Trace element levels: How Substance Use Disorder (SUD) contributes to the alteration of urinary essential and toxic element levels.

Increasing illicit drug use is one of the main problems in most countries or societies. Monitoring heavy metals and trace elements in this vulnerable group seems to be necessary. Therefore, we assessed the urinary trace element and toxic metals/metalloids concentrations (Zinc (Zn), Iron (Fe), Copper (Cu), Chromium (Cr), Lead (Pb), Cadmium (Cd), Arsenic (As), Nickel (Ni), and Mercury (Hg)) in opium, tramadol, and cannabis users compared to healthy subjects. In this cross-sectional study, patients with substance use disorder (SUD) (n = 74) were divided into four groups: cannabis, tramadol, opium, and mixed (simultaneous use of more than one of the three studied substances), along with a healthy group (n = 60). Urine samples were prepared by dispersive liquid-liquid microextraction method so that heavy metals/metalloids could be measured by ICP-MS. The mean urinary concentration of Cu (48.15 vs. 25.45; 89.2%, p<0.001), Hg (1.3 vs. 0.10; 1200%, p < 0.001), and Zn (301.95 vs. 210; 43.8%, p < 0.001) was markedly lower among patients with SUD. The mean urinary concentration of other elements including As (1.9 vs. 4.1; 115.8%), Cd (0.1 vs. 1.10; 1000%), Cr (6.80 vs. 11.65; 71.3%), Ni (2.95 vs. 4.95; 67.8%), and Pb (1.5 vs. 7.9; 426.6%) were significantly higher among patients with SUD compared to healthy subjects. When sub-groups were compared, no significant differences were observed between their trace element levels (Kruskal-Wallis test, p > 0.05). This can be an indication that regardless of the type of drug, the levels of trace elements are changed with respect to healthy individuals. Our results showed that illicit drug use causes changes in urinary trace element/heavy metal/metalloid levels and highlights the need for monitoring heavy metals and trace elements in individuals with substance use disorder. Assessment of different elements in biological samples of drug dependents may be useful for implementing new prevention and treatment protocols. In case of changes in their levels, complementary recommendations, attention to diet, and periodic assessment of toxic metal levels within treatment programs will be needed.

Comparative Evaluation of the Local Anesthetic Action of Tramadol Hydrochloride With Adrenaline Versus Lidocaine Hydrochloride With Adrenaline for Maxillary Exodontia: A Randomized Control Trial.

BACKGROUND: Tramadol hydrochloride (T-HCl) has demonstrated to have a local anesthetic effect similar to lidocaine hydrochloride (L-HCl) when administered locally for minor oral surgical procedures. PURPOSE: Our study aimed to compare the anesthetic effect of T-HCl versus L-HCl in maxillary premolar extraction. STUDY DESIGN, SETTING AND SAMPLE: The study is a split-mouth, double-blind randomized clinical trial at the Faculty of Dental Sciences, Ramaiah University of Applied Sciences, Bengaluru, India. The study sample was composed of patients referred for maxillary bicuspid extraction. Patients were excluded from the sample if, allergic to the study drugs, pregnant or lactating females, and smokers. EXPOSURE VARIABLE: The variable is an anesthetic drug administered for local anesthesia and it is grouped into 2 categories, T-HCl and L-HCl. A supraperiosteal infiltration of T-HCl with adrenaline on one side and L-HCl with adrenaline on the contralateral side was injected. MAIN OUTCOME VARIABLE: The primary outcome variable was profound anesthesia of T-HCl, where the patient sensed the loss of sensation of touch, temperature, and pain. Secondary outcomes were onset and duration of anesthesia, intraoperative pain, postoperative analgesia, and adverse reactions, were recorded. ANALYSES: Inferential statistics, the χ2 Test, the Mann-Whitney Test, and the Wilcoxon signed-rank test were used to compare the parameters. The level of significance was set at ≤ 0.05. RESULTS: A total of 40 patients were included, and 80 teeth were extracted. Profound anesthesia was achieved in all the cases. The mean subjective duration of anesthesia in the T-HCl and L-HCl groups was 130.80 ± 20.01 minutes and 111.40 ± 14.87 minutes, respectively, with a P value of .001. The mean Visual Analogue Scale (VAS) score for pain during the procedure in the T-HCl and L-HCl groups was 0.60 ± 0.67 and 1.10 ± 0.71, respectively, with a P value of .002. The mean Visual Analogue Scale score for pain postoperatively in the T-HCl and L-HCl groups was 0.70 ± 0.72 and 1.40 ± 0.67, respectively, with a P value of .001. Six patients in T-HCl required postoperative analgesia when compared to 18 patients in L-HCl (P value < .003). CONCLUSIONS AND RELEVANCE: T-HCl provides similar anesthetic outcomes in the extraction of maxillary bicuspids as L-HCl.

