Dose Of Tramadol Research Articles

Effect of tramadol hydrochloride on neural tube development in 48-hr chick embryos: Argyrophilic nucleolar organizing region and genetic analysis study.

Tramadol hydrochloride or tramadol is an opioid analgesic that acts on the central nervous system. The pregnancy category of tramadol is determined as "C" according to the Food and Drug Administration. There are no adequate and well-controlled studies in pregnant women. In this study, we aimed to reveal the effects of tramadol on neural tube (midline) closure by analyzing morphologically, histologically and genetically in chick embryos. Ninety White Leghorn species, fertile and 0-day-old specific pathogen-free eggs (60 ± 5g) were used in the study. Eggs were divided into a total of six groups (control, sham, and drug groups). Four different doses of tramadol (1, 2.5, 5, and 7.5mg/egg) were administered subblastodermically at the 28th hour of the incubation. All eggs were opened at the 48th hour of incubation and evaluated. Embryos in the control group according to Hamburger-Hamilton classification were compatible with stages 13 and 14. In the groups treated with tramadol, it was determined that the embryos had neural tube closure defects (such as neck, tail regions) and some embryos showed developmental retardation due to the increase in the drug dose. In the statistical analysis performed, a significant difference was found between the control group and the group receiving the highest dose of tramadol in terms of crown-rump length and number of somites (p< .05). The brain and reproductive expression gene expression was upregulated in embryos at each of tramadol doses compared to control group. It was determined that tramadol causes neural tube closure defects in embryos depending on the dose.

Spectrum of Substance Use, Reasons for Use and Perceived Effects on Treatment among People Living with Human Immunodeficiency Virus (PLWHIV) in Benue State, Nigeria; A Qualitative Study

INTRODUCTION: Substance use is on increase and a major public health problem contributing about 1.7 million deaths among teenagers globally. Ironically, some are socially acceptable and freely consumed during social activities. They are consumed commonly for social, religious and medicinal reasons. This study aims to assess substance use, types, reasons and its perceived effects among PLHIV in Benue State, Nigeria&#x0D; &#x0D; METHODS: The study was at Centre for Infectious Diseases Control (CIDC), 161 Nigerian Air Force Hospital, Makurdi at Benue state, Nigeria. Qualitative data was collected using Focus Group Discussions (FGDs) among five homogeneous groups involving 40 discussants [30 and 10 health care workers]. The recorded discussions were transcribed verbatim, coded based on predetermined themes and reported. &#x0D; &#x0D; RESULTS: The commonest psychoactive substance used by People living with Human Immunodeficiency Virus (PLWHIV) for both males and females was Alcohol followed by Kola nut and Bitter Cola. Others were; cannabis, overdose dose of Rohypnol, Tramadol and diazepam; paracitamol mixed with &amp;lsquo;la-cassera&amp;rsquo; soft drink and codeine in cough syrup as well as Marijuana. Major reasons for use included to increase work, sexual performance, reading time and appetite; reduce nausea, vomiting and to manage stress or boredom. They perceived most substance to be safe though few expressed their concern on the possible interaction with Antiretroviral (ARV) medications and possibility of increasing Gastrointestinal tract (GIT) effect of some drugs. This they said depends on type and dose of consumption.&#x0D; &#x0D; CONCLUSION: Substance use among PLWHIV is common. Misconceptions and poor appreciation of effect of these substance use among these clients abound. Every effort should be made to tame this menace.

8525 Efficacy and Safety of Single Port Robotic Hysterectomy with Concomitant Urogynecologic and Gynecologic Oncology Procedures

