Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia.

Morphine is a drug used in chronic pain such as diabetic neuropathy, but the development of tolerance to its antinociceptive effect is an important clinical problem. Aspirin is an analgesic and antiapoptotic drug used in combination with morphine as an adjuvant in diabetic neuropathy. Our aim in this study was to investigate the effects of aspirin on morphine-induced neuronal apoptosis and analgesic tolerance in rats with diabetic neuropathy. The antinociceptive effects of aspirin (50 mg/kg) and morphine (5 mg/kg) were evaluated by thermal pain tests. Streptozotocin (65 mg/kg) was injected intraperitoneally to induce diabetic neuropathy. To evaluate apoptosis, ELISA kits were used to measure caspase-3, Bax and Bcl-2 levels. Apoptotic cells were detected histologically by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. Study results indicate that prior administration of aspirin to diabetic rats significantly increased the antinociceptive efficacy of morphine compared to morphine alone. Thermal pain tests showed that aspirin significantly reduced morphine tolerance in rats with diabetic neuropathy. Biochemical analysis revealed that aspirin significantly decreased the levels of pro-apoptotic proteins, caspase-3 and Bax, while increasing the anti-apoptotic Bcl-2 in DRG neurons. Semiquantitative scoring demonstrated that aspirin provided a significant reduction in apoptotic cell counts in diabetic rats. In conclusion, these data suggested that aspirin attenuated morphine antinociceptive tolerance through anti-apoptotic activity in diabetic rat DRG neurons.

Metformin prevents morphine-induced apoptosis in rats with diabetic neuropathy: a possible mechanism for attenuating morphine tolerance.

Morphine is a drug of choice for the treatment of severe and chronic pain, but tolerance to the antinociceptive effect limits its use. The development of tolerance to morphine has recently been associated with neuronal apoptosis. In this study, our aim was to investigate the effects of metformin on morphine-induced neuronal apoptosis and antinociceptive tolerance in diabetic rats. Three days of cumulative dosing were administered to establish morphine tolerance in rats. The antinociceptive effects of metformin (50 mg/kg) and test dose of morphine (5 mg/kg) were considered at 30-min intervals by thermal antinociceptive tests. To induce diabetic neuropathy, streptozotocin (STZ, 65 mg/kg) was injected intraperitoneally. ELISA kits were used to measure caspase-3, bax, and bcl-2 levels from dorsal root ganglion (DRG) tissue. Semi-quantitative scoring system was used to evaluate apoptotic cells with the the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. The findings suggest that co-administration of metformin with morphine to diabetic rats showed a significant increase in antinociceptive effect compared to morphine alone. The antinociceptive tests indicated that metformin significantly attenuated morphine antinociceptive tolerance in diabetic rats. In addition, metformin decreased the levels of apoptotic proteins caspase 3 and Bax in DRG neurons, while significantly increased the levels of antiapoptotic Bcl-2. Semi-quantitative scoring showed that metformin provided a significant reduction in apoptotic cell counts in diabetic rats. These data revealed that metformin demonstrated antiapoptotic activity in diabetic rat DRG neurons and attenuated morphine tolerance. The antiapoptotic activity of metformin probably plays a significant role in reducing morphine tolerance.

The effect of postoperative serratus anterior plane block on postoperative analgesia in patients undergoing breast surgery.

OBJECTIVES: This study aimed to evaluate the effect of serratus anterior plane block (SAP) on postoperative morphine consumption. We aimed to determine the differences between both similar blocks and evaluate the effect of the methods of application of this block on patients' postoperative pain scores and morphine consumption. MATERIAL AND METHODS: This study is a single-center, prospective and observational study performed with 40 volunteer patients with American Society of Anesthesiologists (ASA) I-III, who were 18-70 years of age, scheduled for breast surgery. A total of 40 patients who underwent general anesthesia were divided into two groups each with 20 patients. While SAP block was applied to the study group, no block was applied to the control group. SAP block was made by injecting a total of 40 ml of 0.25% bupivacaine between 2 muscles after the test dose was injected with saline. All patients were followed up for 12 hours postoperatively with patient-controlled analgesia (PCA) pump. Morphine consumption, visual analogue score (VAS) values and side effects were recorded at the postoperative 1st, 6th and 12th hours. RESULTS: There was no significant difference between the two groups in terms of hemodynamic parameters and demographic data. Postoperative morphine consumption and postoperative analgesic requirement were significantly lower in the SAP block group (p <0.001). Postoperative VAS values were significantly lower in the SAP block group (p <0.001). No complication was observed related to the block. CONCLUSION: It was found that the SAP block reduced morphine consumption, significantly decreased VAS values, and reduced side effects due to opioids postoperatively.

Views of algology inpatients about ethical issues related to pain.

