Nurcan Doruk

Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model

In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Tramadol group (n = 10), received the drug intraperitoneally at doses of 20, 40 and 80 mg/kg/day in the first, second and the third ten days of the study, respectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinin, blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were measured in the serum. Liver and kidney specimens were evaluated by light microscopy. Serum ALT, AST, LDH, BUN and creatinin levels were significantly higher in morphine group compared to the control group. Serum LDH, BUN and creatinin levels were significantly increased in the morphine group compared to the tramadol group. The mean MDA level was significantly higher in morphine group compared to the tramadol and control groups (P<0.05). Light microscopy revealed severe centrolobular congestion and focal necrosis in the liver of morphine and tramadol groups, but perivenular necrosis was present only in the morphine group. The main histopathologic finding was vacuolization in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage

OPIOID NEUROTOXICITY: COMPARISON OF MORPHINE AND TRAMADOL IN AN EXPERIMENTAL RAT MODEL

Histopathologic changes in rat brain due to chronic use of morphine and/or tramadol in progressively increased doses were investigated in this study. Thirty male Wistar rats (180-220 g) were included and divided into three groups. Normal saline (1 ml/kg) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4 mg/kg/day for the first 10 days, 8 mg/kg/day between 11-20 days, and 12 mg/kg/day between 21-30 days. The tramadol group (n = 10) received the drug intraperitoneally at doses of 20, 40, and 80 mg/kg/day in the first, second, and the third 10 days of the study, respectively. All rats were decapitated on the 30th day and the brain was removed intact for histology. The presence and the number of red neurons, which are a histologic marker of apoptosis, were investigated in the parietal, frontal, temporal, occipital, entorhinal, pyriform, and hippocampal CA1, CA2, CA3 regions. Red neurons were found in morphine and tramadol groups but not in the control group. The total number of red neurons was not different in morphine and tramadol groups, but the numbers of red neurons were significantly higher in the temporal and occipital regions in tramadol group as compared with the morphine group (p < .05). In conclusion, chronic use of morphine and/or tramadol in increasing doses is found to cause red neuron degeneration in the rat brain, which probably contributes to cerebral dysfunction. These findings should be taken into consideration when chrome use of opioids is indicated.

The comparison of the efficacy of scoring systems in organophosphate poisoning

The purpose of this study was to evaluate the impact of the Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II scoring systems for organophosphate poisoning (OPP) in an intensive care unit (ICU). The following data were collected on all consecutive patients who were admitted to the ICU between June 1999 and December 2004. Demographic data, GCS, APACHE II and SAPS II scoring systems were recorded. Predicted mortality was calculated using original regression formulas. Standardized mortality ratio (SMR) was computed with 95% confidence intervals (CI). The sensitivity and specificity for each scoring system were evaluated by calculating the Area Under the Receiver Operating Characteristic Curves. The actual mortality in OPP was 21.9%. Predicted mortality by all systems was not significantly different from actual mortality [SMR and 95% CI for GCS: 1.00 (0.65-1.35), APACHE II: 0.87 (0.54-1.03), SAPS II: 1.40 (0.98-1.82)]. The area under the ROC curve for APACHE II is largest, but there is no statistically significant difference when compared with SAPS II and GCS (GCS 0.9009 / 0.059, APACHE II 0.9299 / 0.045 and SAPS II 0.8919 / 0.057). In our ICU group of patients, in predicting the mortality rates in OPP, the three scoring systems, which are GCS, APACHE II and SAPS II, had similar impacts; however, GCS system has superiority over the other systems in being easy to perform, and not requiring complex physiologic parameters and laboratory methods.

