Combination Of Tramadol Research Articles

Investigating predictors in parenteral to oral switch of Analgesia in postoperative patients: An observational study

Introduction: A thorough understanding of various routes of analgesic administration and their limitations enables pain therapists to effectively manage postoperative pain, reduce the risk of chronic pain development, and enhance patient satisfaction. Considerations such as pain type, patient preferences and medical conditions guide the selection of the most appropriate administration method and dosage form for optimal outcomes. This observational study aimed to investigate the factors associated with the switch of analgesic medication from parenteral to oral in postoperative patients. Methods: This study was conducted for six months among 305 patients at a tertiary care teaching hospital, Davangere, India. The data about patient was collected through case sheets and was analyzed with IBM SPSS Version 25 for windows. Results: The study conducted on 305 patients found that the switch was mostly done within the time interval of 2-4 days. The combination of paracetamol and tramadol (22.6%) was the main drug of choice for switch. The switch from parenteral to oral analgesia was not found to be significantly associated with age, severity of pain, or length of hospital stay. Conclusion: Although switching between parenteral and oral routes of analgesic administration appears to be effective in managing surgical patients, but the decision to switch does not seem to be influenced by the hypothesized factors.

Coadministration of Novel Analgesic Isovaline with Tramadol Reduces Inflammatory Pain Response in Rats

Aim: Isovaline is a new and promising analgesic with an antinociceptive effect and, unlike µ-opioid agonists, interacts with aminobutyric acid receptors without causing sedation or respiratory depression. In this study, we compare the effect on thermal hyperalgesia and mechanical allodynia coadministration of subcutaneous isovaline and tramadol with individual administrations in a carrageenan-induced hind paw inflammatory pain model in rats. Methods: In this study, isovaline, tramadol, and the combination of isovaline and tramadol were subcutaneously administered to rats with carrageenan-induced inflammation of the hind paws. Hyperalgesia in response to thermal stimuli and allodynia in response to mechanic stimuli were assessed by using a thermal plantar test and a dynamic plantar aesthesiometer, respectively. Results: The administration of subcutaneous isovaline 400mg/kg and tramadol 4mg/ kg combination effect was higher than the other groups on latencies and thresholds (P

Polysubstance use patterns among individuals applying for opioid-use disorder treatment in the U.S.

ABSTRACT Objective The prevalence of polysubstance use is known to be high among individuals who use/misuse drugs. This study aims to extend existing research by (a) measuring polysubstance use through objective drug testing rather than fallible self-reports, (b) determining the most frequent three- and four-substance combinations instead of being limited to typical two-substance combinations, and (c) examining a comprehensive panel of substances beyond those commonly studied. Method Participants were a convenience sample of individuals applying for methadone maintenance treatment in 11 clinics across 7 states (n = 1098, 43.2% female). Participants voluntarily provided oral fluid and urine specimens for the study during clinic intake that were tested for 22 types of substances using liquid chromatography/tandem mass spectrometry (LC-MS-MS). Results Polysubstance use was high (89.6%), with the mean number of substances used by participants = 3.3, up to a maximum of 11. There were 10 three-substance combinations with prevalences of 5% or greater, the most frequent being opiates, fentanyl, and cocaine (10.5%). There were nine four-substance combinations with prevalences of 2% or greater, the most frequent being opiates, fentanyl, cocaine, and cannabis (4.5%). Many of these combinations can produce serious and even life-threatening interactions and side effects. The combination with perhaps the most severe potential consequence of concurrent use is the combination of opiates, fentanyl, and tramadol (5.1%), which all have sedative or central nervous system (CNS) depressive effects. Conclusion Clinicians should consider that symptoms of substance use are likely due to diverse combinations of substances, not only problematic use of a single presenting “substance of choice.”

