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.

Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats.

Ghrelin, a peptide hormone released from the gastric endocrine glands, shows analgesic activity apart from its various physiological effects. Nevertheless, the effects of ghrelin receptor (GHS-R) agonists on morphine analgesia and tolerance have not yet been elucidated. The purpose of this study was to evaluate the effects of the ghrelin receptor agonist hexarelin and antagonist [d-Lys3]-GHRP-6 on morphine antinociception and tolerance in rats. A total of 104 Wistar albino male adult rats (weighing approximately 220-240 g) were used in the experiments. To induce morphine tolerance, a three-day cumulative dose regimen was used in the rats. Then, randomly selected rats were evaluated for morphine tolerance on day 4. The analgesic effects of hexarelin (0.2 mg·kg-1), [d-Lys3]-GHRP-6 (10 mg·kg-1), and morphine (5 mg·kg-1) were measured at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. The findings suggest that hexarelin in combination with morphine attenuates analgesic tolerance to morphine. On the other hand, ghrelin receptor antagonist [d-Lys3]-GHRP-6 has no significant analgesic activity on the morphine tolerance in analgesia tests. Furthermore, co-administration of hexarelin and morphine increases the analgesic effect. In conclusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.

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.

The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats.

The role of the cannabinoid (CB) system in the tolerance to analgesic effect of opioid remains obscure. The aim of the present study was to evaluate the effects of the endocannabinoid nonselective receptor agonist anandamide (AEA) and CB1 receptor antagonist rimonabant (SR141716) on morphine analgesia and tolerance in rats. Male Wistar albino rats weighing 215-230 g were used in these experiments. To constitute morphine analgesic tolerance, a 3-day cumulative dosing regimen was used. The analgesic effects of AEA (10 mg/kg), SR141716 (10 mg/kg), and morphine (5 mg/kg) were considered at 30-min intervals by tail flick (TF) and hot plate (HP) analgesia tests. The analgesic effects of the drugs were measured as TF and HP latencies in all groups for each rat and converted to %MPE. The data were analysed by analysis of variance followed by Tukey test. The findings suggested that AEA in combination with morphine produced a significant increase in expression of analgesic tolerance to morphine. Conversely, cannabinoid receptor antagonist SR141716 attenuated morphine analgesic tolerance. In addition, administration of AEA with morphine increased morphine analgesia. In conclusion, we observed that the cannabinoid receptor agonist anandamide and CB1 receptor antagonist SR141716 plays a significant role in the opioid analgesia and tolerance.

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.

Comparison of the effects of desflurane and sevoflurane on middle ear pressure: a randomized controlled clinical trial.

OBJECTIVE: The aim of the present study was to compare the effects of two inhalation anesthetics, desflurane and sevoflurane, on middle ear pressure. METHODS: After we obtained written consent from the patients and the approval from our institutional ethical committee, we included 56 ASA I-II patients aged between 18 and 60 years in this study. They were randomly divided into two groups of 28 patients each. Desflurane 4-6% (Group D) or sevoflurane 1-2% (Group S) were used for anesthesia management in patients. Baseline tympanometry was carried out and recorded before the induction of anesthesia on both ears, and 3 more measurements were done and recorded 5, 15 and 30 min after induction. RESULTS: In both groups, middle ear pressure values were found to be significantly elevated when compared to baseline measurements (p < 0.05). When middle ear pressure was compared between the groups, no difference was found between the values obtained at baseline and at 5 min in Group S, while especially the values obtained at 15 min revealed significantly higher middle ear pressures in Group D. CONCLUSION: It was observed that the increase in middle ear pressure caused by sevoflurane was significantly lower than that caused by desflurane.

Ineffective doses of dexmedetomidine potentiates the antinociception induced by morphine and fentanyl in acute pain model.

The aim of this study was to evaluate the synergistic potentiation effect of ineffective doses of dexmedetomidine on antinociception induced by morphine and fentanyl in acute pain model in rats. Seventy albino Wistar rats were separated into 7 groups. Data for the control and sham groups were recorded. The ineffective dose of dexmedetomidine was investigated and found to be 3 µ g/kg. Each group was administered the following medications: 3 mg/kg morphine (intraperitoneal) to Group 3, 5 µg/kg fentanyl (intraperitoneal) to Group 4, dexmedetomidine 3 µ g/kg (subcutaneously) to Group 5, dexmedetomidine 3 µg/kg (subcutaneous)+3 mg/kg morphine (intraperitoneal) to Group 6 and finally 3 µg/kg dexmedetomidine (subcutaneous)+5 µg/kg fentanyl (intraperitoneal) to Group 7. Just before the application and 15, 30, 60, 90 and 120 min after the administration of medication, two measurements of tail flick (TF) and hot plate (HP) tests were performed. The averages of the measurements were recorded. TF and HP latencies were the main outcomes. The analgesic effect of the combinations with dexmedetomidine+morphine (Group 6) and dexmedetomidine+fentanyl (Group 7), compared to the analgesic effect of morphine alone and fentanyl alone was significantly higher at 15, 30, 60 and 90 minutes after administration. In this study, dexmedetomidine in ineffective doses, when combined with morphine and fentanyl, potentiates the effects of both morphine and fentanyl.

