Ultra-low dose (+)-naloxone restores the thermal threshold of morphine tolerant rats.

BACKGROUND/PURPOSE: As known, long-term morphine infusion leads to tolerance. We previously demonstrated that both co-infusion and post-administration of ultra-low dose (±)-naloxone restores the antinociceptive effect of morphine in morphine-tolerant rats. However, whether the mechanism of the action of ultra-low dose (±)-naloxone is through opioid receptors or not. Therefore, in the present study, we further investigated the effect of ultra-low dose (+)-naloxone, it does not bind to opioid receptors, on the antinociceptive effect of morphine. METHODS: Male Wistar rats were implanted with one or two intrathecal (i.t.) catheters; one catheter was connected to a mini-osmotic pump, used for morphine (15 µg/h), ultra-low dose (+)-naloxone (15 pg/h), morphine plus ultra-low dose (+)-naloxone (15 pg/h) or saline (1 µl/h) infusion for 5 days. On day 5, either ultra-low dose (+)-naloxone (15 pg) or saline (5 µl) was injected via the other catheter immediately after discontinued morphine or saline infusion. Three hours later, morphine (15 µg in 5 µl saline) or saline were given intrathecally. All rats received nociceptive tail-flick test every 30 minutes for 120 minutes after morphine challenge at different temperature (45-52°C, respective). RESULTS: Our results showed that, both co-infusion and post-treatment of ultra-low dose (+)-naloxone with morphine preserves the antinociceptive effect of morphine. Moreover, in the post administration rats, ultra-low dose (+)-naloxone further enhances the antinociceptive effect of morphine. CONCLUSION: This study provides an evidence for ultra-low dose (+)-naloxone as a therapeutic adjuvant for patients who need long-term opioid administration for pain management.

Intrathecal ultra-low dose naloxone enhances the antihyperalgesic effects of morphine and attenuates tumor necrosis factor-α and tumor necrosis factor-α receptor 1 expression in the dorsal horn of rats with partial sciatic nerve transection.

BACKGROUND: Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. We designed this investigation to examine whether ultra-low dose naloxone administered alone or in combination with morphine could alter the concentration of the excitatory amino acids (EAAs) glutamate and aspartate, as well as the expression of tumor necrosis factor-α (TNF-α) and its receptors (TNFR1 and TNFR2) in the spinal cord dorsal horn of rats with partial sciatic nerve transection (PST). METHODS: Male Wistar rats underwent intrathecal catheter implantation for drug delivery and were divided in 7 groups: sham-operated + saline (sham), PST + saline (S), PST + 15 ng naloxone (n), PST + 15 µg naloxone (N), PST + 10 µg morphine (M), PST + 15 ng naloxone + 10 µg morphine (Mn), PST + 15 µg naloxone + 10 µg morphine (MN). Thermal withdrawal latency and mechanical withdrawal threshold, TNF-α and TNFR expression in the spinal cord and dorsal root ganglia, and EAAs glutamate and aspartate concentration in cerebrospinal fluid dialysates were measured. RESULTS: Ten days after PST, rats developed hyperalgesia (P < 0.0001) and allodynia (P < 0.0001), and increased TNF-α (P < 0.0001) and TNFR1 expression (P = 0.0009) were measured in the ipsilateral spinal cord dorsal horn. The antihyperalgesic and antiallodynic effects of morphine (10 µg) were abolished by high-dose naloxone (15 µg; P = 0.0031) but enhanced by ultra-low dose naloxone (15 ng; P = 0.0015), and this was associated with a reduction of TNF-α (P < 0.0001) and TNFR1 (P = 0.0009) expression in the spinal cord dorsal horn and EAAs concentration (glutamate: P = 0.0001; aspartate: P = 0.004) in cerebrospinal fluid dialysate. Analysis of variance (ANOVA) or Student t test with Bonferroni correction were used for statistical analysis. CONCLUSIONS: Ultra-low dose naloxone enhances the antihyperalgesia and antiallodynia effects of morphine in PST rats, possibly by reducing TNF-α and TNFR1 expression, and EAAs concentrations in the spinal dorsal horn. Ultra-low dose naloxone may be a useful adjuvant for increasing the analgesic effect of morphine in neuropathic pain conditions.