The use of psychotropic drugs in oncological diseases (review)

Background: It is estimated that at least 25-30% of cancer patients experience mental disorders. Due to the high prevalence of these disorders among this patient population, psychotropic drugs have been successfully utilized in oncology for an extended period of time. The use of psychotropic drugs enables targeted symptom management to improve the quality of life of cancer patients. However, it is essential to carefully evaluate the risks of drug interactions and potential side effects when prescribing any psychotropic medication. The aim of the study: The aim of this study was to analyze the utilization of psychopharmacotherapy in oncology practice for treating comorbid mental disorders and symptoms related to oncological diseases. An evaluation of the side effects and drug interactions of psychopharmacological and oncological drugs was conducted. Materials and methods: The eLibrary, PubMed, and Google Scholar databases were searched using the keywords “psychooncology” and “psychopharmacotherapy”. Reviews, meta-analyses, and therapy recommendations were selected from the obtained results, which provided the most comprehensive coverage of the current scientific data on this topic. Results: Anxiety disorders and depressive reactions are prevalent in cancer patients and can be successfully treated with psychopharmacological intervention. Additionally, symptoms associated with the oncological process or side effects of treatment such as anorexia, pain, and nausea can be alleviated through the use of antidepressants and antipsychotics. However, it is crucial to carefully evaluate the risks of drug interactions when prescribing any psychotropic drugs. For instance, strong cytochrome CYP2D6 inhibitors can lead to a decrease in the concentration of the active metabolite tamoxifen, while the combination of antidepressants and tramadol increases the risk of serotonin syndrome. Conclusion: The application of psychotropic drugs in the treatment of cancer can greatly enhance the patients' quality of life. However, potential side effects and drug interactions must be carefully evaluated.

Off-label use of tramadol combined with Lacasera® soft drink: A sub-acute toxicological study using Wistar rats to evaluate the effects of combination on human basic haematological parameters and weight changes

Tramadol is a synthetic opioid that is used to treat moderate to severe pain in both acute and chronic conditions. Tramadol is predominantly used off-label for premature ejaculation and euphoria among male youth in Nigeria, especially when dissolved in Lacasera® soft drink, which gives it a pleasant taste. Research has not yet examined the effects of this combination on hematological parameters, despite the fact that this type of abuse is common among young people and poses a public health risk. A 28-day subacute study was conducted with Wistar rats weighing 160-180g. The rats were separated into 8 groups of 6 each. The control groups: 1 and 2 were treated with Lacasera® and deionized water respectively. Groups 3, 4 and 5 received 35mg/kg per day, 70.7mg/kg per day and 106mg/kg per day of Tramadol dissolved in deionized water respectively. Groups 6, 7 and 8 received similar doses of Tramadol dissolved in Lacasera®. Blood samples were analyzed using auto-analyzer and standard methods. The data was analyzed using a statistical tool software (SPSS version 27). All results were presented as mean ± SD. Values were considered significant at p<0.05. Hematological analysis of groups treated with Lacasera®-Tramadol combination shows dose-dependent significant decreases (p<0.05) in PCVs, RBCs, and Hbs. WBCs and platelets increased in groups that received Lacasera®-Tramadol combination. The study concludes that regular or infrequent users of Lacasera® without Tramadol are unlikely to experience serious hematological complications. However, chronic Tramadol-Lacasera® users will experience increased toxicity over time, leading to hemolytic anemia.

A comparison of fascia iliaca compartment block with intravenous analgesia to improve pain control in patients with femoral fracture.

The most common approach to managing severe pain following femoral fracture is with intravenous systemic analgesics, such as opioid analgesics and non-steroidal anti-inflammatory drugs associated with side effects such as respiratory depression, nausea, and vomiting. These side effects might be intolerable in trauma patients and may result in under treatment of pain. Improving the quality of analgesia may reduce these intolerable side effects. Our study compared the efficacy of fascia iliaca compartment block (FICB) with intravenous analgesics for preoperative pain management of femoral fractures. The study was a quality improvement prospective randomised study, where 50 patients aged between 18 and 65 years, and American society of anesthesiologists I and II were recruited into two groups. Group A received FICB with a combination of 0.4 mL/kg of 0.5% plain bupivacaine and adrenaline 1:200,000 made up to 30 mL, while group B received placebo FICB using 30 mL normal saline. Also, group B received a combination of intravenous paracetamol 15 mg/kg not exceeding 900 mg and tramadol 1 mg/kg not exceeding 100 mg, while group A received an equal volume as normal saline intravenously. The study revealed no significant difference in age, gender, associated injuries, X-ray description of fractures, and mechanism of injuries; however, there was a significant difference in the NRS-pain score at 30 min, summed pain intensity difference for 4 h and patient satisfaction in the FICB group compared to the standard group. The study revealed that FICB results in better pain control compared to a combination of intravenous tramadol and paracetamol in patients with femoral fractures.