The investigation of host genetic variants of toll-like receptor 7 and 8 in COVID-19.

Toll-like receptors (TLRs) recognize infectious agents and play an important role in the innate immune system. Studies have suggested that TLR single nucleotide polymorphisms (SNPs) are associated with poor antiviral responses against SARS-CoV-2. Therefore, we aimed to investigate the relationship of TLR7 and TLR8 (SNPs) with COVID-19 disease prognosis. A total of 120 COVID-19 patients, 40 outpatients, 40 clinical ward patients and 40 intensive care unit (ICU) patients were included in the study. TLR7 (rs179009), TLR8-129 C/G (rs3764879) and TLR8 Met1Val (rs3764880) SNPs were genotyped using the PCR-RFLP method. In female patients, individuals carrying AG genotype and G allele for TLR8 Met1Val SNP were found at a higher frequency in patients hospitalized in the ICU than in patients followed in the clinical ward (p < 0.05). In terms of the other two SNPs, no significant difference was found between the groups in females. Furthermore, in male patients, A allele of TLR7 rs179009 SNP was at a higher frequency in patients who have at least one comorbidity than in patients who have no comorbidity (p < 0.05). Our results suggest that TLR8 Met1Val SNP is important in the COVID-19 disease severity in females. Furthermore, TLR7 rs179009 SNP is important in male patients in the presence of comorbid diseases.

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.

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 nitric oxide-cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine.

Although the phenomenon of opioid tolerance has been widely investigated, neither opioid nor nonopioid mechanisms are completely understood. The aim of the present study was to investigate the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in the development of morphine-induced analgesia tolerance. The study was carried out on male Wistar albino rats (weighing 180-210 g; n = 126). To develop morphine tolerance, animals were given morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), BAY 41-2272, S-nitroso-N-acetylpenicillamine (SNAP), N(G)-nitro-L-arginine methyl ester (L-NAME), and morphine were considered at 15 or 30 min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests (n = 6 in each study group). The results showed that YC-1 and BAY 41-2272, a NO-independent activator of soluble guanylate cyclase (sGC), significantly increased the development and expression of morphine tolerance, and L-NAME, a NO synthase (NOS) inhibitor, significantly decreased the development of morphine tolerance. In conclusion, these data demonstrate that the nitric oxide-cGMP signal pathway plays a pivotal role in developing tolerance to the analgesic effect of morphine.

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.

The effects of hyperventilation on seizure length and cerebral oxygenation during electroconvulsive therapy.

OBJECTIVE: Previous studies have reported that hyperventilation prolongs seizure length. However, there is no clear consensus in clinical guidelines on how to perform hyperventilation during Electroconvulsive Therapy (ECT). The present study aims to investigate the effects of hyperventilation on seizure length and cerebral oxygenation. METHODS: Forty patients aged 18-65 and classified as ASA I-II, who would have their first ECT course were included in the study. Ethics committee approval was obtained and all patients' consent was taken. The consecutive patients were randomized into two groups as follows: group H (20 patients; target etCO2: 25-30 mmHg) and group N (20 patients; target etCO2 35-40 mmHg). All patients were ventilated with a facial mask for two minutes and later were ventilated by a laryngeal mask (LMA) for one minute. Vital signs, peripheric oxygen saturation (SpO2), and regional oxygen saturation (rSO2) were measured before general anesthesia induction, on the 3rd minute of ventilation with an LMA (LMA3), on the 1st minute postictal (PI1), on the 5th (PI5), and 10th (PI10) minutes. The motor seizure duration, Richmond sedation-agitation scale, and the time needed to reach Aldrete Score 9 were also recorded. RESULTS: There was a significant difference between the groups when they were compared concerning seizure length and recovery time. However, when we compared the rSO2 values that were measured at different times in group H, the difference between the measurements was statistically significant. When rSO2 values in group H were compared in doubles, there were significant differences between measurements between the basal and LMA3, basal and PI1, and the basal and PI5. When Richmond agitation scores in both groups are compared, there were no significant differences between the groups. CONCLUSION: This study found that seizure length was longer, and the recovery time was shorter in group H. There was a contribution of hyperventilation on cerebral oxygenation that was measured on the same person at different times, but cerebral oxygenation was not statistically different from patients that were normoventilated. More studies are required to form a consensus regarding how hyperventilation applies to ECT.

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.

The effects of intravenous ephedrine during spinal anesthesia for cesarean delivery: a randomized controlled trial.

