Modified thoracoabdominal nerves block through perichondrial approach for laparoscopic cholecystectomy.

OBJECTIVE: A new block, namely, modified thoracoabdominal nerves block through perichondrial approach, is administered below the costal cartilage. We sought to compare the analgesic efficacy of the modified thoracoabdominal nerves block through perichondrial approach block with local anesthetic infiltration at the port sites in an adult population who underwent laparoscopic cholecystectomy. METHODS: Patients who will undergo laparoscopic cholecystectomy were randomized to receive bilateral ultrasound-guided modified thoracoabdominal nerves block through perichondrial approach blocks or local anesthetic infiltration at the port insertion sites. The primary outcome was the total amount of tramadol used in the first 12 h postoperatively. The secondary outcomes were total IV tramadol consumption for the first postoperative 24 h and visual analog scale scores. RESULTS: The modified thoracoabdominal nerves block through perichondrial approach group had significantly less tramadol use in the first 12 h postoperatively (p<0.001). The modified thoracoabdominal nerves block through perichondrial approach group's visual analog scale scores at rest (static) and with movement (dynamic) were significantly lower compared with the port infiltration group (p<0.05). CONCLUSION: Patients who received modified thoracoabdominal nerves block through perichondrial approach block had significantly less analgesic consumption and better pain scores than those who received port-site injections after laparoscopic cholecystectomy.

A novel comparison of erector spinae plane block and paravertebral block in laparoscopic cholecystectomy.

OBJECTIVE: Erector spinae plane block is an updated method than paravertebral block, possessing a lower risk of complications. This study aimed to compare erector spinae plane and paravertebral blocks to safely reach the most efficacious analgesia procedure in laparoscopic cholecystectomy cases. METHODS: The study included 90 cases, aged 18-70 years, classified as American Society of Anesthesiologists I-II, who underwent an laparoscopic cholecystectomy procedure. They were randomly separated into three groups, namely, Control, erector spinae plane, and paravertebral block. No block procedure was applied to Control, and a patient-controlled analgesia device was prepared containing tramadol at a 10 mg bolus dose and a 10-min locked period. The pain scores were recorded with a visual analog scale for 24 h postoperatively. RESULTS: The visual analog scale values at 1, 5, 10, 20, and 60 min at rest and 60 min coughing were found to be significantly higher in Control than in paravertebral block. A significant difference was revealed between Control vs. paravertebral block and paravertebral block vs. erector spinae plane in terms of total tramadol consumption (p=0.006). Total tramadol consumption in the first postoperative 24 h was significantly reduced in the paravertebral block compared with the Control and erector spinae plane groups. CONCLUSION: Sonography-guided-paravertebral block provides sufficient postoperative analgesia in laparoscopic cholecystectomy surgery. Erector spinae plane seems to attenuate total tramadol consumption.

Post craniotomy pain management in Copenhagen rat by intraperitoneal or oral dosage of Tramadol: a comparative evaluation.

Calvarial craniotomy in animal models involves pain and distress. Moderate to severe pain in laboratory animals requires adequate pain management strategies. According to previous studies, the options available for suitable analgesia for rat calvarial craniotomy are very few. For most analgesic treatments, injectable routes of administration are predominantly used. However, these routes require restraining the animals, which may cause unnecessary pain, distress and suffering. As a well-fare measure, we focused on pain management by oral administration of analgesia. In this particular study, which is a sub-study of a major experiment on bone regeneration with different polymeric scaffold materials, we have compared the analgesic efficacy of intraperitoneal (I/P) and oral administration of tramadol (10 mg/kg) over a period of 96 h post-surgery in rat craniotomy models. The focus of our study is to evaluate the potential pain reduction efficacy of orally administered Tramadol without any restraining involved. We have used various non-invasive methods to assess the pain-alleviating efficacy of tramadol administered through different methods. We found that the efficacy of oral administration of tramadol is comparable to I/P administration in alleviating pain. Additionally, oral administration through drinking water has the benefit of not putting the animal under unwanted restraining stress.

Effect of sacral erector spinae plane block on post-hemorrhoidectomy pain: A randomized controlled trial.