OBJECTIVES: To determine the views of patients hospitalized in the algology clinic about ethical issues related to pain. METHODS: A total of 135 patients admitted to the algology clinic comprised the population of this descriptive study. Data were collected using the visual analogue scale (VAS) and the questionnaire on ethical issues related to pain. To evaluate the data, percentage distribution and the Tukey test of variance were used. RESULTS: Of the patients, 92.6% believed that they had the right to pain relief, and 94.8% believed that they should be consulted when decisions about them were made. It was determined that 43.0% of the patients disagreed with Proposition 1, 'When a terminal-stage cancer patient with unrelievable pain requests an overdose of pain medication, possibly to cause death, the physician must prescribe it,' while 51.9% of the participants disagreed with Proposition 2, 'When a terminal-stage cancer patient with unrelievable pain and his or her family request an overdose of pain medication, possibly to cause death, the physician must prescribe it,' and 44.4% of them disagreed with Proposition 3, 'When a terminal-stage cancer patient with unrelievable pain requests an overdose of pain medication, possibly to cause death even though his or her family refuses, the physician must prescribe it.' A statistically significant relationship (p<0.05) was found between the mean VAS scores and Propositions 1 and 3. CONCLUSION: The patients were willing to be informed and to be asked about their views regarding the issue, but they did not want to be prescribed a high dose of pain medication, possibly to cause overdose and death.

Comparison of In Vitro Effects of Opioid Analgesics on Spontaneous Proximal and Distal Colon Contractions in Healthy Rats and Rats with Peritonitis.

OBJECTIVE: The goal of this study was to investigate and compare the effects of opioids on proximal and distal colon contractions in normal rats and rats with peritonitis, with and without the presence of naloxone in the environment. METHODS: The study was approved by Cumhuriyet University Ethics committee. In this study, 16 Wistar Albino male rats were used. Rats were divided into two groups. Peritonitis was induced using a cecum ligation and perforation method, 24 h before the tissues of rats in the peritonitis group were collected, and sham surgery was performed 24 h before the tissues of rats in the control group were collected. Twenty-four hours after the surgery, rats' organs were harvested and hung in organ baths. Concentration-dependent inhibitory effects of morphine and meperidine on spontaneous intestinal movements were observed. Any differences between the groups were tested using the Kruskal-Wallis test, and any differences between the groups were tested using the Tukey test. RESULTS: No significant difference was observed between the proximal and distal colon smooth muscle contraction responses in both groups after 80 mM Potassium Chloride (KCl) injection (p>0.005). In the peritonitis group, amplitudes and frequencies of spontaneous contractions in proximal and distal colon significantly increased (p<0.05). Drugs decreased the amplitude and frequency responses in the control group (p<0.05). In the peritonitis group, whereas morphine decreased the amplitude and frequency responses in comparison with the control group (p<0.05), meperidine did not cause any significant changes (p>0.05). In both groups, adding naloxone to the organ baths before adding opioids completely blocked the morphine's inhibitory effect on the amplitude and frequency (p<0.05), but it could not completely block the inhibition caused by meperidine. CONCLUSION: Morphine and meperidine exhibit an inhibitory effect on the intestinal motility in both groups. This effect can be blocked by naloxone completely in morphine, and partially in meperidine.

Effects of extremely low frequency electromagnetic fields on morphine analgesia and tolerance in rats.

Several studies have demonstrated that the electromagnetic fields produce analgesic activity. The aim of this study was to investigate the effects of extremely low frequency (ELF) electromagnetic fields (EMF) on morphine analgesia and tolerance in rats. In the study, 78 adult male Wistar albino rats (approximately 240 ± 12 g) were used. The application of 50 Hz magnetic field, each day the same times for 30 minutes for 15 days, and a total of four times every 15 minute intervals. To constitute morphine tolerance, high dose of morphine (50 mg/kg) were administered for 3 days in rats and tolerance was evaluated on day 4. Prior to analgesia tests, the effective dose (5 mg/kg) of morphine was injected into rats. In the statistical analyzes of the data, analysis of variance (two-way ANOVA) was used and the multiple comparison determined by Tukey tests. The maximum analgesic effect of the 5 mT magnetic field was determined on 7 days. Administration of morphine (5 mg/kg) in rats exposed to a magnetic field, the analgesic effect was significantly higher compared to the morphine group (p < 0.05). Morphine tolerant animals exposed to a magnetic field, the analgesic effect was found significantly higher than morphine tolerant group rats (p < 0.05). Analgesia test data demonstrated that application of ELF-EMFs to rats increases the morphine analgesia and reduces morphine tolerance.

Bloqueio dos nervos ilioinguinal e ílio-hipogástrico com dexcetoprofeno intravenoso melhora a analgesia após histerectomia abdominal / Ilioinguinal-iliohypogastric nerve block with intravenous dexketoprofen improves postoperative analgesia in abdominal hysterectomies / Bloqueo de los nervios ilioinguinal e ilio-hipogástrico con dexketoprofeno intravenoso mejora la analgesia después de la histerectomía abdominal

