Tramadol Poisoning Research Articles

Tramadol Overdose Induced Transient Paresthesia and Decreased Muscle Strength: A Case Series

Background: Tramadol overdose is relatively common in Iran. A series of tramadol poisoned patients with paresthesia and decreased muscle strength are described. Methods: In this prospective cross-sectional study, all referred cases to Mashhad Medical Toxicology Center with suspected tramadol poisoning between 1st July 2010 and 1st September 2012 were included. Patients with mixed overdose, history of neurologic and musculoskeletal disorders including primary seizure, and history of addiction were excluded. Patients were visited on admission, 6 and 12 hours later. All cases underwent complete neurologic examination. Muscle strength was assessed with manual muscle testing. Results: Tramadol overdose accounted for 1026 cases during the study period. Eight hundred eighty nine cases were excluded and finally 137 cases were tramadol only overdose. Most patients (92%) were men. Mean (SD, min-max) age was 24.5 (6.9, 10-42) years. The strength of upper and lower limbs symmetrically declined in the first visit and increased gradually in 6 and 12 hours post-admission, but the strength of lower limbs was more significantly affected on admission and after 6 hours (P < 0.001) compared to upper limbs. Paresthesia happened in 64%, 9% and 0% in upper limbs and 86%, 35% and 3% in lower limbs on admission, and after 6 and 12 hours. No spasticity and flaccidity were observed. On admission, pupils were symmetrically reactive and 6.7 (2.3, 1-11) mm wide. Pupil size significantly declined to 5.6 (2.1, 1.3-9.0) mm 6 hours later (P < 0.001). Conclusion: Transient paresthesia and transient symmetrical decline in muscle strength of upper and lower limbs are potential neurologic complications following tramadol abuse and overdose. Further studies are needed to fully clarify the pathogenesis and mechanism of these complications following tramadol overdose.

G28(P) Tramadol intoxication: an emerging entity in paediatrics?

AimTramadol is a synthetic opioid widely used to treat pain in adults and children over 12 years old. Extensive research on the toxicity of tramadol in adults has been published...

Epidemiological Study of Poisoning in Patients of Karaj Shariati Hospital in 2011 to 2012

Background : Acute poisoning is one of the most problems of health systems in the world. The aims of this study are evaluation of demographic characteristics and causes of poisonings in patients referred to Karaj Shariati hospital. Methods: A cross sectional study was done in one year. With a non-probability convenience sampling, all of poisoning patients admitted in Karaj Shariati hospital from June 2011 to June 2012 were studied. Data collected from patients records and then analyzed. Results: One hundred seventy two drug poisoning patients with mean age of 29.8 (SD=13.4) years evaluated. The most common drugs which caused poisoning were: Benzodiazepines, Tramadol, Psychiatry drugs and Acetaminophen. 12.8 percent of patients had drug-induced seizure and mortality rate was 5.8 %. There was a relation between Tramadol poisoning and drug-induced seizure ( p value=0.000, Odds Ratio=12.8, 95%Confidence of Interval (4.7-34.8)). Conclusion: This study showed that Tramadol poisoning prevalence is high and opiates are the most common cause of death in drug poisonings, which show need to more educations in schools and addiction-disuse centers and more controls on pharmacies.

Postmortem Redistribution of Tramadol and O-Desmethyltramadol

Tramadol is a widely used analgesic opioid for moderate-to-severe pain due to its efficacy and safety. Although tramadol induces less adverse effects compared with other opioids, an increased number of documented cases of dependence, abuse, intentional overdose or intoxication have been described. In fatal intoxication, the interpretation of the probable cause of death often relies on the measurement of the tramadol concentration in blood. However, postmortem redistribution (PMR) may affect the results and therefore bias the autopsy report. In the present study, the postmortem cardiac and femoral blood samples from 15 cases of fatal tramadol intoxication were obtained to assess the PMR of tramadol and its main active metabolite, O-desmethyltramadol (M1). Toxicological analysis was performed by the gas chromatography-electron impact-mass spectrometry (GC-EI-MS) method, previously developed and validated for the quantification of both analytes. The cardiac-to-femoral blood ratios of 1.40 and 1.28 were obtained for tramadol and M1, respectively. Results were compared with those in the literature and it was possible to conclude that femoral blood should be considered for quantitative interpretations in fatal cases of tramadol intoxication.

Promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning

Promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning

Clinical Study of Acute Tramadol Poisoning in the Poison Control Center, Ain Shams University in 2012

An increasingly alarming phenomenon of tramadol abuse in Egypt has been demonstrated in the recent years. Although the issue of drug abuse is not a newly introduced issue to Egyptian society but the wide range of usage and illegal transactions associated with tramadol abuse making it the most easily accessible and readily provided drug at low cost. Aim of the work: is to highlight the magnitude of tramadol poisoning and its patterns during the year 2012. Interpretation of the poisoning data through an annual report would be essential to face continuously challenging hazards. Patients and methods: This study was carried out on 1581patients presented to the emergency department of the Poison Control Center, Ain Shams University Hospitals (PCCA)due to acute tramadol poisoning, in the period from 1, January 2012 to 31,December 2012.A descriptive analysis and statistics of the medical records is accomplished. Results: The majority of patients (54.6%) were between 19 and 30 years, with male predominance representing (79.8%)of the total presented cases. The majority of admitted patients (56.6%) were male drug addicts, followed by suicidal attempt in (26.6%).Co- ingestion of other drugs or agents was recorded in (16%) of admitted tramadol patients which increase toxicity significantly. The most frequent clinical manifestations in admitted tramadol patients were coma in (52%), Constricted pupil in (30%)and seizures in (17.5%). Respiratory failure was present in 12.6% of admitted patients. Death occurred in 14 cases (0.9%) of the presented cases. The main cause of death was acute respiratory failure.

Should activated charcoal be given after tramadol overdose?

Letter to the editor The efficacy of oral activated charcoal (AC) for the adsorption of drugs and poisons has been widely described in the literature [1]. AC can prevent systemic absorption of drugs if administrated within 1–2 h of ingestion and possibly longer after ingestion of sustained-release preparations or drugs that delay gastric emptying, such as opioids or antimuscarinic drugs. Since routine use of AC is discouraged [1], it is important to consider the risks and benefits of AC on a drug-by-drug basis. This brings us to the question of whether AC should be administrated to patients with tramadol overdose? Balancing the hazards of tramadol poisoning versus the potential risks of charcoal administration is important for answering this question. In general, AC is considered to be a benign type of management, but some risks are associated with its use. Many patients vomit while some aspirate gastric contents into the lungs, causing pneumonitis [2-4]. Significant predictive factors for aspiration pneumonitis after drug overdose include a Glasgow Coma Scale score of <15, emesis, seizure, and ingestion of tricyclic antidepressants [2]. The mortality for patients with aspiration pneumonitis has been reported to be 8.5% compared with 0.4% for those without aspiration pneumonitis, with patients with aspiration pneumonia having a significantly longer hospitalization [2]. In recent years, tramadol poisoning has become one of the most common causes of admissions to emergency departments in Iran [5-11]. Important complications of tramadol poisoning include seizures as well as depression of the central nervous system (CNS) and respiratory system. It has been reported that 15% to 35% of hospital referred patients with tramadol poisoning experience

A suicidal poisoning due to tramadol. A metabolic approach to death investigation

Tramadol is a synthetic opioid, widely used for post-surgical and chronic pain. Lethal overdose due only to tramadol is not common; more often the poisoning is due to tramadol in combination with other substances.Reported is a suicidal case of lethal tramadol poisoning in a 48-year-old woman. Tramadol and its metabolites O-desmethyltramadol (M1), N-desmethyltramadol (M2), N,N-didesmethyltramadol (M3), N,O-didesmethyltramadol (M5) were detected by GC/MS in biological fluids (femoral blood, bile, urine, gastric content) and viscera (brain, lung, liver and kidney). The tramadol concentration in femoral blood was 61.83 mcg/ml which is approximately 30 times higher than that believed to be lethal.According with other Authors, a preferential formation of M1 over M2 (M1/M2 ratio >1) is indicative of acute death, while M1/M2 ratio <1 suggests that death occurred after a longer time lapse from ingestion.

