OBJECTIVES: Severe complications of tramadol overdose have been reported; however, few large-scale studies have investigated this issue. Therefore, this study aimed to explore the presentation and complications of tramadol overdose in patients admitted to an intoxication referral center in northwestern Iran.METHODS: Patients with tramadol overdose admitted to Sina Teaching Hospital in Tabriz, Iran during 2013-2017 were included. For each patient, the following data were collected: demographics, previous drug or medication overdose, whether the patient was in the process of quitting drug use, ingested dose of tramadol and co-ingestants, Glasgow Coma Scale (GCS) score, clinical symptoms at the time of admission, and admission characteristics. Serotonin toxicity was diagnosed in patients who fit the Hunter criteria. Multiple logistic regression was performed to identify variables associated with the incidence of severe complications of tramadol overdose.RESULTS: In total, 512 cases of tramadol overdose were evaluated, of which 359 patients were included, with a median age of 41 years (range, 16-69) and a median tramadol dose of 1,500 mg (range, 500-4,000). The most frequent complications associated with tramadol overdose were hypertension (38.4%), tachycardia (24.8%), and seizure (14.5%). No serotonin toxicity was detected in patients. Having a GCS score <15, having taken a tramadol dose of >1,000 mg, being in the process of quitting drug use, being 30-49 years old, and male sex were significantly related to the incidence of severe complications of tramadol overdose.CONCLUSIONS: Although seizure was prevalent among Iranian patients with tramadol poisoning, serotonin toxicity and cardiogenic shock were rare findings.
Demography ; Glasgow Coma Scale ; Hospitals, Teaching ; Humans ; Hypertension ; Incidence ; Iran ; Logistic Models ; Male ; Poisoning ; Referral and Consultation ; Seizures ; Serotonin ; Serotonin Syndrome ; Shock, Cardiogenic ; Tachycardia ; Tramadol

Paeonol has neuroprotective function, which could be useful for improving central nervous system disorder. The purpose of this study was to characterize the functional mechanism involved in brain transport of paeonol through blood-brain barrier (BBB). Brain transport of paeonol was characterized by internal carotid artery perfusion (ICAP), carotid artery single injection technique (brain uptake index, BUI) and intravenous (IV) injection technique in vivo. The transport mechanism of paeonol was examined using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) as an in vitro model of BBB. Brain volume of distribution (V(D)) of [³H]paeonol in rat brain was about 6-fold higher than that of [¹⁴C]sucrose, the vascular space marker of BBB. The uptake of [³H]paeonol was concentration-dependent. Brain volume of distribution of paeonol and BUI as in vivo and inhibition of analog as in vitro studies presented significant reduction effect in the presence of unlabeled lipophilic compounds such as paeonol, imperatorin, diphenhydramine, pyrilamine, tramadol and ALC during the uptake of [³H]paeonol. In addition, the uptake significantly decreased and increased at the acidic and alkaline pH in both extracellular and intracellular study, respectively. In the presence of metabolic inhibitor, the uptake reduced significantly but not affected by sodium free or membrane potential disruption. Similarly, paeonol uptake was not affected on OCTN2 or rPMAT siRNA transfection BBB cells. Interestingly. Paeonol is actively transported from the blood to brain across the BBB by a carrier mediated transporter system.
Animals ; Blood-Brain Barrier ; Brain ; Carotid Arteries ; Carotid Artery, Internal ; Central Nervous System ; Diphenhydramine ; Endothelial Cells ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Membrane Potentials ; Perfusion ; Pyrilamine ; Rats ; RNA, Small Interfering ; Sodium ; Tramadol ; Transfection

OBJECTIVES: Severe complications of tramadol overdose have been reported; however, few large-scale studies have investigated this issue. Therefore, this study aimed to explore the presentation and complications of tramadol overdose in patients admitted to an intoxication referral center in northwestern Iran. METHODS: Patients with tramadol overdose admitted to Sina Teaching Hospital in Tabriz, Iran during 2013-2017 were included. For each patient, the following data were collected: demographics, previous drug or medication overdose, whether the patient was in the process of quitting drug use, ingested dose of tramadol and co-ingestants, Glasgow Coma Scale (GCS) score, clinical symptoms at the time of admission, and admission characteristics. Serotonin toxicity was diagnosed in patients who fit the Hunter criteria. Multiple logistic regression was performed to identify variables associated with the incidence of severe complications of tramadol overdose. RESULTS: In total, 512 cases of tramadol overdose were evaluated, of which 359 patients were included, with a median age of 41 years (range, 16-69) and a median tramadol dose of 1,500 mg (range, 500-4,000). The most frequent complications associated with tramadol overdose were hypertension (38.4%), tachycardia (24.8%), and seizure (14.5%). No serotonin toxicity was detected in patients. Having a GCS score <15, having taken a tramadol dose of >1,000 mg, being in the process of quitting drug use, being 30-49 years old, and male sex were significantly related to the incidence of severe complications of tramadol overdose. CONCLUSIONS: Although seizure was prevalent among Iranian patients with tramadol poisoning, serotonin toxicity and cardiogenic shock were rare findings.
Demography ; Glasgow Coma Scale ; Hospitals, Teaching ; Humans ; Hypertension ; Incidence ; Iran ; Logistic Models ; Male ; Poisoning ; Referral and Consultation ; Seizures ; Serotonin ; Serotonin Syndrome ; Shock, Cardiogenic ; Tachycardia ; Tramadol