JUSTIFICATIVA E OBJETIVO: O objetivo deste estudo foi avaliar os efeitos da aplicação intravenosa(IV) de dexcetoprofeno trometamol em bloqueio dos nervos ilioinguinal e ílio-hipogástrico na qualidade analgésica e no consumo de morfina após histerectomia abdominal total. MÉTODO: Estudo clínico controlado e randomizado conduzido com 61 pacientes. O estudo foi feito em sala de operação, sala de recuperação pós-anestésica e ambulatório. Os 61 pacientes foram randomicamente alocados em três grupos: grupo controle (Grupo C), grupo bloqueio (Grupo B) e grupo bloqueio com dexcetoprofeno (Grupo BD). Antes da incisão cirúrgica feita após a indução da anestesia, fizemos o bloqueio dos nervos ilioinguinal e ilio-hipogástrico (Grupo C recebeu solução salina e grupos B e BD receberam levobupivacaína). Em contraste com os grupos C e B, o Grupo BD recebeu dexcetoprofeno. Administramos morfina a todos os pacientes para analgesia, com o uso do método de analgesia controlada pelo paciente (ACP) durante o pós-operatório de 24 horas. Registramos os escores para dor pela escala visual analógica (EVA), os índices de satisfação, o consumo de morfina e os efeitos colaterais durante o pós-operatório de 24 horas. RESULTADOS: Os escores EVA do Grupo BD foram menores do que os dos grupos C e B no pós-operatório (p < 0,05) nos intervalos de 1, 2, 6 e 12 horas. Os escores EVA do Grupo C foram maiores do que os do Grupo B nas primeiras 2 horas de pós-operatório. O tempo até a primeira demanda de ACP foi mais longo, os valores de consumo de morfina mais baixos e os índices de satisfação maiores no Grupo BD do que nos outros dois grupos (p < 0,05). CONCLUSÃO: O bloqueio dos nervos ilioinguinal e ílio-hipogástrico com dexcetoprofeno IV aumenta a satisfação do paciente e diminui o consumo de opioides e sugere que dexcetoprofeno trometamol é um analgésico anti-inflamatório não esteroide eficaz em analgesia pós-operatória.

BACKGROUND AND OBJECTIVE: In this study, our aim was to evaluate the effects of intravenous dexketoprofen trometamol with ilioinguinal and iliohypogastric nerve block on analgesic quality and morphine consumption after total abdominal hysterectomy operations. METHODS: We conducted this randomized controlled clinical study on 61 patients. The study was conducted in the operation room, post-anesthesia care unit, and inpatient clinic. We randomly grouped the 61 patients into control group (group C), block group (group B) and dexketoprofen-block group (group DB). Before the skin incision performed after anesthesia induction, we performed ilioinguinal iliohypogastric block (group C given saline and group P and DB given levobupivacaine). In contrast to group C and B, group DB was given dexketoprofen. We administered morphine analgesia to all patients by patient-controlled analgesia (PCA) during the postoperative 24 hours. We recorded Visual Analogue Scale (VAS), satisfaction scores, morphine consumption and side effects during postoperative 24 hours. RESULTS: We found the DB group's VAS scores to be lower than the control group and block group's (p < 0.05) values at postoperative 1st, 2nd, 6th and 12th hours. VAS scores of group C were higher than of group B at postoperative first 2 hours. Time to first PCA demand was longer, morphine consumption values were lower and satisfaction scores were higher in group DB than in the other two groups (p < 0.05). CONCLUSIONS: Ilioinguinal-iliohypogastric nerve block with IV dexketoprofen increases patient satisfaction by decreasing opioid consumption, increasing patient satisfaction, which suggests that dexketoprofen trometamol is an effective non-steroidal anti-inflammatory analgesic in postoperative analgesia.

JUSTIFICATIVA Y OBJETIVO: El objetivo de este estudio fue evaluar los efectos de la aplicación intravenosa (IV) del dexketoprofeno trometamol en el bloqueo de los nervios ilioinguinal e Ilio-hipogástrico en la calidad analgésica y en el consumo de morfina después de la histerectomía abdominal total. MÉTODO: Estudio clínico controlado y aleatorio llevado a cabo con 61 pacientes. El estudio se hizo en un quirófano, en la sala de recuperación postanestésica y en el ambulatorio. Los 61 pacientes fueron aleatoriamente divididos en tres grupos: grupo control (Grupo C), grupo bloqueo (Grupo B) y grupo bloqueo con dexketoprofeno (Grupo BD). Antes de la incisión quirúrgica hecha después de la inducción de la anestesia, hicimos el bloqueo de los nervios ilioinguinal e ilio-hipogástrico (Grupo C recibió solución salina y grupos B y BD recibieron levobupivacaína). En contraste con los grupos C y B, el Grupo BD recibió dexketoprofeno. Administramos morfina a todos los pacientes para la analgesia con el uso del método ACP durante el postoperatorio de 24 horas. Registramos las puntuaciones EVA, los índices de satisfacción, el consumo de morfina y los efectos colaterales durante el postoperatorio de 24 horas. RESULTADOS: Los puntuaciones EVA del Grupo BD fueron menores que las de los grupos C y B en el postoperatorio (p < 0,05) en los intervalos de 1, 2, 6 y 12 horas. Las puntuaciones EVA del Grupo C fueron mayores que las del Grupo B en las primeras 2 horas del postoperatorio. El tiempo hasta la primera demanda de ACP fue más largo, los valores de consumo de morfina más bajos y los índices de satisfacción mayores en el Grupo BD que en los otros dos grupos (p < 0,05). CONCLUSIONES: El bloqueo de los nervios ilioinguinal e Ilio-hipogástrico con dexketoprofeno IV, aumenta la satisfacción del paciente y reduce el consumo de opioides, sugiriendo que el dexketoprofeno trometamol es un analgésico antiinflamatorio no esteroide eficaz en analgesia postoperatoria.