Effects of levosimendan on myocardial ischaemia-reperfusion injury

Background and objective: Levosimendan has a cardioprotective action by inducing coronary vasodilatation and preconditioning by opening KATP channels. The aim of this study was to determine whether levosimendan enhances myocardial damage during hypothermic ischaemia and reperfusion in isolated rat hearts. Methods: Twenty‐one male Wistar rats were divided into three groups. After surgical preparation, coronary circulation was started by retrograde aortic perfusion using Krebs‐Henseleit buffer solution and lasted 15 min. After perfusion Group 1 (control; n = 7) received no further treatment. In Group 2 (non‐treated; n = 7), hearts were arrested with cold cardioplegic solution after perfusion and subjected to 60 min of hypothermic global ischaemia followed by 30 min reperfusion. In Group 3 (levosimendan treated; n = 7), levosimendan was added to the buffer solution during perfusion and the hearts were arrested with cold cardioplegic solution and subjected to 60 min of hypothermic global ischaemia followed by 30 min reperfusion. At the end of the reperfusion period, the hearts were prepared for biochemical assays and for histological analysis. Results: Tissue malondialdehyde levels were significantly lower in the levosimendan‐treated group than in the non‐treated group (P = 0.019). The tissue Na+‐K+ ATPase activity was significantly decreased in the non‐treated group than in the levosimendan‐treated group (P = 0.027). Tissue myeloperoxidase (MPO) enzyme activity was significantly higher in the non‐treated group than in the levosimendan‐treated group (P = 0.004). Electron microscopic examination of the hearts showed cardiomyocytic degeneration at the myofibril, mitochondria and sarcoplasmic reticulum in both non‐treated and levosimendan‐treated groups. The severity of these findings was more extensive in the non‐treated group. Conclusions: Treatment with levosimendan provided better cardioprotection with cold cardioplegic arrest followed by global hypothermic ischaemia in isolated rat hearts.

The Effect of Preventive Use of Alanyl-Glutamine on Diaphragm Muscle Function in Cecal Ligation and Puncture-Induced Sepsis Model

BACKGROUND Low muscle glutamine levels during sepsis are associated with reduced protein synthesis and elevated protein breakdown, in particular myofibrillar protein breakdown. Thus, in a cecal ligation and puncture (CLP)-induced sepsis model in the rat, we hypothesized that glutamine pretreatment would protect the diaphragm muscle function. METHODS Eighty-four male Wistar rats weighing between 180 g and 200 g received standard amino acid solution 1.2 g kg(-1) per day intraperitoneally (IP) or standard amino acid solution 1.2 g kg(-1) per day plus alanyl-glutamine (GLN) 0.25 g kg(-1) per day (IP) during the first 6 days of the experiment. On the seventh day, CLP or sham procedures were applied. The sham and CLP groups were equally divided into 3 subgroups according to the termination of the experiment, which took place at either the 24th hour, 48th hour, or 72nd hour. After the compound muscle action potentials (CMAP) were recorded from the diaphragms of the rats at these selected times, they were decapitated under ketamine/xylazine anesthesia, and diaphragms were harvested for biochemical and histopathological examination. RESULTS The mean area and amplitude of CMAP were significantly larger in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p < .05). Diaphragm Ca+2 -ATPase levels were found to be significantly decreased in CLP group at all times compared to sham groups (p < .05). Diaphragm reduced glutathione levels were significantly higher in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p < .05). In histopathologic assessment, moderate neutrophil infiltration, which was observed in CLP48, was significantly reduced with alanyl-glutamine supplementation in CLP+GLN48 group (p < .05). CONCLUSIONS This study showed that glutamine pretreatment did not improve diaphragm muscle function, but prevented the biochemical and histopathological changes in diaphragmatic muscle in CLP-induced sepsis. However, further studies are needed to clarify whether a higher dose of glutamine supplementation might protect the diaphragmatic muscle functions.