<h3>Study Objective</h3> To assess the feasibility of the DaVinciâ Single Port (SP) robotic platform for urogynecologic and gynecologic oncology surgical procedures. <h3>Design</h3> Retrospective cohort analysis. <h3>Setting</h3> The first SP robotic procedures performed as same day surgeries at an academic tertiary medical center by board certified Female Pelvic Medicine and Reconstructive Surgery and/or Gynecologic Oncology surgeons from December 2021-April 2022. <h3>Patients or Participants</h3> 15 patients underwent SP robotic hysterectomy (RH) and either bilateral salpingectomy (BS) or salpingo-oophorectomy (BSO) with or without concomitant procedures. <h3>Interventions</h3> SP RH and concomitant procedures were performed using a 1.5 cm umbilical incision, the Access Port ä (Intuitive Surgical) and the SP platform robotic camera and instruments. <h3>Measurements and Main Results</h3> Our primary outcome was conversion to a multiport procedure and intraoperative complications. Perioperative details were abstracted from the chart including operative time, estimated blood loss (EBL), and intraoperative complications, PACU length of stay (LOS) and pain scores POD#1 Surgical Pain Scale (SPS) scores. Indications for the 15 SP RH with BS or BSO included prolapse (N=10), risk reduction (N=2,) endometrial cancer (N=1), cervical (N=1), and endometrial (N=1) intraepithelial neoplasia. Concomitant procedures included: 10 (67%) SP sacrocolpopexies, 9 (60%) midurethral slings, 2 (13%) SP sentinel lymph node mapping, and 1 breast reconstruction. There was no conversion to a multiport procedure, intraoperative or immediate postoperative complications with a mean EBL of 66.7 ± 26.1 cc. Mean operative time and PACU LOS were 182 ± 53 and 216 ± 57 min. Median PACU pain scores were low (2, IQR 4) and only one patient required a single dose of postoperative tramadol. Similarly, median POD#1 SPS scores were low for pain at rest and with activity (3 (IQR 4) and 3 (IQR 4.75)) and for the worst pain 5.5 (IQR 4,25). <h3>Conclusion</h3> SP robotic approach for urogynecologic and gynecologic oncology hysterectomy with concomitant procedures performed by sub-specialty surgeons is safe and feasible.

Role of daytime variation in pharmaceutical effects of sufentanil, dezocine, and tramadol: A matched observational study.

The role of daytime variation in the comprehensive pharmaceutical effects of commonly used opioid analgesics in clinical setting remains unclear. This study aimed to explore the differences in daytime variation among elective surgery patients who were scheduled to receive preemptive analgesia with equivalent doses of sufentanil, dezocine, and tramadol in the morning and afternoon. The analgesic effect was assessed by changes in the pressure pain threshold before and after intravenous administration of sufentanil, dezocine, and tramadol. Respiratory effects were evaluated using pulse oximetry, electrical impedance tomography, and arterial blood gas analysis. Other side effects, including nausea, sedation, and dizziness, were also recorded, and blood concentration was measured. The results showed that the analgesic effects of sufentanil, dezocine, and tramadol were significantly better in the morning than in afternoon. In the afternoon, sufentanil had a stronger sedative effect, whereas dezocine had a stronger inhibitory respiratory effect. The incidence of nausea was higher in the morning with tramadol. Additionally, significant differences in different side effects were observed among three opioids. Our results suggest that the clinical use of these three opioids necessitates the formulation of individualized treatment plans, accounting for different administration times, to achieve maximum analgesic effect with minimal side effects.

Tramadol and Codeine Stacking/Boosting Dose Exposure Induced Neurotoxic Behaviors, Oxidative Stress, Mitochondrial Dysfunction, and Neurotoxic Genes in Adolescent Mice

In spite of the increasing epidemic of pharmaceutical opioids (codeine and tramadol) misuse and abuse among the adolescents, little is known about the neurotoxic consequences of the widespread practice of tramadol and codeine abuse involving increasing multiple doses across days, referred to as stacking and boosting. Hence, in this study, we replicated stacking and boosting doses of tramadol, codeine alone, or in combination on spontaneous motor activity and cognitive function in adolescent mice and adduced a plausible mechanism of possible neurotoxicity. Ninety-six adolescent mice were randomly distributed into 4 groups (n = 24 per group) and treated thrice daily for 9days with vehicle, tramadol (20, 40, or 80mg/kg), codeine (40, 80, or 160mg/kg), or their combinations. Exposure of mice to tramadol induced hyperactivity and stereotypic behavior while codeine exposure caused hypoactivity and nootropic effect but tramadol-codeine cocktail led to marked reduction in spontaneous motor activity and cognitive function. In addition, tramadol, codeine, and their cocktail caused marked induction of nitroso-oxidative stress and inhibition of mitochondrial complex I activity in the prefrontal cortex (PFC) and midbrain (MB). Real-time PCR expression profiling of genes encoding neurotoxicity (RT) showed that tramadol exposure upregulate 57 and downregulate 16 neurotoxic genes, codeine upregulate 45 and downregulate 25 neurotoxic genes while tramadol-codeine cocktail upregulate 52 and downregulate 20 neurotoxic genes in the PFC. Findings from this study demonstrate that the exposure of adolescents mice to multiple and increasing doses of tramadol, codeine, or their cocktail lead to spontaneous motor coordination deficits indicative of neurotoxicity through induction of oxidative stress, inhibition of mitochondrial complex I activity and upregulation of neurotoxicity encoding genes in mice.

