Opiate Research Articles

Prescription Patterns and Risk Factors for Prolonged Opioid Dependence in Elective Anterior Cruciate Ligament Reconstruction in a Military Population.

Background:Limited data are available regarding excessive opioid prescribing in the perioperative period after routine orthopaedic procedures in US military personnel.Purpose:To examine the demographic profile of the patients receiving these medications and to identify potential risk factors for prolonged opioid use after anterior cruciate ligament reconstruction (ACLR) in the active duty military population.Study Design:Case-control study; Level of evidence, 3.Methods:The Military Analysis and Reporting Tool (M2) was used to search the Military Health System Data Repository (MDR) for patients undergoing ACLR from 2012 through 2015 and specifically for active duty personnel with an arthroscopically assisted ACLR (Current Procedural Terminology [CPT] code 29888). Complete opioid prescription filling history was also obtained. This study had 2 primary outcomes: (1) use of opiate analgesics more than 90 days after surgery, representing prolonged opiate prescriptions, and (2) high levels of postoperative opiate use, defined as having filled prescriptions accounting for greater than the 95th percentile of morphine equivalents for patients in the study cohort. Data were analyzed via multivariate regression analysis to identify potential associations with the primary outcomes.Results:A total of 9474 patients met the inclusion criteria. Median patient age was 27 years, and the sample included 1316 (14%) female and 8158 (86%) male patients. A total of 66 (0.7%) patients had a preoperative diagnosis for substance abuse; 2656 (28%) patients continued to receive opioid prescriptions more than 90 days after surgery, and 502 (5%) patients were in the top 95th percentile of all opioid users within the study cohort. Total preoperative morphine equivalents per day and total perioperative morphine equivalents per day were highly important risk factors for both outcomes, although other demographic factors such as race, sex, and age may play minor roles.Conclusion:We identified total preoperative morphine equivalents, total perioperative morphine equivalents, sex, and race as potential predictors of prolonged opioid use after ACLR. This information may prove useful in developing a predictive model to identify at-risk patients before surgery. This could help mitigate future misuse or abuse and improve preoperative patient counseling regarding pain management expectations.

COVID-19: Studying the Global Pandemic – Foreword

COVID-19: Studying the Global Pandemic – Foreword

Determining the Concentration of Morphine and Codeine in Poppy Seeds for Drug Test Defense

TRAVIS HARDING, MARK FLOOD, ANDREAS BAUR, and KRISTY HENSON. Department of Natural Sciences, Fairmont State University, Fairmont, WV, 26554. Determining the Concentration of Morphine and Codeine in Poppy Seeds for Drug Test Defense.The purpose of this research was to determine the concentration of opiates, morphine and codeine, in poppy seeds in effort to combat the “poppy seed defense”. Morphine and codeine are naturally occurring substances belonging to a class of drugs labeled opioid analgesics, commonly known as narcotics. There has been an increase in concerns involving false-positive opiate drug test. Distinguishing between legitimate dietary poppy seed ingestion versus non-prescribed opiate or heroin abuse is important for individuals subject to routine drug testing. Poppy seeds were purchased from supermarkets and were mechanically ground up by either 1) a blender or 2) a mortar and pestle, which best simulates human mastication. The ground up seed products were placed in a solution matrix to simulate a human oral cavity (target concentration of 30 ng/mL). Morphine and codeine concentrations from the samples will be tested using Thin Layer Chromatography, immunoassay (Opiate ELISA), and a validated Gas Chromatography-Mass Spectroscopy (GC-MS) Selected Ion Monitoring (SIM) system. The screening cutoff concentration ranges from 0 ng/mL to 40 ng/mL. Preliminary results from previous constructed experiments showed a positive color change for the opiate assay from blue to yellow within one hour (National Institute on Drug Abuse Research). The average absorbance at a dual wavelength of 450 nm and 650 nm was 1.238 correlating to a morphine concentration of about 5.1 ng/mL. Initial GC-MS results showed morphine and internal standard morphine-D3 had mass to charge ratios of 432 m/z and 429 m/z with an average concentration of 7.5 ng/mL respectively. This research was made possible by NASA West Virginia Space Grant Consortium, Training Grant #NNX15AI01H.

Mu opioid receptor in microglia contributes to morphine analgesic tolerance, hyperalgesia, and withdrawal in mice.

