Is naloxone the best antidote to reverse tramadol-induced neuro-respiratory toxicity in overdose? An experimental investigation in the rat

Lagard, Camille; Malissin, Isabelle; Indja, Wassila; Réant, Patricia; Chevillard, L; Mégarbane, Bruno

doi:10.1080/15563650.2017.1401080

Cited by 27 publications

(37 citation statements)

References 35 publications

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“…It was clear that co-ingestion of other drugs or agents significantly affect the PSS of the studied patients. This result was extremely logic as the co-ingested drugs were mostly tramadol accounting for 44.59% of coingested substances followed by antipsychotics, mainly clozapine (14.86%), which are well-known to be unsafe medications and greatly affect the clinical course of poisoning owing to tramadol-induced respiratory depression and antipsychotics-induced cardiotoxicity (Lagard et al, 2018;Li et al, 2019). In studies done by Bonar et al (2014) and Law et al (2015), alcohol topped the list of co-ingested agents (96%), followed by cannabis and prescriptive opioids in USA.…”

Section: Discussionmentioning

confidence: 99%

Pattern of Acute Synthetic Cannabinoids Toxicity in Patients Presented to the Poison Control Center of Ain Shams University Hospitals

Hashem

Mahmoud

Anza

et al. 2021

Ain Shams Journal of Forensic Medicine and Clinical Toxicology

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Section: Discussionmentioning

confidence: 99%

Pattern of Acute Synthetic Cannabinoids Toxicity in Patients Presented to the Poison Control Center of Ain Shams University Hospitals

Hashem

Mahmoud

Anza

et al. 2021

Ain Shams Journal of Forensic Medicine and Clinical Toxicology

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“…[15]. On the other hand, while the evidence could not support the preventive effect of naloxone in such patients [54], seizures may be precipitated by injecting naloxone, accompanying high doses of tramadol [2,7,31,60,75]. Interestingly, recent meta-analyses have shown that the occurrences of seizures was not related to naloxone administration [67].…”

Section: Central Nervous Systemmentioning

confidence: 99%

“…Intubation/ventilation and administration of naloxone are implemented to treat respiratory depression or tramadolinduced apnea [16,70,131,132]. Some studies suggested that naloxone administration might cause seizure in tramadol intoxication and recommended against routine administration of naloxone for treating tramadol poisoning [10, 60,133]. However, a recent meta-analysis showed that naloxone administration does not increase the risk of seizure in tramadol poisoned patients [67].…”

Section: Treatmentmentioning

confidence: 99%

“…Naloxone can be used for the treatment of post-seizure complaints [134]. A combination of diazepam/naloxone is reported as an efficient antidote to reverse tramadol-induced CNS toxicity [75]. Due to the low risk of multiple seizures in tramadol toxicity, anticonvulsant treatment should not be routinely prescribed even for cases of initial seizures [10].…”

Section: Treatmentmentioning

confidence: 99%

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A review on tramadol toxicity: mechanism of action, clinical presentation, and treatment

et al. 2021

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Aims As an analgesic that acts upon the central nervous system (CNS), tramadol has gained popularity in treating moderate to severe pain. Recently, it has been increasingly reported as a drug of misuse with intentional overdoses or intoxications. This review focuses on tramadol intoxication in humans and its effects on different systems. Subject and method This narrative review provides a comprehensive view of the pharmacokinetics, mechanism of action, and incidence of tramadol toxicity with an in-depth look at its side effects. In addition, the main approaches to the management of tramadol poisoning are described. Results Tramadol poisoning can affect multiple organ systems: gastrointestinal, central nervous system (seizure, CNS depression, low-grade coma, anxiety, and over time anoxic brain damage), cardiovascular system (palpitation, mild hypertension to life-threatening complications such as cardiopulmonary arrest), respiratory system, renal system (renal failure with higher doses of tramadol intoxication), musculoskeletal system (rhabdomyolysis), endocrine system (hypoglycemia), as well as, cause serotonin syndrome. Seizure, a serious nervous disturbance, is more common in tramadol intoxication than with other opioids. Fatal tramadol intoxications are uncommon, except in ingestion cases concurrent with other medications, particularly CNS depressants, most commonly benzodiazepines, and ethanol. Conclusion With the increasing popularity of tramadol, physicians must be aware of its adverse effects, substantial abuse potential, and drug interactions, to weigh its risk–benefit ratio for pain management. Alternative therapies might be considered in patients with a previous overdose history to reduce risks for adverse outcomes.