Clinical Effect of Ultrasound-Guided Adductor Block on Postoperative Analgesia After Total Knee Replacement.

Objective: To explore the clinical effects of ultrasound-guided adductor block (UGAB) on postoperative analgesia after total knee replacement. Methods: From March 2022 to June 2022, 60 patients in the First Affiliated Hospital of Chongqing Medical University were included. They were divided into control (n = 30) and ultrasonic groups (n = 30). They all received total knee arthroplasty. Before total knee arthroplasty, patients in the control and ultrasonic groups underwent general anesthesia and UGAB, respectively. Visual Analogue Scale (VAS) was used to assess the pain. The time of the first straight leg elevation and the first landing time were recorded. Knee joint function was evaluated. Information about the dosage of tramadol intramuscular injection and the number of times patient-controlled analgesia pump pressing was collected. The serum levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were detected. Results: Compared with the control group, UGAB increased the rate of muscle contraction and relaxation and total and relaxation after total knee replacement in the ultrasonic group (P < .05). UGAB reduced VAS scores of pain during passive activity after operation (P < .05). UGAB also facilitated the first straight leg lifting time after the operation and the time of the first landing after the operation (P < .05). Meanwhile, UGAB reduced the dose of tramadol and press times of the self-control analgesia pump after operation (P < 0.05). UGAB also suppressed postoperative IL-6 and hs-CRP levels and increased postoperative joint range of motion (P < .05). Conclusion: UGAB promotes early recovery of knee function with high safety in patients undergoing total knee replacement, with reduced postoperative pain and inflammatory reaction.

Topical Traditional Chinese Medicines for Cancer Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Safe and effective management of cancer-related pain is a worldwide challenge. In the search for treatment options, natural products used in Chinese herbal medicines (CHMs) have received attention in clinical studies for their effects on cancer-related pain. The objective of this systematic review is to evaluate the clinical evidence for topically applied CHMs as adjunctive treatments for cancer pain management. METHODS: Nine biomedical databases and 4 clinical trial registries were searched for randomized-controlled trials (RCTs) that reported measures of pain and/or quality of life. Risk of bias was assessed using the Cochrane tool. Meta-analysis employed mean difference (MD) with 95% confidence intervals (random effects). RESULTS: Twenty (20) RCTs (1636 participants) met the inclusion criteria. Meta-analyses were grouped based on the comparisons and outcome measures. For pain intensity, there was a greater reduction in the topical CHM group versus placebo (MD -0.72 [-1.04, -0.40]), no difference when compared to tramadol (MD -0.15 [-0.38, 0.08]), and a greater reduction when topical CHMs were combined with conventional analgesic medications (MD -0.67 [-0.93, -0.40]). Analgesic onset time was reduced in the CHM group compared to tramadol (MD -26.02 [-27.57, -24.47] minutes), and for CHMs combined with conventional medications (MD -19.17 [-21.83, -16.52] minutes). When CHMs were combined with analgesic medications, improvements were found for duration of analgesia (MD 1.65 [0.78, 2.51] hours), analgesic maintenance dose (MD -31.72 [-50.43, -13.01] milligrams/day), and quality of life. CONCLUSION: Addition of topical CHMs to conventional analgesic medications was associated with improved outcomes for pain intensity, some other pain-related outcomes, and measures of quality of life. Limitations included methodological issues in some studies and considerable heterogeneity in some pooled results.

[Electrophysiological appropriateness technique based on TCM meridian theory for postoperative pain after urethral reconstruction: A real-world study].