BACKGROUND: Hemorrhoidectomy is a common surgical procedure associated with significant postoperative pain. The conventional analgesic methods used for hemorrhoidectomy often have adverse effects and may not provide adequate pain relief. The sacral erector spinae plane block (ESPB) is a newly introduced technique that has shown promise in various surgical procedures. This prospective, randomized, controlled trial aimed to evaluate the analgesic effects of sacral ESPB following hemorrhoidectomy. METHODS: Seventy patients undergoing hemorrhoidectomy were divided into 2 groups: the control group and the sacral ESPB group. Bilateral sacral ESPB was performed in the sacral ESPB group, whereas no intervention was performed in the control group. The numeric rating scale at rest and during the active period (mobilizing) was used as the primary outcome measure. Secondary outcome measures were the cumulative doses of tramadol, the number of patients who required rescue analgesia postoperatively, and quality of recovery-15 Turkish version patient recovery quality. RESULTS: The sacral ESPB group had significantly low numeric rating scale scores at various time points (P < .05). More patients in the control group needed rescue analgesia during the postoperative period (P < .001). The dosages of tramadol consumption after the first 24 hours postoperatively were significantly lower in the sacral ESPB group compared with the control group (P < .001). Furthermore, quality of recovery-15 Turkish version scores were high in the sacral ESPB group (P < .001). CONCLUSION: The results suggest that sacral ESPB is an effective method for post-hemorrhoidectomy pain management, reducing the need for additional analgesics and improving patient recovery.

The Role of Pharmacogenomics in Opioid Prescribing.

OPINION STATEMENT: Pharmacogenomics is increasingly important to guide objective, safe, and effective individualised prescribing. Personalised prescribing has revolutionised treatments in the past decade, allowing clinicians to maximise drug efficacy and minimise adverse effects based on a person's genetic profile. Opioids, the gold standard for cancer pain relief, are among the commonest medications prescribed in palliative care practice. This narrative review examines the literature surrounding opioid pharmacogenomics and its applicability to the palliative care cancer population. There is currently limited intersection between the fields of palliative care and pharmacogenomics, but growing evidence presents a need to build linkages between the two disciplines. Pharmacogenomic evidence guiding opioid prescribing is currently available for codeine and tramadol, which relates to CYP2D6 gene variants. However, these medications are prescribed less commonly for pain in palliative care. Research is accelerating with other opioids, where oxycodone (CYP2D6) and methadone (CYP2B6, ABCB1) already have moderate evidence of an association in terms of drug metabolism and downstream analgesic response and side effects. OPRM1 and COMT are receiving increasing attention and have implications for all opioids, with changes in opioid dosage requirements observed but they have not yet been studied widely enough to be considered clinically actionable. Current evidence indicates that incorporation of pharmacogenomic testing into opioid prescribing practice should focus on the CYP2D6 gene and its actionable variants. Although opioid pharmacogenomic tests are not widely used in clinical practice, the progressively reducing costs and rapid turnover means greater accessibility and affordability to patients, and thus, clinicians will be increasingly asked to provide guidance in this area. The upsurge in pharmacogenomic research will likely discover more actionable gene variants to expand international guidelines to impact opioid prescribing. This rapidly expanding area requires consideration and monitoring by clinicians in order for key findings with clinical implications to be accessible, meaningfully interpretable and communicated.

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.

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.

Uso fuera de indicación de la combinación a dosis fija de tramadol/dexketoprofeno en atención primaria de salud: ¿Basado en la evidencia científica o motivo de preocupación? / Off-label use of fixed-dose combination of tramadol and dexketoprofen in primary health care. Evidence-based or cause for concern?