Attenuation of neurological injury with early baicalein treatment following subarachnoid hemorrhage in rats.

OBJECT: Baicalein has been shown to offer neuroprotection in the ischemic brain, but its effect in subarachnoid hemorrhage (SAH) is unknown. The authors used a double-hemorrhage model to study the role of early baicalein treatment in SAH. METHODS: Subarachnoid hemorrhage was induced in male Wistar rats through a repeat injection of autologous blood at a 48-hour interval. Rats subjected or not subjected to SAH received a 30-mg/kg baicalein injection 3 hours after SAH and daily for 6 consecutive days, and results were compared with those obtained in vehicle-treated control rats. Mortality of the rats was recorded. Neurological outcome was assessed daily. Cerebrospinal fluid dialysates were collected and examined for glutamate concentrations. Cerebral vasospasm (CVS), brain water content, neuron variability, expression of glutamate transporter-1 (GLT-1), immunoreactivity of astrocyte, and level of malondialdehyde, activities of superoxide dismutase (SOD), and catalase in brain tissues content were determined on post-SAH Day 7. RESULTS: Mortality rate, neuronal degeneration, brain water content, and CVS were decreased and neurological function improved in the baicalein-treated rats. Baicalein increased astrocyte activity and preserved GLT-1, which attenuated the glutamate surge after SAH. Baicalein also provided antioxidative stress by preserving activities of SOD and catalase and decreased malondialdehydelevel after SAH. The glutamate, body weight, neurological scores, and glial fibrillary acidic protein activity were significantly correlated. The CVS was correlated with neuronal degeneration, and GLT-1 was correlated with oxidative stress. CONCLUSIONS: Early baicalein treatment attenuated CVS and limited neurological injury following SAH. These data may indicate clinical utility for baicalein as an adjunct therapy to reduce brain injury and improve patient outcomes.

Intrathecal glutamate release during hindlimb tourniquet inflation and femoral artery occlusion in rats.

BACKGROUND/PURPOSE: A tourniquet is commonly used in limb surgery. Tourniquet inflation after a period of time may produce painful sensation. While the mechanisms of tourniquet-induced pain are still unknown, two components, pressure and ischemia, have been proposed. In this study, in vivo microdialysis was used to detect changes in intrathecal glutamate, an excitatory amino acid highly relevant to pain transmission, following hindlimb tourniquet application and femoral artery occlusion in the rat. METHODS: Male Wistar rats were used. For the tourniquet study, 6 rats of the study group received 30 minutes right hindlimb tourniquet inflation and another 6 rats as the control group received only tourniquet application without inflation. In the femoral artery occlusion study, 6 rats of the study group received 30 minutes right femoral artery occlusion and another 6 rats as the control group received only sham operation without femoral artery occlusion. Cerebrospinal fluid dialysates were collected prior to, during, and after tourniquet application or femoral artery occlusion. Glutamate was measured by HPLC. RESULTS: A significant increase in intrathecal glutamate release was found during the tourniquet inflation period, and it returned to baseline after tourniquet deflation. No change of glutamate release was noted during femoral artery occlusion or after femoral artery reperfusion. CONCLUSION: The intrathecal glutamate release was increased by the hindlimb tourniquet inflation, but not influenced by femoral artery occlusion in the rat.

Amitriptyline attenuates astrocyte activation and morphine tolerance in rats: role of the PSD-95/NR1/nNOS/PKCγ signaling pathway.