PURPOSE: The efficacy of periarticular multimodal drug injection and adductor canal block after a medial opening-wedge high tibial osteotomy was compared in terms of the postoperative pain level. MATERIALS AND METHODS: From November 2016 to March 2017, 60 patients underwent a medial opening-wedge high tibial osteotomy under spinal anesthesia. Preemptive analgesic medication, intravenous patient controlled anesthesia were used for pain control in all patients. Thirty patients received a periarticular multimodal drug injection (group I), and 30 patients received an adductor canal block (group II). These two groups were compared regarding the postoperative pain level, frequency of additional tramadol injections, total amount of patient-controlled analgesia, and number of times that the patients pushed the patient-controlled analgesia button at each time interval. RESULTS: The visual analogue scale scores over the two-week postoperative period showed no statistical significance. The frequency of additional tramadol hydrochloride injections was similar in the two groups over time. The mean number of times that patients pushed the patient-controlled analgesia button was similar in two groups over time. The total amount of patient-controlled analgesia was similar in the two groups over time. CONCLUSION: This study shows that intraoperative periarticular multimodal drug injections and adductor canal block may have a similar effect on postoperative pain control in patients who have undergone a medial opening-wedge high tibial osteotomy for unicompartmental osteoarthritis of the knee.
Analgesia, Patient-Controlled ; Anesthesia ; Anesthesia, Spinal ; Humans ; Knee ; Nerve Block ; Osteoarthritis ; Osteotomy ; Pain, Postoperative ; Postoperative Period ; Tramadol

BACKGROUND: The transversus abdominis plane (TAP) block is an effective technique to block the thoracolumbar nerves innervating the anterolateral abdominal wall. This study was conducted to evaluate the analgesic efficacy and opioid consumption with the use of perineural buprenorphine or dexamethasone in TAP blocks after unilateral inguinal hernioplasties. METHODS: This prospective, randomized, double-blinded, placebo-controlled study enrolled 93 patients scheduled for unilateral inguinal hernioplasty, followed by an ultrasound-guided TAP block. The participants were randomized into 3 groups (31 patients each). Group L received 20 ml 0.25% levobupivacaine + 1 ml normal saline (NS); group LB, 20 ml 0.25% levobupivacaine + 0.3 mg (1 ml) buprenorphine; and group LD, 20 ml 0.25% levobupivacaine + 4 mg (1 ml) dexamethasone. The patients were observed postoperatively for 24 h for first rescue analgesic requirement, total rescue analgesic consumption, and pain scores on the numeric rating scale (NRS). RESULTS: The time to first rescue analgesic requirement was significantly longer in Group LB than in groups LD and L (688.87 ± 36.11 min, 601.45 ± 39.85 min, and 383.06 ± 36.21 min, respectively; P < 0.001). The mean total tramadol consumption in the first 24 h was the lowest in group LB (P < 0.001, L vs. LB / LD). Groups LB and LD displayed significantly lower NRS scores than group L (P < 0.001 both). CONCLUSIONS: Levobupivacaine with perineural buprenorphine in a TAP block after unilateral open inguinal hernioplasty facilitates prolonged analgesia and reduced requirement for rescue analgesics compared to perineural dexamethasone, without significant side effects.
Abdominal Wall ; Analgesia ; Analgesics ; Buprenorphine ; Dexamethasone ; Hernia, Inguinal ; Herniorrhaphy ; Humans ; Prospective Studies ; Tramadol ; Ultrasonography