Promising Effects of Intravenous Lipid Emulsion as an Antidote in Acute Tramadol Poisoning

In recent years, research has provided experimental and subjective evidence that intravenous lipid emulsions (ILEs) reverse some hemodynamically considerable poisonings with various drugs. The aim of this study was to investigate the possible antidotal effect of ILE on acute tramadol poisoning. Thirty male New Zealand rabbits weighing 2.5 to 3 kg were divided into 6 groups, 5 in each. Two groups were considered controls, and the rest were treated intravenously with a dose of 50 mg/kg of tramadol. Thirty minutes later, infusions of either ILE 20% (3 doses of 6, 12, and 18 mL/kg) or normal saline (dose of 18 mL/kg) were administered. The survival of animals, total seizure time, and hemodynamic parameters were monitored immediately after infusions and subsequently for 3 observations during 24 hours. Survival percentages at doses of 6 and 12 mL/kg of ILE were both 100% (P < 0.001), and 80% at a dose of 18 mL/kg (P < 0.01). Intravenous lipid emulsion reduced tramadol-induced tachycardia when administered within 30 minutes of poisoning (P < 0.01) and showed positive effects on normalizing mean arterial pressure and diastolic blood pressure (P < 0.05). However, ILE did not have major effect on systolic blood pressure. Intravenous lipid emulsion also prevented tramadol-related seizures in doses of 6 and 12 mL/kg (P < 0.001) and reduced elevated creatine phosphokinase levels with the 2 higher doses (P < 0.001). Intravenous lipid emulsion significantly reduced mortality due to acute toxicity with tramadol in rabbits, although increasing the ILE dose may cause reverse effects.

Danger of Hypoglycemia Due to Acute Tramadol Poisoning

To report a case of prolonged hypoglycemia after acute tramadol poisoning. We describe a patient's clinical presentation and outcome with prolonged hypoglycemia attributable to acute tramadol poisoning. In addition, the possible mechanism for the hypoglycemia is discussed, and a brief review of the pertinent literature is presented. A 54-year-old woman had previously undergone a partial hepatectomy because of involvement of her liver by a gastrointestinal stromal tumor. After ingestion of 3,000 mg of tramadol with suicidal intent, she developed prolonged hypoglycemia that necessitated treatment with continuous intravenous glucose infusion for 24 hours. Reports in the literature have described central nervous system depression, nausea, vomiting, tachycardia, seizures, and even death from tramadol overdoses. This report alerts clinicians to the potential danger of severe hypoglycemia in tramadol poisoning.

Continuing Professional Development: Tramadol overdose and the potential for seizure after naloxone administration

Overview Tramadol is the most widely prescribed opiate analgesic (National Treatment Agency for Substance Misuse, 2011) and, as a result, is present in a large number of overdoses that present in the pre-hospital arena. Naloxone is indicated for use by ambulance personnel where the level of conciousness is reduced due to a known, or possible, overdose of an opiate containing substance (JRCALC, 2006). A case study of a tramadol overdose shows a close temporal relationship between naloxone administration and a seizure. While seizure is a symptom of tramadol intoxication (Saidi et al, 2008), the speed with which it occurred after naloxone administration seemed too fast to be merely coincidence. A study of the literature shows evidence that naloxone can instigate seizure in the case of a tramadol overdose (Raffa and Stone, 2008; Rehni et al, 2008). This information is particularly pertinent to the ambulance clinician as the consequence of a seizure can be important, both practically and clinically. The findings do not suggest that naloxone should be withheld, but that the potential for seizure should be noted and any forthcoming seizure dealt with. More research is needed to further define the factors that affect the seizurogenicity of naloxone in tramadol overdose. Learning Outcomes After completing this module you will: • Understand the use of tramadol and its mechanism of action • Have an awareness of the potential presentations of a patient with Tramadol poisoning • Understand the pre-hospital management of tramadol poisoning, and the measures that can assist with hospital care • Be aware of the potential for seizure following naloxone administration, and the steps needed to manage it

Tramadol-induced apnea

Background and ObjectivesIn contrast with other opioids, there are few cases of tramadol-related respiratory depression described in the literature, and renal impairment is a proposed risk factor. The aim of this study is to determine the prevalence of and predisposing factors for tramadol-related apnea in patients referred to our center. Patients and MethodsAll patients referred to Loghman-Hakim Hospital between February 2009 and April 2010 with pure tramadol intoxication were identified retrospectively. Data collected included the patient's age, sex, ingested dose, route of exposure, reason for poisoning (acute overdose or supratherapeutic use), previous history of suicidal attempts, previous history of drug or substance abuse (including tramadol), and clinical features on admission including seizures and apnea. ResultsWe identified 525 patients with deliberate self-poisoning (359; 68.4%) or abuse (146; 27.8%), and in 114 (21.7%) of these, there was a history of tramadol abuse. Four hundred twenty-nine (81.7%) of patients had acute poisoning and were referred to hospital within 6 hours of ingestion. Nineteen patients (3.6%) experienced apnea and received respiratory support (16; 84.2%) or naloxone administration (3; 15.8%) within 24 hours of ingestion (mean, 7.7 ± 7 hours; range, 1-24 hours). The mean dose ingested by patients experiencing apnea was 2125 ± 1360 mg (range, 200-4600 mg), which was significantly higher than those who did not experience apnea, 1383 ± 1088 mg (range, 100-6000 mg), P < .001. One death occurred in each group, which was significant (P < .001). Renal impairment was not observed in any of the patients who experienced apnea.