Introducción: La utilización de la combinación a dosis fija de tramadol/dexketoprofeno en España y en otros países ha aumentado de forma conside-rable. La indicación terapéutica autorizada de este medicamento es el tratamiento sintomático a corto plazo del dolor agudo de moderado a intenso en pacientes adultos. El objetivo de este estudio fue describir el patrón de uso de tramadol/dexketopro-feno en el ámbito de la atención primaria de salud.Método: Se realizó un estudio transversal, descrip-tivo y multicéntrico. La población de estudio incluyó a todos los pacientes de una Dirección de Atención Primaria (53 equipos de Atención Primaria) que tenían activa la prescripción de tramadol/dexke-toprofeno el 28 de marzo de 2018. La población diana fueron aquellos pacientes a los que se les prescribió tramadol/dexketoprofeno durante más de 20 días.Resultados: Un total de 176 pacientes tenía activa la prescripción de tramadol/dexketoprofeno. Todos los pacientes (100%) tuvieron una duración del tratamiento superior a 5 días y el 72,7% (N=128) su-perior a 20 días. La duración media del tratamiento fue de 14±160,9 días en pacientes que tenían me-nos de 20 días de tratamiento y de 224±160,8 días en pacientes que tenían más de 20 días de trata-miento. El 35,1% de los pacientes estaban tratados con más de 2 medicamentos para aliviar el dolor de forma concomitante con tramadol/dexketoprofeno. El médico de atención primaria inició un 65,6% de las prescripciones.Conclusiones: La combinación a dosis fija de tramadol/dexketoprofeno se utilizó con frecuencia fuera de indicación, de acuerdo con la ficha técnica y la evidencia científica disponible. Este estudio alerta sobre los riesgos potenciales asociados a la utilización de este medicamento en la práctica clíni-ca, como son la falta de efectividad y/o la aparición de efectos adversos. (AU)

Introduction: The use of the fixed-dose combi-nation of tramadol/dexketoprofen in Spain and in other countries has increased considerably. The authorized therapeutic indication for this medicinal product is the short-term symptomatic treatment of moderate to severe acute pain in adult patients. The objective of this study was to describe the pat-tern of use of tramadol/dexketoprofen in the field of primary health care.Method: A cross-sectional, descriptive and mul-ticenter study was carried out. The study popu-lation included all patients from a Primary Care Department (53 Primary Care teams) with an active prescription of tramadol/dexketoprofen on March 28, 2018. The target population was those patients who were prescribed tramadol/dexketoprofen. dexketoprofen for >20 days.Results: A total of 176 patients had an active pre-scription for tramadol/dexketoprofen. All patients (100%) had a duration of treatment greater than 5 days and 72.7% (N=128) greater than 20 days. The mean duration of treatment was 14±160.9 days in patients who had less than 20 days of treatment and 224±160.8 days in patients who had more than 20 days of treatment. 35.1% of the patients were treated with >2 pain medications and concomi-tantly with tramadol/dexketoprofen. The general practitioner initiated 65.6% of the prescriptions.Conclusions: The fixed-dose combination of tra-madol/dexketoprofen was frequently used off-la-bel, according to the product characteristics and the available scientific evidence. This study warns about the potential risks associated with the use of this drug in clinical practice, such as lack of effec-tiveness and/or the appearance of adverse effects (AU)

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.

Multivariate Assessment for Bioequivalence Based on the Correlation of Random Effect.

BACKGROUND AND OBJECTIVE: Bioequivalence tests are fundamental step in assessing the equivalence in bioavailability between a test and reference product. In practice, two separate linear mixed models (LMMs) with random subject effects, which have an area under the concentration-time curve (AUC) and the peak concentration (Cmax) as the responses, have become the gold standard for evaluating bioequivalence. Recently, Lee et al developed a multivariate hierarchical generalized linear model (HGLM) for several responses that modeled correlations among multivariate responses via correlated random effects. The objective of this study was to apply this multivariate analysis to the bioequivalence test in practice and to compare the performance of multivariate HGLM and separate LMMs. METHODS: Three pharmacokinetic datasets, fixed-dose combination (naproxen and esomeprazole), tramadol and fimasartan data were analyzed. We compared the 90% confidence interval (CI) for the geometric mean ratio (GMR) of a test product to a reference product using the multivariate HGLM and two conventional separate LMMs. RESULTS: We found that the 90% CIs for the GMRs of both AUC and Cmax from the multivariate HGLM were narrower than those from the separate LMMs: (0.843, 1.152) vs (0.825, 1.177) for Cmax of esomeprazole in fixed-dose combination data; (0.805, 0.931) vs (0.797, 0.941) for Cmax in tramadol data; (0.801, 1.501) vs (0.762, 1.578) for Cmax and (1.163, 1.332) vs (1.009, 1.341) for AUC in fimasartan data, consistent with the random subject effects from two separate LMMs being highly correlated in the three datasets (correlation coefficient r = 0.883; r = 0.966; r = 0.832). CONCLUSION: This multivariate HGLM had good performance in the bioequivalence test with multiple endpoints. This method would provide a more reasonable option to reduce the 90% CI by adding correlation parameters and thus an advantage especially in evaluating the bioequivalence of highly variable drugs with broad 90% CIs.