A major challenge in medicine is developing potent pain therapies without the adverse effects of opiates. Neuroinflammation and in particular microglial activation have been shown to contribute to these effects. However, the implication of the microglial mu opioid receptor (MOR) is not known. We developed a novel conditional knockout (cKO) mouse line, wherein MOR is deleted in microglia. Morphine analgesic tolerance was delayed in both sexes in cKO mice in the hot plate assay. Opioid-induced hyperalgesia (OIH) as measured in the tail immersion assay was abolished in male cKO mice, and physical dependence to morphine as assessed by naloxone-induced withdrawal was attenuated in female cKO mice. Our results show a sex-dependent contribution of microglial MOR in morphine analgesic tolerance, OIH, and physical dependence. In conclusion, our data suggest that blockade of microglial MOR could represent a therapeutic target for opiate analgesia without the opiate adverse effects.

A Concise Review of Concepts in Opioid Pharmacology up to the Discovery of Endogenous Opioids.

This brief review covers concepts in opioid pharmacology that were promoted during the period leading up to the establishment of the International Narcotics Research Conference (INRC) in the early 1970s and the discovery of endogenous opioid peptides in 1975. The founders of INRC, meeting together during the International Union of Pharmacology meeting in Basel in 1969, recognized that the time was ripe for the creation of an international society that would provide a venue for the discussion of research across disciplines in this rapidly expanding area of science. The emphasis here is on studies leading to the demonstration that specific receptors for morphine-like analgesics exist, the search for endogenous ligands for these receptors, and early attempts to elucidate the mechanisms underlying opiate drug tolerance, dependence, and addiction. SIGNIFICANCE STATEMENT: Research on opioids in the 20th century was driven by the search for nonaddicting analgesics. This review discusses the development of the "analgesic" receptor concept, the demonstration that such receptors existed, and the search for an endogenous ligand. Conceptual models were proposed to explain tolerance to the actions of opiate drugs and the development of dependence and addiction. This review explains these models and indicates how they foreshadowed more recent discoveries on the acute and chronic actions of opiate drugs.

تحليل المورفين، المورفين -3 غلوكورونيد، المورفين -6-غلوكورونيد، الكودايين والكودايين -6-الغلوكورونيد باستخدام جهاز الفصل السائل عالي الكفاءة

في علم السموم الشرعي والتفسير السريري، هناك حاجة كبيرة لتحديد واكتشاف العقاقير الأفيونية ومستقلبات الجلوكورونيد المختلفة. عادة ما يتم تحديد الجلوكورونيدات عن طريق انشقاق رابطة الجلوكورونيد مع إنزيم (على سبيل المثال، جلوكورونيداز) أو التحلل المائي الحمضي لإنتاج المركب الأصلي، الذي يتم اكتشافه لاحقًا. بالنسبة لتحليل الطيف الكتلي للغاز GC-MS، قد يكون هذا عن طريق الاشتقاق إلى شكل أكثر تقلبًا أو ثباتًا. الكشف المباشر عن اتحادات الجلوكورونيد يتغلب على القيود الحرجة لهذه الطرق. في هذا البحث، اختبار كروماتوجرافي السائل عالي الأداء وعكسي الطور عكسي انتقائي مع شطف التدرج والكشف عن الأشعة فوق البنفسجية للمورفين، المورفين 3-الجلوكورونيد، المورفين 6-الجلوكورونيد، الكوكايين، الكودايين -6-الجلوكورونيد والهيدروكودون تم تطويره. تم إجراء الفصل على عمود تحليلي C18 (سلسلة الكربون من Octadecyl) (150  2.0 مم، 5 ميكرون) واكتشفه كاشف الأشعة فوق البنفسجية (UV) عند 210 نانومتر. يتكون الطور المتحرك من مخزن مؤقت من الأسيتون تريل - الفوسفات (0.0125 ، درجة الحموضة 7.5) مع شطف في وضع التدرج تتراوح من 7.5 إلى 60% من الأسيتون تريل على مدى 25 دقيقة (دقيقة) مع معدل تدفق 0.2 مل / دقيقة. كانت منحنيات المعايرة خطية (نطاق R2 من 0.997 إلى 0.999) في نطاق التركيز 0.025-2 ميكروغرام / مل لكل التحليلات، باستخدام الهيدروكودون كمعيار داخلي. لذلك يهدف هذا السلوك إلى تطوير طريقة فعالة لفصل المورفين والكوديين والغلوكورونيدات بواسطة HPLC-UV وتقييم استخدام نصائح SPME LCلاستخراج المورفين والكوديين والجلوكورونيدات من عينات البول.