The tricyclic antidepressant amitriptyline binds with high affinity to N-methyl-d-aspartate receptors (NMDARs) and inhibits NMDAR-mediated events. Activation of the postsynaptic density protein-95 (PSD-95)/NMDAR-mediated downstream signaling cascade, including neuronal nitric oxide synthase (nNOS) and protein kinase gamma (PKCγ), has been shown to be involved in morphine tolerance. The present study examined the potential effect of amitriptyline on chronic morphine infusion-induced spinal PSD-95/NMDAR/nNOS/PKCγ signaling in morphine tolerance. Male Wistar rats were implanted with an intrathecal catheter and received an intrathecal infusion of saline or amitriptyline (15 µg/h), morphine+saline (tolerance induction, 15 µg/h), or morphine+amitriptyline for 5 days. Co-administration of amitriptyline with morphine not only preserved the antinociceptive effect of morphine, but also attenuated astrocyte activation in the rat spinal cord dorsal horn. On day 5 after drug infusion, increased expression and phosphorylation of spinal membrane NMDAR NR1 subunit and expression of PSD-95 were observed following chronic morphine infusion and these effects were attenuated by amitriptyline co-infusion. Upregulation of NMDAR-induced intracellular nNOS expression was also inhibited by amitriptyline co-infusion in chronic morphine-infused rats. Furthermore, amitriptyline co-infusion significantly inhibited morphine-induced PKCγ expression in both the cytosol and membrane of spinal neurons. These findings suggest that the attenuation of morphine tolerance caused by amitriptyline is due to downregulation of NMDAR NR1 subunit expression in the synaptosomal membrane accompanied by decreased expression of the scaffolding protein PSD-95. The effects of amitriptyline in attenuating astrocyte activation and reversing tolerance to morphine may be due, at least in part, to inhibition of the PSD-95/NMDAR NR1/nNOS/PKCγ signaling cascade.

Comparison between intraoperative fentanyl and tramadol to improve quality of emergence.

BACKGROUND: Cough causes poor quality of emergence from anesthesia and risks of several complications. We compared fentanyl and an antitussive action of tramadol on the quality of emergence and postoperative outcome. METHODS: A total of 110 adults (18 to 83 y) of American Society of Anesthesiologists physical status I-III undergoing elective lumbar microdiscectomy with intubated total intravenous anesthesia were randomly divided into 2 groups of 55 each. The patients assigned to the fentanyl group received a dose of 1 µg/kg of fentanyl, whereas those assigned to the tramadol group received 1 mg/kg of tramadol, at the beginning of skin closure. We recorded the incidence of cough, quality of extubation at fixed times, maximal heart rates, maximal blood pressure during emergence, postoperative pain scores, and consumption of fentanyl. In addition, postoperative sore throat (POST), hoarseness, postoperative nausea and vomiting, and other anesthetic and surgical-related complications were recorded. RESULTS: Tramadol reduced cough incidence, improved extubation quality, and provided more stable hemodynamics during emergence. There was no significant difference in postoperative pain, fentanyl consumption, incidence and severity of POST, hoarseness, and postoperative nausea and vomiting between groups. Moreover, we found that the incidence of POST did not correlate with cough incidence. CONCLUSIONS: A dose of 1 mg/kg of tramadol administered intravenously 30 minutes before the expected extubation, compared with 1 µg/kg of fentanyl, decreased cough incidence, improved emergence quality, and provided stable hemodynamics. However, there was no significant difference between tramadol and fentanyl in pain scores and fentanyl consumption postoperatively.

Neuroprotective effect of curcumin in an experimental rat model of subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat. METHODS: A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed. RESULTS: Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats. CONCLUSIONS: Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.

Intrathecal ultra-low dose naloxone enhances the antinociceptive effect of morphine by enhancing the reuptake of excitatory amino acids from the synaptic cleft in the spinal cord of partial sciatic nerve-transected rats.