OBJECTIVE: To investigate the clinical efficacy of electrophysiological appropriateness technique (EAT) therapy based on the traditional Chinese medicine (TCM) meridian theory in managing postoperative pain after urethral reconstruction surgery. METHODS: Using the real-world study approach, we enrolled 61 male patients undergoing urethral reconstruction and divided them into a control group (n = 30) and an observation group (n = 31), the former receiving patient-controlled intravenous analgesia (PCIA), while the latter PCIA plus EAT at 4 pairs of acupoints (Hegu, Neiguan, Zusanli and Sanyinjiao bilaterally) and the Ashi point, with 100 mg tramadol hydrochloride given orally as remedial analgesia in both groups in case of postoperative Visual Analogue Scale (VAS) score ≥4. We compared the VAS scores at 4, 12, 24 and 48 hours postoperatively, the dose of cumulative fentanyl used at 48 hours, the number of cases needing remedial analgesia, the time to first flatus and the incidence of adverse reactions between the two groups of patients. RESULTS: The VAS scores were markedly lower in the observation than in the control group at 4, 12, 24 and 48 hours after surgery (P < 0.05), with statistically significant differences in time-dependent effect and interactive effect (P < 0.05). Significant reduction was observed in the doses of cumulative fentanyl (P < 0.05) and remedial tramadol analgesia (P < 0.05), time to first flatus (P < 0.05), and incidence of adverse reactions (P < 0.05) in the observation group in comparison with the controls. CONCLUSION: Electrophysiological therapy based on the TCM meridian theory can safely and effectively alleviate postoperative pain after urethral reconstruction, reduce opioid consumption, and decrease adverse events.

Persistent socket pain in a dog after the enucleation of the eye and its clinical management.

Persistent socket pain is a condition described in humans after enucleation of the eye. This report aims at describing this condition in dogs. A 10-year-old male-neutered crossbreed was presented to the referral veterinary surgeon for enucleation of the right ocular globe. Anaesthesia and surgery were uneventful although during the postoperative period the dog was reluctant to open the mouth and to be explored by the referral veteterinary surgeon. Despite treatment with meloxicam, paracetamol and tramadol, no improvements were observed. Ten weeks after surgery, the dog was referred to the Dick White referrals for further investigations. Ophthalmic examination was normal, though palpation of the wound triggered an avoidance response. Magnetic resonance imaging showed changes compatible with orbital cellulitis. The area of interest was evaluated with the use of the mechanical Von Frey filaments. A response, characterised by sudden turning of the head and attempts to withdraw it, was evoked with filament 4.93 (8.0 g) during stimulation of the periorbital area. After induction of anaesthesia, an ultrasound-guided injection containing levobupivacaine 0.5% and methylprednisolone was performed within the retrobulbar area. Three hours after recovery from anaesthesia, no discomfort was observed during palpation of the area. Re-evaluation was performed with the Von Frey filaments; no response could be evoked during testing with all 20 filaments (from 2.36 to 6.65) applied on either side of the face. The patient was discharged with a course of gabapentin and, 3 weeks after the intervention, the dog showed no clinical signs of pain. Persistent socket pain is an unpleasant sensation at the level of the enucleated orbit, and it should be regarded as a challenging condition to diagnose and treat. The MRI findings appeared to be essential to select the most appropriate interventional treatment. The injection of local anaesthetic and steroid into the retrobulbar space was useful for both confirming the diagnosis and treating pain by reducing the peripheral signalling and decreasing the residual inflammation.

Blended smartphone intervention for patients in opioid maintenance treatment in Iran: protocol for a randomized controlled trial.

BACKGROUND: The pattern of substance use in Iran is characterized by a high prevalence of opioid use and opioid use disorder (OUD). Although opioid maintenance therapy (OMT) has been introduced in Iran, approximately 50% of people with opioid use disorder remain unreached. Moreover, psychosocial treatment of OUD and common mental health symptoms during OMT is limited. Digital interventions have been shown to improve psychological distress, depression, anxiety, and post-traumatic stress disorder symptoms. In addition, providing psychoeducation and risk reduction counseling to prevent communicable diseases like HIV and infectious hepatitis is common via the Internet. However, despite these promising advances, no smartphone intervention in OMT has been investigated for the treatment of OUD and common comorbid mental health symptoms. OBJECTIVE: We examine the effectiveness of adding a blended smartphone intervention based on community reinforcement approach, motivational interviewing- and cognitive behavioral therapy compared to OMT as usual that aims to improve OMT outcomes and addresses common mental health symptoms in OMT patients in Iran. METHOD: Adults with opioid dependence entering 8 treatment centers in Tehran, Iran will be randomly assigned to receive either OMT plus a smartphone intervention or OMT as usual. The primary outcomes will be the percentage of negative urine tests for illicit, non-prescribed use of opioids (opium, heroin, tramadol) and treatment retention. Secondary outcomes will include the longest period of abstinence from the illicit, non-prescribed use of opioids (opium, heroin, and tramadol) confirmed by urine samples, changes in communicable disease risk-taking behaviors, changes in stress and common mental health symptoms, and client satisfaction. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models. DISCUSSION: This study will provide substantial knowledge for designing effective blended interventions for OUD. Moreover, it will investigate if treatment retention and OMT-related outcomes and common mental health symptoms can be improved by adding a smartphone intervention to OMT. TRIAL REGISTRATION: https://en.irct.ir/trial/53578 .

