still given under the direction or supervision of a physician because the physician

must order the drug, the dosing, the frequency and the route of administration.” Such

statements appear to be based on two faulty presumptions: that propofol is like any other

drug (which, as we have established, it is not), and that the SEDASYS™ device

developed to administer propofol is a simple mechanism (which it is not).

V. The FDA Itself Has Indicated the Issues Surrounding Propofol Administration

are Complex, Raising Reasonable Concerns About a Device that Would Administer

Propofol Without an Anesthesia Professional Present

The agency has invested considerable time examining the merits of a 2005 citizen

petition recommending that FDA amend the “Warning” labeling of propofol, so that the

labeling would permit persons other than those expert in general anesthesia to administer

the drug. Following months of expert comments, including comments from AANA, the

agency stated to the petitioner, the American College of Gastroenterology (Axelrad, J.

Letter from FDA to Cooper and Stern of Williams & Connolly re: Docket No. 2005P-

0267/CP1, Dec. 21, 2005):

In closing, we ask the FDA to take seriously our patient safety concerns as the agency

evaluates pre-market approval of the SEDASYS™ device. This device is intended to

administer a drug, propofol, which is different from other drugs, in that there is

absolutely no agent available to reverse its effects. Failure of the device, or of the

personnel using the device, leaves the patient in need of immediate cardiopulmonary

rescue by a professional knowledgeable about anesthesia, and trained, credentialed and

immediately available to provide this care.

Thank you for the opportunity to submit written testimony to the Anesthesiology and

Respiratory Therapy Devices Panel of the Medical Devices Advisory Committee of the

Food and Drug Administration regarding the SEDASYS™ device. We stand ready to

answer any further questions you may have. Please direct any questions or comments

about this testimony to our AANA Washington, DC office by contacting Frank Purcell,

Sincerely,

Jackie S. Rowles, CRNA, MBA, MA, FAAPM

President