Is there enough naloxone to deter the diversion? Effect of concurrent administration of intravenous naloxone on opioid agonist effects of intravenous buprenorphine: A randomised, double-blind, within-subject, crossover study among opioid-dependent subjects.

We aimed to evaluate and compare the effect of different intravenous doses of naloxone on reinforcing effect of intravenous buprenorphine (2 mg) in patients stabilised on sublingual buprenorphine. This is a double-blind, within-subject, randomised, crossover study. Opioid-dependent patients, with history of intravenous drug use, stabilised on buprenorphine maintenance treatment were included after informed consent (n = 14). We administered and assessed the reinforcing effects of six test conditions: buprenorphine and naloxone co-formulation (BNX) in 4:1, 2:1 and 1:1 dose ratio (i.e. buprenorphine 2 mg + naloxone 0.5, 1 and 2 mg, respectively), buprenorphine alone (2 mg), pheniramine maleate (45.5 mg) and saline at 24 hourly intervals. No significant opioid withdrawals were precipitated during any test conditions. Compared to buprenorphine alone, 4:1 BNX had comparable euphoria, drug recognition, subjective opiate sensations and drug liking (P > 0.05); 2:1 BNX condition had significantly different subjective euphoria (P = 0.001), opioid recognition (P = 0.002), subjective opioid sensations at 60 min (P = 0.027) and drug liking (P < 0.001), while 1:1 BNX had significantly different objective euphoria (P = 0.002), opioid recognition (P = 0.030), subjective opioid sensations (P < 0.001) and drug liking (P < 0.001). No significant difference was noted on sedation scores between buprenorphine alone and all three combinations of BNX. The 4:1 BNX condition did not impact the reinforcing agonist effects of buprenorphine. None of the intravenous BNX combination ratios precipitated opioid withdrawals. Findings emphasise the need for exploring more abuse deterrent mechanisms.

A single nucleotide polymorphism in OPRM1(rs483481) and risk for heroin use disorder

Opioid receptor mu1 (OPRM1) is the target of many opioid drugs, and it is known to have affinity toward both endogenous and exogenous opioids, opiate and opioid analgesic drugs. The present study was undertaken to explore association of single nucleotide polymorphisms (SNPs) in the OPRM1 gene with heroin use disorder. Ten OPRM1 polymorphisms were analyzed in 132 cases and 147 healthy controls. The SNP rs483481 showed significant allelic, genotypic and haplotypic association (Allelic: p-value = 0.003, OR = 1.75, CI = 1.21-2.55) (Genotypic: p-value = 0.003, OR = 1.72, CI = 1.08-2.75) with heroin use disorder. Allelic and genotypic association remained significant even after multiple testing corrections with 1000 permutations. A significant positive correlation between ‘Number of times drug abstained’ and ‘rs483481-AA genotype’ (p-value = 0.002; Pearson correlation = 0.265) was also observed. One-way ANOVA analysis demonstrated significant association of rs483481 with ‘number of times drug abstained’ (F = 4.86, p-value =0.009). ‘A’ allele and ‘AA’ genotype of marker rs483481 seem to confer protective effect while ‘G’ allele and ‘GG’ genotype potentiates risk for heroin use disorder. OPRM1 is found to be associated with heroin use disorder in the studied Manipuri cohort. The study suggests that individuals with G allele and GG genotypes at rs483481 could be more vulnerable to heroin dependence, and it could be taken into consideration in prevention and intervention programs.

Opiate drug use in the city of Madrid: Associated health and sociodemographic factors.