BACKGROUND: In this study, we examined the effects of ultra-low dose naloxone on the antinociceptive effect of morphine and on spinal cord dorsal horn glutamate transporter expression in rats with neuropathic pain. METHODS: Neuropathic pain was induced in male Wistar rats by partial transection of the left sciatic nerve and an intrathecal catheter was implanted for drug administration; in some rats, an intrathecal microdialysis probe for cerebrospinal fluid (CSF) dialysate collection was also implanted. Nociception was assessed using the plantar test, a Hargreaves radiant heat apparatus, and by the von Frey test, using a dynamic plantar anesthesiometer. Glutamate transporter protein expression in the left spinal cord dorsal horn was examined by Western blotting and immunohistochemistry. Levels of the excitatory amino acids (EAAs) glutamate and aspartate in the CSF dialysate were measured using high-performance liquid chromatography. RESULTS: Reduced astrocyte expression of glutamate transporters (GLT-1 and GLAST levels were 55% and 53%, respectively, of that in sham-operated rats) in laminae I and II of the spinal cord dorsal horn ipsilateral to the partial sciatic nerve transection (PST), and hyperalgesia and allodynia in the PST hindlimb were observed. High-dose naloxone (15 µg) attenuated the antihyperalgesia and antiallodynia effects of the morphine (10 µg). In contrast, ultra-low dose (15 ng) naloxone enhanced the antinociceptive effect of morphine (10 µg), with an increase in the paw withdrawal threshold to thermal stimulus (from 19% to 35%) and to tactile stimulus (from 33% to 55%) compared with morphine treatment alone, and this was associated with restoration of GLAST and GLT-1 expression to control levels (102% and 114%, respectively) in the astrocytes of laminae I and II in the spinal cord dorsal horn ipsilateral to the PST hindlimb and a decrease in EAA levels in the CSF dialysate (glutamate: 10.0 µM; aspartate: 1.1 µM). CONCLUSIONS: Ultra-low dose naloxone enhanced the antinociceptive effect of morphine in PST rats, possibly by restoration of GLAST and GLT-1 expression in astrocytes, which inhibited the accumulation of EAAs in the synapses, resulting in a neuroprotective effect.

Glutamate release and neurologic impairment after intrathecal administration of lidocaine and bupivacaine in the rat.

BACKGROUND: Local anesthetic-induced neurotoxicity is one of the potential causes of postspinal anesthesia neurologic injury. Many experimental and clinical studies have demonstrated that lidocaine is more neurotoxic than bupivacaine. The mechanisms of local anesthetic-induced neurotoxicity remain unclear. Glutamate is an excitatory amino acid and widely exists in the central nervous system. Overstimulation of the glutamate receptors may produce neuronal toxic effect. In this study, we used in vivo microdialysis to examine the glutamate release in cerebrospinal fluid (CSF) after intrathecal lidocaine and bupivacaine injection. METHODS: Male Wistar rats were used. Administration of lidocaine (5 groups: normal saline, 2.5%, 5%, 10%, and 10% + MK-801 intrathecally injected) and bupivacaine (4 groups: normal saline, 0.25%, 0.5%, and 1% intrathecally injected) was performed in both microdialysis and postinjection neurologic sequelae studies. After intrathecal injection of the studied agents, the CSF dialysates were collected in 10-minute intervals for 2 hours. Cerebrospinal fluid glutamate concentrations were measured by high-performance liquid chromatography. In addition, tail-flick latencies were examined daily before and after microdialysis for 4 days. RESULTS: Intrathecal lidocaine concentration-dependently elevated glutamate release in CSF. Pretreatment with MK-801 significantly inhibited the glutamate release induced by 10% lidocaine. Intrathecal bupivacaine has no influence on glutamate release in CSF. The tail-flick latencies were significantly prolonged for 4 days after intrathecal lidocaine injection, and these effects were in a concentration-dependent manner. Pretreatment with MK-801 significantly reversed the 10% lidocaine-induced prolonged tail-flick latencies. There was no difference of the tail-flick latencies among the bupivacaine-treated groups. CONCLUSIONS: Intrathecal lidocaine caused a concentration-dependent increase of the CSF glutamate release and postinjection neurologic impairment; these effects can be reversed by MK-801. However, intrathecal bupivacaine shows no influence. We suggest that glutamate may be involved in the pathogenesis of lidocaine-induced spinal neurotoxicity.