Effects of naloxone and diazepam on blood glucose levels in tramadol overdose using generalized estimating equation (GEE) model; (an experimental study).

BACKGROUND: Tramadol is a synthetic opioid and poisoning is increasing around the world day by day. Various treatments are applied for tramadol poisoning. Due to the unknown effects of tramadol poisoning and some of its treatments on blood glucose levels, this study was conducted to investigate the overdose of tramadol and its common treatments (naloxone, diazepam), and their combination on blood glucose levels in male rats. METHODS: This study was conducted in 45 male Wistar rats. The animals were randomly divided into five groups of 9. They received a 75 mg/kg dose of tramadol alone with naloxone, diazepam, and a combination of both of these two drugs. On the last day, animals' tail vein blood glucose levels (BGL) were measured using a glucometer at different times, including before the tramadol injection (baseline) and 1 hour, 3 hours, and 6 hours after wards. The rats were anesthetized and sacrificed 24 h after the last injection. Blood samples were then taken, and the serum obtained was used to verify the fasting glucose concentration. Data were analyzed using SPSS software at a significance level of 0.05 using a one-way analysis of variance (ANOVA) and a generalized estimating equation (GEE). RESULTS: According to the GEE model results, the diazepam-tramadol and naloxone-diazepam-tramadol groups showed blood glucose levels five units higher than the tramadol group (p < 0.05). The diazepam-tramadol group had significantly higher blood glucose levels than the naloxone-tramadol group (p < 0.05). The mean blood glucose levels before the intervention, 3 hours and 6 hours after the injection of tramadol did not differ between the groups, but the blood glucose levels 1 hour after the injection of tramadol in the group of naloxone-tramadol were significantly lower than in the control group (p < 0.05). Blood glucose levels did not differ between the groups 24 h after injection of tramadol. CONCLUSION: The results of the present study showed tramadol overdose does not affect blood glucose levels. The diazepam-tramadol combination and the diazepam-naloxone-tramadol combination caused an increase in blood glucose levels.

Patient-Centered Decision-making for Postoperative Narcotic-Free Endocrine Surgery: A Randomized Clinical Trial.

