Tramadol Overdose Research Articles

P17: Analytical evaluation of newly developed enzymelinked immunosorbent assay kit for the detection of tramadol and the metabolite O-desmethyl tramadol in urine and blood

Introduction Tramadol, a synthetic analogue of codeine, is used clinically as an analgesic for the treatment of moderate to moderately- severe pain. Tramadol expresses dual mechanism of action that includes weak agonistic effects at the μ-opioid receptors as well as inhibition of serotonin and norepinephrine uptake. Tramadol has two primary metabolites, N-desmethyl and O-desmethyl tramadol, the latter presenting greater affinity for μ-opioid receptors and twice the analgesic potency of the parent compound. Impairing side effects from the usage of tramadol include dizziness, confusion, light-headedness or fainting spells, drowsiness, seizures and respiratory depression. Much of the toxicity in tramadol overdose appears to be attributable to the monoamine uptake inhibition. This study reports the analytical evaluation of a newly developed enzyme-linked immunosorbent assay (ELISA) for the sensitive detection of tramadol and the active metabolite O-desmethyltramadol in urine and blood. This represents a useful analytical tool for applications in toxicology. Methods A colorimetric competitive immunoassay was employed. The capture antibody was immobilised and stabilised on the 96-well microtitre plate surface. The analyte, if present in the sample, competes with the horseradish peroxidase labelled conjugate for antibody binding sites. Absorbances were read at 450nm. The signal is inversely proportional to the concentration of the analyte in the sample. Results The assay was standardised to tramadol and the metabolite O-desmethyl tramadol was also detected with a % cross-reactivity of 57 %. The limit of detection values were 1.40 ng/ml (urine) and 0.86 ng/ml (blood) for an assay range 0–100 ng/ml. The intraassay precision (n=12), expressed as % CV, was Conclusion The results indicate that the newly developed ELISA kit is applicable to the detection of tramadol and the metabolite Odesmethyl tramadol in urine and blood. The reagents are liquid and ready to use. This represents a useful analytical tool for applications in toxicology.

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...

Opioid Antagonists

Opioid Antagonists

Serotonin Syndrome in a Patient on Tramadol, Bupropion, Trazodone, and Oxycodone

Because of their known serotonergic activity, antidepressants are well recognized in the precipitation of serotonin syndrome (SS). Serotonergic effects of the analgesic tramadol, however, are not as well understood. Several reports detail cases of SS caused by tramadol overdose. To our knowledge, only one case report has ever raised the possibility of SS in a patient on a therapeutic dose of tramadol alone. Other reports demonstrate the development of SS on nonexcessive doses of tramadol due to interactions with other drugs, usually serotonin-specific reuptake inhibitors. Here, we describe a case of SS in a patient on a routine dose of tramadol, combined with several nonserotonin-specific reuptake inhibitor medications: bupropion, trazodone, and oxycodone.

Is prophylactic administration of the anticonvulsants necessary in tramadol-intoxicated patients after an initial seizure?

Shadnia et al. [11] 2012 100 7% Letter to the editor Tramadol is nowadays one of the most commonly abused drugs in Iran. In our country, few emergency physicians have never visited a tramadol-intoxicated patient referring after overdose or with side effects of its use. One of the complications of tramadol use, abuse, or overdose is seizure [1-4]. It has been shown that the tramadol-induced seizures are not dose-dependent [5]. To date, the incidence rate of recurrent/multiple seizures in tramadol-intoxicated patients has been determined in several studies as shown in Table 1 [3,6-11]. The important question is that is there a need for prophylactic administration of anticonvulsants in tramadolintoxicated patients referring with an initial seizure? Of note, in some poison treatment centers of Iran, administration of benzodiazepine is a routine treatment in such patients. As you know, in the setting of clinical toxicology, except for the intravenous overdose of vincristine [12], severe toxicity with methylxanthines [13], strychnine toxicity [14], and withdrawal of ethanol and some benzodiazepines [15], no other condition exists for whose prevention of recurrent or multiple seizures, prophylactic anticonvulsants have been recommended [16]. This certainly applies to the tramadol-induced seizures, as well, because these seizures have no special characteristic for which we believe them to be different from other drugand toxin-induced seizures. For instance, tramadol-induced seizures are tonic-clonic, short-lived, and self-limited similar to the most of other drug-induced seizures [16]. In addition, in the setting of poisoning, even where there is the likelihood of recurrent seizures (except for the above-mentioned conditions), prophylactic administration of the anticonvulsants has not been recommended and in the case of