The use of opiate analgesics has led to a health and social emergency in the United States. In Spain, according to official data, the prescription of these drugs has risen dramatically in the last decade. This study explores the prevalence of the use of these drugs and the health and socio-demographic characteristics of their consumers in the city of Madrid. A telephone survey was carried on a stratified, randomised sample, asking about the use of these drugs and whether or not they were medically prescribed. The sample consisted of n=8,845 subjects aged between 15 and 98 years. Sixteen percent stated that they had used these drugs in the last year and 9.1% had taken them in the last two weeks. Consumption was more frequent among women, lower social class and lower level of education. Among the youngest group (15-29 years old) 12.5% had already used it. Those who use opioids report worse perceived health, lower quality of life, more mental health problems, more loneliness, more use of other psychoactive drugs, more frequent daily use of tobacco and less problematic consumption of alcohol. Ten percent of those who use them do so without a doctor's prescription. Combining these data with the prescription data offered by the Ministry of Health, it is necessary to pay attention to a problem that may become apparent in the coming years, and the adoption of urgent measures to tackle it before it brings the Spanish situation closer to that already well known in countries of our socio-political environment is advised.

Effects of plant-derived analgesic compounds sinomenine and salvinorin A in infant rats

ObjectivePremature and ill neonates undergo painful but medically necessary procedures while hospitalized. Although opiate drugs are administered as analgesics, problems associated with their side effects, tolerance, and potential dependence necessitate research into alternative pain-relieving medications. Here we test two plant-derived compounds in infant rats: sinomenine, which targets the Mas-related G-protein-coupled receptor member X2 opioid receptor; and salvinorin A, which is a κ opioid receptor agonist. In adult animals both sinomenine and salvinorin A are analgesic, but neither has been tested in infants. MethodsWe used the formalin and thermal plantar tests in rats 7 and 21 days of age (PN7 and PN21) for behavioral signs of pain. In addition, brain sections were stained using Fos immunohistochemistry to examine patterns of brain activation in the midbrain periaqueductal gray and the paraventricular nucleus of the hypothalamus. ResultsSinomenine was analgesic in both the formalin and thermal tests on animals 21 days of age. At PN7 only the highest dose elevated response latencies in the thermal test and there were no effects of sinomenine in the formalin test. Analysis of Fos expression in the sinomenine-treated animals showed no drug effect, in contrast to the behavioral results. Salvinorin A was analgesic in the formalin test only at the highest dose at 21 days of age but not in the thermal test at either age. ConclusionThe increased modest effectiveness of sinomenine in older animals and the minimum salvinorin A drug effect suggest that the compounds act on sites that develop during the preweaning period (sinomenine) or after weaning (salvinorin A).

Network meta-analysis of local and regional analgesia following colorectal resection.

Postoperative pain management after colorectal surgery remains challenging. Systemic opiates delivered on demand or via a patient-controlled pump have traditionally been the mainstay of treatment. Opiate analgesia is associated with slower gastrointestinal recovery and unpleasant side-effects; many regional and local analgesic techniques have been developed as alternatives. MEDLINE, Embase and CENTRAL databases were searched systematically for RCTs comparing analgesic techniques after major colorectal resection. A network meta-analysis was performed using a Bayesian random-effects framework with a non-informative prior. Primary outcomes included pain at rest and cumulative opiate consumption 24 h after surgery. Secondary outcomes included pain at rest and cumulative opiate consumption at 48 h, pain on movement and cough at 24 and 48 h, time to first stool, time to tolerance of oral diet, duration of hospital stay, nausea and vomiting, and postoperative complications. Seventy-four RCTs, including 5101 patients and 11 different techniques, were included. Some inconsistency and heterogeneity was found. SUCRA scores showed that spinal analgesia was the best intervention for postoperative pain and opiate reduction at 24 h. Transversus abdominus plane blocks were effective in reducing pain and opiate consumption 24 h after surgery. Subgroup analysis showed similar results for open versus minimally invasive surgical approaches, and enhanced recovery after surgery programmes. Spinal analgesia and transversus abdominus plane blocks best balanced pain control and opiate minimization in the immediate postoperative phase following colorectal resection. Multimodal analgesia reduces pain, minimizes systemic opiate use and optimizes postoperative recovery.

Can adequate analgesia be achieved in patients with cirrhosis without precipitating hepatic encephalopathy? A prospective study.

