Episode #111 Off-Label Drug Use During Anesthesia Care

Hello and welcome back to the Anesthesia Patient Safety Podcast.  My name is Alli Bechtel, and I am your host. Thank you for joining us for another show. Last week we talked about keeping patients safe during low-flow anesthesia. There are several benefits including decreased waste of inhaled anesthetics, decreased cost, and less greenhouse gas effects as well as less heat and humidity loss from the lungs. During our last episode, we discussed patient safety when administering sevoflurane using flows lower than recommended on the package insert. Our featured article today focuses on FDA approval and off-label use.

Before we dive into the episode today, we’d like to recognize Medtronic a major corporate supporter of APSF. Medtronic has generously provided unrestricted support to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Medtronic – we wouldn’t be able to do all that we do without you!”

We are jumping back into the June 2022 APSF Newsletter for our featured article today, “Off-Label Low-Flow Sevoflurane: Regulatory Red Herring or Liability Landmine?” by Brian Thomas. To follow along with us, head over to APSF.org and click on the newsletter heading. First one down is the current issue. Then, scroll down until you get to our featured article today. I will include a link in the show notes as well.

Before we get into the article, we are going to hear from the author, Brian Thomas. Let’s take a listen.

[Thomas] “Hi, my name is Brian Thomas and I’m an attorney and vice president of risk management for Preferred Physicians Medical, the nation’s only professional liability insurance company insuring anesthesia professionals and their practices exclusively. I also serve on the Anesthesia Patient Safety Foundation’s Board of Directors and the editorial board for the APSF Newsletter.”

To kick off the show today, I asked Thomas why he wrote this article. Here is what he had to say.

[Thomas] “I wrote this article as a companion piece to Dr. Jeffrey Feldman’s’ and Dr. Samsun Lampotang’s excellent article addressing patient safety and low flow anesthesia. My goals in writing the article was to explain the FDA required labeling for low flow Sevoflurane and address potential malpractice, liability concerns from off-label use of low flow anesthesia.”

[Bechtel] Thank you so much to Thomas for helping to introduce the article. Have you administered sevoflurane at flows that were lower than recommended by the FDA or have you been hesitant to turn down the flows? Using low-flow anesthesia and sevoflurane is an off-label use, so let’s head into the court room and get into the article.

The article opens with a description of the controversy surrounding the practice of low-flow anesthesia with sevoflurane given the FDA required labeling. The US labeling requires “no less than 1L/min for up to 2 minimum alveolar concentration (MAC)-Hours and no less than 2L/min during longer exposures.” This recommendation comes from the concerns for the accumulation of compound A which has subsequently been found to not be toxic to humans and not be created with many carbon dioxide absorbents that are in use today. The difference between the drug label and off-label clinical practice brings up questions about safety and the standard of care.

Let’s take a minute for some definitions. What is off-label use? Off-label use occurs when a drug is used for a purpose not approved by the FDA. Another important definition is the legal term, Medical Standard of Care, which is the level and type of care that a reasonably competent and skilled anesthesia professional, with a similar background and in the same medical community or specialty would have provided under the same or similar circumstances.

The next step is to talk about the Food and Drug Administration and its role, which is quite expansive. It includes the approval, marketing, labeling, advertising, and promotion of both over-the-counter and prescription drugs. Let’s look a little closer at these roles. First up, approval. FDA approval occurs following clinical trials and evidence for the following:

• Drug safety and efficacy for the proposed uses
• Benefits of use outweigh the risks
• Appropriate drug labeling and if any changes need to be made
• Drug manufacturing methods with appropriate controls to ensure quality production

Okay, now that the drug has been approved for a specific purpose, it can be used for other treatments that were not included in the initial FDA approval. This is the off-labeled practice that we talked about earlier. Is this legal? Thomas tells us that off-label use is legal when used for clinical treatment, but off-label use may not be used for research purposes. The limitation on off-label use for research is due to FDA regulations of the development and clinical investigation of new drugs. However, the FDA is not responsible for regulating medical practice. This means that anesthesia professionals may prescribe and use approved drugs for off-label use as long as it is not for research.

So, it is legal for anesthesia professionals to administer drugs for off-label use during clinical practice. However, Thomas points out that legal action may be taken against an anesthesia professional for allegedly improper off-label use in the setting of lack of informed consent. Obtaining consent for anesthesia care is something that anesthesia professionals are responsible for prior to performing procedures and providing treatment. Anesthesia professionals can be held liable if informed consent is not obtained. In addition, if invasive procedures are performed without the patients’ consent, this is considered battery and monetary damages may be awarded. If the patient is not informed about risks of a procedure and alternative treatments, then the anesthesia professional may be liable for negligence if the patient suffers an injury from the treatment.