Ex-vivo study of the percutaneous absorption of a tramadol formulation through feline inner pinna skin

ObjectivesOral medication of small animals, particularly cats, is often challenging. The transdermal route may provide an easier option for owners to administer chronic treatment. Tramadol is an analgesic mainly used in humans; it is also commonly used in dogs, despite some controversy over its clinical efficacy. Recent studies have suggested that tramadol is efficacious for pain management in cats. In cats, the inner pinna is the most commonly used site for transdermal drug therapy; the use of this site has been validated in experimental studies of methimazole and mirtazapine treatment. This ex vivo study aimed to characterise the percutaneous absorption pharmacokinetics of a formulation of tramadol in Pentravan through feline inner pinna skin. MethodsHigh-performance liquid chromatography was used to assess the stability of the tramadol formulation (100 mg/ml in Pentravan) over three months at room temperature. Forced degradation was also assessed in neutral, acidic, alkaline, and oxidative conditions. A Franz cell system was employed to evaluate percutaneous absorption of a finite dose of tramadol. ResultsThe tramadol formulation was stable for three months at room temperature. Tramadol penetrated through ex vivo feline inner pinna skin, but considerable intra- and inter-individual variability in kinetics was observed. Comparison with another vehicle, Lipoderm, revealed no significant difference in the percutaneous absorption of tramadol. Conclusions and relevanceThe Pentravan formulation assessed in this study supported tramadol absorption across the feline inner ear skin. In vivo studies are necessary to evaluate the pharmacokinetics and efficacy of this formulation.

Multiple suicide attempts associated with addiction to tramadol

BackgroundThe opioid tramadol is used as analgesic drug, and more recently was also proposed for the management of major depressive disorder. However, growing evidence suggests a link between opioid system dysfunction and suicidal behaviors, raising the question of tramadol use in view of the high addictive and suicidal risk. Here, we present the case of a young adult woman with multiple suicide attempts related to tramadol addiction.Case presentationA 25-year-old woman was admitted for suicide attempt by phlebotomy in the Department of Psychiatric Emergency and Acute Care, Montpellier (France), in March 2020. The suicide attempt occurred 3 days after an abrupt tramadol withdrawal. In 2018, due to spinal disc herniation, she had a first prescription of tramadol to which she became addicted. The patient described an effect on psychological pain and suicidal ideation. However, she had to increase tramadol dose to obtain the desired effects, and for several months her intake was 2 000 mg per day. When she could not obtain tramadol any longer, suicidal ideation and psychological pain increased, leading to the suicide attempt. At the time of a worldwide opioid crisis that contributes to increasing suicidal behaviors, this case raises questions about tramadol prescription (often considered to be less addictive and with lower abuse potential) to individuals at risk of suicide.

Comparative study of intrathecal tramadol and fentanyl as adjuvants in lower abdominal surgeries

Spinal anesthesia is preferred choice of anesthesia in lower abdominal surgeries for a long time. However, the problem with this is limited duration of action, so for long duration surgeries alternatives are required.&#x0D; The aim: to compare the intra-operative effects of a low dose of intrathecal tramadol and intrathecal fentanyl with hyperbaric bupivacaine hydrochloride.&#x0D; Materials and methods: prospective randomized control study for a duration of study is one year. 50 patients, aged 18 years to 60 years, belonging to ASA physical status I and II, posted for elective lower abdominal surgeries under spinal anaesthesia were chosen.&#x0D; These patients were divided into two groups: group BT- this group of patients received 2.5 mL volume of 0.5 % hyperbaric bupivacaine with 25 mg of tramadol intrathecally. Group BF- this group of patients received 2.5 mL volume of 0.5 % hyperbaric bupivacaine with 25 μg of fentanyl intrathecally.&#x0D; Results: demographic parameters in both the groups are not statistically significant. The association between the differences in duration of surgeries of both the study groups is not statistically. The association between the differences in mean time of onset of sensory block and motor block of both the study groups was comparable with p&gt;0.05&#x0D; The duration of sensory block (analgesia) and duration of motor block difference between the two means was statistically significant with p&lt;0.0000001. The difference between the mean VAS score at 3 hours and at 20 hours was statistically significant with p&lt;0.05. Among the study BT group, 52 % needed 2 analgesics and 48 % needed 3 doses of analgesics. Among BF group, 6 % needed only one dose of analgesics and 44 % needed 2 doses of analgesics. The difference between the two was statistically significant with p&lt;0.000002. The association between the hemodynamic variables between both the groups at the end of procedure was statistically significant with p&lt;0.05.&#x0D; Conclusions: Intrathecal fentanyl and tramadol produced a similar onset of sensory and motor blocks. Fentanyl provided better duration and quality of postoperative analgesia compared to tramadol