The importance of needle echogenity in ultrasound guided axillary brachial plexus block: a randomized controlled clinical study.

OBJECTIVE: In this study we aimed to compare the echogenic needles and the nerve stimulation addition to non-echogenic needles in ultrasound guided axillary brachial plexus block for upper extremity surgery. METHODS: 90 patients were enrolled to the study. The patients were allocated into three groups randomly: Group E (n=30): ultrasound guided axillary block using echogenic needle, Group N (n=30): ultrasound guided axillary block using non-echogenic needle, Group NS (n=30): ultrasound guided axillary block using non-echogenic needle with nerve stimulator assistance. Duration of block procedure, mean arterial pressure, heart rate, pulse-oximetry, onset time of sensory and motor block, duration of sensory and motor block, time to first analgesic use, total need for analgesics, postoperative pain scores, patient and surgeon satisfaction scores were recorded. RESULTS: Duration of block procedure values were lower in group E and NS, sensory and motor block durations, were significantly lower in group N. Sensorial and motor block onset time values were found lower in group NS but higher in group N. Patient and surgeon satisfaction scores were found lower in group N. CONCLUSION: We conclude that ultrasound guided axillary block may be performed successfully using both echogenic needles and nerve stimulation assisted non-echogenic needles.

Effects of adding dexmedetomidine to levobupivacaine in axillary brachial plexus block.

BACKGROUND: Although several studies have described effects of dexmedetomidine on peripheral nerve blocks, to date there is limited knowledge available on the impact of dexmedetomidine adjunct to levobupivacaine in axillary brachial plexus block. OBJECTIVE: In this study, we aimed to investigate the effects of adding dexmedetomidine to levobupivacaine for an axillary brachial plexus block. METHODS: A total of 64 patients of American Society of Anesthesiologists physical status I/II scheduled to undergo forearm and hand surgery, in which an axillary block was used, were enrolled. The patients were randomly divided into 2 groups: in group L patients (n = 32), an axillary block was performed with 39 mL levobupivacaine 5% plus 1 mL of isotonic sodium chloride. In group D patients (n = 32), an axillary block was performed with 39 mL levobupivacaine 5% and 1 mL dexmedetomidine 1 µg/kg(-1) plus isotonic sodium chloride. Demographic data, mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (Spo2), sensory and motor block onset times and block durations, time to first analgesic use, total analgesic need, intraoperative verbal analog scale, postoperative visual analog scale (VAS) data, and side effects were recorded for each patient. RESULTS: There were no significant differences in patient and surgery characteristics between the 2 groups. Sensory block onset time was shorter in group D (P < 0.05). Sensory and motor block duration and time to first analgesic use were significantly longer in group D (P < 0.05), and the total need for analgesics was lower in group D (P < 0.05). Intraoperative 5- and 10-minute verbal analog scale values and postoperative VAS value at 12 hours were significantly lower in group D (P < 0.05). Intraoperative MAP and HR values, except at 5 minutes and postoperatively at 10 and 30 minutes and 1 and 2 hours, were significantly lower in group D (P < 0.01). Bradycardia, hypotension, hypoxemia, nausea, vomiting, and any other side effects were not seen in any patients. CONCLUSIONS: It was concluded in our study that adding dexmedetomidine to axillary brachial plexus block shortens sensory block onset time, increases the sensory and motor block duration and time to first analgesic use, and decreases total analgesic use with no side effects. ClinicalTrials.gov identifier ISRCTN67622282.

Investigation of the cardiac effects of pancuronium, rocuronium, vecuronium, and mivacurium on the isolated rat atrium.

BACKGROUND: Pancuronium, vecuronium, rocuronium, and mivacurium are nondepolarizing neuromuscular blocking agents that affect the cardiovascular system with different potencies. Their cardiovascular effects are clinically significant in the anesthetic management of patients, particularly those undergoing cardiac surgery. OBJECTIVE: We aimed to compare the cardiac effects of these compounds, such as heart rate and developed force, in one species under identical experimental conditions in isolated rat atria. METHODS: The left or right atria of rats were removed and suspended in organ baths. Pancuronium, vecuronium, rocuronium, or mivacurium were added cumulatively (10(-9)-10(-5) M) in the presence and absence of the nonselective ß-blocker propranolol (10(-8) M) and the noradrenaline reuptake inhibitor desipramine (10(-7) M), and heart rate changes were recorded in spontaneously beating right atria. Left atrial preparations were stimulated by electrical field stimulation using a bipolar platinum electrode, and the effects of cumulative concentrations of these nondepolarizing neuromuscular blocking agents on the developed force in the presence and absence of propranolol (10(-8) M) and desipramine (10(-7) M) were recorded. RESULTS: Pancuronium increased heart rate in a dose-dependent manner compared with the control group (P < 0.027). Vecuronium, rocuronium, and mivacurium also increased heart rate in a dose-dependent manner, but the changes were not statistically significant. Although propranolol decreased the pancuronium heart rate effect (P < 0.05), it did not change the heart rate effects with vecuronium, rocuronium, or mivacurium. Desipramine did not change the heart rate effects of vecuronium, rocuronium, mivacurium, or pancuronium. All 4 drugs increased developed force in a dose-dependent manner; the increases were significant at 10(-5) M concentration for pancuronium and at 10(-6) and 10(-5) M concentrations for vecuronium, rocuronium, and mivacurium (P < 0.038). These increases in developed force were abolished with the addition of propranolol. Desipramine did not change the developed force effects of any of the 4 drugs. CONCLUSIONS: The heart rate effect of pancuronium and developed force effects of pancuronium, vecuronium, rocuronium, and mivacurium may occur via direct stimulation of ß receptors. Although our investigation was an in vitro study, the effects found may be important especially under pathologic conditions, such as hypertension, in which patients usually use ß-blocking agents, which cause ß receptor upregulation.

