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Fentanyl is a synthetic opioid drug that is 50 to 100 times more potent than morphine and exhibits vastly different properties and pharmacokinetics.¹ The Belgian pharmaceutical company Janssen Pharmaceutica first developed fentanyl in 1959.² In the 1960s, fentanyl was introduced into medical practice as an anesthetic agent, and is now used for both anesthesia and analgesia.² Fentanyl is classified as a United States Drug Enforcement Administration (DEA) Schedule II drug, which means that it has “a high potential for abuse, with use potentially leading to severe psychological or physical dependence.”³ In December 2018, the Centers for Disease Control and Prevention (CDC) pronounced fentanyl the deadliest drug in America due to its potency, addictive properties and role in the opioid crisis.⁴ Because of fentanyl’s potential to cause rapid death, anesthesia providers should understand its biological mechanisms, surgical applications and side effects.⁴

The molecular formula for fentanyl, also known as fentanyl citrate, is C₂₂H₂₈N₂O.⁵ Fentanyl is lipophilic, meaning that it tends to spread to fatty tissues and thus has greater bioavailability than hydrophilic (water-soluble) drugs.⁵ Like other opioids, fentanyl binds to the m-opioid receptor in the central nervous system (CNS), thus reducing neuronal excitability.⁵ However, fentanyl also serves as an agonist for other opioid receptors such as the delta and kappa receptors.¹ Activation of these opioid receptors produces analgesia, while increases in the release of dopamine elicits exhilaration and relaxation effects.¹ Fentanyl is metabolized extensively in the liver and intestines via the enzyme CYP3A4.⁵ Less than 11 percent of the dose is excreted through urine and feces as inactive metabolites or as unchanged drug.⁵ Fentanyl metabolism, elimination and duration of effects may be affected by medications or substances that inhibit the CYP3A4 enzyme.⁶

Fentanyl comes in several forms, which allow it to serve a variety of purposes.⁷ When used to treat breakthrough pain for patients who use opioids on a long-term basis, fentanyl comes as a lozenge on a handle, a sublingual tablet, a film and a buccal tablet.⁷ Fentanyl is also administered intravenously, intramuscularly, transdermally as skin patches, intranasally via a nasal spray and intrathecally.¹ In contrast to other opioid drugs, fentanyl is less common as an oral tablet or powder.¹ For surgical procedures, fentanyl can be used preoperatively, during surgery and in the immediate postoperative period.⁵ Before surgery, fentanyl provides anxiolysis and relaxation.⁵ In combination with other anesthetic drugs, fentanyl is useful for procedures that require patients to be lightly anesthetized or awake.⁵ However, it may be administered with oxygen and a muscle relaxant to provide anesthesia without the use of additional anesthetic agents.⁵ Fentanyl can prevent or relieve postoperative emergence delirium.⁵ Clearly, fentanyl has various uses as an analgesic and anesthetic drug.

Unfortunately, fentanyl’s many uses are accompanied by many side effects. Fentanyl’s side effects are similar to those of heroin, including euphoria, confusion, drowsiness, nausea, visual disturbances or hallucinations, delirium and constipation.¹ Serious adverse effects include addiction, hypotension, coma, respiratory depression and death.¹ Fentanyl and its derivatives can produce rigidity in the diaphragm, chest wall and upper airway—known as “wooden chest syndrome” (WCS)—within a narrow dosing range.⁴ WCS can be fatal and causes rapid death without proper airway management.⁴ Because fentanyl is so potent and overdose is likely, anesthesia providers must be extremely diligent when providing patients with fentanyl.⁸ Patients who have respiratory issues or liver failure or who are using drugs such as alcohol, antibiotics or antifungal agents may not be able to use fentanyl.¹ Fentanyl can be habit forming, so patients should be educated about its proper use and addictive properties.⁷

Fentanyl is an extremely potent synthetic opioid that is used for analgesia and anesthesia. By activating certain opioid receptors, fentanyl inhibits neuronal activity. Fentanyl is primarily used for analgesia in combination with other anesthetics. Fentanyl’s side effects range from drowsiness and nausea to coma, respiratory depression and even death. Because fentanyl is a highly addictive substance, anesthesiology professionals should prescribe it cautiously.

1.         Ramos-Matos CF, Lopez-Ojeda W. Fentanyl. StatPearls. Web: StatPearls Publishing LLC; October 3, 2019.

2.         Dale E, Ashby F, Seelam K. Report of a patient chewing fentanyl patches who was titrated onto methadone. BMJ Case Reports. 2009;2009:bcr01.2009.1454.