Suicidal ideation and behavior among subjects with substance abuse disorder related to pregabalin

BackgroundAlthough pregabalin abuse is increasing worldwide and may be associated with increased suicidal ideation and behavior, few studies were done in Egypt searching for the effect of pregabalin on suicide. Eighty-three patients meeting DSM-IV criteria for substance abuse disorders related to pregabalin were identified from the addiction clinic of EL Khanka Psychiatric Hospital in Egypt for this observational cross–sectional study. We intended to assess suicidal ideation and behavior in patients with substance abuse disorder related to pregabalin and to identify the effects of other comorbid substances of abuse. All participants were subjected to semi-structured interview designed to collect and identify the socio-demographic data and patterns of substances 'use ,The Structured Clinical Interview for DSM-IV Axis I Disorders to diagnose patients with substance abuse disorder “related to pregabalin,” Beck Scale for Suicidal Ideation for assessment of suicidal ideation and behavior and urine screening test for pregabalin and other substances of abuse.ResultsMost of participants used pregabalin continuously {86.7%}. More than seventy nine percent of the patients abused both pregabalin and other substances, tramadol 67.4%, heroin 66.3%, cannabis 65.1%, other drugs 44.6%, and benzodiazepines 27.7%. Screening urine test was positive in 62.7% of participants most frequently was heroin 41% and cannabis 34.9%. No suicidal ideation was found in 67.4%, 19.3% had low risk of suicide, and 13.3% had high risk of suicide so total participants who had suicidal ideation were 32.6%. There was statistical significant increase in risk of suicide among patients who were continuously abusing pregabalin and who had positive pregabalin urine test. There was significant positive correlation between Beck Suicidal Ideation score and duration of abusing pregabalin, maximum and daily dose of pregabalin. Also, there was a statistical significant relation between suicidal ideation and associated tramadol abuse and this was positively correlated with dose and duration of tramadol abuse.ConclusionsAbout one third of patients abusing pregabalin had a risk of suicide and this risk increased with associated tramadol abuse so pregabalin abuse is dangerous like other substances of abuse and must be used with caution under strict medical supervision

Predicting factors for electrocardiographic findings in patients with tramadol-induced seizure

Seizure and electrocardiographic (ECG) abnormalities are of the most common complications of tramadol toxicity. This study aimed to show the prevalence and predictive value of various factors for ECG findings in patients with tramadol-induced seizures. In a descriptive cross-sectional study, 146 patients with tramadol-induced seizures referred to Poursina Hospital, Guilan, Iran, between June and November 2018 were enrolled. The clinical manifestations, such as blood pressure, respiratory rate, and pulse rate (PR), and ECG parameters, including PR interval, QRS duration, R wave in aVR lead, and corrected QT interval, were assessed. Appropriate statistical tests were used to analyze the data. We showed that tramadol dose was significantly higher in patients with abnormal ECG findings compared with those with normal ECG pattern both upon admission (p = 0.001) and after 6 hours of admission (p = 0.001). The results found the predictive value of tramadol dose for abnormal ECG patterns upon admission (odds ratio (OR) 1.014, 95 percent CI 1.008 to 1.020) and 6 hours later (OR 1.008, 95 percent CI 1.003 to 1.013) in these patients. In addition, it was revealed that PR was a strong predictor of abnormal ECG findings in patients with tramadol-induced seizures upon admission (OR 1.085, 95 percent CI 1.038 to 1.134). Nevertheless, age only predicted abnormal findings 6 hours later (OR 1.104, 95 percent CI 1.019 to 1.195). Tramadol dose, age, PR, and seizures frequency could be used as indicators of abnormal ECG findings in patients with tramadol-induced seizures. The results of our study showed a high prevalence of sinus tachycardia, terminal S and R waves in aVR lead terminal S wave, and the combination of these abnormalities in this subset of patients.