N-methyl-D-aspartate receptor antagonist MK-801 suppresses glial pro-inflammatory cytokine expression in morphine-tolerant rats.

Chronic opioid therapy induces tolerance and hyperalgesia, which hinders the efficacy of opioid treatment. Previous studies have shown that inhibition of neuroinflammation and glutamatergic receptor activation prevents the development of morphine tolerance. The aim of the present study was to examine whether N-Methyl-D-aspartate receptors are involved in the regulation of chronic morphine-induced neuroinflammation in morphine-tolerant rats. Morphine tolerance was induced in male Wistar rats by intrathecal infusion of morphine (15 µg/h) for 5 days. Tail-flick latency was measured to estimate the antinociceptive effect of morphine. Morphine challenge (15 µg, intrathecally) on day 5 at 3h after discontinuation of morphine infusion produced a significant antinociceptive effect in saline-infused rats, but not in morphine-tolerant rats. Pretreatment with MK-801 (20 µg, intrathecally) 30 min before morphine challenge preserved its antinociceptive effect in morphine-tolerant rats. Morphine-tolerant rats expressed high levels of the pro-inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α and the increase in interleukin-1ß and interleukin-6, and tumor necrosis factor-α levels was prevented by MK-801 pre-treatment at both the protein and mRNA levels. The results show that a single dose of MK-801 reduces the increase in pro-inflammatory cytokines in the spinal cord, thus re-sensitizing neurons to the antinociceptive effect of morphine in morphine-tolerant rats. This study provides a piece of theoretical evidence that NMDA antagonist can be a therapeutic adjuvant in treating morphine tolerant patients for pain relief.

Anaphylaxis to pantoprazole during general anesthesia.

The most frequent causes of anaphylaxis during anesthesia are neuromuscular blocking agents, antibiotics, and latex. Proton pump inhibitors (PPI) are widely used during major surgery for the prevention of stress ulcers, but cases of perioperative anaphylactic reactions to these have rarely been reported. We present a 50-year-old male patient who experienced an episode of anaphylaxis with hypoxemia, hypotension, tachycardia, and generalized erythema after intravenous injection of pantoprazole 40 mg and methylprednisolone 1 g during general anesthesia. After resuscitation, the patient recovered without any sequelae. Six months after the surgery, a skin test was positive to pantoprazole.

Temporal changes in glutamate, glutamate transporters, basilar arteries wall thickness, and neuronal variability in an experimental rat model of subarachnoid hemorrhage.

BACKGROUND: Glutamate and glutamate transporters (GTs) (including glutamate/aspartate transporter, glutamate transporter-1, and excitatory amino acid carrier 1) have important roles in the pathogenesis of ischemic neurological injury. The changes in glutamate, GTs, and neuronal injury after subarachnoid hemorrhage (SAH) have not been widely investigated. In this study, we examined the changes in extracellular glutamate concentration, GTs, wall thickness of basilar arteries (BAs), and neuronal degeneration in experimental SAH rats. METHODS: An intrathecal microdialysis probe was inserted into male Sprague Dawley rats. SAH was induced using a double-hemorrhage model. To measure glutamate concentrations, extracellular dialysates were collected for 30 minutes before, and daily for 7 days after SAH. Changes in neurological scores, body weight, and BA wall thickness were measured. The neuron degeneration in the hippocampus and the changes of GTs in the cerebral cortex and hippocampus were measured. RESULTS: Glutamate concentrations were significantly higher in SAH rats from day (D)1 to D7 after SAH compared with the sham rats, especially at D1. A significant body weight reduction and neurological defects were observed at D3 after SAH. The walls of BAs in SAH rats were significantly thicker compared with those of sham rats; the maximum change was observed at D7. Hippocampal neuronal degeneration was observed after SAH and the highest severity was at D7. The expression of GTs was downregulated after SAH and persisted for 7 days. CONCLUSIONS: SAH induced in the double-hemorrhage rat model may produce an excessive and prolonged increase of extracellular glutamate concentrations and downregulation of GTs, which are accompanied by BA wall thickness, and hippocampal neuronal degeneration.