Ethnopharmacological evaluation of Poppy seed oil in combination with Tramadol on behavioral paradigm and on dopamine, and cytokines levels.

OBJECTIVE: The present study was taken up to evaluate the combination of two drugs in the management of behavioral disorders such as locomotor activity, muscle relaxation, analgesic, and anxiolytic activity. MATERIALS AND METHODS: In the methodology, Wistar rats weighing (150-180 g) were divided into six groups of 6 each (n=6). All the animals (groups II to VI) were subjected to stress and analyzed for anxiolytic activity using an elevated plus maze. The animals were treated for 28 days with poppy seed oil in lower and higher doses (1,000 and 2,000 mg/kg), tramadol in lower and higher doses (1.5 and 3 mg/kg) as individual groups, and one group with a combination of both drugs in lower doses. RESULTS: The results depicted showed that the combined treatment had significantly (**p <0.001) improvised behavior deficits, extemporized, and diminished anxiety-like attitude in rats, and showed the analgesic property in a significant manner. The pro-inflammatory cytokines TNF-α and IL-1ß were evaluated in the serum and were observed to be lessened the values of both in a significant manner with the co-administration of both the test drugs. The dopamine concentrations were also determined in the serum, which disclosed a decline (**p <0.001) significantly. CONCLUSIONS: It was concluded from the results that a combined effect of drugs might be beneficial in the management of behavioral disorders and pain management.

A case of musical hallucinations induced by tramadol.

AIM: Although tramadol has been suggested to have a higher risk of producing hallucinations than other opioids, reports of musical hallucinations are extremely rare. CASE PRESENTATION: A 72-year-old woman came to our department complaining of auditory hallucinations. She had been diagnosed with lumbar spinal canal stenosis associated with herniated and slipped disks. Due to persistent back pain, tramadol was started, and the dose was increased to 300 mg/day. The next day, she began to hear nursery rhymes, songs of the Ministry of Education, and folk songs. The musical auditory hallucinations disappeared with the use of antipsychotics and the discontinuation of tramadol. No relapse of musical auditory hallucinations was observed after the discontinuation of antipsychotics. CONCLUSION: Based on the clinical course, we concluded that the auditory hallucinations were musical hallucinations induced by tramadol.

Pharmaceutical treatment of osteoarthritis.

OBJECTIVE: To review the current state of pharmaceutical treatment recommendations for the management of osteoarthritis. METHOD: A narrative review was drafted to describe treatment guidelines, mechanism of action, pharmacokinetics, and toxicity for nine classes of pharmaceuticals: 1) oral nonsteroidal anti-inflammatory drugs (NSAIDs), 2) topical NSAIDs, 3) COX-2 inhibitors, 4) duloxetine, 5) intra-articular corticosteroids, 6) intra-articular hyaluronic acid, 7) acetaminophen (paracetamol), 8) tramadol, and 9) capsaicin. RESULTS: In general, oral and topical NSAIDs, including COX-2 inhibitors, are strongly recommended first-line treatments for osteoarthritis due to their ability to improve pain and function but are associated with increased risks in patients with certain comorbidities (e.g., heightened cardiovascular risks). Intra-articular corticosteroid injections are generally recommended for osteoarthritis management and have relatively minor adverse effects. Other treatments, such as capsaicin, tramadol, and acetaminophen, are more controversial, and many updated guidelines offer differing recommendations. CONCLUSION: The pharmaceutical management of osteoarthritis is a constantly evolving field. Promising treatments are emerging, and medicines that were once considered conventional (e.g., acetaminophen) are gradually becoming less acceptable based on concerns with efficacy and safety. Clinicians need to consider the latest evidence and recommendations to make an informed decision with their patients about how to optimize treatment plans for patients with knee, hip, polyarticular, or hand osteoarthritis.