We designed a randomized, double-blinded study to determine the efficacy and safety of 0.5 mg/kg intravenous ephedrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Patients were randomly allocated into two groups: ephedrine group (n=21) and control group (n=21). Intravenous preload of 15 mL/kg lactated Ringer's solution was given. Shortly after the spinal injection, ephedrine 0.5 mg/kg or saline was injected intravenous for 60 sec. The mean of highest and lowest heart rate in the ephedrine group was higher than those of control group (P<0.05). There were significant lower incidences of hypotension and nausea and vomiting in the ephedrine group compared with the control group (8 [38.1%] vs. 18 [85.7%]); (4 [19%] vs. 12 [57.1%], respectively) (P<0.05). The first rescue ephedrine time in the ephedrine group was significantly longer (14.9+/-7.1 min vs. 7.9+/-5.4 min) than that of the control group (P<0.05). Neonatal outcome were similar between the study groups. These findings suggest, the prophylactic bolus dose of 0.5 mg/kg intravenous ephedrine given at the time of intrathecal block after a crystalloid fluid preload, plus rescue boluses reduce the incidence of hypotension.

Investigation of the relaxant effects of pancuronium, rocuronium, vecuronium and mivacurium on rat thoracic aorta.

BACKGROUND AND OBJECTIVE: Pancuronium, vecuronium, mivacurium and rocuronium are nondepolarizing neuromuscular blocking agents, which are competitive antagonists against acetylcholine at nicotinic receptors, and considered to have no direct actions on vascular smooth muscle. We aimed to investigate the relaxant effects and possible underlying mechanisms of these agents on isolated rat thoracic aorta. METHODS: The preparations were precontracted with prostaglandin F2alpha (10(-7) mol l(-1)) and pancuronium (10(-7)-10(-4) mol l(-1)), rocuronium (10(-7)-10(-4) mol l(-1)), vecuronium (10(-7)-10(-4) mol l(-1)) and mivacurium (10(-7)-10(-4) mol l(-1)) added at cumulative concentrations in the presence or absence of a prostaglandin synthesis inhibitor, indomethacin (10(-6) M), and a nitric oxide synthesis inhibitor, N(omega)-nitro-L-arginine methylester (3 x 10(-5)). The same protocol was applied to both endothelia (+) and endothelia (-) aortic rings. The preparations precontracted with prostaglandin F2alpha (10(-7) mol l(-1)) were stimulated with electrical field stimulation at a frequency of 10 Hz as square-wave pulses of 50 V (0.2 ms) in the presence of a noradrenaline reuptake inhibitor desipramine (10(-7) mol l(-1)) and a nonselective beta-blocker propranolol (10(-6) mol l(-1)). Drugs were added at ineffective concentration of 10(-7) mol l(-1). Tetrodotoxin (10(-7) mol l(-1)) was added to test whether the changes were dependent on the neuronal response. RESULTS: Pancuronium and rocuronium relaxed aortic rings precontracted by prostaglandin F2alpha in a dose-dependent manner, but vecuronium and mivacurium did not. The relaxation effect of pancuronium and rocuronium was endothelium independent because there was not a significant response difference from the endothelium-denuded group. CONCLUSION: In conclusion, their relaxation effect may be due to an increase in prostaglandin synthesis. The increased relaxation effect of these agents at electrical field stimulation may be by the decreasing effect of noradrenaline reuptake from nerve endings because a noradrenaline reuptake inhibitor desipramine did not change this effect. Also, these neuromuscular agents may affect beta-receptors, because a nonselective beta-blocker agent, propranolol, decreased their electrical field stimulation-induced relaxations.

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.

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.

A comparison of sedation with dexmedetomidine or propofol during shockwave lithotripsy: a randomized controlled trial.

BACKGROUND: Dexmedetomidine, because it has both sedative and analgesic properties, may be suitable for conscious sedation during painful procedures. Extracorporeal shockwave lithotripsy (ESWL) is a minimal to mildly painful procedure that requires conscious sedation. We thus evaluated the utility of dexmedetomidine compared with propofol during an ESWL procedure. METHODS: Forty-six patients were randomly allocated into two groups to receive either dexmedetomidine or propofol for elective ESWL. Dexmedetomidine was infused at 6 microg x kg(-1) x h(-1) for 10 min followed by an infusion rate of 0.2 microg x kg(-1) x h(-1). Propofol was infused at 6 mg x kg(-1) x h(-1) for 10 min followed by an infusion of 2.4 mg x kg(-1) x h(-1). Fentanyl 1 microg/kg IV was given to all patients 10 min before ESWL. Pain intensity was evaluated with a visual analog scale at 5-min intervals during ESWL (10-35 min). Sedation was determined using the Observer's Assessment of Alertness/Sedation. The Observer's Assessment of Alertness/ Sedation scores and hemodynamic and respiratory variables were recorded regularly during ESWL (35 min) and up to 85 min after. RESULTS: Forty patients were evaluated. Visual analog scale values with dexmedetomidine were significantly lower than those with propofol only at the 25-35 min assessments (P < 0.05). During sedation, the respiratory rate with dexmedetomidine was significantly slower but Spo2 was significantly higher than with propofol (P < 0.05). Other clinical variables were similar (P > 0.05). CONCLUSION: A combination of dexmedetomidine with fentanyl can be used safely and effectively for sedation and analgesia during ESWL.