Comparison of A-line autoregressive index and observer assessment of alertness/sedation scale for monitored anesthesia care with target-controlled infusion of propofol in patients undergoing percutaneous vertebroplasty.

BACKGROUND: Percutaneous vertebroplasty (PV) with monitored anesthesia care (MAC) is a growing trend. Without adequate sedation, patient movement can affect and even interrupt the procedure during MAC. The aim of this study was to compare the performance of the auditory-evoked potential (AEP) index and the Observer Assessment of Alertness/Sedation (OAA/S) scale as indicators of depth of sedation in patients undergoing PV. METHODS: Two hundred and twenty patients in ASA II to III, aged 43 to 92 years, undergoing elective PV with MAC, were randomly allocated to the AEP or the OAA/S group (n = 110 each). Initially, all patients received 1 µg/kg of fentanyl and 0.02 mg/kg of midazolam intravenously and sedation with a target-controlled infusion (TCI) of propofol at a target concentration of 1.2 µg/mL. The concentration for the propofol TCI was adjusted in 0.2 µg/mL increments or decrements according to the A-Line autoregressive index (AAI) or the OAA/S scale. A blinded study nurse recorded the measured parameters. RESULTS: Some parameters were significantly different in the AEP group compared with the OAA/S group: lower AAI, lower OAA/S score, lower respiratory rates, and higher end-tidal carbon dioxide pressure were noted from local anesthetic infiltration to bone cement implantation, fewer patients whose movements affected the procedure (10 vs. 36, respectively, P < 0.001), and more adjustments of TCI (twice vs. once, respectively, P < 0.006). The surgeons' satisfaction was greater for the AEP group than for the OAA/S group. CONCLUSIONS: TCI propofol with AEP monitoring can provide less patient movement, better sedation, and higher surgeon satisfaction in patients during prone-position PV procedures than can TCI propofol with OAA/S monitoring.

Interference of patent blue dye with pulse oximetry readings, methemoglobin measurements, and blue urine in sentinel lymph node mapping: a case report and review of the literature.

Patent blue (PB) dye has been successfully used worldwide in breast and cervix surgeries with few complications. Interference of oxyhemoglobin saturation reading by pulse oximetry (SpO(2)) and methemoglobinemia, from injection of PB dye, have rarely been reported in breast and cervix surgeries. We report here the first case of interference of SpO(2) reading, advent of methemoglobinemia, and blue urine from the use of PB dye, which occurred concurrently in a female undergoing bilateral modified radical mastectomy. The unexpected events might be a consequence of excessive administration of PB dye. We also reviewed the published discourses in literature on the adverse effects of PB dye.

Effect of epidural neuraxial blockade-dependent sedation on the Ramsay Sedation Scale and the composite auditory evoked potentials index in surgical intensive care patients.

