Meperidine-induced serotonin syndrome in a susceptible patient

Guo, Shu Lin; Wu, Tzong-Jeng; Liu, Chih Chung; Ng, Chen-Chuan; Chien, Chih Cheng; Sun, Hsiao-Lun

doi:10.1093/bja/aep167

Cited by 23 publications

(10 citation statements)

References 5 publications

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“…However, a more severe manifestation of 5‐HT toxicity is the potentially fatal serotonin syndrome, which includes a triad of effects: mental state changes (delirium, agitation, confusion and coma), autonomic stimulation (hyperthermia, tachycardia and diaphoresis) and neuromuscular excitation (tremor, hyperreflexia and rigidity; Gillman, ). The serotonin syndrome has been associated with several opioids or combinations of opioids with other serotonergic drugs in numerous case reports (Schwartz et al, ; Guo et al, ; Monte et al, ; Rastogi et al, ; Walter et al, ; Shakoor et al, ; Abadie et al, ). In a small analysis of pharmacovigilance data from a single country, tramadol was the opioid that was most frequently associated with the serotonin syndrome (Chassot et al, ).…”

Section: Introductionmentioning

confidence: 99%

Opioid‐induced inhibition of the human 5‐HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome

Rickli

Liakoni

Hoener

et al. 2018

British J Pharmacology

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Background and PurposeOpioids may inhibit the 5‐HT transporter (SERT) and the noradrenaline transporter (NET). NET inhibition may contribute to analgesia, and SERT inhibition or interactions with 5‐HT receptors may cause serotonergic toxicity. However, the effects of different opioids on the human SERT, NET and 5‐HT receptors have not been sufficiently studied.Experimental ApproachWe determined the potencies of different opioids to inhibit the SERT and NET in vitro using human transporter‐transfected HEK293 cells. We also tested binding affinities at 5‐HT1A, 5‐HT2A and 5‐HT2C receptors. Additionally, we assessed clinical cases of the serotonin syndrome associated with each opioid reported by PubMed and a World Health Organization database.Key ResultsDextromethorphan, l(R)‐methadone, racemic methadone, pethidine, tramadol and tapentadol inhibited the SERT at or close to observed drug plasma or estimated brain concentrations in patients. Tapentadol was the most potent NET inhibitor. Pethidine, tramadol, l(R)‐methadone, racemic methadone, dextromethorphan and O‐desmethyltramadol also inhibited the NET. 6‐Monoacetylmorphine, buprenorphine, codeine, dihydrocodeine, heroin, hydrocodone, hydromorphone, morphine, oxycodone and oxymorphone did not inhibit the SERT or NET. Fentanyl interacted with 5‐HT1A receptors and methadone, pethidine and fentanyl with 5‐HT2A receptors, in the low micromolar range. Opioids most frequently associated with the serotonin syndrome are tramadol, fentanyl, tapentadol, oxycodone, methadone and dextromethorphan.Conclusions and ImplicationsSome synthetic opioids interact with the SERT and NET at potentially clinically relevant concentrations. SERT inhibition by tramadol, tapentadol, methadone, dextromethorphan and pethidine may contribute to the serotonin syndrome. Direct effects on 5‐HT1A and/or 5‐HT2A receptors could be involved with methadone and pethidine.

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Section: Introductionmentioning

confidence: 99%

Opioid‐induced inhibition of the human 5‐HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome

Rickli

Liakoni

Hoener

et al. 2018

British J Pharmacology

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“…The syndrome usually occurs in the context of usage of antidepressants or other medications that increase serotonin prior to surgery. However, a previous report described the occurrence of meperidine-induced serotonin syndrome in a patient with a past history of clomipramine-induced serotonin syndrome [2]. The present report is the first case of meperidine-induced serotonin syndrome in a patient with no use of other serotonergic medication and also with no history of susceptibility.…”

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confidence: 63%

Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report

Joe

Kim

Park

et al. 2017

Korean J Anesthesiol

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Serotonin syndrome is an unexpected fatal adverse event related to serotonergic medication. This case report is the first report describing the possible treatment effect of famotidine on serotonin syndrome. Furthermore, this is the first case report of serotonin syndrome induced by meperidine alone in a patient with no previous history suggesting a susceptibility to serotonin syndrome. A 70-year-old male with no recent history of serotonergic drug use presented with severe serotonin syndrome following ureteroscopy, possibly due to postoperative meperidine administration. The patient's symptoms included hypertension, tachycardia, tachypnea, hyperthermia, myoclonus, diaphoresis, retching, nausea, agitation, and semicoma mentality with no pupillary light reflex. Symptoms began to subside immediately after the administration of intravenous famotidine for prevention of aspiration pneumonia, with mental and neurological symptoms showing improvement initially, followed by autonomic symptoms. This case report suggests that the histamine type 2 receptor antagonist famotidine may be an effective emergency treatment for serotonin syndrome.

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“…(Five years earlier, the patient had experienced a life-threatening episode whilst taking clomipramine. 138 ) The 2 week half-life of fluoxetine's active metabolite norfluoxetine (Table 3) is the probable explanation for the former case. 139 The relative risk of a patient experiencing ST in the perioperative period is influenced by a combination of factors that includes a history of taking a serotonergic drug(s) and the perioperative administration of additional serotonergic drugs, including OADs.…”

Section: Risk Assessment and Planning Of Anaesthesiamentioning

confidence: 95%

The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review

Baldo

Rose

2020

British Journal of Anaesthesia

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Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthrenes. Symptoms of serotonin toxicity are attributable to an effect on monoaminergic transmission caused by an increased synaptic concentration of serotonin. The serotonin transporter (SERT) maintains low serotonin concentrations and is important for the reuptake of the neurotransmitter into the presynaptic nerve terminals. Some opioids inhibit the reuptake of serotonin by inhibiting SERT, thus increasing the plasma and synaptic cleft serotonin concentrations that activate the serotonin receptors. Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity. Tramadol also has a direct serotonin-releasing action. Fentanyl produces an efflux of serotonin, and binds to 5hydroxytryptamine (5-HT) 1A and 5-HT 2A receptors, whilst methadone, meperidine, and more weakly tapentadol, bind to 5-HT 2A but not 5-HT 1A receptors. The perioperative period is a time where opioids and other serotonergic drugs are frequently administered in rapid succession, sometimes to patients with other serotonergic drugs in their system. This makes the perioperative period a relatively risky time for serotonin toxicity to occur. The intraoperative recognition of serotonin toxicity is challenging as it can mimic other serious syndromes, such as malignant hyperthermia, sepsis, thyroid storm, and neuroleptic malignant syndrome. Anaesthetists must maintain a heightened awareness of its possible occurrence and a readiness to engage in early treatment to avoid poor outcomes.

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Meperidine-induced serotonin syndrome in a susceptible patient

Abstract: We present a patient with a history of clomipramine-induced serotonin syndrome 5 yr prior who developed serotonin syndrome after a single dose of meperidine. This report heightens appreciation of population at risk and also recognition of potential toxicity in meperidine.

Cited by 23 publications

References 5 publications

Opioid‐induced inhibition of the human 5‐HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome

Opioid‐induced inhibition of the human 5‐HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome

Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report

The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review

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