By Drs. Amber Borucki and Rakhi Dayal 

Recent headlines about the death of “Friends” actor Matthew Perry have pointed to ketamine as a contributing cause. Perry drowned in his hot tub last October, which the medical examiner’s office attributed to the “acute effects of ketamine,” as well as coronary artery disease and the opioid buprenorphine.

With this news, the public became more familiar with a medication they may never have heard of previously.  Ketamine is a classified by the Drug Enforcement Administration (DEA) as a “dissociative anesthetic,” meaning that it can cause the user to feel disconnected and alter their perceptions of sight or sound. 

Ketamine is used in hospital or surgical settings for anesthesia purposes, for acute pain management, in the emergency room or intensive care, and in some cases for chronic pain management. A form of ketamine (esketamine) is also used to treat mental health conditions. 

Appropriate monitoring and medical supervision are necessary for safe ketamine use. While it is important to recognize the risks of this medication when used improperly, it is also important to make sure that people don’t become overly fearful of a drug that serves an important role in patient care when delivered properly by trained healthcare providers. 

When the news broke that Michael Jackson’s death was attributed to propofol, patients were suddenly concerned about the use of this drug in their anesthesia treatment. As physicians, it is our responsibility to make sure patients understand the proper and improper uses of medications, and that we help alleviate concerns through education. As with any treatment, we need to strike the right balance between providing information on the risks, while also communicating the benefits. 

While ketamine is in the spotlight and more stories are published about its use, it is important that we take a moment to provide greater clarity about this medication.  

What Is Ketamine?  

Ketamine is an anesthetic agent that was originally developed in 1963 and gained approval from the Food and Drug Administration (FDA) as a general anesthetic in 1970. It is well established that ketamine has tremendous clinical value in providing sedation and pain relief when patients undergo anesthesia, and can also be beneficial as part of a comprehensive pain management plan. More recently, the FDA approved a form of ketamine in a nasal spray for treatment-resistant depression.   

Ketamine is used for a variety of indications, with some being FDA-approved and some being considered "off-label" uses.  

• General anesthesia (FDA-approved): Ketamine can be used as part of a general anesthetic given for surgery, and in certain clinical situations is one of the preferred medications.  When ketamine is given by a trained anesthesia provider, it is a safe and effective part of the anesthesia regimen.     

• Acute pain (off-label): Ketamine can be given to treat pain after surgery or for other significant acute pain conditions. This is commonly done by providing a low-dose infusion of ketamine through an IV while a patient recovers in the hospital. Although this is considered "off-label” use, there are joint guidelines issued in 2018 by the American Society of Regional Anesthesia and Pain Medicine (ASRA), the American Society of Anesthesiologists (ASA), and the American Academy of Pain Medicine (AAPM) to guide safe use for acute pain.

• Chronic pain management (off-label): Ketamine for chronic pain is also considered "off-label" use, but there are also consensus guidelines by the ASRA, ASA and AAPM that discuss chronic pain clinical scenarios where research found ketamine to be beneficial. 

If a patient is considering the use of ketamine for chronic pain, it is important to understand what type of medical supervision is provided and by whom. Patients should consider seeking treatment from a physician who is board certified in pain medicine, as they have extra training in pain management. The use of ketamine for chronic pain should be part of a larger umbrella of comprehensive pain treatment strategies provided in a multidisciplinary care team model.

What Are the Risks of Ketamine?

Ketamine is classified a schedule III controlled substance by the DEA, and therefore has some addictive potential. Side effects include increased heart rate, high blood pressure, increased saliva production, blurry vision, dizziness, sedation, nausea, urinary symptoms, dissociation (out of body sensation) and respiratory depression. It can even cause hallucination at certain doses. 

Caution is advised when ketamine is used with other medications that have similar adverse effects, such as sedation, respiratory depression, confusion, and delirium. Medication interactions and overdose with ketamine can lead to unconsciousness, slowed breathing, and rare severe consequences such as death. 

The medical use of ketamine in general anesthesia under the medical supervision of a trained provider is generally considered safe. Off-label use of ketamine for acute and chronic pain also has established national guidelines for medical practitioners to follow. This treatment can provide pain relief to patients safely, when provided by a board-certified anesthesiologist or pain physician using proper monitoring and safety guidelines.

Unsupervised and non-medical use of ketamine, particularly when taken in combination with other sedating medications, can lead to adverse outcomes and even death, as we saw with Matthew Perry. We encourage patients to have conversations with providers about their treatment plan and to discuss any concerns they have about the medications they are prescribed.

Amber Borucki, MD, is an Associate Professor of Anesthesiology, Perioperative and Pain Medicine at Stanford University.

Rakhi Dayal, MD is Chair of the Pain Committee for the California Society of Anesthesiologists, and Program Director of Pain Medicine and Professor of Anesthesiology & Perioperative Care at University of California, Irvine.