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“…Given the increasing numbers of tramadol overdose and fatalities in recent decades, this drug has been classi ed as controlled substance in several countries [2]. Tramadol overdose can lead to loss of consciousness, seizures, respiratory depression, serotonin syndrome, and death [3,4]. However, the molecular and biochemical mechanisms of tramadol toxicity are still poorly understood [5].…”

Section: Introductionmentioning

confidence: 99%

The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: An experimental study

Nakhaee

Farrokhfall

Miri‐Moghaddam

et al. 2021

Preprint

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Background: Tramadol is a widely used synthetic opioid. Substantial research has previously focused on the neurological effects of this drug, while the efficacy of various treatments to reduce the associated side effects has not been well studied. This study aimed to evaluate the protective effects of naloxone, diazepam, and quercetin on tramadol induced seizure and sedation level in male rats. Methods: The project was performed with 72 male Wistar rats with an average weight of 200-250 g. The rats were randomly assigned to 8 groups. Tramadol was administered intraperitoneally at an initial dose of 25 mg/kg/day. On the 14th day, tramadol was injected at 75 mg/kg, either alone or together with naloxone, diazepam, and quercetin (acute and chronic) in different combinations. The rats were monitored for 6 hours on the last day, and the number, the duration, and the severity of seizures (using the criteria of Racine) were measured at different times. The sedation level was also assessed based on a 4-point criterion, ranging from 0 to 3, at different times after injection. Data were analyzed in SPSS software using Kruskal-Wallis, Chi-square, multivariate regression, and generalized estimating equation (GEE) tests. The significance level was set at P <0.05.Results: The naloxone-diazepam combination reduced the number of seizures, severity, and duration of seizures compared to the tramadol use alone and reduced the number of higher-intensity seizures to a greater extent than other treatments. Naloxone alone reduced the number and duration of seizures, as well as the duration of mild seizures. Diazepam decreased the severity and duration of seizures. However, it increased the number of mild seizures. In comparison with the tramadol alone group, the acute quercetin group had a lower duration of mild and severe seizures, and higher numbers of mild and moderate seizures. Chronic quercetin administration decreased the duration of seizures and significantly increased the number of mild seizures. Naloxone-Quercetin also reduced the duration of mild and severe seizures significantly. In the GEE model, all groups had higher sedation levels than the saline only group (P <0.001). None of the protocols had a significant effect on sedation levels compared to the other groups.Conclusion: The combined administration of naloxone and diazepam in acute on chronic tramadol poisoning can effectively reduce most seizure variables, compared to the tramadol use alone. However, none of the treatments can improve sedation levels.

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Is naloxone the best antidote to reverse tramadol-induced neuro-respiratory toxicity in overdose? An experimental investigation in the rat

Abstract: Diazepam/naloxone combination is the most efficient antidote to reverse tramadol-induced CNS toxicity in the rat.

Cited by 27 publications

References 35 publications

Pattern of Acute Synthetic Cannabinoids Toxicity in Patients Presented to the Poison Control Center of Ain Shams University Hospitals

Pattern of Acute Synthetic Cannabinoids Toxicity in Patients Presented to the Poison Control Center of Ain Shams University Hospitals

A review on tramadol toxicity: mechanism of action, clinical presentation, and treatment

The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: An experimental study

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