Keywords
Dear Editor,
Pethidine (meperidine) was discovered in 1939 and has long been recognized as an analgesic in routine clinical practice (1). Painless delivery is one of the oldest fields in which this drug has been used for analgesia (2). In recent years, many concerns have been raised regarding the use of pethidine as an analgesic (3). Seizures are a major concern with meperidine use, as it is one of the drugs with high epileptogenic potential (4). Normeperidine, a neurotoxic metabolite of meperidine, is known to be the primary culprit in causing seizures. Although the risks of pethidine use in patients with liver dysfunction are well established, long-term use, especially at high doses, can also be hazardous for individuals without hepatic impairment. The key factor is the individual's cytochrome system, which determines the production of this dangerous metabolite (5).
Seizures are not the only risks associated with pethidine. Meperidine is considered the most dangerous opioid for causing perioperative delirium (6, 7). However, some authors argue that concerns about the use of this drug are exaggerated (8). In response to this perspective, two points should be considered. First, when equally or more effective drugs are available and have been proven safer, what justifies the use of an older medication with documented safety concerns? Secondly, even these authors do not provide definitive recommendations, leaving final conclusions to further future research.
The reality is that pethidine use has declined over the past two decades due to growing concerns regarding its adverse effects, primarily seizures and serious drug-drug interactions (9). However, its relatively exclusive property as an antishivering agent remains noteworthy. Although no definitive gold standard for the prevention and treatment of shivering has been established, pethidine consistently appears at the forefront of any list of effective medications for this purpose (10-13).
Given that the most rational use of pethidine today is for the prevention and treatment of shivering, it may be more appropriate to refer to this drug as an antishivering agent rather than a narcotic analgesic. This reclassification could help shift the traditional perspective of pethidine as a primary analgesic for surgical patients, encouraging the use of newer and safer drugs for pain management while reserving pethidine for its unique antishivering properties.
References
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Lee MC, Abrahams M. Pain and analgesics. In: Bennett PN, Brown MJ, Sharma P, editors. Clinical Pharmacology. Oxford: Churchill Livingstone; 2012. p. 278-94. https://doi.org/10.1016/b978-0-7020-4084-9.00057-4.
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Cameron SJ. Pethidine. Br Med J. 1947;1(4503):579. [PubMed ID: 20343513]. [PubMed Central ID: PMC2053090]. https://doi.org/10.1136/bmj.1.4503.579-b.
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Ching Wong SS, Cheung CW. Analgesic Efficacy and Adverse Effects of Meperidine in Managing Postoperative or Labor Pain: A Narrative Review of Randomized Controlled Trials. Pain Physic J. 2020;23(2):175-201. https://doi.org/10.36076/ppj.2020/23/175.
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Swart LM, van der Zanden V, Spies PE, de Rooij SE, van Munster BC. The Comparative Risk of Delirium with Different Opioids: A Systematic Review. Drug Ag J. 2017;34(6):437-43. [PubMed ID: 28405945]. [PubMed Central ID: PMC5427092]. https://doi.org/10.1007/s40266-017-0455-9.
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Moy KV, Ma JD, Best BM, Atayee RS. Factors impacting variability of the urinary normeperidine-to-meperidine metabolic ratio in patients with chronic pain. J Anal Toxicol. 2014;38(1):1-7. [PubMed ID: 24133175]. https://doi.org/10.1093/jat/bkt087.
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Schlick KH, Hemmen TM, Lyden PD. Seizures and Meperidine: Overstated and Underutilized. Ther Hypothermia Temp Manag. 2015;5(4):223-7. [PubMed ID: 26087278]. [PubMed Central ID: PMC4677539]. https://doi.org/10.1089/ther.2015.0013.
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Boyle JM, McCall KL, Nichols SD, Piper BJ. Declines and pronounced regional disparities in meperidine use in the United States. Pharmacol Res Perspect. 2021;9(4). e00809. [PubMed ID: 34128348]. [PubMed Central ID: PMC8204095]. https://doi.org/10.1002/prp2.809.
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Lopez MB. Postanaesthetic shivering – from pathophysiology to prevention. Romanian J Anaesth Intens Care. 2018;25(1):73-81. https://doi.org/10.21454/rjaic.7518.251.xum.
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Choi KE, Park B, Moheet AM, Rosen A, Lahiri S, Rosengart A. Systematic Quality Assessment of Published Antishivering Protocols. Anesth Analg. 2017;124(5):1539-46. [PubMed ID: 27622717]. https://doi.org/10.1213/ANE.0000000000001571.
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Park SM, Mangat HS, Berger K, Rosengart AJ. Efficacy spectrum of antishivering medications: meta-analysis of randomized controlled trials. Crit Care Med. 2012;40(11):3070-82. [PubMed ID: 22890247]. https://doi.org/10.1097/CCM.0b013e31825b931e.
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Solhpour A, Jafari A, Hashemi M, Hosseini B, Razavi S, Mohseni G, et al. A comparison of prophylactic use of meperidine, meperidine plus dexamethasone, and ketamine plus midazolam for preventing of shivering during spinal anesthesia: a randomized, double-blind, placebo-controlled study. J Clin Anesth. 2016;34:128-35. [PubMed ID: 27687359]. https://doi.org/10.1016/j.jclinane.2016.03.036.