Addition of dexmedetomidine or lornoxicam to prilocaine in intravenous regional anaesthesia for hand or forearm surgery: a randomized controlled study.

BACKGROUND AND OBJECTIVES: Intravenous regional anaesthesia (IVRA) is a simple and cost-effective technique that is ideally suited for surgery involving the distal arm. This study compared the effect of lornoxicam or dexmedetomidine in IVRA with prilocaine in patients who underwent hand or forearm surgery. M ethods: This randomized, double-blind study enrolled 75 patients scheduled for hand or forearm surgery. IVRA was achieved with 2% prilocaine 3 mg/kg in the control group (n=25), 2% prilocaine 3 mg/kg plus dexmedetomidine 0.5 microg/kg in the dexmedetomidine group (n=25), and 2% prilocaine 3 mg/kg plus lornoxicam 8 mg in the lornoxicam group (n=25). In all groups, 0.9% NaCl solution was added to make up a total volume of 40 mL. Sensory and motor block onset and recovery times, haemodynamic variables, visual analogue scale (VAS) pain and sedation scores, duration of analgesia, total analgesic consumption over 24 hours, adverse effects and quality of anaesthesia were recorded. RESULTS: Sensory block onset was shorter and sensory block recovery time longer in the dexmedetomidine group compared with the lornoxicam and control groups (p<0.05). Sensory and motor block recovery times and duration of analgesia for tourniquet were prolonged in the dexmedetomidine and lornoxicam groups compared with the control group (p<0.05). Median VAS scores for tourniquet pain in the dexmedetomidine and lornoxicam groups were lower than that of the control group at 15 and 30 minutes (p<0.05). Postoperatively, the duration of analgesia time was longer and median VAS scores were lower during the first 12 hours in the dexmedetomidine and lornoxicam groups compared with the control group (p<0.05). Total analgesic consumption over 24 hours was lower in the dexmedetomidine and lornoxicam groups compared with the control group (p<0.05). Anaesthesia quality as determined by the anaesthesiologist was better in the dexmedetomidine and lornoxicam group than in the control group (p<0.05). CONCLUSIONS: Addition of dexmedetomidine or lornoxicam to prilocaine in IVRA decreased VAS pain scores, improved anaesthesia quality and decreased analgesic requirement. We suggest that addition of dexmedetomidine or lornoxicam at the doses used in this study to IVRA with prilocaine in this setting can be useful without causing adverse effects. No hypotension, bradycardia or hypoxia requiring treatment was seen in any of the patients. Addition of dexmedetomidine had a more potent effect, shortening sensory block onset time and prolonging sensory block recovery time more than lornoxicam.

Controlled hypotension with desflurane combined with esmolol or dexmedetomidine during tympanoplasty in adults: A double-blind, randomized, controlled trial.