Effects of combination of tramadol and sildenafil citrate (Viagra) on hepatic and renal function parameters in Male Albino Rats

Erectile dysfunction, premature ejaculation and pleasure seeking have increased the use of sildenafil citrate, tramadol and their combination by youths who believe these drugs could positively impact their sexual life. Sildenafil citrate and tramadol are metabolized in the liver, and their by-products excreted through the kidneys, making these organs possible targets for toxicity. Aim: This study evaluates the effects of combination of tramadol and sildenafil citrate on hepatic and renal function parameters in male albino rats. Methodology: A total of forty-nine (49) male albino rats weighing between 150 to 180g were used for the study. Sildenafil citrate and tramadol were administered to the rats by means of oral gavage for 28 days. The liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using the Reitman-Frankel method. Alkaline phosphatase (ALP) was determined using the Colorimetric endpoint method. Total protein (TP) was determined using the biuret method. Albumin (ALB) was determined using the bromocresol green method. Sodium (Na+), potassium (K+) and chloride (CL-) were determined using ion selective electrode (ISE) method. Bicarbonate (HCO3-) was determined using titrimetric method. Urea was determined using Urease bertholet method. Creatinine was determined using Jaffe-Slot method. Results: There were no significant differences (P>.05) in the liver enzymes ALT, AST and ALP in all the treatment groups compared to the negative control. Total protein (TP) and albumin (ALB) also showed no significant differences (P>.05) in the groups, compared to the negative control. there were no significant differences (P>.05) in the electrolyte levels in the treatment groups, compared to the negative control. Urea and creatinine levels were also not significantly different (P>.05) in the treatment groups, compared to the negative control. Conclusion: Administration of sildenafil citrate singularly and in combination with tramadol, at recommended and double doses for 28 days, did not impact the liver and was also non-toxic to the kidneys.

Case Report on a Cocktail Drug Abuser Developing Rhabdomyolysis

Rhabdomyolysis is a medical emergency characterized by the break down of skeletal muscle leading to the release of intracellular contents into the blood stream, which can lead to acute kidney injury and even death. Drug abuse is one of the potential causes of rhabdomyolysis. This case report describes a 18-year-old male with a history of drug abuse who presented to the emergency department with severe muscle pain, weakness, dark and reduced amount of urine. The patient was diagnosed with rhabdomyolysis, which was likely due to a combination of high doses Marijuana, Chlorpheniramine, Dextromethorphan (Corex Syrup), Dicyclomine, Tramadol, Acetaminophen and cigarette smoking over period of 4-5 years, landed up in rhabdomyolysis after joining gym. The patient was immediately started on aggressive intravenous fluid resuscitation, and his urine output and electrolyte levels were closely monitored. Patient required initiation of Hemodialysis over period of 15 days. Patient's muscle pain and weakness gradually improved over the next few days, and he was discharged with a diagnosis of AKI due to Rhabdomyolysis due to drug abuse. Prompt recognition and treatment of rhabdomyolysis are crucial to prevent serious complications, and addiction treatment should be pursued to prevent future episodes of rhabdomyolysis and other drugrelated complications.

Pain and Palliative Management in Advanced Gastrointestinal Malignancies – How Are We Doing?