EFFECTS OF TRAMADOL ADMINISTRATION ON SOME BIOCHEMICAL PARAMETERS IN WISTER ALBINO RATS UNDER NON-INDUCTION OF PAIN

This study investigates the effect of tramadol under non-induction of pain on some biochemical parameters in albino rats. A total of 24 albino rats were randomly divided into four groups of 6 members each. Group 1 received pellet and was allowed free access to water. This was the control. Groups 2, 3 and 4 received 50, 100 and 200 mg/Kg body weight of tramadol respectively. All the administrations were via oral intubation and were done once daily for 30 days. Neurotransmitters, glutamine dehydrogenase, glutaminase, and oxidative stress markers were determined in the brain homogenate using standard methods. Liver function markers, kidney function parameters and pancreatic markers were equally determined in the serum using standard methods. The results showed that levels of serotonin, dopamine, reduced glutathione, albumin and activities of catalase, super oxide dismutase, glutathione transferase, glutathione peroxidase, glutaminase and lipase were significantly (p&lt;0.05) lowered in rats administered tramadol only in dose dependent manner when compared with the control. The results also revealed that administration of different doses of tramadol caused significant (p&lt;0.05) increase in the activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, α-amylase, glutamine dehydrogenase and levels of total bilirubin, uric acid, urea, creatinine and malondialdehyde in dose dependent manner when compared with control. These results generally revealed that intake of tramadol under non-induction of pain caused significant alterations of some biochemical markers, which could lead to health consequences

Association between male sex hormones and tramadol abuse

BackgroundTramadol dependence is prevalent across Egypt. The allegation that it can improve sexual function is the main reason for its popularity among young men. This study aims to determine the serum level of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in tramadol abusers.ResultsSerum testosterone (5.18 ± 1.95) and LH (7.79 ± 1.63) of abusers showed highly significant lower levels than control subjects, while FSH showed no significant difference between abusers and controls. There was no significant difference of hormonal levels in subjects according to the duration of abuse and dose of tramadol.ConclusionsThe results indicate that tramadol abuse causes a pronounced lowering of testosterone and LH levels that is not correlated to the duration of abuse and dose of tramadol.

Potential Impact of 3% Hypertonic Saline Infusion on Tramadol Poisoning-Induced Electrocardiogram Changes; a Randomized Clinical Trial

Introduction:Tramadol is a synthetic analgesic with weak mu-opioid receptor agonist activity. Tramadol overdose is associated with adverse cardiac effects due to inhibiting cardiac Na+ and K+ channels. This study aimed to investigate the potential ameliorative role of 3% hypertonic saline on the electrocardiogram (ECG) changes in patients presenting with tramadol poisoning.Methods:This was a single-center, controlled, randomized, single-blind clinical trial. Patients were randomized into the case (received hypertonic saline) and control (received placebo) groups. ECG was obtained twice in each group (upon arrival and following the intervention). Response to therapeutic interventions was evaluated using Wilcoxon Signed Ranks Test. Results:A total of 76 patients were included. The mean age of patients was 24.88 ± 4.29 years, and 62 (81.6%) were male. The mean ingested dose of tramadol was 1673.68 ± 608.85 (range: 550-2750) mg. The number needed to treat and the absolute risk reduction of 3% hypertonic saline in the treatment of wide QRS were 1 (95% CI: 1.00 – 1.00) and 100%, respectively. In the treatment of long QTc, these measures were 1.9 (95%CI: 1.2 – 4.5) and 53.85% (95%CI: 22.00 – 85.69), respectively.Conclusion:Given that hypertonic saline infusion can significantly ameliorate tramadol-mediated ECG changes, including QRS prolongation and QT lengthening, it can be regarded as a potential therapeutic strategy to prevent the development of life-threatening ventricular arrhythmias caused by tramadol toxicity.