BACKGROUND: Controlled hypotension is a technique that is used to limit intraoperative blood loss to provide the best possible surgical field during surgery. OBJECTIVE: The aim of this double-blind, randomized, controlled study was to compare the effects of desflurane combined with esmolol or dexmedetomidine on the amount of blood in the surgical field, recovery time, and tolerability in adult patients undergoing tympanoplasty. METHODS: Turkish patients aged 18 to 60 years, classified as American Society of Anesthesiologists physical status I or II, who were scheduled for tympanoplasty were randomly divided into 2 groups: the esmolol group or the dexmedetomidine group. After the anesthesia induction in the esmolol group, a loading dose of esmolol was infused intravenously over 1 minute at 1 mg/kg, followed by a maintenance rate of 0.4 to 0.8 mg/ kg/h. In the dexmedetomidine group, a loading dose of dexmedetomidine was infused intravenously over 10 minutes at a rate of 1 µg/kg, followed by a maintenance rate of 0.4 to 0.8 µg/kg/h. The infusion rates were then titrated to maintain mean arterial pressure (MAP) of 65 to 75 mm Hg. General anesthesia was maintained with desflurane 4% to 6%. Heart rate (HR) and MAP were recorded during anesthesia. The following 6-point scale was used to assess the amount of bleeding in the operative field: 0 = no bleeding, a virtually bloodless field; 1 = bleeding that was so mild that it was not a surgical nuisance; 2 = moderate bleeding that was a nuisance but did not interfere with accurate dissection; 3 = moderate bleeding that moderately compromised surgical dissection; 4 = bleeding that was heavy but controllable and that significantly interfered with surgical dissection; and 5 = massive bleeding that was uncontrollable and made dissection impossible. Scores ≤2 were considered to be optimal surgical conditions. The sedation score was determined at 15, 30, and 60 minutes after tracheal extubation using the following scale: 1 = anxious, agitated, or restless; 2 = cooperative, oriented, and tranquil; 3 = responsive to commands; 4 = asleep, but with brisk response to light, glabellar tap, or loud auditory stimulus; 5 = asleep, sluggish response to glabellar tap or auditory stimulus; and 6 = asleep, no response. Time to extubation and to total recovery from anesthesia (Aldrete score ≥9 on a scale of 0-10), adverse effects (eg, intraoperative hypotension [blood pressure <65 mm Hg], bradycardia [HR <50 beats/min]), intraoperative fentanyl consumption, and postoperative nausea and vomiting were recorded. Arterial blood gas analysis and kidney and liver function tests were conducted. All patients were evaluated by the same attending surgeon and anesthesiologist, both of whom were blinded to the administered study drugs. RESULTS: Fifty-two consecutive white patients undergoing tympanoplasty were identified. Two patients had to be excluded because of hypertension and 2 refused to participate. Forty-eight patients were equally randomized to either the esmolol group (n = 24 [16 women, 8 men]; mean [SD] age, 38.4 [10.5] years) or the dexmedetomi-dine group (n = 24 [17 women, 7 men]; mean age, 35.5 [14.7] years). Sedation scores were not collected for 1 patient in the esmolol group; therefore, analysis was conducted for 23 patients. The median (range) of the scores for the amount of blood in the surgical field in the esmolol and dexmedetomidine groups was 1 (0-3) and 1 (0-2), respectively (P = NS). Mean intraoperative fentanyl consumption in the esmolol group was significantly higher than in the dexmedetomidine group (50.0 [3.0] vs 25.0 [2.5] µg/min; P = 0.002). In the esmolol group, the mean times to extubation and to recovery from anesthesia were significantly shorter than those of the dexmedetomidine group (7.0 [1.4] vs 9.1 [1.9] minutes, respectively; 5.9 [2.1] vs 7.9 [2.3] minutes; both, P = 0.001). The mean sedation scores were significantly lower in the esmolol group (n = 23, because of intent-to-treat analysis) compared with the dexmedetomidine group at 15 minutes (2.5 [0.6] vs 3.6 [0.5]; P = 0.001) and 30 minutes (2.6 [0.6] vs 3.3 [0.6]; P = 0.001) postoperatively. No significant differences were found between the study groups in regard to blood urea nitrogen or creatinine concentration, aspartate aminotransferase or alanine aminotransferase activities, pH, partial pressure of carbon dioxide, or bicarbonate, before or after the operation. CONCLUSIONS: Both esmolol and dexmedetomidine, combined with desflurane, provided an effective and well-tolerated method of achieving controlled hypotension to limit the amount of blood in the surgical field in these adult patients undergoing tympanoplasty. Esmolol was associated with significantly shorter extubation and recovery times and significantly less postoperative sedation compared with dexmedetomidine.

The effects of different doses of remifentanil on intraocular pressure after tracheal intubation: a randomized, double-blind and prospective study.

We investigated the effects of alfentanil and different doses of remifentanil on intraocular pressure (IOP) and hemodynamic responses during laryngoscopy and endotracheal intubation in 60 patients. IOP values decreased significantly from 30 seconds before the intubation to 5 minutes after intubation measurements compared to baseline values in all the groups. However, a significant increase in IOP was recorded in the 0.5-microg remifentanil group after tracheal intubation.

Effects of intravenous anesthetics on the human radial artery used as a coronary artery bypass graft.

OBJECTIVE: Intravenous anesthetics are often used for anesthesia, sedation, and analgesia in the intraoperative and postoperative periods of coronary artery bypass graft (CABG) surgery. This study was designed to investigate the direct effects of intravenous anesthetics on the human radial artery (RA). DESIGN: In vitro, prospective with repeated measures. SETTING: University research laboratory. PARTICIPANTS: RA segments (n = 20) were obtained from CABG surgery patients and were divided into 3- to 4-mm vascular rings. INTERVENTIONS: Using the organ bath technique, the endothelium-independent vasodilatation function was tested in vitro by the addition of cumulative concentrations of thiopental, ketamine, etomidate, and propofol after vasocontraction by phenylephrine in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin. MEASUREMENTS AND MAIN RESULTS: Thiopental (10(-8) to 10(-4) mol/L), ketamine(10(-8) to 10(-4) mol/L), propofol (10(-8) to 3 x 10(-4) mol/L), and etomidate (10(-8) to 3 x 10(-4) mol/L) caused concentration-dependent vasorelaxation in human RA rings precontracted with phenylephrine in the presence of L-NAME and indomethacin (n = 20, for each drug). The pEC(50) and maximum relaxant effect values of thiopental and ketamine were significantly higher than for etomidate and propofol (p < 0.05). CONCLUSIONS: These findings indicate that thiopental, ketamine, etomidate, and propofol produce concentration-dependent relaxation on RA rings from humans. Thiopental and ketamine are more potent relaxant agents than etomidate and propofol. Intravenous anesthetics may be effective as alternative vasodilators for treatment of intraoperative and postoperative spasm of coronary artery grafts.