Aims: The aim of the study is to study the different methods and their efficacy in pain management in advanced gastrointestinal (GI) malignancies. Methods: The study included patients with advanced and inoperable GI malignancies. Demographic data, laboratory parameters and radiological investigations, baseline visual analog scale (VAS) score, and subjective global assessment (SGA) were recorded on the first contact along with details of medical, endoscopic, and palliative interventions as performed. Analgesic pain step ladder approach was followed for pain management. Follow-up to assess response was done using VAS score and SGA at the end of 3 months or death within this period. Results: Seventy-one patients were included. Most of them were elderly males. Out of 7 malignancies noted, hepatocellular carcinoma (HCC) was the most common tumor (41; 57.8%). Thirty-five patients (49.3%) had vascular invasion, while 29 (40.8%) had metastatic cancer. The most common vascular invasion was the portal vein (29; 40.8%). The liver was the most common metastatic site (12; 16.9%). The baseline mean VAS score was 5.13 ± 2.38 and the highest was in carcinoma gallbladder patients (8.0 ± 2.0). Most patients were having baseline SGA rating B (69%). Tramadol was the most commonly used analgesic (35.22%) followed by a combination of tramadol and fentanyl (26.76%). The most common palliation was transarterial chemoembolization in HCC (80.5%) and biliary self-expandable metallic stent in carcinoma pancreas (77.8%). There was a statistically significant reduction in VAS score in HCC (P < 0.001), carcinoma pancreas (P = 0.009), and colorectal cancer (P = 0.022). One-sixth patients moved from SGA rating B to rating A, 9.9% moved from SGA rating B to rating C, and 9.9% moved from SGA rating C to rating B. Conclusion: There was an improvement in quality of life at 3-month follow-up. There was significant pain improvement in the studied patients. However, almost one-third patients did not get adequate pain relief.

Modulatory effects of Cannabis sativa co-administration with tramadol and codeine on cognitive function in male rats

Most teenagers mix up various psychoactive cocktail substances in combinations to get intoxicated. The role of the mixture combination of codeine (CDE), tramadol (TMD), and Cannabis sativa (CNB) on brain cognition, purinergic, cholinergic, and antioxidant enzyme activities remains unknown. This study sought to assess the mechanism of action of combinations of CDE+ TMD+ CNB on the function and activities of the brain of male Wistar rats. Forty-eight male Wistar rats were divided into 8 groups, n = 6. Group 1 served as a control, groups 2, 3, and 4 were exposed to CDE (2 mg/kg bw), TMD (10 mg/kg bw), and CNB (200 mg/kg bw), while groups 5, 6, 7, and 8 were co-administered with CDE+TMD, CNB+ TMD, CNB+CDE, and CNB+TMD+CDE orally for 28 days. This study revealed the effect of prolonged administration of CNB, TMD, and CDE on the suppression of cognitive function, acetyl-cholinesterase (AChE), butyl-cholinesterase (BChE), monoamine oxidase (MAO) enzyme activities, and antioxidant enzyme activities in rats’ brains when compared against control rats (P < 0.05). However, the activities of ectonucleosides (NTPdase), adenosine deaminase (ADA), and malondialdehyde levels produced in the brain of rats were significantly elevated (P < 0.05). This study reported the mechanism behind the neurotoxicity of CNB, TMD, and CDE on rats’ cognitive, cholinergic, purinergic, and antioxidant enzymes as a consequence of the drastic reduction in cholinesterase enzyme activities leading to neurotransmitter poisoning.

Evaluation the combination of chlorpheniramine and tramadol at a level of thermal and visceral antinociceptive in a mouse acute pain model

Evaluation the combination of chlorpheniramine and tramadol at a level of thermal and visceral antinociceptive in a mouse acute pain model

Real-World Evidence on the Efficacy and Tolerability of Tramadol/Dexketoprofen (TRAM/DKP) Fixed-Dose Combination for the Management of Acute Non-surgical Pain in Asian Patients: A Multicentre Retrospective Case Series.