2022 Taiwan Guidelines for Acute Treatment of Migraine.

The Taiwan Headache Society published its guidelines for acute migraine treatment in 2017. Since then, emerging drugs and treatment options have developed rapidly. The migraine-specific drugs gepants and ditans and several noninvasive neuromodulation devices have been approved for use in Europe and the United States. Although not all emerging drugs and treatment options have been approved for use in Taiwan, keeping pace with international trends and updating treatment guidelines are imperative. Therefore, the Treatment Guideline Subcommittee of the Taiwan Headache Society reviewed the quality of recent trials, evaluated the corresponding grade of evidence, and appraised the reported clinical efficacy to reach a new consensus. To ensure that the updated Taiwan guidelines are appropriate and feasible, the subcommittee also referred to the guidelines from the United States, Europe, Canada, and other countries concerning the main roles, recommendation levels, clinical efficacy, and adverse reactions of drugs for the acute migraine treatment. Several types of drugs are currently available for acute migraine treatment in Taiwan. These drugs can be categorized into migraine-specific and migraine-non-specific. Among them, migraine-specific triptans (oral or nasal spray formulations) and migraine-nonspecific acetaminophen and NSAIDs (diclofenac, ibuprofen, naproxen) are highly recommended because they are supported by strong evidence and demonstrate high efficacy. Prochlorperazine injection has been upgraded to a highly recommended level because of the rich clinical experience for this treatment. Ergotamine/caffeine remains a second-line drug because of its lower specificity and efficacy compared with triptans. High-dose aspirin was downgraded to rescue treatment because of potential gastrointestinal side effects. Although evidence supports the combination of oral tramadol and acetaminophen, this combination should be used as a rescue treatment due to concerns about dependence. Evidence supporting the use of intravenous tramadol or morphine is insufficient; therefore, their use is not recommended. As for non-pharmacological approaches, there are only limited controlled data. The choice of treatment for acute migraine attacks should follow the concept of "stratified care." For mild to moderate migraine attacks, oral NSAIDs are the first choice, with combination analgesics, intravenous/intramuscular NSAIDs as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine/caffeine compounds are recommended and should be administered in the early stage of migraine attacks. Antiemetics can be used as supplements to alleviate nausea and vomiting. Other emerging migraine-specific drugs, such as gepants or ditans, may also have a role in the future. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either therapy alone. Parenteral steroids and fluid supply are the first-line treatment for status migrainosus. Acetaminophen is suitable for mild to moderate migraine attacks and remains the first choice for children and pregnant women. To prevent medication overuse headache, the use of acute treatment should be limited to a maximum of 2 days per week. Key words: acute migraine treatment, evidence-based medicine, treatment guidelines, triptans, ergotamine, neuromodulation.

Antioxidants (selenium and garlic) alleviated the adverse effects of tramadol on the reproductive system and oxidative stress markers in male rabbits.

Tramadol has been used by millions of patients as an analgesic drug to relief the severe pain caused by cancers and other diseases. The current study aimed to investigate the protective effects of antioxidants (garlic and selenium) against the toxic effects of tramadol on semen characteristics, steroid hormones, the protein expressions of different cytochrome P450 isozymes [CYP 21A2, CYP 19, and 11A1], and on antioxidant enzyme activities in testes of rabbits. Western immunoblotting, spectrophotometric, and histological methods were used in this study. Tramadol (1.5 mg/kg body weight) was administered orally to male rabbits for up to three months (three times/week), and after pretreatment of rabbits with garlic (800 mg/kg) and/or selenium (1 mg/kg body weight) by 2 h. The present study showed that motilities, semen volumes, morphologies, sperm counts, testosterone, and estrogen levels were significantly decreased after 4, 8, and 12 weeks of tramadol treatment. In addition, the protein expressions of CYP 21A2, CYP 19, and 11A1 were down-regulated in the testes of the tramadol-treated rabbits. On the other hand, pretreatment of rabbits with garlic, selenium, and/or garlic-selenium for 2 h before administration of tramadol restored the downregulated CYP 21A2 and 11A1 to their normal levels after 12 weeks of tramadol treatment. Activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase, and levels of glutathione were inhibited in the testes of tramadol-treated rabbits. On the other hand, free radical levels were significantly increased in the testes of tramadol-treated rabbits for 12 weeks. Interestingly, such changes in the activities of antioxidant enzymes as well as free radical levels caused by tramadol were restored to their normal levels in the rabbits pretreated with either selenium, garlic, and/or their combination. Histopathological investigations showed that tramadol caused substantial vacuolization with the presence of damaged immature spermatozoid in the testes. However, selenium and garlic treatments showed an increase in healthy sperm production with normal mitotic and meiotic divisions. The present study illustrated for the first time the mechanisms of low steroid hormone levels in the testes of tramadol-treated rabbits which could be due to the downregulation of CYPs proteins, induction of oxidative stress, and inhibition of antioxidant enzyme activities. In addition, the present data showed that such toxic effects of tramadol were attenuated and restored to their normal levels after pretreatment of rabbits with garlic, selenium, and/or their combination. This finding may pave the way for a new approach to reducing the toxicity of tramadol.