BACKGROUND/PURPOSE: Peripheral deafferentation induced by neuraxial anesthesia reduces the degree of cortical arousal. This study investigated whether epidural analgesia blockade decreased sedation, as measured by the rapidly extracted auditory evoked potentials index, A-line autoregressive index (AAI) and Ramsay Sedation Scale (RSS) in sedated surgical intensive care patients, and looked at whether this was a concentration-dependent effect of lidocaine. METHODS: Forty patients underwent major lower abdominal surgery and received epidural analgesia in the surgical intensive care unit. Patients were continuously sedated with propofol to achieve an RSS value of 3, randomly divided into two groups, and received epidural analgesia with 10 mL of 0.5% or 1% lidocaine. Sedation was evaluated using the RSS and AAI, and analgesia was evaluated using a visual analog scale (VAS). RSS, AAI, electromyography (EMG) activity of AAI and VAS values were recorded at 5 minutes before and 30, 60 and 90 minutes after epidural lidocaine administration. RESULTS: Epidural 0.5% lidocaine produced a reduction of AAI, EMG and VAS at 30, 60 and 90 minutes after administration. For 1% epidural lidocaine administration, AAI, EMG and VAS were also reduced at 30, 60 and 90 minutes after epidural lidocaine administration. However, there was no difference in the AAI between the two concentrations; moreover, no significant change was observed in the RSS. CONCLUSION: Epidural lidocaine analgesia could potentiate sedation in patients evaluated by the AAI, but had no effect on the RSS. The present study suggests that the AAI could provide an objective and more precise index than the RSS in evaluation of sedation level in patients who are undergoing epidural pain management in the intensive care unit.

Video-assisted thoracoscopic surgery using single-lumen endotracheal tube anaesthesia in primary spontaneous pneumothorax.

BACKGROUND AND OBJECTIVE: Primary spontaneous pneumothorax (PSP) is a common condition that typically affects young adults. With recent advances in techniques, VATS is now a safe and accepted procedure for treating PSP. Lung isolation techniques have been commonly used to facilitate surgical procedures in the past. The purpose of this study was to evaluate the feasibility of using a single-lumen endotracheal tube for thoracoscopic surgery in patients with PSP. METHODS: A series of 121 consecutive patients with PSP, who underwent VATS using a double-lumen or single-lumen endotracheal tube between January 2000 and December 2002, were assessed retrospectively. The clinical features, operation times, complications, hospital stays and recurrences of PSP in these patients were recorded and analysed. RESULTS: There were no significant differences in gender, BMI, smoking habits, blebs/bullae on CT, duration of surgery or recurrence of PSP between the two groups. Patients in the single-lumen endotracheal tube group had a shorter duration of anaesthesia (15.4 +/- 2.6 vs 25.6 +/- 3.2 min, P < 0.001), lower early complication rates, lower costs and shorter hospital stays (3.6 +/- 3.0 vs 4.5 +/- 2.8 days, P = 0.02) compared with those in the double-lumen endotracheal tube group. The follow-up period was 40-68 months (mean 54 months). There were two recurrences in each group (3.1% vs 3.4%). CONCLUSIONS: VATS for the treatment of PSP was easily performed using a single-lumen endotracheal tube, and resulted in lower intubation-related costs, fewer complications and equivalent outcomes, compared with procedures performed using double-lumen endotracheal tube anaesthesia.

The effectiveness of benzydamine hydrochloride spraying on the endotracheal tube cuff or oral mucosa for postoperative sore throat.

BACKGROUND: The etiology of postoperative sore throat (POST) is considered to be the result of laryngoscopy, intubation damage, or inflated cuff compression of the tracheal mucosa. In this study, we compared the effectiveness in alleviating POST using different approaches to benzydamine hydrochloride (BH) administration by spraying the endotracheal tube (ET) cuff or the oropharyngeal cavity, or both. METHODS: Three hundred eighty patients were included in this prospective and double-blind study, which was randomized into 4 groups: group A, oropharyngeal cavity spray of BH, and distilled water on the ET cuff; group B, both the oropharyngeal cavity and the ET cuff received BH spray; group C, the ET cuff received BH spray, and the oropharyngeal cavity received distilled water; and group D, distilled water sprayed on both the ET tube and into the oropharyngeal cavity. The patients were examined for sore throat (none, mild, moderate, severe) at 0, 2, 4, and 24 hours postextubation. RESULTS: The incidence of POST was 23.2%, 13.8%, 14.7%, and 40.4% in groups A, B, C, and D, respectively. POST occurred significantly less frequently in groups B and C compared with group D (odds ratio: 0.36; 95% confidence interval: 0.21-0.60; P < 0.05). However, there was no significant difference between groups A and D (odds ratio: 0.62; 95% confidence interval: 0.38-1.01). Moreover, there was no significant interaction between spraying BH over the oropharyngeal cavity and the ET cuff on the incidence of POST (P = 0.088). The severity of POST was significantly more intense in group D compared with groups B and C (P < 0.001). Group B had a significantly higher incidence of local numbness, burning, and/or stinging sensation compared with patients in group D (P < 0.05). CONCLUSIONS: This study indicates that spraying BH on the ET cuff decreases the incidence and severity of POST without increased BH-related adverse effects.