3.         United States Drug Enforcement Administration. Drug Scheduling. Drug Information 2020; https://www.dea.gov/drug-scheduling.

4.         Torralva R, Janowsky A. Noradrenergic Mechanisms in Fentanyl-Mediated Rapid Death Explain Failure of Naloxone in the Opioid Crisis. Journal of Pharmacology and Experimental Therapeutics. 2019;371(2):453–475.

5.         Fentanyl. PubChem Database. Web: National Center for Biotechnology Information; 2020.

6.         Kharasch ED, Whittington D, Hoffer C. Influence of hepatic and intestinal cytochrome P4503A activity on the acute disposition and effects of oral transmucosal fentanyl citrate. Anesthesiology. 2004;101(3):729–737.

7.         Fentanyl. MedlinePlus. Bethesda, MD: National Institutes of Health; October 15, 2019.

8.         Simmons B, Kuo A. 40—Analgesics, Tranquilizers, and Sedatives. In: Brown DL, ed. Cardiac Intensive Care (Third Edition). Philadelphia: Elsevier; 2019:421–431.e425.

Humans have used herbs and plants for medicinal purposes since ancient times.¹ The oldest written evidence of medicinal plants’ usage for drug preparation is on a 5000-year-old Sumerian clay slab from Nagpur.¹ It includes 12 recipes for drug preparation with over 250 various plants, including poppy, henbane, and mandrake.¹ These plants contain pharmacologically active components that can treat illness.¹ Today, herbal medicines’ therapeutic potential should not be dismissed, given the long history of their successful use.² Herbal products may also interfere with other contemporary medicines, so medical providers must be aware of their potential effects and mechanisms of action.² Anesthesia providers in particular should be aware of commonly used herbal supplements and their functions, as well as their potential to affect anesthetic drugs.

Herbal products, also known as dietary supplements, alternative therapies, complementary medicine and homeopathic or holistic health care, are common in many societies.³ According to the World Health Organization (WHO), up to 80 percent of the world’s population still depends on herbal medicines.⁴ Patient surveys have reported that 12 percent of Americans, 12 percent of Australians, and 4.8 percent of patients in the UK use herbal remedies.⁴ Commonly used compounds include feverfew, garlic, ginseng, ginkgo, St. John’s wort, hoodia, kava, valerian and echinacea.^3,5 Because the United States Food and Drug Administration (FDA) considers these pharmacologically active agents as foods or supplements, they are not subject to standard drug regulations.² There are limited instructions on proper use, dosage requirements, possible side effects, toxicity and drug interactions.³ Also, a lack of pharmacokinetic and pharmacodynamic data on herbal products makes it difficult to predict a patient’s reaction to the product or know if the product has any therapeutic value.⁴ Due to unstandardized dosage policies and unclear pharmacological effects, herbal supplements can be harmful to patients whether or not they are taking other medications.

Because of the possible interference with anesthetic medications, the American Society of Anesthesiologists recommends that patients discontinue the use of herbal supplements two to three weeks before surgery.⁴ However, patients are often unaware of this recommendation or in need of emergency surgery, in which case preoperative preparation time is limited.⁴ According to a study by Levy et al., 44 percent of patients hospitalized for surgery reported dietary and herbal supplement use, with 16.5 percent using substances that could potentially interact with anesthesia.⁶ In a separate study, Kaye et al. found that among 1,017 patients surveyed before outpatient anesthetic administration, 482 were using at least one herbal supplement.⁷ Despite some of the benefits of these supplements, they can negatively impact postoperative analgesia, bleeding and level of sedation.² Wong et al.’s review thoroughly describes the medicinal uses, pharmacological effects and potential anesthetic interactions of several common herbal supplements.⁴ Garlic, ginger, gingko and ginseng contribute to intraoperative risk of bleeding; kava, St. John’s wort and valerian have sedative effects and may reduce anesthetic requirements; ephedra causes sympathetic nervous system issues and arrhythmia; and echinacea can cause liver failure when combined with hepatotoxic drugs.⁴ Despite the potential perioperative dangers of these drugs on their own or in combination with anesthetic agents,³ documentation and identification of herbal remedies in medical records remain subpar. For example, in Levy et al.’s study, supplement use was only documented in 11 percent of the medical files of patients who used them.⁶ It is the anesthesia provider’s duty to ask patients open-ended questions about their herbal supplement use during the preoperative assessment.⁸ Adequate reporting of patient use and proper understanding of herbal supplement pharmacology are key to an anesthesia provider’s practice.⁸

Medicinal herbs have been used for thousands of years, and many herbs contribute to the pharmacological effects of modern-day medications. Despite their widespread use, herbal supplements are not heavily regulated and may pose dangers to patients, whether or not they use other medicines. Anesthesia providers should consider the pharmacology and possible perioperative effects of these supplements. Ideally, the anesthesia provider should ensure the patient’s discontinuation of such products well before surgery.⁴ Future research should investigate the possible uses of herbal supplements for anesthesia and analgesia to aim for a more symbiotic relationship between herbal supplements and allopathic medicine.  

1.         Petrovska BB. Historical review of medicinal plants’ usage. Pharmacognosy Reviews. 2012;6(11):1–5.

2.         Abe A, Kaye AD, Gritsenko K, Urman RD, Kaye AM. Perioperative analgesia and the effects of dietary supplements. Best Practice & Research Clinical Anaesthesiology. 2014;28(2):183–189.

3.         American Society of Nurse Anesthetists. Herbal Products and Your Anesthesia. Patients 2019; https://www.aana.com/patients/herbal-products-and-your-anesthesia.

4.         Wong A, Townley SA. Herbal medicines and anaesthesia. Continuing Education in Anaesthesia Critical Care & Pain. 2010;11(1):14–17.

5.         Skinner CM, Rangasami J. Preoperative use of herbal medicines: A patient survey. BJA: British Journal of Anaesthesia. 2002;89(5):792–795.

6.         Levy I, Attias S, Ben-Arye E, et al. Perioperative Risks of Dietary and Herbal Supplements. World Journal of Surgery. 2017;41(4):927–934.

7.         Kaye AD, Clarke RC, Sabar R, et al. Herbal medicines: Current trends in anesthesiology practice—a hospital survey. Journal of Clinical Anesthesia. 2000;12(6):468–471.

8.         Lyons TR. Herbal medicines and possible anesthesia interactions. AANA Journal. 2002;70(1):47–51.

A concussion is a traumatic brain injury caused by a bump, blow or jolt that causes the head and brain to move rapidly back and forth.¹ This sudden movement can make the brain bounce or twist within the skull, creating chemical changes and damaging brain cells.¹ Concussion signs and symptoms include loss of consciousness, amnesia, clumsiness, nausea or vomiting, light or noise sensitivity, headache and confusion.² Concussions are common sports injuries; according to estimates by the Centers for Disease Control and Prevention (CDC), an estimated 1.6 to 3.8 million sports- and recreation-related concussions occur in the United States each year.³ Lack of proper diagnosis or poor management of a concussion can result in long-term consequences, including coma or death.⁴ Some patients may need urgent or elective surgery immediately after a concussion, which can be complicated given the stress associated with any procedure.⁵ Anesthesia providers should be especially cautious with patients who have had a recent concussion diagnosis, as a concussed brain may be particularly vulnerable.⁶ In order to give the best care to their patients, anesthesiology practitioners need to understand the complexities of concussion, the problems surgery might pose to a concussed patient and the anesthesia provider’s role.

Concussion refers to the functional issues of a mild traumatic brain injury (mTBI).⁶ The diagnosis of a concussion can be difficult, as brain imaging after mTBI is usually nondiagnostic, nonpredictive and nonspecific for concussion.⁶ Though the majority of concussion symptoms, such as headache, resolve within one week, patients who have suffered a previous concussion may not show such a quick recovery.⁷ Additionally, post-concussive symptoms such as dizziness, fatigue, anxiety and cognitive deficits can result in functional impairment and societal costs extending months after the initial injury.⁷ These extended symptoms may be due to profound brain changes after concussion.⁶ Immediately after the head injury, the brain’s metabolic rate increases.⁶ Then, in the hours, days and weeks following a concussion, the brain enters a state of increased blood flow, reduced metabolism, altered vascular responsiveness and dysfunctional neuronal axon activity.⁶ Evidence suggests that even after signs and symptoms of a concussion subside, cerebral physiology may remain altered for months.⁶