Multimodal analgesia is key in the effective management of acute pain. Previous clinical trials have demonstrated good results with the use of a fixed-dose combination (FDC) of tramadol 75 mg and dexketoprofen 25 mg (TRAM/DKP) in acute pain management. However, there is a dearth of real-world evidence on the efficacy and safety of this combination in the management of acute non-surgical pain, especially among Asian patients. The case series reported herein investigates the real-world experiences of physicians and Asian patients with the use of TRAM/DKP FDC in the management of acute non-surgical pain. Data were collected retrospectively on 11 Asian patients across multiple hospitals who had received a short course of TRAM/DKP FDC for acute non-surgical orthopaedic and non-orthopaedic pain. Data on baseline characteristics, medical history, treatment regimen, clinical outcomes, and patient satisfaction were compiled and shared at a peer-to-peer expert meeting in October 2022. All patients experienced a reduction in pain intensity and were very satisfied with pain management, with a mean satisfaction score of 4.3/5. Five patients (range: 63-74 years) experienced mild adverse events, including nausea, vomiting, and dizziness, which resolved with no need for additional treatment in the majority of cases. No serious adverse events were recorded. Asian patients with acute non-surgical orthopaedic and non-orthopaedic pain achieved good pain control with TRAM/DKP FDC. The regimen was well tolerated, and patients reported high levels of satisfaction with the outcomes, indicating that TRAM/DKP FDC is an effective choice for the control of acute non-surgical pain in Asian patients.

The driving factors facilitating non-medical use of tramadol: a qualitative study of Nigerian youths

Background: The paper explores the opinions of Nigerian youth regarding their reasons behind the use of tramadol for non-medical purposes and learns their preferences in choosing tramadol. Methods: We conducted In-depth Interviews (IDIs) and Focus Group Discussions (FGDs) among students in secondary schools, tertiary schools and out-of-school youths in Lagos, Ekiti, Edo and Delta states in Nigeria. A total of 20 IDIs and 6 FGDs were conducted among 92 Nigerian youths of age 15 – 25 years. Data was also complemented from school reports, participants’ feedback from youth drug abuse sensitization workshops and desk reviews. Data were analyzed using thematic analysis to describe emerging themes. Results: The sex distribution of the participants was 60.1% males and 39.1% females. The main findings for non-medical use of tramadol among the youths were; to enhance sexual excitement (prolong ejaculation), to feel less hungry (reduce the desire for and food) to sustain hard labor (reduce pain, withstand prolong manual labor). The respondents also revealed that tramadol in combination with other substances will give them a euphoric effect. However, many of youths are ignorant of the risk of the non-medical use of tramadol. Conclusion: Tramadol abuse has become widespread in the Nigerian environment among the youths. The findings from this study revealed that the choice of tramadol use for non-medical purposes is a result of different effects discovered in the use which could pose potential harm to the abuser. Therefore, public health approaches should be adopted in preventing the abuse of tramadol among the youth.

(236) Flibanserin for Post-Orgasmic Illness Syndrome: A Case Report

Abstract Introduction Postorgasmic illness syndrome (POIS) is a rare disorder with ~50 cases recorded in the literature over the last 10 years. POIS is characterized by symptoms of flu-like fatigue, myalgias, fevers, mood disturbance, congestion, rhinorrhea and conjunctival pruritus, that begin within seconds to hours after an orgasm for a duration of 2-7 days. The most well described pathophysiologic hypothesis to date is immunologic based hypersensitivity reaction, but other hypotheses include withdrawal from endogenous opioids, dysregulated neuroendocrine response or autonomic nervous system. These mechanisms are elucidated by patient responses to different treatments including, antihistamines, dopamine agonists, benzodiazepines, NSAIDs and SSRIs. However, no standardized treatment has yet been developed. Objective Here we describe a case of intractable POIS in a patient physician, who had a remarkable response to flibanserin nightly and gabapentin nightly for pain. Methods Patient is a 40 year old male with acquired post orgasmic illness syndrome that started 10 years prior. Symptoms include headaches, muscle pain, numbness, weakness, irritability, low energy, anhedonia, and brain fog. Symptoms start 30 minutes after every orgasm and persist for 1 week. He reports fluctuations in his libido when experiencing these symptoms. Orgasms feel good to him and do not change with POIS. Pre-ejaculate and ejaculate trigger his POIS. He reports no problems with erections. He has tension headaches with arousal which affect his day but he does not experience full POIS symptoms. He does not report issues with stress except during POIS symptoms. He is a nonsmoker and has up to two drinks per month. He denies trauma, general pain, back injuries or pain, bowel dysfunction or abnormal penile curvature. He has been able to reduce symptom duration from 1 week to 4 days with a combination of bupropion, lexapro, silodosin, ritalin, and tramadol; however, the duration and intensity of symptoms is still significant. Patient was trialed on a combination of flibanserin and gabapentin. He was advised to take 200 mg gabapentin nightly and 100 mg flibanserin nightly. Results The combination of flibanserin and gabapentin significantly improved the patient's symptom duration and intensity. He now experiences mild symptoms for one day and has stopped taking his other medications. He also reports that his libido has markedly improved, helping him and his wife restore their intimate relationship. Conclusions The use of flibanserin, a serotonin receptor 2A antagonist and serotonin receptor 1A partial agonist has not yet been described in the literature, and supports a role of serotonin in the pathogenesis of POIS. Serotonin 2A is a known inhibitor of the sexual response and has a significant impact on mood, memory and cognition. As such this neuroendocrine dysregulation could modulate many of the symptoms present in POIS including brain fog, anhedonia and low energy. The variability of medications that provide relief in different patients emphasizes the importance of taking a multidimensional and individualized approach to treating patients' distinct presentations. Disclosure No