The effect of continuous intercostal nerve block vs. single shot on analgesic outcomes and hospital stays in minimally invasive direct coronary artery bypass surgery: a retrospective cohort study

BackgroundMinimally invasive direct coronary artery bypass (MIDCAB) grafting surgery is accompanied by severe pain. Although continuous intercostal nerve block (CINB) has become one of the multimodal analgesic techniques in single port thoracoscopic surgery, its effects on MIDCAB are unclear. The purpose of this study was to compare the effects of CINB and single shot on analgesic outcomes and hospital stays in patients undergoing MIDCAB in a real-world setting.MethodsA retrospective cohort study was carried out at Peking University Third Hospital, China. Two hundred and sixteen patients undergoing MIDCAB were divided into two groups: a CINB group and a single block (SI) group. The primary outcome was postoperative maximal visual analog scale (VAS); secondary outcomes included the number of patients with maximal VAS ≤ 3, the demand for and consumed doses of pethidine and tramadol, and the length of intensive care unit (ICU) and hospital stays. The above data and the area under the VAS curve in the 70 h after extubation for the two subgroups (No. of grafts = 1) were also compared.ResultsThe maximum VAS was lower in the CINB group, and there were more cases with maximum VAS ≤ 3 in the CINB group: CINB 52 (40%) vs. SI 17 (20%), P = 0.002. The percentage of cases requiring tramadol and pethidine was less in CINB, P = 0.001. Among all patients, drug doses were significantly lower in the CINB group [tramadol: CINB 0 (0–100) mg vs. SI 100 (0–225) mg, P = 0.0001; pethidine: CINB 0 (0–25) mg vs. SI 25 (0–50) mg, P = 0.0004]. Further subgroup analysis showed that the area under the VAS curve in CINB was smaller: 28.05 in CINB vs. 30.41 in SI, P = 0.002. Finally, the length of ICU stay was shorter in CINB than in SI: 20.5 (11.3–26.0) h vs. 22.0 (19.0–45.0) h, P = 0.011.ConclusionsCINB is associated with decreased demand for rescue analgesics and shorter length of ICU stay when compared to single shot intercostal nerve block. Additional randomized controlled trial (RCT) is needed to support these findings.

Exposure to immediate-release tramadol in children 6 years and under – a nationwide French poison control center study

Introduction Data regarding immediate-release (IR)-tramadol exposures in children remain sparse. We aimed to investigate the incidence of IR-tramadol exposures in ≤6-year-old children, to describe the characteristics and resulting outcome of ingestions involving IR-tramadol alone, and to estimate a clinically relevant toxic dose in this population. Methods Retrospective analysis of IR-tramadol exposures in ≤6-year-old children, collected by the French Poison Control Centers (PCCs) in 2003–2019. The incidence was estimated using IR-tramadol prescription data from the Health Improvement Network database (the French version of THIN). The Poison severity score (PSS) was used to grade severity. Results We found 1260 IR-tramadol exposures in ≤6-year-old children. The number of cases per 100,000 IR-tramadol-treated patients increased over time (p < .0001). One hundred forty-five cases involving IR-tramadol alone were analyzed. The median age was 3.0 years (IQR: 1.9, 4.0), the M/F ratio was 1.5 and the median dose was 5.0 mg/kg (IQR 3.3–11.1). Half of the children (49.7%) remained asymptomatic (PSS0) while 29.6% and 14.5% developed minor (PSS1) or moderate-to-severe (PSS2–PSS3) neurological symptoms, respectively. Twelve children developed respiratory depression. No seizures and no fatality were reported. All symptomatic children recovered within 24 h. The ingested IR-tramadol dose was positively correlated with the PSS (p < .0001). Using a receiver operating characteristic (ROC) curve approach (area under the curve, 0.92; p < .001), ingestion of ≥7.4 mg/kg IR-tramadol was appropriate to recommend hospital referral (sensitivity, 100% [95% confidence interval (CI), 85–100]; specificity, 73% [95% CI, 64–80]; predictive positive value, 39% [95% CI, 35–57]; negative predictive value, 100% [95% CI, 96–100]). Children who ingested <7.4 mg/kg IR-tramadol developed no (n = 68) or minor (n = 22) neurological symptoms. Conclusions Despite increasing tramadol prescriptions in adults during the study period in France, oral exposure to IR-tramadol in ≤6-year-old children was rare but possibly responsible for severe toxicity. Children with no underlying disease and concomitant medication ingesting <7.4 mg/kg IR-tramadol alone could be observed at home. However, given the observed variability in the onset of seizures after tramadol ingestion, which can occur at ingested tramadol doses below 7.4 mg and even at therapeutic doses, parents or guardians should be specifically warned about the risk of seizures.

Population Pharmacokinetic Model for Tramadol and O-desmethyltramadol in Older Patients.