Aim of the studyAnalgesic use in patients with liver cirrhosis can be associated with increased morbidity and mortality and presents clinicians with a significant and challenging management issue. We evaluated the efficacy of opiate analgesia in patients with cirrhosis, while closely monitoring the side effect profile.Material and methodsThis prospective cohort pilot study compared inpatients with cirrhosis who required regular opiate analgesia to non-cirrhotic patients requiring opiates and patients with cirrhosis who did not require opiates. Participants completed daily surveys to assess for analgesic efficacy and encephalopathy.ResultsFifty-two patients were initially recruited, of whom 50 patients were analysed in three groups (40 male, 10 female, median age 52 years). These included 13 cirrhotic patients (69% Child-Pugh B or C) requiring regular opiate analgesia, 18 cirrhotic patients (67% Child-Pugh B or C) not receiving regular opiate analgesia, and 19 non-cirrhotic controls. Two patients were excluded due to past stroke and acquired brain injury. All cirrhotic patients received regular lactulose. There was no statistical difference in the adequacy of analgesia between the three groups. The modified orientation log score for encephalopathy remained in the normal range in all but two cirrhotic patients receiving regular opiate analgesia.ConclusionsEffective pain control is achievable with opiate analgesia in most patients with advanced liver disease without precipitating hepatic encephalopathy.

Prikaz slučaja - rabdomioliza izazvana metadonom

Methadone is the most used opiate drug in opiate addiction therapy and there are recent indications of its nephrotoxicity. The most likely mechanism of action of methadone is increasing muscle demand for oxygen, which causes the muscle to act as if it is in ischemia, which consequently leads to myoglobin release and destruction of tubules by myoglobin products breakdown. Rhabdomyolysis occurs, and as a result acute renal failure is possible. In addition, methadone is also more potent in causing rhabdomyolysis if in concomitant use with benzodiazepines. In this paper, we present a case of a 35-year-old opiate addict on withdrawal therapy. Following methadone and concomitant Benzodiazepine abuse the patient developed rhabdomyolysis and epileptic seizures. We further discuss the methadone nephrotoxicity as well as therapeutic options for rhabdomyolysis caused by methadone poisoning. Methadone is the standard therapy for opiate addiction. However, it cannot be considered to be a completely safe drug. It is vital to raise awareness about the risks of rhabdomyolysis, among physicians, in patients undergoing methadone therapy. Timely diagnosis and an adequate therapeutic response can be vital for the patient.

Prospective study regarding the management of acute pain in neonates with surgical diseases through the correlation of the CRIES pain scale with the staged therapeutic protocol

Materials and method. The aim of the study is to evaluate the management of acute pain in newborn patients hos­pi­ta­lized in the neonatal intensive care unit of the “Sf. Maria” Emergency Clinical Hospital for Children, Iaşi. The study is pros­pec­tive, conducted between 1.10.2020 and 1.12.2020, on a group of 15 newborn patients with surgical conditions. For each of these maneuvers, the intensity of pain was assessed using the baseline CRIES scale, at 1 minute, at 10 minutes, and one hour after starting the maneuver, considering as an indicator of insufficient analgesia a CRIES score higher than 4. Based on a predetermined protocol, analgesic drugs were administered preventively, as well as curatively. The quality of the treatment was finally evaluated according to the one-hour CRIES score and to the parental satisfaction score. Results. The one-hour CRIES score (Ch1) for low-in­ten­sity pain-generating maneuvers (PGM) was 2.30/patient. No pa­tient had a score greater than or equal to 4, so as to re­quire therapeutic intervention. The one-hour CRIES score (Ch1) for PGM of moderate intensity had a mean value of 2.26/patient. All patients had a score lower than 4 and did not require therapeutic intervention, demonstrating that the therapeutic protocol was effective. For the maneuvers pro­du­cing high intensity pain, the CRIES score per hour had an average value of 2.4 per patient, all patients having score values below 4, proving that the drug therapeutic pro­to­col was effective. The average satisfaction score of the pa­rents was 6.73, with values ​​over 5 to 12 of the relatives, out of a total of 15 respondents, representing 80% of the to­tal, which we consider satisfactory. Conclusions. The CRIES scale is an effective tool for assessing newborn pain for all types of pain-generating maneuvers. Preventive the­ra­peu­tic intervention is extremely important. The the­ra­peu­tic protocol must be modified to combine at least two analgesics administered preventively, with sufficient time before the onset of pain-generating maneuvers. The cura­tive treatment should be performed according to the CRIES score at 1 and at 10 minutes after the onset of PGM, using the polymodal technique, opiate drugs being an important re­source.

Neonatal Admission and Its Relationship to Maternal Pain: Pain Scores and Analgesia.