Comparison of urine trace element levels in tramadol addiction alone and its co-abuse with cigarette and opium in Western Iran.

Tramadol is an opioid pain medication used to treat moderate to severe pain. Tramadol consumers tend to co-abuse some other substances such as opium, cigarettes, alcohol, and cannabis and each of these substances may impair trace elements homeostasis in the body. Therefore, this case-control study aimed to compare the urinary concentration of some essential and toxic elements in tramadol addiction alone and its co-abuse with cigarette and opium in Western Iran. For this purpose, urine samples were collected in two groups of tramadol (n = 72) and control subjects (n = 62) from March to November 2020. The case group was divided into three groups: tramadol alone, tramadol + opium, and tramadol + cigarettes. Moreover, ICP-MS (Agilent 7900) was used to measure trace element concentrations in the urine samples. Based on our results, Fe was the only element markedly higher among controls as compared to tramadol users (p < 0.001). Moreover, the concentration levels of As appeared to be the same among both groups, but the levels of other elements including Ca, Cd, Cr, Mn, Cu, Zn, Co, Ni, Se, and Pb were all significantly higher among tramadol users as compared to control group. The rank-based regression analysis illustrated that no contribution of sex and age effect was found by the regression model on the levels of all 12 studied elements. While, smoking was found to affect the levels of Fe (ß = 0.163, P = 0.025) and Co (ß = 0.411, p < 0.001) so that smoking reduced Fe levels but elevated Co concentration levels. Abuse of tramadol along with cigarettes and opium increased the concentration of some heavy metals in urine samples compared to the control group. However, these results showed no significant effect of age, sex, smoking habit, and amount of tramadol usage on the levels of trace elements.

Intoxication related to substances use in patients presenting to Ain Shams University Poisoning Treatment Center, Cairo, Egypt (2015-2019).

INTRODUCTION: Illicit drug use may result in several emergencies. Hospital emergency data can help to detect new patterns of substance use and high-risk trends of drug use. This epidemiological study aimed to investigate the pattern and outcome of cases with substance use intoxication who presented to Ain Shams University Poisoning Treatment Centre, Cairo, Egypt. METHODS: This retrospective study included all cases of acute intoxication due to use/misuse of substances who presented to the centre during the period (2015-2019). RESULTS: The study included 11 281 cases; young adults (aged 20-40 years) represented the greatest proportion of cases (6519, 57.8%). Males were the predominant gender in all age groups (representing 79.2% of the cases). Tramadol was the most common substance of exposure in all age groups except for children and adolescents where cannabis was the most common one. There were 162 fatalities (1.4% of all cases) and opioids had the greatest case fatality rate. DISCUSSION AND CONCLUSIONS: Tramadol was the most used drug that resulted in acute intoxication, followed by cannabis. A total of 43.6% of the cases of acute intoxications were due to recreational use/misuse of prescription drugs.

The Effect of Perianal Tramadol Infiltration on Postoperative Pain Following Hemorrhoidectomy.

INTRODUCTION: The present study was attempted to evaluate the effect of perianal infiltration of tramadol on postoperative pain in patients undergoing hemorrhoidectomy. METHOD: This double-blind clinical trial study was carried out on 90 patients with grade 3 and 4 hemorrhoids undergoing hemorrhoidectomy. Patients were randomly assigned into 3 groups of control or bupivacaine or tramadol. Before the surgery, perianal infiltration of .25% bupivacaine or tramadol or normal saline was prescribed to each group, respectively. Data on pain severity (based on the visual analog scale (VAS), the duration of surgery, sedation score, pain at the first defecation, first request time for additional analgesia, nausea and vomiting, and analgesic intakes) were evaluated and analyzed. RESULTS: Duration of surgery was almost similar in all 3 groups (P = .974). The results showed a significant difference in pain score between 3 groups (P ≤.05) at all times after the surgery. In addition, the means of sedation scores (P = .03), pain score at the first defecation (P = .001), the time to first analgesic request (P = .001), and ketorolac administration times (P = .01) were significantly different between 3 groups. Finally, no complication was reported regarding postoperative nausea and vomiting. CONCLUSION: Given the notable efficacy of tramadol in reducing pain after hemorrhoidectomy and its minor side effects, this medication is suggested as an effective topical anesthetic to decrease pain after hemorrhoidectomy.