Efficacy of preventive analgesia with tramadol or lornoxicam for percutaneous nephrolithotomy: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: Prevention of postoperative pain provides better and more rapid convalescence for patients. OBJECTIVE: The aim of this study was to compare the preventive analgesic effect of tramadol and lornoxicam in the early postoperative period in patients undergoing percutaneous nephrolithotomy (PCNL). METHODS: Patients who were scheduled for elective PCNL at the Cumhuriyet University Hospital, Sivas, Turkey, were enrolled in this prospective, double-blind, placebo-controlled study. The patients were randomly assigned to 1 of 3 groups: tramadol, lornoxicam, and normal saline (NS). Ten minutes before induction of anesthesia, the tramadol group received tramadol 100 mg IV, the lornoxicam group received lornoxicam 8 mg IV, and the NS group received NS 2 mL IV. Anesthesia was induced using fentanyl 1 µg/kg and thiopental sodium 4 to 7 mg/kg. Vecuronium 0.1 mg/kg was used for muscle relaxation. Desflurane 4% to 6% and 50%:50% oxygen/nitrous oxide were used for maintenance. Oxygen saturation, heart rate, and mean blood pressure were recorded before induction and during the postoperative period. During the postoperative period, visual analogue scale O/AS) scores, time to first analgesic (TFA), total analgesic consumption (TAC), and patient satisfaction scores were determined. Data about postoperative nausea and vomiting and other adverse events and complications were also collected. RESULTS: Seventy-three patients were assessed for enrollment and 60 (33 women, 27 men; mean [SD] age, 44.69 [11.27] years; age range, 20-62 years) were included in the study. The baseline demographic characteristics and duration of surgery were similar in all 3 groups. The mean (SD) VAS scores in the tramadol group were significantly lower than in the NS group at 15 and 30 minutes and 1, 2, 4, and 12 hours after surgery (all, P < 0.05). The VAS scores in the lornoxicam group were significantly lower than in the NS group at 15 and 30 minutes and 1 hour (all, P < 0.05). The VAS score at 1 hour after surgery was significantly lower in the tramadol group than in the lornoxicam group (18 [8] vs 32 [16]; P < 0.05); however, there were no other significant differences in VAS scores between the active groups. A significantly shorter TFA was associated with the NS group when compared with the tramadol and lornoxicam groups (46 [27] vs 354 [187] and 180 [118], respectively; both, P < 0.05). TFA was significantly shorter in the lornoxicam group when compared with the tramadol roup (180 [118] vs 354 [187]; P < 0.05). TAC was significantly higher in the NS group than in the tramadol and lornoxicam groups (270 [47] vs 115 [74] and 145 [72], respectively; both, P < 0.05). Patient satisfaction score (range) was significantly lower in the NS group when compared with the tramadol and lornoxicam groups (0 [0-1] vs 3 [0-3] and 2 [0-3], respectively; both, P < 0.05). There were no other significant between-group differences observed. CONCLUSIONS: Tramadol and lornoxicam were more effective than NS in preventing early postoperative pain. The preventive analgesic effect of tramadol was comparable with that of lornoxicam, except at 1 hour when tramadol was more effective among these patients undergoing PCNL. Both drugs were well tolerated.

Closure or nonclosure of the peritoneum at gynecological operations. Effect on postoperative pain.

OBJECTIVE: To compare the analgesic requirement and pain scores in the postoperative period between closure and nonclosure of the peritoneum in women undergoing gynecological abdominal surgery. METHODS: We conducted this study as a 2 parallel grouped, double blind, randomized, controlled trial between February 2002 and March 2003. The current study consists of 79 eligible women who were enrolled and completed baseline assessments. We carried out this study at the Cumhuriyet University Hospital, Sivas, Turkey. RESULTS: When the age, gravidity, parity, body mass index, type of surgery, operative time and length of hospital stay were compared, between the 2 groups, no statistically significant difference was found (p>0.05). The postoperative pain was found higher in the closure group than the nonclosure group (p<0.05) when the pain with visual analogue scale (VAS) scores compared. CONCLUSION: There was no significant difference in analgesic requirements between the 2 groups in the postoperative period. However, less pain and low VAS scores were evident especially after postoperative 2nd and 48th hours in the nonclosure group. We recommend non-closure of peritoneum at abdominal gynecologic procedure as the method of choice.

A functioning-desensitization paraganglioma which caused hemodynamic instability during tumoral resection: report of a case.

Paragangliomas are uncommon tumors arising from the neuroendocrine elements of the paraganglia. Their successful management is associated with many problems. We herein present the findings of a 22-year-old man in whom a paraganglioma was incidentally found and in which the clinical and previous operative behavior was functioning desensitization. As a result, preoperative medication was not performed; however, during the tumor resection the patient demonstrated hemodynamic instability.

Altered contractile responsiveness in ileal longitudinal muscle after total gastrectomy in a rat model.

