Introduction
Methods
Results
Incidence
Tramadol metabolism
Mechanism of action
MOR Ki binding affinity (μM) | NET Ki binding affinity (μM) | SERT Ki binding affinity (μM) | |
---|---|---|---|
Racemic tramadol | 2.4 | 14.6 | 1.19 |
( +) Tramadol | 1.33 | NA | 0.53 |
(−) Tramadol | 24.8 | 0.43 | NA |
Tramadol ( +) M1 | 0.0034 | NA | NA |
Tramadol (−) M1 | 0.24 | NA | NA |
Tramadol (+ / −) M5 | 0.1 | NA | NA |
Clinical presentations of tramadol intoxication
Gastrointestinal system
Central nervous system
References | Study | Patients (n) | Gender | Age (years) | Dose | Cause of intoxication | Note |
---|---|---|---|---|---|---|---|
Ryan [11] | Retrospective cases series | 71 | 39% M, 61% F | Median: 41 (range: 17–69) | > 400 mg (median: 1000 mg | Seizures were dose-related and occurred in 8 patients; one of them co-ingested a benzodiazepine | |
Eizadi-Mood [54] | Prospective cohort | 104 | 67% M, 33% F | Mean: 26.3 | The incidences of seizure were 14.1% vs. 5.1% between patients received naloxone (18.3% of patients) and those who did not, respectively | ||
Farajidana [59] | Retrospective | 232 | Mean: 1420 ± 1120 mg | Therapeutic and overdose | Seizure episodes occurred once (89.2%), twice (9.1%), and three times (1.7%). The prevalence of trauma was 24.6% | ||
Shadnia [10] | Retrospective cohort | 100 | 82% M, 18% F | Mean: 23.3 ± 7.7 | Mean: 1160 ± 985 mg (range, 100–7000 mg) | 93% with suicidal intent | 7% had recurrent seizures and all patients recovered without squeals; 3–15% co-ingested other drugs; The mean dose in those patients who had recurrent seizures were approximately 2000 mg and in those with only a single seizure, it was approximately 1100 mg |
Taghaddosinejad [2] | Prospective case series | 401 | 83% M, 17% F | Mean: 22.9 (range, 14–50) | Mean: 1510 mg ± 1350 (range, 200–7000 mg) | 51.9% intentional overdoses | 71% of patients experienced just one seizure; 30.2% of patients had a history of seizure; 3–13% of seizure cases co-ingested other medications or chemicals |
Petramfar [66] | Cross-sectional study | 106 | 96.2% M, 3.8% F | Mean: 26.7 ± 6.9 | Mean: 363 ± 303 (range, 50–1500 mg) | 18.9% therapeutic and 81.1% abused | 86.8% had new-onset provoked seizure(s) induced by tramadol and in 13.2%, tramadol ingestion was considered as a precipitating factor in the setting of previously-known epilepsy |
Talaie [9] | Cross-sectional study | 132 | 73.5% M, 26.5% F | 24.13 (range 15–69) | Mean: 2060 mg | Tramadol overdose | The seizure occurred in 46.2% of patients (all were generalized tonic–clonic seizures); Most patients with seizure used tramadol in the dose range of 500–1000 mg; Mean tramadol dose was lower among females than males (1706 mg vs. 2413 mg), but the difference was statistically insignificant |
Jovanovic-Cupic [34] | Prospective | 57 | 82.5% M, 17.5% F | 22.3 (range 16–43 years) | 250–2500 mg | Tramadol abuse or intoxication | Tonic–clonic seizures occurred in 54.4% of patients, which were single in 45%; Seizures occurred within 24 h after tramadol intoxication in 84% of patients; Compared to addicts without seizures, the abusers with seizures were younger |
Farzaneh [60] | Case–Control | 124 | 92%M, 8% F | 27 | – | Tramadol overdose | In the naloxone group, the incidence of seizure was higher than in the control group. The possibility of seizure occurrence was significantly higher in naloxone group than the control group |
Goodarzi [62] | Cross-sectional study | 54 | – | 26.48 | Range: 200–11,000 mg Mean: 3250 mg | – | The route of poisoning in all of patients was oral. 20.4% required intensive care unit (ICU) during treatment. The mortality rate was 7.4%. There was a significant difference between male and female according to coma grading. The significant difference between number of seizure and ingested dose, ICU admission, and mortality was observed. There was also a significant difference between mortality and ingested dose and ICU admission |
Rahimi [3] | Cross sectional | 144 | 77% M 23% F | 23.7 ± 6.9 (range = 15–57) | 1970 ± 233 mg (range: 100–20,000 mg) | Tramadol overdose | Seizure (47.91%) was the most frequent symptom There was correlation between ingested dose and seizure (OR: 2.7, 95% CI:1.03–7.09) |
Abbasi [136] | Cross sectional | 150 | 94% M,6% F | 23.23 ± 5.94 (17–52) | NM | Tramadol overdose | No differences were observed between patients with seizure and without seizure in terms of ingested dose. seizures were more likely to occur in males and patients with a previous history of tramadol use |
Eizadi mood [137] | Cross-sectional | 184 | 76.6% M, 23.4% F | 24 ± 7 years | 2010 ± 7470 mg (100–10,000) | Tramadol overdose | Significant relationships between tramadol dose and seizure no significant differences between males and females in terms of seizure |
Farzaneh [138] | Cross-sectional | 122 | 89.5% M, 10.5% F | 27.0 ± 7.2 years | 2210 ± 1170 mg (ranged:8000–15) | Tramadol overdose | Seizure had no relationship with gender, age, and history of addiction to tramadol ingested dose of tramadol was not different between two groups of patients with seizure and without seizure |
Ahmadimanesh [139] | Cross-sectional | 120 | 75.8% M, 24.1% F | 22.8 ± 5.8 years (range: 14–37 years) | Median(IQR) with seizure:1000 (475, 2000) without seizure:1000(500, 1850) | Tramadol overdose | Seizure correlated with gender and concentrations of tramadol. There was no significant difference between the groups of patients with and without seizure in the median of ingested dose. Co-ingestion of other opioids and a history of sedative-hypnotics use resulted in lower incidences of seizure. history of tramadol use and/or addiction to opioids do not influence seizure occurrence |
Mohammadpour [73] | Cross-sectional | 121 | 67.7% M, 32.3% F | 25 (14–35) year | 500 and 800 mg were the lowest and highest doses, in seizure group, | Tramadol users | There was no significant difference in tramadol concentrations between the seizure and non-seizure groups |
Ahmadi [140] | Cross-sectional | 546 | 75.6% M, 24.4% F | 22.5 ± 6.25 (range = 13–80) | 40.7% ingested lower than 1000 mg | Tramadol overdose | Seizure incidence in males was higher than females There was significant correlation between Tramadol dosages and occurrence of seizure |
Murray [141] | Cross-sectional | 80 | 60% M, 40% F | 26 (IQR: 17–49) years | NM | Tramadol overdose | Seizure occurred in 52.5% There was no significant difference in tramadol concentrations between males and females Seizure and naloxone administration had no relationship |
Nasr [74] | Cross-sectional | 100 | 80% M, 20% F | 26.3 ± 12.1 years | NM | Tramadol overdose | Seizure occurred in 46% There was no significant relationship between tramadol blood levels and seizures |
Adree [17] | Cross-sectional | 102 | 86.2% M, 13.8% F | 26.24 ± 9.50 (range:5–55 years) | Mean dose of seizure group: 686 ± 318 mg (300–1500) | Tramadol overdose | Seizure occurred in 27.4% There was significant relationship between ingested dose and seizures There was no significant relationship between tramadol concentration and seizure |