The seizurogenecity of naloxone in tramadol overdose

Tramadol is the most widely prescribed opiate analgesic ( National Treatment Agency for Substance Misuse, 2011 ) and, as a result, is present in a large number of overdoses that present in the pre-hospital arena. Naloxone is indicated for use by ambulance personnel where the GCS is reduced due to a known, or possible, overdose of an opiate containing substance ( JRCALC (Joint Royal Colleges Service Liaison Committee), 2006 ). A case study of a tramadol overdose shows a close temporal relationship between naloxone administration and a seizure. While seizure is a symptom of tramadol intoxication (Saidi et al, 2008), the speed with which it occurred after naloxone administration seemed too fast to be merely coincidence. A study of the literature shows evidence that naloxone can instigate seizure in the case of a tramadol overdose ( Rehni et al, 2008 ; Raffa and Stone, 2008 ). This information is particularly pertinent to the ambulance clinician as the consequence of a seizure can be important, both practically and clinically. The findings do not suggest that naloxone should be withheld, but that the potential for seizure should be noted and any forthcoming seizure dealt with. More research is needed to further define the factors that affect the seizurogenicity of naloxone in tramadol overdose.

Recurrent Seizures in Tramadol Intoxication: Implications for Therapy Based on 100 Patients

Tramadol is an atypical opioid analgesic used in the treatment of mild to moderate pain. Despite being a GABA(A) agonist, seizures are a prominent complication with its therapeutic use, abuse or overdose. For patients who have had a tramadol-induced seizure, the likelihood of recurrent seizures and the need for emergent anticonvulsant prophylaxis is unknown. However, treatment of patients with anticonvulsants prophylactically may cause adverse effects and increased morbidity in tramadol poisoning. We studied the outcome and frequency of recurrent seizures in tramadol-intoxicated patients in an attempt to determine the need for prophylactic anticonvulsant therapy. This was a retrospective cohort study of tramadol-intoxicated patients who had at least one seizure. Patients' age, sex, cause(s) of intoxication, route of poisoning, dose or number of capsules or tablets taken, vital signs, other signs or symptoms, numbers of seizures, length of stay, co-ingestions and past medical history were ascertained. Exactly 100 patients met the inclusion criteria. Eighty-two per cent were men, and 50% were between 21 and 30 years old. By our standard clinical protocol, none were treated with seizure prophylaxis after their first seizure. Only 7% had recurrent seizures and all patients recovered without sequelae. Because of the low risk of multiple seizures in tramadol poisoning and the lack of morbidity in patients who do seize, it appears to be unnecessary to administer prophylactic anticonvulsant therapy in patients with tramadol poisoning, even if they have an initial seizure.