Acupuncture against chronic postsurgical pain in non-small cell lung cancer patients: A protocol of randomized controlled trial.

INTRODUCTION: Video-assisted thoracoscopic lobectomy is the prior recommended treatment for non-small cell lung cancer (NSCLC), with the advantages of small trauma, less postoperative pain, and quick recovery. However, a large number of patients may suffer chronic postsurgical pain (CPSP), which makes the patients unwilling to practice pulmonary exercises, and it would directly affect patient's cough, sputum expectoration, and mobility. Opioids could greatly improve the quality of postoperative analgesia and the quality of life after surgery, but it is accompanied with obvious side effects. A number of clinical studies have proved that acupuncture could improve postoperative pain and reduce opioid use. In this study, we try to conduct a randomized controlled study to evaluate the efficacy and safety of plum-blossom needle acupuncture combined with Tramadol in improving CPSP after lobectomy in NSCLC patients. METHODS: Patients will be randomly divided into treatment group (acupuncture plus Tramadol) and control group (sham acupuncture plus Tramadol) with a random number table in 1:1 ratio. The patients, outcome assessor, and statistician will be blinded. The outcomes are changes of numerical rating scale, Karnofsky performance score, brief pain inventory, blood routine, liver and kidney function. The data will be analyzed by SPSS 22.0. CONCLUSIONS: The results will help to evaluate the efficacy and safety of plum-blossom needle acupuncture in improving CPSP after lobectomy in NSCLC patients.

Deep Cervical Plexus Block for Neck and Shoulder Pain Due to Myofascial Pain: A Randomized Clinical Trial.

OBJECTIVES: Myofascial pain is one of the most common causes of regional pain with no definitive treatment. This randomized clinical trial was conducted to assess the efficacy of deep cervical plexus block versus placebo injection (sham block) for the treatment of myofascial neck and shoulder pain in terms of analgesic consumption and pain during a follow-up period of 2 weeks after the block. MATERIALS AND METHODS: Patients were randomly divided into 2 groups. Group I (block) received deep cervical plexus block and group II (placebo) received normal saline. A total of 66 patients were included in the study, 34 patients in the block group and 32 patients in the placebo group. RESULTS: Two weeks after the intervention, the average pain duration was significantly lower in the block group: 1.38±1.39 versus 5.25±1.72 for the block and placebo groups, respectively (P<0.0001). Pain intensity was significantly less in the block group such that 2.9% of patients in the block group had severe pain compared with 53.1% of patients in the placebo group (P<0.0001). Two weeks after receiving the block, the mean opioid consumption calculated as tramadol equivalent was 21.1±44.2 mg compared with 166.1±118.8 mg for the block and placebo groups, respectively. Multivariate analysis showed that patients with a longer history of pain had a higher pain score after 2 weeks. The possibility of recovery is affected by pain duration as patients with a history of chronic pain were least affected by the block. DISCUSSION: This technique could be an alternative to pharmacological and other nonpharmacological treatments for myofascial pain.

Preconditioning by ultra-low dose of tramadol reduces the severity of tramadol-induced seizure: Contribution of glutamate receptors.

Tramadol, a weak agonist of mu-opioid receptors, causes seizure via several mechanisms. Preconditioning has been purposed to reduce the epileptic seizures in animal models of epilepsy. The preconditioning effect of tramadol on seizure is not studied yet. This study was designed to evaluate the preconditioning effect of ultra-low dose of tramadol on the seizures induced by tramadol at high dose. Furthermore, regarding the critical role of glutamate signaling in the pathogenesis of epilepsy, the effect of preconditioning on some glutamate signaling elements was also examined. Male Wistar rats received tramadol (2 mg/kg, i.p) or normal saline (1 mL/kg, i.p) in preconditioning and control groups, respectively. After 4 days, the challenging tramadol dose (150 mg/kg) was injected to all rats. Epileptic behaviors were recorded during 50 min. The expression of Norbin (as a regulator of metabotropic glutamate receptor 5), Calponin3 (as a regulator of excitatory synaptic markers), NR1 (NMDA receptor subunit 1) and GluR1 (AMPA receptor subunit 1) was measured in hippocampus, prefrontal cortex (PFC) and amygdala. Preconditioning decreased the number and duration of tremors and tonic-clonic seizures. Norbin, Calponin3, NR1 and GluR1 expression were decreased in hippocampus, and preconditioning had no effect on them. In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose. These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.