BACKGROUND: Surgical-site, multimodal drug injection has recently evolved to be a safe and useful method for multimodal pain management even in patients with musculoskeletal trauma. METHODS: Fifty consecutive patients who underwent plating for mid-shaft and distal clavicular fractures were included in the study. To evaluate whether surgical-site injections (SIs) have pain management benefits, the patients were divided into two groups (SI and no-SI groups). The injection was administered between the deep and superficial tissues prior to wound closure. The mixture of anesthetics consisted of epinephrine hydrochloride (HCL), morphine sulfate, ropivacaine HCL, and normal saline. The visual analogue scale (VAS) pain scores were measured at 6-hour intervals until postoperative hour (POH) 72; stress biomarkers (dehydroepiandrosterone sulfate [DHEA-S], insulin, and fibrinogen) were measured preoperatively and at POH 24, 48, and 72. In patients who wanted further pain control or had a VAS pain score of 7 points until POH 72, 75 mg of intravenous tramadol was administered, and the intravenous tramadol requirements were also recorded. Other medications were not used for pain management. RESULTS: The SI group showed significantly lower VAS pain scores until POH 24, except for POH 18. Tramadol requirement was significantly lower in the SI group until POH 24, except for POH 12 and 18. The mean DHEA-S level significantly decreased in the no-SI group (74.2 ± 47.0 µg/dL) at POH 72 compared to that in the SI group (110.1 ± 87.1 µg/dL; p = 0.046). There was no significant difference in the insulin and fibrinogen levels between the groups. The correlation values between all the biomarkers and VAS pain scores were not significantly different between the two groups (p > 0.05). CONCLUSIONS: After internal fixation of the clavicular fracture, the surgical-site, multimodal drug injection effectively relieved pain on the day of the surgery without any complications. Therefore, we believe that SI is a safe and effective method for pain management after internal fixation of a clavicular fracture.
Anesthetics ; Biomarkers* ; Clavicle ; Epinephrine ; Fibrinogen ; Humans ; Insulin ; Methods ; Morphine ; Pain Management ; Pain, Postoperative ; Tramadol ; Wounds and Injuries

BACKGROUND: Immune responses appear to be affected by anesthetics and analgesics. We investigated the effects of caudal tramadol on the postoperative immune response and pain management in pediatric patients. METHODS: Sixty ASA-I pediatric patients aged 3–10 years undergoing lower abdominal surgery. Patients were randomly assigned either to a caudal bupivacaine (0.25%) group (group B), or a group that received caudal tramadol (1 mg/kg) added to the bupivacaine (0.25%) (group T). Both were diluted in a 0.9% NaCl solution to a total volume of 1ml/kg. The systemic immune response was measured by collecting blood samples preoperatively, at the end of anesthesia, and at 24 and 72 hours postoperatively, and studied for interleukin IL-6, C-reactive proteins (CRP) cortisol levels, and leucocytes with its differential count. Postoperative pain was assessed along with sedation scales. RESULTS: Postoperative production of IL-6 was significantly higher in group B at the end of anesthesia, than at the 24th hour, and at the 72nd hour in group B and group T, respectively. The immune response showed leukocytosis with increased percentages of neutrophil and monocytes, and a decreased lymphocyte response rate within both groups with no significant differences between the groups. Cortisol and CRP were significantly higher in group B. CONCLUSIONS: Adding tramadol to a caudal bupivacaine block can attenuate the pro-inflammatory cytokine response, Cortisol, and CRP in children undergoing lower abdominal surgery.
Abdomen ; Analgesics ; Anesthesia ; Anesthesia, Caudal ; Anesthetics ; Bupivacaine ; C-Reactive Protein ; Child ; Humans ; Hydrocortisone ; Interleukin-6 ; Interleukins ; Leukocyte Count ; Leukocytes ; Leukocytosis ; Lymphocytes ; Monocytes ; Neutrophils ; Pain Management ; Pain, Postoperative ; Pediatrics ; Tramadol ; Weights and Measures