Serotonin Syndrome Induced by Tramadol Intoxication in an 8-Month-Old Infant

I read with interest the case presented by Maréchal et al. [ [1] Maréchal C. Honorat R. Claudet I. Serotonin syndrome induced by tramadol intoxication in an 8-month-old infant. Pediatr Neurol. 2011; 44: 72-74 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar ]. They reported, for the first time, on moderate serotonin syndrome in an 8-month-old girl after tramadol intoxication, and concluded that pediatricians should be aware of specific clinical manifestations of serotonin syndrome, to avoid any delay in management. Interestingly, the management used by the authors for their patients remains unclear. As is well known, patients who develop serotonin syndrome and present with agitation or neuromuscular hyperactivity (similar to the patient of Maréchal et al. [ [1] Maréchal C. Honorat R. Claudet I. Serotonin syndrome induced by tramadol intoxication in an 8-month-old infant. Pediatr Neurol. 2011; 44: 72-74 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar ]) should initially be managed with benzodiazepines [ [2] Lappin R.I. Auchincloss E.L. Treatment of the serotonin syndrome with cyproheptadine. N Engl J Med. 1994; 331: 1021-1022 Crossref PubMed Scopus (116) Google Scholar ]. Furthermore, the administration of cyproheptadine may improve the patient’s condition sooner. Cyproheptadine is a first-generation, histamine-1 receptor blocking agent with nonspecific antagonist properties at the 5HT-1A and 5HT-2A receptors. Patients with mild to moderate signs of serotonin syndrome, and who are not hyperthermic, typically respond to this pharmacologic agent within 30 minutes to 2 hours of administration [ 2 Lappin R.I. Auchincloss E.L. Treatment of the serotonin syndrome with cyproheptadine. N Engl J Med. 1994; 331: 1021-1022 Crossref PubMed Scopus (116) Google Scholar , 3 Graudins A. Stearman A. Chan B. Treatment of serotonin syndrome with cyproheptadine. J Emerg Med. 1998; 16: 615-619 Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar ]. Although this medication is not available in an intravenous form, tablets may be crushed and administered by nasogastric tube in pediatric patients. Moreover, despite the authors’ statement in their Discussion about the association of tramadol with selective serotonin reuptake inhibitors in the development of serotonin syndrome, an overdose of a single serotonin-potentiating agent such as tramadol may also produce serotonin syndrome [ [2] Lappin R.I. Auchincloss E.L. Treatment of the serotonin syndrome with cyproheptadine. N Engl J Med. 1994; 331: 1021-1022 Crossref PubMed Scopus (116) Google Scholar ]. Serotonin Syndrome Induced by Tramadol Intoxication in an 8-Month-Old InfantPediatric NeurologyVol. 44Issue 1PreviewSevere cases of pediatric tramadol intoxication are rarely reported. We report on serotonin syndrome after tramadol intoxication. An 8-month-old girl developed extreme agitation after accidentally ingesting a tablet of her father’s medication (Monocrixo LP (Thérabel Lucien Pharma, Levallois Perret, France), 200 mg tramadol). Unable to sleep, she was admitted the next morning to our Pediatric Emergency Department after an episode of epistaxis. Vital signs were significant for sinus tachycardia and a neurologic examination revealed intermediately reactive pupils, agitation alternating with drowsiness with a Glasgow Coma Scale of 10, and increased lower-limb reflexes. Full-Text PDF ResponsePediatric NeurologyVol. 46Issue 3PreviewI thank Dr. Sanaei-Zadeh for his accurate and expert comments about our case report. The management of this patient was not specified because it was mainly supportive. We did not need to use benzodiazepines because the girl manifested episodic agitation alternating with drowsiness. Her agitation was moderate at hospital, compared with her described neurologic status on the preceding night at home. Cyproheptadine was not prescribed because the staff pediatrician in the emergency unit did not recognize serotonin syndrome during the patient’s admission, and did not know that cyproheptadine was recommended for patients with severe toxicity, including children. Full-Text PDF

Response

I thank Dr. Sanaei-Zadeh for his accurate and expert comments about our case report. The management of this patient was not specified because it was mainly supportive. We did not need to use benzodiazepines because the girl manifested episodic agitation alternating with drowsiness. Her agitation was moderate at hospital, compared with her described neurologic status on the preceding night at home. Cyproheptadine was not prescribed because the staff pediatrician in the emergency unit did not recognize serotonin syndrome during the patient’s admission, and did not know that cyproheptadine was recommended for patients with severe toxicity, including children. The diagnosis was rendered the next morning during the clinical case review by a pediatrician experienced in toxicology. We experienced a delayed diagnosis because serotonin syndrome is rare in pediatric patients, and is often misdiagnosed. We published this case report because we hoped that sharing such an experience could increase the recognition of serotonin syndrome and reduce the delay of its management in children. Serotonin Syndrome Induced by Tramadol Intoxication in an 8-Month-Old InfantPediatric NeurologyVol. 46Issue 3PreviewI read with interest the case presented by Maréchal et al. [1]. They reported, for the first time, on moderate serotonin syndrome in an 8-month-old girl after tramadol intoxication, and concluded that pediatricians should be aware of specific clinical manifestations of serotonin syndrome, to avoid any delay in management. Interestingly, the management used by the authors for their patients remains unclear. As is well known, patients who develop serotonin syndrome and present with agitation or neuromuscular hyperactivity (similar to the patient of Maréchal et al. Full-Text PDF