Tratamiento conservador de la artrosis de cadera / Conservative treatment of hip osteoarthritis

Ante un escenario clínico de coxalgia por artrosis de cadera se planteó la necesidad de conocer los tratamientos con-servadores más seguros y efectivos para el manejo del dolor. El tratamiento de la artrosis requiere un enfoque integral e individualizado en función de las preferencias del paciente para lograr el máximo beneficio clínico. Existen numerosas estrategias útiles para el manejo del dolor en pacientes con artrosis de cadera siendo fuertemente recomendados de inicio la actividad física, los antiinflamatorios no esteroideos (AINE) orales y en ciertos casos los corticoides intraarticulares, tramadol o duloxetina, siempre asociado con la actividad física. Los ejercicios más recomendados son los aeróbicos y el Tai Chi o yoga. (AU)

Faced with a clinical scenario of coxalgia due to hip osteoarthritis, the need to know the safest and most effective conservative treatments for pain management arose. The treatment of osteoarthritis requires a comprehensive and individualised approach based on the patient's preferences to achieve maximum clinical benefit. There are numerous useful strategies for pain management in patients with hip osteoarthritis being strongly recommended from the beginning such as physical activity, oral non-steroidal anti-inflammatory drugs (NSAID) and in certain cases intra-articular corticosteroids, tramadol or duloxetine, always associated with physical activity. The most recommended exercises are aerobics and Tai Chi or yoga. (AU)

Influência do tramadol associado à levobupicavaína epidural sobre a taxa de propofol e variáveis fisiológicas, em cadelas submetidas à mastectomia e à ovário-histerectomia / [Influence of tramadol combined with epidural levobupicavaine, on the propofol infusion rate and physiological variables, in female dogs undergoing mastectomy and ovariohysterectomy]

Objetivou-se avaliar os efeitos fisiológicos e sobre o consumo do propofol, relativos à anestesia epidural com levobupivacaína isolada ou associada a diferentes doses de tramadol. Para tal, 18 cadelas foram pré-tratadas com acepromazina, utilizando-se propofol para indução e manutenção anestésicas. Conforme o protocolo epidural instituído, formaram-se três grupos (n=6) tratados com levobupivacaína isolada (1,5mg/kg) (GL) ou acrescida de 2mg/kg (GLT2) ou 4mg/kg (GLT4) de tramadol, respectivamente. As fêmeas foram submetidas à mastectomia e à ovário-histerectomia (OH), registrando-se as variáveis fisiológicas nos períodos pré (TB e T0) e transanestésicos (T10 a T70), bem como a taxa mínima de propofol necessária. Houve redução da FC para o GL e o GLT4 em relação ao GLT2 (T30 a T70), detectando-se, no GL, redução da PAS e da PAD em relação ao TB. Maiores taxas de infusão do propofol foram necessárias para o GL (0,70±0,12mg/kg/min) em relação ao GLT2 (0,50±0,19mg/kg/min) e ao GLT4 (0,50±0,19mg/kg/min). Conclui-se que o tramadol potencializou o propofol, ao ofertar analgesia, independentemente da dose administrada. Todos os protocolos testados foram seguros e eficazes em cadelas submetidas à mastectomia e à OH.(AU)

The aim of this study was to evaluate the physiological and on propofol-sparing effects related to epidural anesthesia with levobupivacaine alone or combined with different doses of tramadol. For this purpose, 18 female dogs were pretreated with acepromazine, using propofol for induction and maintenance of anesthesia. Based on a previously established epidural (L7-S1) protocol, three groups (n=6) were treated with either levobupivacaine alone (1.5mg.k-1) (GL) or in association with to 2mg.kg-1 (GLT2) or 4mg.kg-1 (GLT4) of tramadol, respectively. These dogs were all undergoing mastectomy and ovariohysterectomy (OH). The physiological data were registered in the pre (TB and T0) and trans-anesthetic periods (T10 - T70), as well as the consumption of propofol. There was a reduction in the HR for GL and GLT4 in relation to GLT2 (T30 - T70) and reductions in SAP and DAP in relation to TB in the GL group. Higher continuous infusion rate of propofol were required for GL (0.70±0.12mg.kg-1.min-1) relative to GLT2 (0.50±0.19mg.kg-1.min-1) and GLT4 (0.50±0.19mg.kg-1.min-1). It was concluded that tramadol potentiated propofol, offering analgesia independently of its administered dose. All protocols tested were safe and effective in female dogs undergoing mastectomy and OH.(AU)