Background and ObjectivesTramadol is commonly prescribed to manage chronic pain in older patients. However, there is a gap in the literature describing the pharmacokinetic parameters for tramadol and its active metabolite (O-desmethyltramadol [ODT]) in this population. The objective of this study was to develop and evaluate a population pharmacokinetic model for tramadol and ODT in older patients.MethodsTwenty-one patients who received an extended-release oral tramadol dose (25–100 mg) were recruited. Tramadol and ODT concentrations were determined using a validated liquid chromatography/tandem mass spectrometry method. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. The performance of the model was assessed by visual predictive check.ResultsA two-compartment, first-order absorption model with linear elimination best described the tramadol concentration data. The absorption rate constant was 2.96/h (between-subject variability [BSV] 37.8%), apparent volume of distribution for the central compartment (V1/F) was 0.373 l (73.8%), apparent volume of distribution for the peripheral compartment (V2/F) was 0.379 l (97.4%), inter-compartmental clearance (Q) was 0.0426 l/h (2.19%) and apparent clearance (CL/F) was 0.00604 l/h (6.61%). The apparent rate of metabolism of tramadol to ODT (kt) was 0.0492 l/h (78.5%) and apparent clearance for ODT (CLm) was 0.143 l/h (21.6%). Identification of Seniors at Risk score (ISAR) and creatinine clearance (CrCL) were the only covariates included in the final model, where a higher value for the ISAR increased the maximum concentration (Cmax) of tramadol and reduced the BSV in Q from 4.71 to 2.19%. A higher value of CrCL reduced tramadol Cmax and half-life (T1/2) and reduced the BSV in V2/F (from 148 to 97.4%) and in CL/F (from 78.9 to 6.61%).ConclusionExposure to tramadol increased with increased frailty and reduced CrCL. Prescribers should consider patients frailty status and CrCL to minimise the risk of tramadol toxicity in such cohort of patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13318-022-00756-x.

Comparing the frequency tramadol abuse in seizure and non-seizure complaint patients referred to neurology emergency department of a university affiliated hospital

Aim: Due to its similar opioid effects, tramadol is commonly abused worldwide. One of the notable side effects of tramadol is seizure. The present study compares the frequency of tramadol abuse among seizure and non-seizure (other reasons) patients referring to the Neurology Emergency Ward of Ali Ibn Abi Talib Hospital, a referral center affiliated to Rafsanjan University of Medical Sciences, Iran. Methods: This cross-sectional study reviewed 141 patients referring to the emergency ward of a referral hospital. The data were collected by clinical examination, face-to-face interviews, and a structured self-questionnaire for each client. The data were analyzed using descriptive statistics, non-parametric chi-square, and independent T-test. Results: In this cross-sectional study, 82 male (58.2%) and 59 female subjects (41.8%) were included. The results revealed the average age of patients being 30.16 ± 9.12. The incidence of tramadol abuse was approximately 36.8% in the total population study. Twenty-five and half percent of the subjects were referred to the neurology emergency ward for seizure while 16.3% of the subjects were referred to other wards for non-seizure complaints. In this study, we no relationship was found between the duration of consumption and the concurrent use of other medications; however, there was a statistically significant correlation between the dose of tramadol and the incidence of seizure. Conclusion: The result of the present study illustrated a significant incidence of seizure in men with tramadol abuse and a direct correlation with medication dose.

Effects of Ultramicronized N-Palmitoylethanolamine Supplementation on Tramadol and Oxycodone Analgesia and Tolerance Prevention.