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

Chlordiazepoxide preventive effect on tramadol overdose induced serotonin syndrome evaluated by Hunter and Radomski criteria: A clinical trial

Introduction:Tramadol is an analgesic medication that is frequently abused. It has two functions; mu-opioid receptors agonism, as well as, serotonergic activities. It has shown that tramadol overdose may induce serotonin syndrome (SS). This study evaluates whether early treatment with chlordiazepoxide could prevent SS in admitted tramadol overdoses.Materials and Methods:In this single blind randomized control trial, 50% of admitted tramadol overdoses in Imam Reza (p) Hospital from 21 September 2011 to 21 January 2012 were recruited. Cases received chlordiazepoxide and controls received placebo. Clinical findings were recorded in a pre-designed spread sheet every 6 hours in the first 24 hours of admission. SS was determined by two independent methods; Hunter Criteria (HC) and Radomski Criteria (RC).Results:In total, five patients developed SS when HC or RC was taken into account. Among them, four cases were shared. None of the SS cases diagnosed with HC received chlordiazepoxide. However, just one SS case diagnosed with RC was from the case group. Based on HC, chlordiazepoxide decreased the Risk Ratio (CI 95%) of SS to 0.80 (0.66-0.97) (P = 0.025). This effect did not reach statistically significant levels when SS was diagnosed with RC.Conclusion:This study supports the fact that pre-treatment with chlordiazepoxide could prevent tramadol overdose induced SS.

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

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.

Profound hyponatraemia following a tramadol overdose

Sir, Hyponatraemia is a common electrolyte disturbance associated with prolonged hospitalization and increased mortality. Among numerous aetiologies, tramadol is not routinely included in the list of causative medications. This case highlights an important biochemical side effect, and symptoms that may be easily overlooked without appropriate investigation. A 56-year-old man presented to hospital 12 h after an intentional overdose of 60 tramadol (50 mg) tablets and 20 co-dydramol (10/500) tablets. The past medical history included COPD, treated with spiriva and seretide inhalers. There was no other current or previous medication use. On examination, he was drowsy with pinpoint pupils and a respiratory rate of six breaths per minute. Blood pressure was 135/80 mmHg and heart rate 110 beats …

Epidemiology Analysis of Poisonings with Tramadol

It is reported that suicide was the most frequent cause of poisoning by tramadol. Seizure is a serious nervous disturbance in tramadol overdose. This study intends to characterize the poisoning with tramadol cases admitted to the Department of Emergency, Imam-Khomeini Hospital in Kermanshah, Iran. The number 1023 patients admitted from March 2008 till March 2010 were evaluated retrospectively. Information of demographic characteristics, cause of poisoning; dose of poisoning; duration of hospitalization; seizure status; co-ingestion; and mortality rate were collected from medical records of the hospital. The most poisoned subjects were bachelor (79.8%) and 20 years old (11.1%). Suicide (55.1%) was the most common mode of tramadol poisoning cause. 41.8% of cases had seizure symptom and seizure incidence in male was greater than female (P<0.001). correlation between dosages of used tramadol and outbreak of seizure was significant. Abuse and poisoning by tramadol led to seizure and death, and frequencies of poisoning by tramadol were among people with less than 30 years old and with the intension of suicide. The essential issue is the necessity to try to increase level of knowledge among youth regarding consumption, approaches of suicide prevention and limitation of approachability and distribution of tramadol especially in younger ages.