Tramadol Provides Similar Pain Relief and a Better Side Effect Profile than Oxycodone (or Hydrocodone) Alone or in Combination With Tramadol After Anterior Cruciate Ligament Reconstruction or Arthroscopic Knee Debridement

To evaluate whether tramadol provides similar postoperative pain relief after anterior cruciate ligament (ACL) reconstruction surgery or arthroscopic debridement surgery compared to oxycodone (or hydrocodone) or a combination of tramadol and oxycodone. Patients over the age of 14 undergoing ACL surgery or arthroscopic debridement surgery performed by the same surgeon were provided a postoperative pain diary over the first 10 postoperative days. Patients were either provided tramadol, oxycodone (or hydrocodone), or a combination of tramadol in addition to oxycodone (or hydrocodone). Pain scores were measured on visual analog scale (VAS), including average pain, maximum pain, and minimum pain throughout the day. Additionally, side effects and number of over-the-counter analgesics were recorded. 121 patient surveys were reviewed. Tramadol alone for ACL with autograft provided lower average pain scores on postoperative day 1-3 (VAS 3.3 vs oxycodone 6.1 and hybrid of 5.1) with lowest maximum pain on postoperative day 1 (VAS 5.3 vs oxycodone 6.6 and hybrid 5.1) and the lowest number of average nights awakened by knee pain (3.6 vs oxycodone 6.0 and hybrid 8.5). Tramadol alone provided the lowest number of days of constipation (3 vs oxycodone 4.68 and hybrid 4.08), nausea (0.42 vs oxycodone 1.48 and hybrid 1.72), and dizziness (0.68 vs oxycodone 0.84 vs hybrid 1.28). Individual medication group breakdown of ACL surgery with allograft, as well as arthrosopic knee debridements did not have a large enough quantity to have three separate comparison groups. Tramadol provides similar, and in most cases better, pain relief for ACL reconstruction and arthroscopic knee debridements compared to oxycodone (or hydrocodone) alone or a combination of tramadol with oxycodone (or hydrocodone), while providing a lower side-effect profile. Alternative analgesic therapies outside of traditional opioids (like oxycodone and hydrocodone) are lacking in popularity or reputation. This retrospective comparative study cohort evaluation can help provide clinicians an alternative analgesic therapy for various knee surgeries that have comparable pain relief with less addictive properties and less side effects.

Antinociceptive and anti-inflammatory activity of DW-1021, the ionic complex of pelubiprofen and tramadol, in rodents