Importance: Historically, opioid pain medications have been overprescribed following thyroid and parathyroid surgery. Many narcotic prescriptions are incompletely consumed, creating waste and opportunities for abuse. Objective: To determine whether limiting opioid prescriptions after outpatient thyroid and parathyroid surgery to patients who opt in to narcotic treatment reduces opioid consumption without increasing postoperative pain compared with usual care (routine narcotic prescriptions). Design, Setting, and Participants: A randomized clinical trial of Postoperative Opt-In Narcotic Treatment (POINT) or routine narcotic prescription (control) was conducted at a single tertiary referral center from June 1 to December 30, 2020. A total of 180 adults undergoing ambulatory cervical endocrine surgery, excluding patients currently receiving opioids, were assessed for eligibility. POINT patients received perioperative pain management counseling and were prescribed opioids only on patient request. Patients reported pain scores (0-10) and medication use through 7 daily postoperative surveys. Logistic regression was used to determine factors associated with opioid consumption. Interventions: Patients in the POINT group were able to opt in or out of receiving prescriptions for opioid pain medication on discharge. Control patients received routine opioid prescriptions on discharge. Main Outcomes and Measures: Daily peak pain score through postoperative day 7 was the primary outcome. Noninferiority was defined as a difference less than 2 on an 11-point numeric rating scale from 0 to 10. Analysis was conducted on the evaluable population. Results: Of the 180 patients assessed for eligibility, the final study cohort comprised 102 patients: 48 randomized to POINT and 54 to control. Of these, 79 patients (77.5%) were women and median age was 52 (interquartile range, 43-62) years. A total of 550 opioid tablets were prescribed to the control group, and 230 tablets were prescribed to the POINT group, in which 23 patients (47.9%) opted in for an opioid prescription. None who opted out subsequently required rescue opioids. In the first postoperative week, 17 POINT patients (35.4% of survey responders in the POINT group) reported consuming opioids compared with 27 (50.0%) control patients (P = .16). Median peak outpatient pain scores were 6 (interquartile range, 4-8) in the control group vs 6 (interquartile range, 5-7) in the POINT group (P = .71). In multivariate analysis, patients with a history of narcotic use were 7.5 times more likely to opt in (95% CI, 1.61-50.11; P = .02) and 4.8 times more likely to consume opioids (95% CI, 1.04-1.52; P = .01). Higher body mass index (odds ratio, 1.11; 95% CI, 1.01-1.23; P = .03) and highest inpatient postoperative pain score (odds ratio, 1.24; 95% CI, 1.04-1.52; P = .02) were also associated with opioid consumption. Conclusions and Relevance: In this trial, an opt-in strategy for postoperative narcotics reduced opioid prescription without increasing pain after cervical endocrine surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04710069.

Chronic exposure to tramadol induces cardiac inflammation and endothelial dysfunction in mice.

Tramadol is an opioid extensively used to treat moderate to severe pain; however, prolonged therapy is associated with several tissues damage. Chronic use of tramadol was linked to increased hospitalizations due to cardiovascular complications. Limited literature has described the effects of tramadol on the cardiovascular system, so we sought to investigate these actions and elucidate the underlying mechanisms. Mice received tramadol hydrochloride (40 mg/kg body weight) orally for 4 successive weeks. Oxidative stress, inflammation, and cardiac toxicity were assessed. In addition, eNOS expression was evaluated. Our results demonstrated marked histopathological alteration in heart and aortic tissues after exposure to tramadol. Tramadol upregulated the expression of oxidative stress and inflammatory markers in mice heart and aorta, whereas downregulated eNOS expression. Tramadol caused cardiac damage shown by the increase in LDH, Troponin I, and CK-MB activities in serum samples. Overall, these results highlight the risks of tramadol on the cardiovascular system.

Effect of erector spinae plane block on the postoperative quality of recovery after laparoscopic cholecystectomy: a prospective double-blind study.

BACKGROUND: Laparoscopic cholecystectomy is a common surgical procedure that frequently results in substantial postoperative pain. Erector spinae plane block (ESPB) has been shown to have beneficial postoperative analgesic effects when used as a part of multimodal analgesia. The aim of this study was to determine whether ESPB improves postoperative recovery quality in patients undergoing laparoscopic cholecystectomy. Evaluation of the effects of ESPB on postoperative pain, opioid consumption, and nausea and vomiting was the secondary objective. METHODS: In this prospective double-blind study, 82 patients undergoing laparoscopic cholecystectomy were randomised into one of two groups: a standard multimodal analgesic regimen in Group N (control) or an ESPB was performed in Group E. Preoperative and postoperative recovery quality was measured using the 40-item quality of recovery (QoR-40) questionnaire; postoperative pain was evaluated using the numerical rating scale scores. RESULTS: Postoperative mean (standard deviation) QoR-40 scores were higher in Group E (181 [7.3]) than in Group N (167 [11.4]); P<0.01. With repeated measures, a significant effect of group and time was demonstrated for the global QoR-40 score, P<0.01, indicating better quality of recovery in Group E. Pain scores were significantly lower in Group E than in Group N, both during resting and motion at T1-T8 times (P<0.01 at each time). The total amount of tramadol consumed in the first 24 h was lower in Group E [median 0 mg, inter-quartile range (IQR) (0-140)], than in Group N [median 180 mg, IQR (150-240); P<0.01]. CONCLUSIONS: ESPB improved postoperative quality of recovery in patients undergoing laparoscopic cholecystectomy. Moreover, ESPB reduced pain scores and cumulative opioid consumption. CLINICAL TRIAL REGISTRATION: NCT04112394.