Tramadol Overdose: A Case Report

Tramadol, a commonly prescribed opioid analgesic, is considered to have a low abuse potential and devoid of side effects like drug dependence. Very few fatalities due to isolated tramadol overdose, either intentional or accidental, have been reported so far. We report a case of a 27-year-old female with isolated tramadol overdose, having a peripheral blood tramadol concentration of 4mg/L, which is exceeding the lethal blood concentration of 2mg/L. This is the first report of a patient in Singapore who survived tramadol overdose despite having a lethal blood concentration. Physicians should be aware that patients with tramadol overdose may only present with signs related to isolated Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) properties and not always associated with the features of classical opioid overdose. Some patients might exhibit a certain degree of tolerance to the drug after prolonged prior exposure to the medication, and this tolerance could extend beyond the therapeutic range. It also emphasises the need for physicians to be more cautious while prescribing tramadol to their patients.

Intoxication au tramadol : mise au point

La France, à l’instar de plusieurs autres pays européens, a décidé de retirer du marché en 2011 toutes les spécialités à base de dextropropoxyphène. De ce fait, une augmentation significative des prescriptions d’antalgiques à base de tramadol pourrait être observée, avec comme conséquence une augmentation des cas de surdosage et d’intoxication. Le tramadol est un opioïde de synthèse à l’origine de nombreux risques y compris vitaux pouvant conduire un patient intoxiqué en réanimation : troubles de la conscience, convulsions, syndrome sérotoninergique et plus rarement hypotension et état de choc. De telles observations ont largement été documentées en Iran, où ce médicament est à l’origine d’un détournement d’usage chez les consommateurs de drogues dépendants aux opioïdes. Une vigilance particulière doit donc être instaurée en France pour éviter que le tramadol ne conduise à son tour à un accroissement significatif de la morbimortalité des intoxications aiguës, comme déjà observé en Iran.

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.

Epidemiology of tramadol overdose in Imam Khomeini hospital, Kermanshah, Iran (2008)

Background: Tramadol is an analgesic drug used for treatment of moderate to severe pain. According to side effects of Tramadol overdose, this study aimed to evaluate epidemiological characteristics of patients who admitted with Tramadol overdose in Imam Khomeini hospital - Kermanshah from March 2008 to March 2009. Methods: In this descriptive- analytical study, all profiles of poisoned subjects with Tramadol who have been referred to the hospital were reviewed. Considerable variables were extracted and data were analyzed using chi-square and Independent t test. Results: The result showed that majority of overdosed subjects was married (80.8%) and aged 19 years old (11.2%). Suicide (98.7%) was the most common cause of using Tramadol. 40% of cases showed a seizure symptom and seizure incidence in male subjects was higher than female (P<0.001). There was a significant correlation between Tramadol dosages and outbreak of a seizure symptoms. Conclusion: Abuse of Tramadol may leads to seizure and death, which threat young generation less than 30 years old committed to suicide. Increasing knowledge and restriction of Tramadol availability and distribution in community is necessary to prevent young generation from suicide commitment.

Isolated Tramadol Overdose Associated with Brugada ECG Pattern

Tramadol is a commonly prescribed synthetic opioid analgesic. In humans, electrocardiogram (ECG) changes consistent with sodium-channel blockade have not been described in overdoses with tramadol. We report a case of isolated tramadol overdose associated with a Brugada ECG pattern. A review of the literature reveals no previous human cases of tramadol overdose causing ECG changes consistent with sodium-channel blockade. However, in vitro blockade of sodium-channels has been demonstrated with high concentrations of tramadol. Tramadol overdose should be recognized as a cause for the manifestation of a Brugada ECG pattern in the setting of suicidal intoxication.