Although drugs such as acetaminophen, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs), are commonly used for pain management, the side effects of these drugs such as hepatotoxicity, nephrotoxicity, nausea, and vomiting, can not be neglected. Therefore, combinations of analgesics with different mechanisms raise the possibility of developing novel analgesics. Therefore, the aim of the present study was to evaluate whether DW-1021, the ionic complex of pelubiprofen (NSAID) and tramadol (opioid), has synergic antinociceptive and anti-inflammatory effects in nociceptive as well as inflammation-induced nociceptive models compared to pelubiprofen- or tramadol-only administration. Strong synergistic antinociceptive efficacy of DW-1021 was observed in the mouse writhing test and von Frey paw withdrawal threshold test in the carrageenan-induced rats. The hot plate test in mice and the Randall-Selitto mechanical paw pressure test in carrageenan-induced rats revealed that DW-1021 had a preferable effect on relieving pain to pelubiprofen, but not as much as tramadol. In the carrageenan-induced rats, DW-1021 had a more potent effect on reducing paw inflammation (paw volume, width, and thickness) via the suppression of PGE2 production than tramadol, but less than that of pelubiprofen. Taken together, our results suggest that the administration of DW-1021, a combination of pelubiprofen and tramadol, exerted a potent effect and can be used as a potential therapeutic agent for relieving pain and inflammation.

Сравнение схем анальгезии на основе нефопама и трамадола у раненых с минно-взрывной травмой в условиях медицинской эвакуации санитарным автотранспортом

Summary. Investigation purpose – to compare an effectivity and safety of implementation of schemes of analgesia based on nefopam and tramadol in conditions of medical evacuation by sanitary vehicles with mine-explosion trauma (MET); to determine a possibility of its usage as an alternative for drugs analgetic. Materials and methods of the investigation. Calls maps (form 110/u) of crews of Center of sanitary aviation and urgent medical treatment of All-Russian Center of Disaster Medicine “Zashchita” of Federal State Budget Organization “SSC – Federal Medical Biophysical Center named after A.I. Burnazyan” of FMBA of Russia. Patients were divided into 2 groups. Each group contained 8 people. A scheme with nefopam and non-steroid anti-inflammation medicines (NSAIM) was used for analgesia in the first group. There was a scheme with tramadol and NSAIM in the second group. Investigation results and their analysis. A usage of nefopam combined with NSAIM in patient with MET in conditions of prolonged medical evacuation by sanitary vehicles is not inferior in its efficiency to the combination of tramadol with NSAIM and has some benefits to stability and frequency of side effects. A nefopam usage as a component of multimodal scheme of analgesia as an alternative to tramadol can be recommended by medical specialists who provide treatment for patients during military actions. Nefopam doesn’t contain in the list of potent and toxic substances. This fact gives organization and logistics benefits during nefopam usage in conditions of emergency situation.

Shiv-mix for perioperative hemodynamic stability and analgesia: A new paradigm for limited resource centres

Dear editor, A very interesting article has been published in your esteemed journal titled “Effect of pre-emptive intravenous paracetamol, magnesium sulfate, and lignocaine on hemodynamic variables during perioperative period in pre-eclampsia patients scheduled for lower segment cesarean section under general anesthesia: A prospective randomized study” by Kothari et al., (December 2022|Vol 13|Issue 12). Research is not complete unless it reaches to its potential audience. We, firstly, would like to congratulate the authors and the journal for publishing their research on such a very important topic. Authors have described their findings in a clear and scientific manner. Randomized and double-blinded studies provide inferences which are considered more authentic. Authors in this study used envelop method for allocating patient in the two groups; the intervention and the control. Findings of this study will definitely help readers and practitioners in providing safe and stable anesthesia to their patients. In this prospective randomized study, authors concluded that combination of paracetamol, magnesium sulfate, and lignocaine is effective in attenuating hemodynamic responses to laryngoscopy and intubation. They also found better hemodynamic stability during intraoperative and post-operative period in pre-eclampsia patients scheduled for lower segment cesarean section under general anesthesia. Finally, they opined that when paracetamol, magnesium sulfate, and lignocaine are given together effective and prolonged post-operative analgesia can be obtained. Authors discussed efficacy and safety of various medications (Lignocaine, fentanyl, esmolol, and magnesium sulfate) comparing with placebo and different combinations used to attenuate laryngoscopy and intubation response. However, in last paragraph of introduction and in discussion, authors wrote that they could not find any single study using all three drugs (intravenous paracetamol, magnesium sulfate, and lignocaine) simultaneously for attenuation of hemodynamic changes during laryngoscopy and intubation. We would like to draw your kind attention published work that have utilized the same combination with similar effects and this study support the conclusions of those studies. We do agree that these were nor RCTs but case series. Two related articles are discussed here. Khan and Singh in their narrative review described efficacy, safety, and patient satisfaction of various combinations of paracetamol, tramadol, magnesium sulfate, and lignocaine (Shiv-mix 1, 2, and 3). Authors found the described opioid free anesthesia (OFA) regimen (Shiv-mix) very effective in attenuating laryngoscopic and intubation response. In their case series, they also found stable intraoperative hemodynamics and absence of some commonly seen post-operative complications such as PONV and shivering. In another case series by Ansari et al., using similar OFA describing ten cases of laparoscopic cholecystectomy, the authors found that OFA using Shiv-Mix (A combination of paracetamol, tramadol, magnesium sulfate, and lignocaine) infusion preoperatively was a safe, opioid‑sparing, and feasible option that provide good perioperative analgesia, stable hemodynamics, and an uneventful recovery profile. We again support the findings of the study by Kothari et al. We hope that this discussion will help researchers and practitioners to provide effective and safe perioperative course of their patients and opening new horizons for multimodal analgesia.