The aim of this study was to determine whether postnatal women whose babies required neonatal intensive care unit (NICU) admission self-reported lower pain scores and required less analgesia than women whose babies remained with them. A prospective matched audit comparing pain scores and analgesia requirements where every woman with a baby admitted to the NICU was matched to 2 women whose babies remained on the ward was undertaken. Matches were based on age, number of previous births, type of birth, episiotomy, and epidural or spinal analgesia use. Data were collected on pain scores and analgesia administered in the first 72 hours postbirth. A total of 150 women were recruited and matched from November 2015 to May 2017. No statistically significant differences were found between the 2 groups for opiate analgesia use (P = .91) or pain scores (P = .89). Regardless of NICU admission, significantly higher pain scores were reported in participants who had episiotomies (P = .03). Birth via cesarean birth resulted in significantly higher pain scores (P < .01) and greater opiate administration (P < .01). This study found no statistically significant difference between pain scores or analgesia use of mothers whose babies required NICU admission and mothers whose babies remained with them.

Community Treatment for Opioid Use Disorders in Urban and Rural Veterans.

The recent opioid crisis is characterized by a relatively greater increase in opioid use disorder and related mortality in rural populations when compared with urban populations.1-5 As almost a quarter of our nation's veterans reside in rural settings, the United States Veterans Health Administration (VHA) is interested in the impact of this epidemic on rural veterans. This study aims to develop a comprehensive understanding of the trends in substance use disorders (SUD) in veterans seeking treatment from community, non-VHA providers. Using Substance Abuse and Mental Health Services Administration (SAMHSA)'s Treatment Episode Data Set (TEDS), this study presents the prevalence of treatment for veterans seeking initial admission into publicly funded non-VHA SUD treatment centers for years 2011-2016. Comparisons were made for all SUD types. Multivariate trend analysis based on annual data from 2011 to 2016 compared urban and rural veterans for opioid use disorder treatment. Both urban and rural veterans had comparable rates of treatment for SUD, though rural veterans had slightly higher rates of injectable (11.2% vs 8.7%; P<.001) and opiate drug use disorder admissions (20.7% vs 18.1%; P=.014). Both urban and rural showed an increase in admissions for opioid, heroin, and injectable drug use disorders between 2011 and 2016 (P<.001). Comprehensive understanding of veteran SUD and treatment should include national-level data on community non-VHA treatment. SAMHSA's TEDS for years 2011-2016 provides clinical information for more than 90,000 veterans and indicates continued increase in treatment seeking for opioid use disorders, particularly for rural veterans.

Pattern of chest diseases among addicts in Poison Control Center of Ain Shams University Hospitals

BackgroundDrug addiction results in serious pulmonary complications. Thoracic complications of drug addiction vary depending on the type and the route of administration of the drug that has been abused.AimTo study the pattern of chest diseases among addicts in Poison Control Center of Ain Shams University Hospitals.Patients and methodsA total of 200 addict patients were selected from Poison Control Center of Ain Shams University Hospitals in the duration between June 2016 and June 2018. All patients with pulmonary complications referred to Abbasia Chest Hospital were included.ResultsA total of 200 addict patients were enrolled in this study. Of them, 100 addicts with drug overdose with no pulmonary complications were excluded, and the other 100 patients were included, comprising 99 males and only one female, with mean age of 39.91±10.75 years. Overall, 63% of drug addicts were cannabis addicts, 27.0% were opiate addicts, 8.0% were polysubstance abusers, and 2.0% were alcohol addicts. Pulmonary tuberculosis was the most common pulmonary complication of all drug addicts. There was a statistically significant correlation between the type of drug addiction and the pulmonary complications. Pulmonary tuberculosis was the most common among cannabis addicts as well as polysubstance abusers. Parenchymal lung diseases (pneumonia and lung abscess) were the most common among opiate and intravenous drug addicts. There was no significant difference between different types of drugs and outcomes of the patients. Mortality represented 3.0% of all drug addicts.ConclusionMany pulmonary complications are associated with drug addiction. Achievement of early diagnosis and treatment can be obtained by proper counseling and therapeutic programs.