BACKGROUND: To compare the effects of adding two different doses of dexamethasone on the duration and quality of the fascia iliaca block in patients undergoing proximal femoral fracture surgery. METHODS: A total of 60 patients (age 18–70 years) undergoing proximal femoral nailing surgery under spinal anesthesia were given fascia iliaca block after random assignment to one of the two groups: Group H received an injection of levobupivacaine (0.5%) 28 ml with 2 ml (8 mg) dexamethasone, and Group L received an injection of levobupivacaine (0.5%) 28 ml with dexamethasone 1 ml (4 mg) with 1 ml normal saline. Assessment of the duration of analgesia and the total tramadol requirement over 48 hours were noted after a successful block. RESULTS: The duration of analgesia was found to be significantly longer in Group H (17.02 ± 0.45 h) than in the Group L patients (14.29 ± 0.45 h) with a p-value of 0.000. Postoperative analgesic requirement (amount of tramadol in mg) was significantly higher in Group L (Q2: 200.0; IQR: 100.0, 200.0) as compared to Group H (Q2: 100.0; IQR: 100.0, 200.0) with a p-value of 0.034. No patient showed any sign of neurotoxicity. CONCLUSIONS: Dexamethasone, in a dose of 8 mg, is superior to 4 mg when used as an adjuvant with levobupivacaine in the FIB. Though both prolonged analgesia and were effective in reducing oral/intravenous analgesics, 8 mg dexamethasone can be recommended as a more efficacious adjuvant to local anesthetics in the FIB.
Analgesia ; Analgesics ; Anesthesia, Spinal ; Anesthetics, Local ; Bupivacaine ; Dexamethasone ; Fascia ; Femoral Fractures ; Humans ; Pain Management ; Prospective Studies ; Tramadol

Imperatorin, a major bioactive furanocoumarin with multifunctions, can be used for treating neurodegenerative diseases. In this study, we investigated the characteristics of imperatorin transport in the brain. Experiments of the present study were designed to study imperatorin transport across the blood-brain barrier both in vivo and in vitro. In vivo study was performed in rats using single intravenous injection and in situ carotid artery perfusion technique. Conditionally immortalized rat brain capillary endothelial cells were as an in vitro model of blood-brain barrier to examine the transport mechanism of imperatorin. Brain distribution volume of imperatorin was about 6 fold greater than that of sucrose, suggesting that the transport of imperatorin was through the blood-brain barrier in physiological state. Both in vivo and in vitro imperatorin transport studies demonstrated that imperatorin could be transported in a concentration-dependent manner with high affinity. Imperatorin uptake was dependent on proton gradient in an opposite direction. It was significantly reduced by pretreatment with sodium azide. However, its uptake was not inhibited by replacing extracellular sodium with potassium or N-methylglucamine. The uptake of imperatorin was inhibited by various cationic compounds, but not inhibited by TEA, choline and organic anion substances. Transfection of plasma membrane monoamine transporter, organic cation transporter 2 and organic cation/carnitine transporter 2/1 siRNA failed to alter imperatorin transport in brain capillary endothelial cells. Especially, tramadol, clonidine and pyrilamine inhibited the uptake of [3H]imperatorin competitively. Therefore, imperatorin is actively transported from blood to brain across the blood-brain barrier by passive and carrier-mediated transporter.
Alzheimer Disease ; Animals ; Blood-Brain Barrier* ; Brain ; Carotid Arteries ; Cell Membrane ; Choline ; Clonidine ; Endothelial Cells ; In Vitro Techniques ; Injections, Intravenous ; Neurodegenerative Diseases ; Perfusion ; Potassium ; Protons ; Pyrilamine ; Rats ; RNA, Small Interfering ; Sodium ; Sodium Azide ; Sucrose ; Tea ; Tramadol ; Transfection

OBJECTIVE: Although little is known about its origins, neck pain may be related to several associated anatomical pathologies. We aimed to characterize the incidence and features of chronic neck pain and analyze the relationship between neck pain severity and its affecting factors. METHODS: Between March 2012 and July 2013, we studied 216 patients with chronic neck pain. Initially, combined tramadol (37.5 mg) plus acetaminophen (325 mg) was administered orally twice daily (b.i.d.) to all patients over a 2-week period. After two weeks, patients were evaluated for neck pain during an outpatient clinic visit. If the numeric rating scale of the patient had not decreased to 5 or lower, a cervical medial branch block (MBB) was recommended after double-dosed previous medication trial. We classified all patients into two groups (mild vs. severe neck pain group), based on medication efficacy. Logistic regression tests were used to evaluate the factors associated with neck pain severity. RESULTS: A total of 198 patients were included in the analyses, due to follow-up loss in 18 patients. While medication was successful in reducing pain in 68.2% patients with chronic neck pain, the remaining patients required cervical MBB. Lateral cervical curvature, such as a straight or sigmoid type curve, was found to be significantly associated with the severity of neck pain. CONCLUSION: We managed chronic neck pain with a simple pharmacological management protocol followed by MBB. We should keep in mind that it may be difficult to manage the patient with straight or sigmoid lateral curvature only with oral medication.
Acetaminophen ; Ambulatory Care Facilities ; Colon, Sigmoid ; Factor Analysis, Statistical* ; Follow-Up Studies ; Humans ; Incidence ; Logistic Models ; Neck Pain* ; Neck* ; Pathology ; Tramadol