Efficacy of Kampo medicine Kakkonto as acute medication to treat tension-type headache among musculoskeletal pain patients using regular analgesics.

Tension-type headache (TTH) is the most prevalent type of primary headache disorder. Its acute pharmacotherapy is acetaminophen or non-steroidal anti-inflammatory drugs based on the Japanese Clinical Practice Guideline for Headache Disorders 2021. With Japan's aging population, however, the number of TTH patients with comorbidities that have been treated by analgesics is increasing. Under this context, it is sometimes difficult to select an acute pharmacotherapy for TTH. Kakkonto, Japanese traditional herbal kampo medicine, is empirically used for TTH. We hypothesized that kakkonto has efficacy for TTH with painful comorbidities. We prospectively collected 10 consecutive TTH patients who had already taken analgesics for comorbidities. We prescribed 2.5g of kakkonto (TJ-1), and patients took it. A numerical rating scale for pain before and 2 hours after kakkonto intake was evaluated. Eight women and 2 men were included. The mean age was 71.0 ± 13.4 years old. Four patients had lower back pain, 2 had lumbar spinal stenosis, 2 had knee pain, 1 had neck pain, and 1 had shoulder myofasciitis. Celecoxib was used for 4 patients, acetaminophen for 3, loxoprofen for 2, and a combination of tramadol and acetaminophen for 1, as routinely used analgesics. The median numerical rating scale statistically improved from the median of 4 to that of 0. There were no side effects of kakkonto. Kakkonto showed efficacy as an acute medication for TTH with comorbidities that have been treated by analgesic.

Neurological Effects of Combining Low Toxic Dose of Tramadol and Nicotine: An Animal Model Evidence of Endoplasmic Reticulum Stress.

Tramadol abuse is a common problem in the Middle East in conjunction with smoking. The current study applied immunohistochemistry, western blot, real-time PCR, and ELISA to test the combination toxicity. Low toxic doses of tramadol induced animal brain cortex inflammation and hippocampus injury. Adding nicotine reverted hippocampus pathological changes without triggering marked brain injury. The expression of CHOP protein with real-time PCR showed mild endoplasmic reticulum stress (ER) in rat's brain. Histological, immunohistochemical, and western blotting analysis of CHOP (CCAAT-enhancer-binding protein homologous protein) and BIP (immunoglobulin heavy chain-binding protein) chaperones demonstrated endoplasmic reticulum stress in the brains of animals. Furthermore, the levels of apoptosis and autophagy markers demonstrated a mild reaction. The blood level of serotonin was high in all study groups, with a marked increase in the combined one. The high serotonin levels in the blood can be critical and associated with a high risk of serious withdrawal and pathological consequences. Serotonin receptor blockers such as olanzapine may increase systemic serotonin levels and need further investigation to utterly pinpoint their roles in managing mood disorders. In conclusion, the combination of tramadol and nicotine is less harmful than expected. However, serious withdrawal effects can occur as a result of high systemic serotonin effects.