Reducing the Hypertensive Effects of the Prolonged Surgical Tourniquet Using a Dual-Cuff Strategy: A Prospective Randomized Controlled Trial

We evaluated whether moving the “line of crush” from thigh to the calf before onset of tourniquet-mediated hypertension would prevent or diminish it. We also evaluated any change in pain or functional outcome. Twenty adult patients were recruited and randomly assigned to either control or intervention groups. Inclusion criteria: any willing participant >18 years old with foot and/or ankle pathology requiring an operation lasting >90 minutes. Exclusion criteria included contraindication to general anesthesia, peripheral neuropathy affecting lower limbs of any etiology, or chronic pain requiring regular opiate analgesia. The intervention group received a thigh tourniquet for 60 minutes, after which a calf tourniquet was inflated and the thigh tourniquet was deflated. The control group received only a thigh tourniquet throughout surgery. At 90 minutes, the control group had mean arterial pressure of 86.8 mmHg, compared with the intervention group at 76.3 mmHg (p ≤ .014). At end of surgery, the difference had increased further (control 98.1 mmHg, intervention 78.3 mmHg (p ≤ .001). Moving the line of crush during limb tourniquet application prevents development of the hypertensive response. For cases in which a prolonged tourniquet application is required, a dual-tourniquet technique will prevent intraoperative hypertension and may influence long-term pain and function.

Gene Expression Survey of Serotonin Receptors (5HTR2A and 5HTR3A) and Monoamine Oxidases Enzyme After Treatment With Methadone in Addicted Individuals

Background : Addiction disrupts the nervous system of the reward system, stimulus, and memory in the brain. The disruption of these systems in the brain causes biological, physiological, social, and psychological complications. Addiction is considered a psychological, social, and economic disorder in terms of medicine, psychology, and sociology, as well as philosophy, law, ethics, and religion. The most important place of narcotic effect is the brain, and receptors affect these substances. Dopamine and serotonin receptors are among the most important receptors, in which drugs affect them. Methadone is also an opiate drug that is even more addictive than morphine and heroin and is often used as a preservative to control heroin and narcotic addiction. Methods : In this study, 3 genes of 5-Hydroxytryptamine Receptor 2 A (5HT2Ra), 5-Hydroxytryptamine Receptor 3 A (5HT3Ra), and Monoamine Oxidases A (MAOA), which play an important role in serotonin function, were examined in Peripheral Blood Mononuclear Cells (PBMCs) of heroin addicts, who had been quitting addiction with methadone for 3 months. Therefore, peripheral blood PBMCs were isolated. cDNA was synthesized from mRNA; then, the expression of the gene was measured by real-time Polymerase Chain Reaction (PCR). Results : The expression of MAOA gene in the PBMCs of the addicted patients with methadone was significantly reduced compared to the control group, while the expression of 5HT2Ra and 5HT3Ra genes showed no change in the two groups. Conclusion : These results suggest that Methadone Maintenance Treatment (MMT) may be moderated by 5HT2Ra and 5 HT3Ra serotonin receptors and returned to their previous efficacy, but MAOA was significantly reduced.

The effect of duration of dependence and daily dose of tramadol in tramadol dependent patients on cognitive performance

BackgroundTramadol dependence represents a major medical and legal hazardous phenomenon in the last decade. It is a synthetic opiate analgesic which exerts its therapeutic effect by its action on μ opioid receptors. It has a weak dependence ability. The present study investigated the effect of duration of dependence and daily dose of tramadol on cognitive performance. Cognitive functions were assessed using the following: the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) test, Brief Visuospatial Memory Test–Revised (BVMT-R), Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the P300 (ERP), and conventional electroencephalogram.ResultsThere was a non-significant negative correlation between the daily dose of tramadol and cognitive performance as regards IQ, Mini-Mental State Examination, MoCA score, P300 reaction time (μs), and deterioration index (r = − 0.08, P = 0.689; r = − 0.02, P = 0.896; r = − 0.11, P = 0.554; r = − 0.11, P = 0.581, r = − 0.17; P = 0.368, respectively). Additionally, the results showed non-significant negative correlation between the duration of dependence and the cognitive performance (r = − 0.19, P = 0.325; r = − 0.15, P = 0.424; r = − 0.30, P = 0.108; r = − 0.02, P = 0.909; r = − 0.02, P = 0.937, respectively).ConclusionDaily dose and duration of tramadol dependence have a negative but non-significant effect on cognitive performance.