Bispectral Index Monitoring in Confirmation of Brain Death in Children

Although the guidelines for the diagnosis of brain death in children are well established, the diagnosis is still under debate, and further confirmatory tests are required. Performing these confirmatory tests presents some drawbacks, such as high costs, the need for specialized personnel and technology, transportation of patients out of the intensive care unit, and the use of contrast media. Bispectral index monitoring can provide real-time, objective, continuous monitoring of the consciousness level in critically ill children. The aim of this prospective study was to define the role of bispectral index monitoring in the confirmation and diagnosis of brain death. Eight children who had fulfilled the diagnostic criteria of brain death were included in the study. The age of patients ranged from 3 months to 15 years. All patients had electrocerebral silence on their electroencephalographic recordings. After the diagnosis of brain death, at least 2-hour monitoring was performed, and all patients expressed a score of 0, indicating brain death. According to our study, the decrease in bispectral index score to 0 in patients with suspected brain death can support and confirm brain death diagnosis in children and can enable scheduling of expensive tests, such as cerebral angiography, in the appropriate time. Nevertheless, further studies are needed to determine the role of the bispectral index in the diagnosis and confirmation of brain death in children. In this article, we review clinical utility, application time, and interpretation of bispectral index monitoring in confirmation of brain death diagnosis in children. (J Child Neurol 2006;21:799—801; DOI 10.2310/7010.2006.00131).

Patient-Controlled Epidural Analgesia after Major Urologic Surgeries

The efficiency and safety of patient-controlled epidural analgesia by using tramadol alone and combined with bupivacaine were investigated for postoperative pain treatment after major urological surgeries. For PCEA: in group I (n = 17) a loading dose of 20 mg tramadol with a continuous infusion of 1 mg/ml tramadol at a rate of 8 ml/h was given. In group II (n = 17), patients received an initial loading dose of 20 ml bupivacaine 0.125% and a supplemental continuous infusion of 8 ml/h. In group III (n = 17), a loading dose of 20 mg tramadol with 20 ml bupivacaine 0.125% were given and a supplemental infusion of 1 mg/ml tramadol in 20 ml bupivacaine 0.125% combination was begun with a rate of 8 ml/h. A demand epidural bolus dose of 5 ml with a lockout time of 30 min was also used in all patients. VAS for pain intensity, vital signs, sedation scale and side effects was monitored at 0, 15, 30 min and 1, 2, 3, 4, 8, 12, and 24 h of the postoperative period. Statistical significance was determined using Kruskal-Wallis, Fisher’s exact, analysis of variance for repeated measurements and Tukey tests. The hemodynamic values and sedation scales were insignificantly different (p > 0.05). The adequate analgesia was provided in all patients. However VAS values were significantly lower in group III than in groups I and II at every measurement (p < 0.05). The incidence of side effects in all three groups was low (p > 0.05). In conclusion, we suggested that a combination of tramadol with bupivacaine can provide the most effective and safe postoperative analgesia with minimal risk for side effects.

The effects of caudal magnesium administration on anaesthesia depth and analgesia requirement: A-613

Background and Goal of Study: Recently most studies reported that magnesium was a N-methyl-D-aspartate (NMDA)-receptor antagonist and its analgesic and perioperative anesthesic effects were discussed with central desentisation pathway. We aimed to study effects of caudal ropivacaine plus magnesium o

Postpartum paradoxical cerebral embolism through an unknown patent foramen ovale

Introduction and Objective. Paradoxical embolism through a patent foramen ovale (PFO) is a frequent cause of cerebral embolim on young patients. In this report, we describe a young woman who presen...

Patient controlled epidural analgesia after major urologic surgery: A comparison of tramadol with morphine

AbstractThe purpose of the paper was to assess and to compare the effectiveness and safety of patient controlled epidural analgesia using tramadol or morphine for postoperative analgesia after major urological surgeries.For patient-controlled epidural analgesia; in group I (n = 30) a loading dose of 20 mg tramadol 0.1% with a continuous infusion of 1 mg/ml at a rate of 8 ml/h was administered preemptly and in group II (n = 30) a loading dose of 2 mg morphine in 20 ml normal saline was administered and a supplemental infusion of 0.2 mg/h morphine was begun at a rate of 2 ml/h. A demand epidural bolus dose of 5 ml with a lockout time of 30 minutes and a background infusion of 8 ml/h in tramadol 0.1% group and 2 ml/h in morphine 0.01% group were administered. VAS for pain intensity, vital signs, sedation scale and side effects were monitored at 0, 15, 30 minutes and 1, 2, 3, 4, 8, 12, 24 hours during the postoperative period.Adequate analgesia was provided in all patients. VAS values were significantly lower...