Chronic pain management requires increasing doses of opioids, the milestone of painkillers, which may result in the onset of tolerance with exacerbated side effects. Maintaining stable analgesia with low doses of opioids is thus imperative. N-palmitoylethanolamine (PEA) is an endogenous lipid compound endowed with pain-relieving as well as anti-inflammatory properties. The ultramicronized formulation of PEA was recently demonstrated to be able to modulate morphine’s effects, delaying tolerance and improving efficacy. To evaluate the possible application to other opioids, in this study, we analysed the capacity of ultramicronized PEA to regulate analgesia and tolerance induced by oxycodone and tramadol. Pre-emptive and continuative treatment with ultramicronized PEA (30 mg kg−1, daily, per os) delayed the onset of opioid tolerance and enhanced opioid analgesia when it was acutely administered in association with tramadol (20 mg kg−1, daily, subcutaneously) or oxycodone (0.5 mg kg−1, daily, subcutaneously). Moreover, PEA exerted antinociceptive effects on tolerant rats, suggesting the use of PEA together with opioids for stable, long-lasting analgesia. To that purpose, the oxycodone dose needed to be increased from 0.3 mg kg−1 (day 1) up to 1 mg kg−1 (day 31) in the oxycodone + vehicle group; the tramadol dose was progressively enhanced from 15 mg kg−1 to 50 mg kg−1 in 31 days in the tramadol + vehicle group. Acute oral co-treatment with PEA (120 mg kg−1) achieved the same analgesia without increasing the dose of both opioids. The behavioural effects of PEA on opioid chronic treatment paralleled a decrease in astrocyte activation in the dorsal horn of the spinal cord (a marker of the development of opioid tolerance) and with a modulation of mRNA expression of IL-6 and serpin-A3. In conclusion, pre- and co-administration of ultramicronized PEA delayed the development of tramadol tolerance, potentiating either oxycodone or tramadol analgesia and allowing a long-lasting analgesic effect with a low opioid dose regimen. The use of PEA is suggested for clinical purposes to support the opioid-based management of persistent pain.

English

BACKGROUND Adequate pain management has a great importance for smooth postoperative recovery, early hospital discharge and early rehabilitation. In this study, we compare the analgesic effect and possible side effects of different routes of magnesium sulphate administration in cases of spinal anaesthesia for knee arthroscopy. METHODS This is an experimental prospective randomized control study. 196 patients undergoing knee arthroscopy were divided into 4 groups (49 each): Group A: Given bupivacaine intrathecally during spinal anaesthesia. Group B: Given magnesium sulphate 50 mg with bupivacaine intrathecally. Group C: Given magnesium sulphate IV 10 min after intrathecal injection (30 mg/kg MgSo4). Group D: Given magnesium sulphate intra-articular route, 10 min before the end of surgery (800 mgSo4 diluted in 12 ml normal saline (0.9 % NaCl). Operative time in minutes, VAS at rest and after procedure, time lapse before first analgesic dose after surgery, total dose of rescue analgesics used, pulse rate, mean arterial pressure and side effects were observed and analysed. RESULTS In regards to the lapse of time between end of surgery and first rescue analgesic given, total doses of tramadol used during the 24 hours after the procedure were significantly better in patients given intra-articular magnesium sulphate than other groups (P = 0.001). Patients of Group C who received IV magnesium sulphate were significantly better than patients who were given intrathecal magnesium sulphate in relation to time taken from end of surgery until first analgesic dose. VAS at rest and during the period of first 24 hours followed by surgery was statistically significant in patients who received intra-articular magnesium sulphate (p- 0.001). CONCLUSIONS Intra-articular administration of magnesium sulphate was observed to be superior to other routes of administration or not using at all. Next to intra-articular route, intravenous magnesium sulphate was found to be superior to intrathecal route in providing post operative analgesia in arthroscopy patients. KEY WORDS Analgesia, Knee Arthroscopy, Pain, Magnesium Sulphate, Intrathecal, Intra-articular

Effects of a Single Opioid Dose on Gastrointestinal Motility in Rabbits (Oryctolagus cuniculus): Comparisons among Morphine, Butorphanol, and Tramadol

The aim of this study was to evaluate and compare the effects of single doses of butorphanol, morphine, and tramadol on gastrointestinal motility in rabbits (Oryctolagus cuniculus) using non-invasive imaging methods, such as radiographic barium follow through and ultrasonographic contraction counts. Time-lapse radiographic and ultrasound examinations were performed before and after a single intramuscular dose of 5 mg kg−1 butorphanol, 10 mg kg−1 morphine, or 10 mg kg−1 tramadol. Pyloric and duodenal contraction counts by ultrasonography and radiographic repletion scores for the stomach and caecum were analysed using a mixed linear model. No significant effect was noted on ultrasound examinations of pyloric and duodenal contractions after administration of an opioid treatment. Morphine had a significant effect on the stomach and the caecum repletion scores, whereas butorphanol had a significant effect only on the caecum repletion score. Tramadol had no significant effect on the stomach or caecum repletion scores. The present findings suggest that a single dose of 5 mg kg−1 butorphanol or 10 mg kg−1 morphine temporarily slows gastrointestinal transit in healthy rabbits, preventing physiological progression of the alimentary bolus without the induction of ileus. In contrast, a single dose of 10 mg kg−1 tramadol has no such effects.