PURPOSE: To test the hypothesis that the changes in ileal smooth muscle contractility accompanying postgastrectomy syndromes are agonist-specific, we investigated the effects of potassium chloride (KCl), carbachol, substance P (SP), and serotonin on ileal smooth muscle contractility after total gastrectomy in rats. METHODS: We performed total gastrectomy in ten rats and a sham operation in another ten rats as a control. All of the rats were killed and their ileums excised 4 weeks postoperatively. The concentration-response relationships for KCl, SP, and serotonin were obtained by adding each agent cumulatively to the organ bath. Morphological changes in the ileum were also examined by light microscopy. RESULTS: There was no significant difference between the responsiveness of gastrectomized and control tissues to KCl. Maximum responses (E(max)) to carbachol and SP were less in the gastrectomized ileal segments than in the control ileal segments. E(max) to serotonin was higher in the gastrectomized ileal segments than in the control ileal segments. The pD(2)value, i.e., the negative logarithm of the concentration for the half-maximal response, EC(50), for carbachol, SP, and serotonin was unchanged in the gastroctomized ileal segments and the control segments. Total gastrectomy also caused morphological changes in the ileum. CONCLUSIONS: These data indicate that the contractile response to various agents is altered after total gastrectomy and that receptor-mediated mechanisms may cause these changes.

Investigation of the mechanism of nicotine-induced relaxation on the sheep sphincter of Oddi.

Possible mechanisms for nicotine-induced relaxation were investigated in the isolated sheep's sphincter of Oddi. Sheep's sphincter of Oddi rings were mounted in tissue bath with modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. Tension was measured with isometric force transducers, and muscle relaxation was expressed as percent decrease of precontraction induced by carbachol. Nicotine (1 x 10(-5) to 3 x 10(-3) mol/L) produced concentration-dependent relaxation on sphincter of Oddi precontracted by carbachol (10(-6) mol/L). Nicotine-induced relaxation was 72.8 +/- 4.2% of precontraction with carbachol (10(-6) mol/L) (mean pD2 value, 3.76 +/- 0.05 mol/L). Nicotine-induced relaxation was not affected by N(w)-nitro L-arginine methyl ester (L-NAME) (3 x 10(-5) mol/L), methylene blue (10(-5) mol/L), indomethacin (10(-5) mol/L), hexamethonium (10(-5) mol/L), glibenclamide (10(-5) mol/L), 4-aminopyridine (10(-3) mol/L), tetraethylammonium (3 x 10(-4) mol/L), clotrimazole (10(-6) mol/L), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) (10(-6) mol/L), and anthracene-9-carboxylate (9-AC) (10(-6) mol/L), but potentiated by bupivacain (10(-5) mol/L). A calcium-antagonizing effect of nicotine was not observed. The results suggest that nicotine-induced relaxation of the sheep's sphincter of Oddi is not mediated by the release of prostaglandins, nitric oxide (NO), or a related substance; by the activation of potassium channels or chloride channels; or by the stimulation of nicotinic cholinoceptors. Potentiation of the nicotine-induced relaxation by bupivacain indicates that blockade of sodium channels may play a role in this relaxation.

The role of K(+) channels on the inhibitor effect of sevoflurane in pregnant rat myometrium.

UNLABELLED: Volatile anesthetics and K(+) channel openers inhibit spontaneous contractions in myometrial smooth muscle. Volatile anesthetics modulate K(+) channel activity. We investigated the role of two K(+) channel blockers on the effect of sevoflurane in pregnant rat myometrium. Term pregnant rat uteri were excised, and cross-sectional myometrial strips were mounted for isometric force recording. Sevoflurane inhibited the amplitude and frequency of spontaneous myometrial contractions in a concentration-dependent manner. The maximal inhibition measured in amplitude and frequency of spontaneous myometrial contractions with sevoflurane (at 3 minimum alveolar anesthetic concentration) was 44.32% and 33.32% of control contractions, respectively. Tetraethylammonium (TEA) and glibenclamide, K(+) channel blockers, increased spontaneous myometrial contractions in a concentration-dependent manner. Sevoflurane responses were repeated at concentrations with no effect on spontaneous contractility of TEA, a Ca(2+)-activated K(+) channel blocker, and glibenclamide, an adenosine triphosphate-sensitive K(+) channel blocker, in myometrial strips. TEA (3.10(-4) M) caused a significant reduction in sevoflurane-induced inhibitor responses, but glibenclamide (10(-6) M) did not. Sevoflurane-induced maximal inhibition (at 3 minimum alveolar anesthetic concentration) on amplitude and frequency of spontaneous myometrial contractions in the presence of TEA (3.10(-4) M) was 31.85% and 22.33% of control contractions, respectively (P < 0.05). These results suggest that the in vitroapplication of sevoflurane inhibited the amplitude and frequency of spontaneous myometrial contractions in pregnant rats in a concentration-dependent manner. Such inhibition was reduced by TEA. The inhibition of myometrial smooth muscle induced by sevoflurane seems to be mediated, at least in part, via activation of Ca(2+)-activated K(+) channels, because inhibition was reduced by TEA. IMPLICATIONS: In this study, we found that sevoflurane causes significantly decreased myometrial contractile activity in pregnant rats. The inhibition of myometrial smooth muscle induced by sevoflurane seems to be mediated, at least in part, via activation of Ca(2+)-activated K(+) channels, because inhibition was reduced by tetraethylammonium.