Comparison between three dosages of intramuscular alfaxalone and a ketamine-dexmedetomidine-midazolam-tramadol combination in golden-headed lion tamarins (Leontopithecus chrysomelas).

OBJECTIVES: To characterize the cardiopulmonary and anesthetic effects of alfaxalone at three dose rates in comparison with a ketamine-dexmedetomidine-midazolam-tramadol combination (KDMT) for immobilization of golden-headed lion tamarins (GHLTs) (Leontopithecus chrysomelas) undergoing vasectomy. STUDY DESIGN: Prospective clinical trial. ANIMALS: A total of 19 healthy, male, wild-caught GHLTs. METHODS: Tamarins were administered alfaxalone intramuscularly (IM) at 6, 12 or 15 mg kg-1, or KDMT, ketamine (15 mg kg-1), dexmedetomidine (0.015 mg kg-1), midazolam (0.5 mg kg-1) and tramadol (4 mg kg-1) IM. Immediately after immobilization, lidocaine (8 mg kg-1) was infiltrated subcutaneously (SC) at the incision site in all animals. Physiologic variables, anesthetic depth and quality of immobilization were assessed. At the end of the procedure, atipamezole (0.15 mg kg-1) was administered IM to group KDMT and tramadol (4 mg kg-1) SC to the other groups; all animals were injected with ketoprofen (2 mg kg-1) SC. RESULTS: A dose-dependent increase in sedation, muscle relaxation and immobilization time was noted in the alfaxalone groups. Despite the administration of atipamezole, the recovery time was longer for KDMT than all other groups. Muscle tremors were noted in some animals during induction and recovery with alfaxalone. No significant differences were observed for cardiovascular variables among the alfaxalone groups, whereas an initial decrease in heart rate and systolic arterial blood pressure was recorded in KDMT, which increased after atipamezole administration. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone dose rates of 12 or 15 mg kg-1 IM with local anesthesia provided good sedation and subjectively adequate pain control for vasectomies in GHLTs. KDMT induced a deeper plane of anesthesia and should be considered for more invasive or painful procedures. All study groups experienced mild to moderate hypothermia and hypoxemia; therefore, the use of more efficient heating devices and oxygen supplementation is strongly recommended when using these protocols.

Morphometric, hematological and oxidative stress changes in Clarias gariepinus following sub-chronic exposure to tramadol.

Tramadol is among the most famous analgesic drugs used for the management, treatment and relief of moderate to severe pain conditions. The present study investigated the effects of tramadol on the behavior, mortality, morphometric, hematology and oxidative stress parameters of C. gariepinus juveniles. The 96 h LC50 value of tramadol determined by probit analysis was 88.76 mg/L. Based on this value, fish were exposed to sublethal concentrations of 4.44, 8.88, 17.75 mg/L tramadol and 0.0 mg/L (control) for the period of 15 days and allowed to recover for 5 days. Fish exposed to tramadol showed some abnormal behavioral responses and mortality increased with increase in the exposure duration and concentrations except for the control. There were variations in hepatosomatic index (HSI) and condition factor (CF) in fish exposed to tramadol. Exposure of C. gariepinus to tramadol elicited reduction in the values of white blood cell (WBC), red blood cell (RBC), hemoglobin (Hb), packed cell volume (PCV) and mean corpuscular volume (MCV) while the values of mean corpuscular hemoglobin (MCH) and the mean corpuscular hemoglobin concentration (MCHC) increased. The values of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), reduced glutathione (GSH) and lipid peroxidation (LPO) increased significantly in the exposed fish compared with the control. The values of glutathione peroxidase (GPx) however decreased. The results of the present study demonstrate that tramadol is toxic to fish and its use should be monitored in the aquatic environment.