Dependence Risk for Common Anesthetics

An anesthetic is a drug or agent used in anesthesia to produce a complete or partial loss of feeling, consciousness, and/or movement. A wide variety of drugs are used in modern anesthetic practice, including inhaled agents, intravenous non-opioid agents, and intravenous opioid agents. These different anesthetics come with different risks for dependence which can be minimized through careful administration and monitoring. This article discusses current information on the dependence risk of common anesthetics.

Desflurane and sevoflurane

Desflurane and sevoflurane are currently the inhalational agents for general anesthesia of choice. The potential drug abuse liability and dependence associated with desflurane have not yet been studied according to the Food and Drug Administration (FDA) [1]. Similarly, little remains known about the risk of dependence on sevoflurane, though a case report of an addictive 28-year-old male anesthesiologist who suffered long-term abuse of sevoflurane after 4 years of occupational exposure was recently published. He was noted to be particularly sensitive to sevoflurane addiction and had to switch careers [2].

Nitrous oxide

Nitrous oxide (N2O) is used clinically as a safe anesthetic (e.g. for dentistry, childbirth, etc.) and is well-appreciated for its anti-anxiety effect. There are usually no significant withdrawal symptoms following the use of nitrous oxide apart from cravings to use more nitrous oxide [3]. However, the recreational use of N2O has been rapidly increasing, with N2O in the United Kingdom for example now being the second most popular recreational drug after cannabis [4].


Midazolam injection may produce physical dependence if it is used more frequently than recommended. As a result, midazolam is subject to Schedule IV control under the Controlled Substances Act of 1970 [5].

Propofol and ketamine

Propofol and ketamine are both intravenous sedatives that are common anesthetics but carry a risk of dependence. There are reports of the abuse of propofol for recreational and other improper purposes resulting in fatalities and other injuries. Instances of self-administration of propofol by healthcare professionals have also been reported [6]. Similarly, ketamine has been reported being used as a drug of abuse. Ketamine dependence and tolerance are possible following prolonged administration [7].

Fentanyl, hydromorphone, and oxymorphone

Fentanyl citrate, as an opioid, is a Schedule II controlled drug substance that can produce drug dependence of the morphine type. Hydromorphone and oxymorphone, also opioids, also can produce drug dependence of the morphine type. These drugs therefore have a strong potential for being abused [8–10]. With greater recognition of the risks of opioids in recent decades, there are continuing efforts to reduce the necessity of opioids in clinical practice.

In some situations, medications with a dependence risk cannot be avoided for clinical reasons. When it comes to reducing dependence risk associated with anesthetics, it is first crucial to have a thorough interview with patients prior to the procedure. An anesthetist will visit a patient preoperatively in order to assess if they are fit enough for surgery and to explain the administration of anesthesia. It is important at this stage to discuss a range of issues, including a patient’s medical history, including any pre-existing conditions, such as diabetes or heart problems, a patient’s surgical history, a patient’s allergies, and any drugs a patient may be on, including cigarettes and alcohol [12].

In particular, screening for substance use and/or substance use disorder is critical. Providers should recognize that individuals often refer to misused or illicit substances by street names while interviewing the patient. Patients presenting for certain case types such as bariatric surgery, certain cardiovascular procedures, or organ transplantation may also be more likely to suffer from a substance use disorder [13]. This information is critical for the anesthesiologists to develop the best treatment regimen possible for each patient depending on their history and background.


1. FDA. SUPRANE (desflurane, USP). Available at:

2. Luo, A., Zhang, X., Li, S. & Zhao, Y. Sevoflurane addiction due to workplace exposure: A case report and literature review. Medicine (United States) (2018). doi:10.1097/MD.0000000000012454

3. Nitrous oxide – Alcohol and Drug Foundation. Available at:

4. van Amsterdam, J., Nabben, T. & van den Brink, W. Recreational nitrous oxide use: Prevalence and risks. Regul. Toxicol. Pharmacol. 73, 790–796 (2015).


6. DIPRIVAN. Available at:

7. KETALAR. Available at:

8. FENTANYL. Available at:

9. HYDROMORPHONE. Available at:

10. OXYMORPHONE. Available at:,021611s001lbl.pdf12. General anaesthetics – Better Health Channel. Available at:

13. Anesthesia for patients with substance use disorder or acute intoxication – UpToDate. Available at: