Virginia Anesthesia Services LLC Marijuana Use in the Anesthetized Patient  - Virginia Anesthesia Services LLC

Marijuana Use in the Anesthetized Patient 

Marijuana extracted from the dried leaves of the Cannabis sativa plant contains about 60 cannabinoids, which are pharmacologically active compounds that agonize G-protein coupled receptors in the endocannabinoid system and affect the nervous system [1]. Due to the interactions between marijuana and organ systems, especially the brain, it is important for anesthesia providers to understand the potential consequences of marijuana use in anesthetized patients. 

In marijuana, ∆-tetrahydrocannabinol (THC) is usually present in the highest concentrations, followed by cannabidiol (CBD) [1]. The ratio of these two compounds is significant since CBD attenuates the more harmful effects of THC. In the past decades, different synthetic cannabinoids with potencies up to 200 times stronger than THC have become available [2]. Two cannabinoid receptors have been implicated in the literature: cannabinoid-1 (CB1) and cannabinoid-2 (CB2) receptors; these G-protein coupled receptors are partially agonized by THC and fully agonized by other synthetic cannabinoids [2]. CB1 receptors are primarily located in the hippocampus, cerebellum, and basal ganglia in the brain, in peripheral nerves, and in the spinal cord, while CB2 receptors are found mainly in immune and hematopoietic cells, which may partially explain the effect of cannabinoids on inflammation and nociception [3]. Activation of these receptors change neural signaling, specifically via direct inhibition of dopamine, acetylcholine, and glutamate release and indirect effects on GABA, NMDA, serotonin, and opioid receptors [3]. CNS effects commonly include euphoria with anti-anxiety components; however, cognitive functions such as learning and memory as well as psychomotor efficiency may become impaired [4]. Cardiovascular effects such as endothelial and myocardial cell damage, atherogenic effects, oxidative stress, and increased carboxyhemoglobin levels may also occur [5]. Preclinical research has shown CB1 antagonists and CB2 agonists lead to short- and long-term hemodynamic changes in animal models of cardiomyopathy, circulatory shock, and heart failure, suggesting excessive signaling of the CB1 receptor may contribute to cardiovascular detriments but signaling through the CB2 receptor may be cardioprotective to some extent [3].  

Because THC is a CNS depressant, anesthesiologists should be aware of additional interactions a patient may have had with other CNS depressants, such as alcohol, benzodiazepines, narcotics, or other sedative hypnotic drugs [4]. Inhalational anesthetics such as sevoflurane may also contribute to diffuse alveolar hemorrhage, as suggested by the authors on a 2014 case study [6,7]. A prospective, randomized clinical study of 60 adult males showed chronic cannabis use increases the propofol dosage necessary for general anesthesia induction [8]. Individual case studies report similar results with thiopental, isoflurane, and sevoflurane [4]. It is hypothesized that cannabis’ impact on the cytochrome p-450 system explains the increased requirement for anesthetic agents. Propofol exerts a concentration-dependent inhibitory effect on cytochrome p-450 2E1, 2B1, and 1A1 [9]. These enzymes are upregulated by long-term cannabis use, which may lead to a decrease in the patient’s response to propofol [10].  

Given the cardiovascular depression induced by marijuana, agents that increase heart rate in the anesthetized patient should be avoided; this includes ketamine, epinephrine, atropine, and pancuronium [4]. In these situations, β-blockers may be beneficial if added to the clinical regimen. On the other hand, cannabis at high doses can also block sympathetic activation and stimulate the parasympathetic system, which may lead to bradycardia and hypotension [11].  

A prospective, randomized double-blinded, placebo-controlled trial confirmed both high- and low-dose dexamethasone was effective at preventing post-extubation airway obstruction. This is a potential risk in habitual cannabis users because increased mucus production and loss of cilia function may lead to a decreased ability to clear airways [4,12]. To reduce coughing and irritation of respiratory pathways, sevoflurane may be the best anesthetic choice as it is the least pungent volatile anesthetic [4].  

Due to the increasing popularity and availability of both medical and recreational marijuana, anesthesiologists should take all the necessary precautions to avoid detrimental drug-drug interactions in anesthetized patients. Thorough patient screenings should become routine and surgical patients should be recommended to avoid cannabis if possible before surgery since the drug can stay in the bloodstream for more than 30 hours. Regardless, more research is warranted to assess the interactions of cannabis and anesthetic agents in varying demographics.  

References 

  1. Oberbarnscheidt, T., & Miller, N. S. (2017). Pharmacology of Marijuana. Journal of Addiction Research & Therapy, S11. DOI: 10.4172/2155-6105.S11-012  
  1. Pacher, P., Steffens, S., Haskó, G., Schindler, T. H., & Kunos, G. (2018). Cardiovascular Effects of Marijuana and Synthetic Cannabinoids: the Good, the Bad, and the Ugly. Nature Reviews Cardiology, 15(3), 151–166. DOI: 10.1038/nrcardio.2017.130  
  1. Hill, K. P. (2015). Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review. JAMA, 313(24), 2474–2483. DOI: 10.1001/jama.2015.6199  
  1. Horvath, C., Dalley, C. B., Grass, N., & Tola, D. H. (2019). Marijuana Use in the Anesthetized Patient: History, Pharmacology, and Anesthetic Considerations. AANA Journal, 87(6), 451–458.  
  1. Goyal, H., Awad, H. H., & Ghali, J. K. (2017). Role of Cannabis in Cardiovascular Disorders. Journal of Thoracic Disease, 9(7), 2079–2092. DOI: 10.21037/jtd.2017.06.104  
  1. Clarke, R. C., & Merlin, M. (2016). Cannabis: Evolution and ethnobotany (First paperback printing). University of California Press.  
  1. Kim, C. A., Liu, R., & Hsia, D. W. (2014). Diffuse Alveolar Hemorrhage Induced by Sevoflurane. Annals of the American Thoracic Society, 11(5), 853–855. DOI: 10.1513/AnnalsATS.201402-067LE  
  1. Flisberg, P., Paech, M., Shah, T., Ledowski, T., Kurowski, I., & Parsons, R. (2009). Induction Dose of Propofol in Patients Using Cannabis: European Journal of Anesthesiology, 26(3), 192–195. DOIL 10.1097/EJA.0b013e328319be59  
  1. Chen, T. L., Ueng, T. H., Chen, S. H., Lee, P. H., Fan, S. Z., & Liu, C. C. (1995). Human Cytochrome P450 Mono-Oxygenase System is Suppressed by Propofol. British Journal of Anesthesia, 74(5), 558–562. DOI: 10.1093/bja/74.5.558  
  1. Lindsey, W. T., Stewart, D., & Childress, D. (2012). Drug Interactions Between Common Illicit Drugs and Prescription Therapies. The American Journal of Drug and Alcohol Abuse, 38(4), 334–343. DOI: 10.3109/00952990.2011.643997  
  1. Ghuran, A., & Nolan, J. (2000). Recreational Drug Misuse: Issues for the Cardiologist. Heart, 83(6), 627–633. DOI: 10.1136/heart.83.6.627  
  1. Lin, C.-Y., Cheng, K.-H., Kou, L.-K., & Lee, C.-H. (2016). Comparison of High- and Low-dose Dexamethasone for Preventing Post-extubation Airway Obstruction in Adults: A Prospective, Randomized, Double-blind, Placebo-controlled Study. International Journal of Gerontology, 10(1), 11–16. DOI: 10.1016/j.ijge.2015.10.002