Given that the concern for off-label drug use revolves around informed consent, it’s time to dive into the area of informed consent. Informed consent for anesthesia care in the United States involves the anesthesia professional providing information to the patient or their legal surrogate about the following:

• The proposed treatment
• Alternatives to treatment which includes no treatment
• The risks and potential benefits of the proposed treatment and alternative treatments including the risks and benefits of no treatment

The next step is for the patient or their legal surrogate to decide to provide their consent for the proposed or alternative treatments. There are more legal terms that come into play during the informed consent process. Reasonable anesthesia professional standard is applied in most states to determine if adequate informed consent was provided. This means that a jury or judge would need to determine whether a reasonable anesthesia professional would have provided the material information so that a patient or their legal surrogate would be able to make an informed decision.

What about the informed consent for off-label drug administration? In many state courts, anesthesia professionals and other healthcare providers have not been held responsible for needing to disclose to patients off-label drug use. Thomas provides an example that the court held:

“The decision whether or not to use a drug for an off-label purpose is a matter of medical judgment, not of regulatory approval. By analogy, the off-label use of a medical device is also a matter of medical judgment, and as such, subjects an [anesthesia professional] to professional liability for exercising professional medical judgment. Off-label use of a medical device is not a material risk inherently involved in a proposed therapy which an [anesthesia professional] should have disclosed to a patient prior to the therapy.”⁷

The informed consent requirements differ between states with the majority of states limiting the anesthesia professional’s duty to provide medical information. In these states, the anesthesia professional is not responsible for discussing the FDA regulatory status of drugs being used for a particular treatment. In addition, using a drug for an FDA approved therapy or for an off-label use does not affect the nature of the treatment. The informed consent requirements are different in the other minority of states with the “reasonable patient or person” standard of review. The question is, “Would a reasonable patient or person have considered that fact that a drug or medical device was going to be administered or used in an off-label manner required information to be able to provide consent for the treatment? Plus, the plaintiff has to be able to prove that if the patient had been aware of the off-label use of a drug or medical therapy, then they would have not given consent for the treatment. There are lack of informed consent cases that continue to be filed related to anesthesia professionals not informing the plaintiff that a drug was administered in an off-label manner. If these cases go to trial, a jury member may consider the fact that the FDA did not approve the drug for the manner in which the anesthesia professional used it even though the off-label use may be widely accepted during anesthesia care. The plaintiff attorneys will be able to find anesthesiology experts who will testify that the off-label use of sevoflurane for low-flow anesthesia is below the stand of care and they will make this claim base on the manufacturer’s and FDA’s warning label that recommends maintaining fresh gas flow rates greater than 1L/min. Since we know that the practice of low-flow anesthesia with sevoflurane is safe with continuous monitoring of oxygen concentration and volatile anesthetic concentration, then as long as the anesthesia professional provided safe and appropriate care, then these cases are likely defensible or would not even go on to trial or settlement.

We made it to the end of the article. There is a long history of safe use of off-label drugs during anesthesia care by anesthesia professionals. In fact, between 1987 and March 2022, a review of Preferred Physicians Medical’s 4,594 anesthesia closed claims files, revealed no claims related to patient injury or death from the use of low-flow sevoflurane anesthesia. Keep in mind that the FDA is not responsible for regulating the practice of medicine. It is the anesthesia professionals responsibility to determine the risks and benefits of prescribing and administering drugs for off-label use in clinical practice and not for research. Thomas tells us that, “While the off-label use of a drug may potentially increase the risk of liability, that risk may be mitigated by an adequate informed consent process and adherence to the standard of care.” For anesthesia professionals with concerns about potential litigation following off-label use of sevoflurane for low-flow anesthesia, this article provides reassurance. Before we wrap up for today, we are going to hear from Thomas again for a little more reassurance. I asked him, What do you hope to see going forward? Let’s take a listen for what he had to say.

[Thomas] “My hope is that the article will provide useful information to anesthesia professionals regarding off-label use of medications and to put into context that litigation involving allegations of negligence due to off label administration of drugs is uncommon and in most cases defensible on behalf of the anesthesia professional.”

[Bechtel] Thank you so much to Thomas for your legal expertise and for contributing to the show today. The considerations about providing safe anesthesia care while using off-label drugs and the legal liability is critical for anesthesia professionals. If you haven’t listened to episode #110, I hope that you will check it out to learn all about the safety of low-flow anesthesia. Let us know if you are team #lowflowanesthesia by tagging us @APSForg on twitter. We would love to hear from you!!

If you have any questions or comments from today’s show, please email us at [email protected]. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today.

Do you have the PediCrisis 2.0 App created by the Society for Pediatric Anesthesia? If not, what are you waiting for? Version 2 was released on July 11 and is now available for free to provide information that a fully trained anesthesia professional would want to know during a pediatric emergency. Don’t miss out on the checklists in the app that are based on new guidelines and evidence as well as clinicians experiences with these aids. The app was tested in simulation and reviewed by experts for content and format. This is a vital resource to support emergency response during a critical event. There is more good news, the app is now available in English and Spanish with future publication of the app in Chinese and French planned.  I will include the link to download the app in the show notes as well. This is a great resource for helping to keep pediatric patients safe during critical events.

Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

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