Tramadol overdose as a cause of serotonin syndrome: a case series

Introduction. Tramadol overdose impairs consciousness and may induce ECG changes and convulsions. These effects may be opioid and/or serotonin related. This study describes clinical manifestations, electrophysiological and hemodynamic findings, and the frequency of potential serotonin syndrome in tramadol overdose in a case series. It also focuses on potential factors by which convulsions could be predicted. Methods. This is a prospective observational case series. All cases admitted with suspected tramadol overdose from September 1, 2006 to August 31, 2007 were included. Results. Tramadol overdose accounted for 1.2% of all poisonings (n = 158), of which 65% were tramadol only. It was predominantly male (63%). Mean (SD) age was 22.6 (7.4) years. Among these cases, 24 (15%) experienced seizure and in 10 (6%) cases creatine phosphokinase increased. Death occurred in one patient. Seizure occurred more frequently in patients with tramadol use only [odds ratio 3.0, 95% confidence interval 1.1, 8.4] and mydriasis (odds ratio 8.9, 95% confidence interval 1.9, 42.4) on admission. Eight cases were treated for potential serotonin syndrome. Concurrent intoxication with central nervous system depressants, age, alleged dose, consciousness level, respiratory rate, history of drug abuse, and naloxone administration was not associated with the occurrence of seizures. Conclusion. In tramadol overdose, mydriasis or tachycardia appears to indicate a higher risk for seizure. Management may need to be focused on both μ-opioid agonism and potential mild serotonin syndrome.

Yüksek Doz Tramadole Bağlı Görsel Halüsinasyonlar

Tramadol is a centrally acting analgesic commonly used in the treatment of moderate to severe pain. Visual hallucinations after tramadol overdose has rarely been reported. In this case report, we describe a 15-year-old girl with no medical history with headache, dizziness, nausea, vomiting, drowsiess and visual hallucinations such as white dressing men, prophet and cemetery due to tramadol intoxication. She transferred to the intensive care unit and discharged from hospital on the third day. Early recognition and proper immediate treatment are essential to reversing this complication. This case warns physicians that visual hallucinations to tramadol overdose, an unusual unpredictable adverse reaction, must be kept in mind, underlying mechanisms and therapeutic approach are discussed.

Tramadol intoxication: a review of 114 cases

Tramadol as a centrally acting analgesic is extensively used in the management of moderate to severe pain. It slightly affects opioid receptors and inhibits the reuptake of norepinephrin and serotonin in the CNS. There are reports about toxicity and abuse of tramadol. The objective of the present study was to evaluate epidemiology of intentional tramadol intoxications. All poisoning cases that admitted to Loghman-Hakim Hospital Poison Center from April to May 2007 were studied. A total of 114 cases (82 men and 32 women) of intentional tramadol intoxications with the median age of 23.66 +/- 6.87 years (range 16-54 years) were identified. Other illicit drugs were found to be used in combination with tramadol in some of the cases, which among them benzodiazepines were the most common. Tramadol overdose has been one of the most frequent causes of drug poisoning in the country in the recent years, especially in male young adults with history of substance abuse and mental disorders. Nausea, vomiting, Central Nervous System (CNS) depression, tachycardia, and seizure are the most common findings in this kind of poisoning. Cardiopulmonary arrest was found as the cause of death in cases who had ingested more than 5000 mg tramadol.

Fatal intoxication due to tramadol alone: Case report and review of the literature

Poisoning may also lead to both coma and multiple organ failure, also in youngsters without a known major medical history. As not all toxic agents are routinely screened when a poisoning is suspected, it is useful to consider less frequently encountered poisons in certain cases. We describe the occurrence of asystole and multiple organ failure which occurred in a young man after a suspected tramadol overdose. The tramadol concentration on admission in the ICU was indeed 8 μg/ml (mg/l), far above the therapeutic range. Subsequently, the patient developed severe acute liver failure, finally leading to death. Post-mortem toxicology did not reveal any other poison responsible for this unfavourable course as only very high serum and tissue tramadol and desmethyltramadol concentrations were found. Only a few fatal poisonings attributable to tramadol alone, as observed in our case, have been reported. An overview of these cases is presented.