Factors Related to Seizure in Tramadol Poisoning and Its Blood Concentration

This study examines the relation between seizure and plasma tramadol concentration in patients with tramadol poisoning, as a novel centrally acting analgesic used for the treatment of mild to severe pain. All patients admitted with a history of tramadol overdose accompanied by unconsciousness or seizures referred to Baharloo Hospital Poison Center, Tehran, Iran from March 2008 to March 2009 were included. Demographic information, clinical findings, and blood tramadol concentrations were studied. There were 401 patients with a history of tramadol overdose; 121 (30.2%) with a history of seizure and 14 (3.5%) with a history of unconsciousness were included. Most of overdoses involved men (83%). The mean age was 22.9 years (range, 14-50 years). Intentional overdose was the most common mode of poisoning (51.9%). The mean dose ingested was 1,511 mg (SD, 1,353; range, 200-7,000). Mean back-extrapolated tramadol blood concentrations were 3,843 ng/mL (3,715; 269-20,049). Back-extrapolated blood concentrations were correlated with dose (r = 0.313; P < 0.001) as well as blood concentration levels (r = 0.801; P < 0.001). Seizure was significantly correlated to higher reported dose (P < 0.001) and tramadol only to overdose (P < 0.001). However, it was neither related to higher tramadol blood concentrations, nor related to time elapsed, age, sex, history of addiction, and observed Glasgow Coma Scale of patients. Most patients experienced just one seizure (76%). The tramadol-induced seizure is dose dependent. Although higher doses of tramadol was related to higher blood concentration, blood tramadol concentrations was not associated with seizure.

Serotonin Syndrome Induced by Tramadol Intoxication in an 8-Month-Old Infant

Severe cases of pediatric tramadol intoxication are rarely reported. We report on serotonin syndrome after tramadol intoxication. An 8-month-old girl developed extreme agitation after accidentally ingesting a tablet of her father's medication (Monocrixo LP (Thérabel Lucien Pharma, Levallois Perret, France), 200 mg tramadol). Unable to sleep, she was admitted the next morning to our Pediatric Emergency Department after an episode of epistaxis. Vital signs were significant for sinus tachycardia and a neurologic examination revealed intermediately reactive pupils, agitation alternating with drowsiness with a Glasgow Coma Scale of 10, and increased lower-limb reflexes. Within 24 hours, she developed hyperthermia and high blood pressure. She did not experience seizures. Neurologic and cardiovascular effects resolved on day 2. Tramadol serum plasma levels confirmed the intoxication (680 μg/L). She was discharged on day 5 with no sequelae. Serotonin syndrome was described in adults when tramadol was associated with selective serotonin-reuptake inhibitors in contexts of therapy or intoxication. Our patient developed moderate serotonin syndrome. The clinical presentation was unusual compared with previous pediatric cases of tramadol intoxication, in which opioid effects and seizures were usually predominant. This case illustrates that serotonin syndrome can occur in children intoxicated with tramadol.

Quantification in Postmortem Blood and Identification in Urine of Tramadol and Its Two Main Metabolites in Two Cases of Lethal Tramadol Intoxication

Tramadol is an opioid analgesic considered to induce fewer side effects than other compounds of this class. It has been extensively prescribed for two decades. However, serious complications may occur in case of intoxication. We report here two cases of fatal intoxication due to tramadol ingestion. Tramadol, O-desmethyltramadol (ODT), and N-desmethyltramadol (NDT) were quantitatively and qualitatively determined in postmortem blood and urine, respectively. An HPLC method coupled with fluorescence detection was validated using total error approach for the analysis of tramadol, ODT, and NDT in blood. In case 1, concentrations of tramadol and its metabolites were 7.7 mg/L (tramadol), 1.33 mg/L (ODT), and 0.6 mg/L (NDT). In case 2, concentrations found were 48.34 mg/L (tramadol), 2.43 mg/L (ODT), and 10.09 mg/L (NDT). The tramadol concentration found in case 2 is one of the highest ever described in the literature. Opposite ratios of ODT/NDT concentrations observed in different cases were suggested to be useful for the evaluation of the delay between ingestion and death. However, the changes in metabolites levels may also be explained by pharmacokinetic interactions and quantitative differences in the activity of the cytochrome-P450 2D6. Interestingly, norfluoxetine was detected in subtherapeutic levels in case 2. Most of these aspects in tramadol-related fatalities are reviewed in this paper, and an overview of fatal intoxications due to tramadol is presented.

Tramadol poisoning induced seizure

Tramadol poisoning induced seizure