Because the brain is vulnerable right after a concussion, clinicians recommend cognitive and physical rest as part of the treatment regimen.⁶ This includes minimized physical activity; reduction of reading, social visits and video games; and avoidance of significant decision making.⁶ The need for surgery after a concussion may interfere with these requirements.⁵ After all, the perioperative period involves a variety of physical and cognitive demands, including exposure to foreign environments, meeting multiple new people, answering questions, making important decisions, bright lights, physical transfers, pain, medications and altered sleep.⁶ Thus, clinicians may need to balance the time sensitivity of a surgery with the potential dangers of overstimulation after a concussion.^5,8

Anesthesiology practitioners in particular should be cautious when administering anesthesia soon after a patient’s concussion.⁹ A review by Tasker states that the effects of anesthetic agents on the autonomic nervous system and on cerebrovascular reactivity to carbon dioxide could further alter the brain’s post-concussive state.⁹ Abcejo et al. found that anesthesia use is common in patients after a concussion, and clinicians may need to alter their anesthesia practice to avoid potential injury in these patients.¹⁰ Though the data are limited on proper anesthetic practices in patients with altered cerebral physiology,^7,11 a review by King and Collins-Yoder shows that anesthesia providers should pay special attention to mean arterial pressures and partial CO₂ pressure in concussed patients.¹¹ Furthermore, while D’Souza et al. found no differences in intraoperative and postoperative outcomes between patients with recent concussion and control patients,¹² Ferrari et al. and Sheshadri et al. emphasize the lack of literature on long-term outcomes of anesthesia after concussion.^8,13 Until the evidence base is better established, Vavilala et al. recommend deferring anesthesia use in post-concussive patients until physical restrictions are lifted.⁷

Concussion is a serious condition resulting in long-term physiological brain changes. Because surgery can be physically and cognitively stressful, it poses challenges to a patient who was recently concussed. Anesthesia providers need to be especially careful when caring for post-concussive patients, as the cerebral changes from anesthesia may cause further injury to the patient’s vulnerable brain. More research is needed on best practices in anesthesia for concussed patients and the long-term outcomes of anesthesia after concussion.

1.         Centers for Disease Control and Prevention. What Is a Concussion? Heads Up February 12, 2019; https://www.cdc.gov/headsup/basics/concussion_whatis.html.

2.         Centers for Disease Control and Prevention. Concussion Signs and Symptoms. Heads Up February 12, 2019; https://www.cdc.gov/headsup/basics/concussion_symptoms.html.

3.         Daneshvar DH, Nowinski CJ, McKee AC, Cantu RC. The Epidemiology of Sport-Related Concussion. Clinics in Sports Medicine. 2011;30(1):1–17.

4.         Brain Injury Research Institute. What is a Concussion? Information and Research 2020; http://www.protectthebrain.org/Brain-Injury-Research/What-is-a-Concussion-.aspx.

5.         Rasouli MR, Kavin M, Stache S, Mahla ME, Schwenk ES. Anesthesia for the patient with recently diagnosed concussion: Think about the brain! Korean Journal of Anesthesiology. July 1, 2019.

6.         Abcejo AS, Pasternak JJ. Is a Concussed Brain a Vulnerable Brain? Anesthesia after Concussion. Anesthesia Patient Safety Foundation. October 2018;33(2).

7.         Vavilala MS, Ferrari LR, Herring SA. Perioperative Care of the Concussed Patient: Making the Case for Defining Best Anesthesia Care. Anesthesia & Analgesia. 2017;125(3):1053–1055.

8.         Ferrari LR, O’Brien MJ, Taylor AM, et al. Concussion in pediatric surgical patients scheduled for time-sensitive surgical procedures. Journal of Concussion. 2017;1:1–8.

9.         Tasker RC. Anesthesia and concussion. Current Opinion in Anesthesiology. 2017;30(3):343–348.

10.       Abcejo AS, Savica R, Lanier WL, Pasternak JJ. Exposure to Surgery and Anesthesia After Concussion Due to Mild Traumatic Brain Injury. Mayo Clinic Proceedings. 2017;92(7):1042–1052.

11.       King D, Collins-Yoder A. Perioperative Considerations in Patients With Concussion. AANA Journal. 2019;87(2):97–104.

12.       D’Souza RS, Sexton MA, Schulte PJ, Pasternak JJ, Abcejo AS. Recent Preoperative Concussion and Postoperative Complications: A Retrospective Matched-cohort Study. Journal of Neurosurgical Anesthesiology. October 23, 2019.

13.       Sheshadri V, Manninen P, Venkatraghavan L. Anesthesia in Patients With Postconcussion Syndrome: Is There Evidence? Journal of Neurosurgical Anesthesiology. April 2017;29(2):185.