Intramuscular bupivacaine injection dose-dependently increases glutamate release and muscle injury in rats.

OBJECTIVE: Local anesthetics may cause reversible skeletal muscle injury, which is most common with bupivacaine. Glutamate is present in most skeletal muscles and may regulate muscular metabolic pathways. The aim of study was to examine the changes in intramuscular glutamate level and the severity of myopathy after intramuscular administration of bupivacaine. METHODS: Twenty-four male Wistar rats were divided into four groups with six rats per group. A microdialysis probe was implanted in the right tibialis anterior (RTA) muscle in all rats. After equilibrating the microdialysis system for 2 hours, 0.2 mL of normal saline or 0.25%, 0.5% or 1% bupivacaine was injected into the RTA muscle and dialysate samples were collected every 30 minutes for 4 hours. Glutamate was measured by high-performance liquid chromatography. Three days later, the RTA muscle was dissected and the injection site was examined histologically to evaluate the severity of muscle damage on a four-point score, representing no damage to severe myonecrosis. RESULTS: Bupivacaine significantly increase the level of glutamate in a dose- dependent manner in the RTA muscle. Histological assessment of the RTA muscle after bupivacaine administration revealed dose-dependent damage (mean score: normal saline, 0; 0.25% bupivacaine, 1.2+/-0.6; 0.5% bupivacaine, 1.8+/-0.7; 1% bupivacaine, 2.4+/-0.8; p<0.05). CONCLUSION: A single intramuscular injection of bupivacaine induced dose-dependent increases in intramuscular glutamate levels and muscular damage.

Effect on postoperative sore throat of spraying the endotracheal tube cuff with benzydamine hydrochloride, 10% lidocaine, and 2% lidocaine.

BACKGROUND: Postoperative sore throat (POST) is a common complication after endotracheal intubation. We compared the effectiveness on POST of spraying the endotracheal tube (ETT) cuff with benzydamine hydrochloride, 10% lidocaine, and 2% lidocaine. METHODS: Three hundred seventy-two patients were randomly allocated into 4 groups. The ETT cuffs in each group were sprayed with benzydamine hydrochloride, 10% lidocaine hydrochloride, 2% lidocaine hydrochloride, or normal saline before endotracheal intubation. After insertion, the cuffs were inflated to an airway leak pressure of 20 cm H(2)O. Anesthesia was maintained with propofol. The patients were examined for sore throat (none, mild, moderate, or severe) at 1, 6, 12, and 24 hours after extubation. RESULTS: The highest incidence of POST occurred at 6 hours after extubation in all groups. There was a significantly lower incidence of POST in the benzydamine group than 10% lidocaine, 2% lidocaine, and normal saline groups (P < 0.05) at each observation time point. At 6 hours after extubation, the incidence of POST was significantly lower in the benzydamine group (17.0%) compared with 10% lidocaine (53.7%), 2% lidocaine (37.0%), and normal saline (40.8%) groups (P < 0.05). The benzydamine group had significantly decreased severity of POST compared with the 10% lidocaine, 2% lidocaine, and normal saline groups (P < 0.05) at each observation time point. Compared with the 2% lidocaine and normal saline groups, the 10% lidocaine group had significantly increased severity of POST at 1, 6, and 12 hours after extubation. There were no significant differences among groups in local or systemic side effects. CONCLUSIONS: Spraying benzydamine hydrochloride on the ETT cuff is a simple and effective method to reduce the incidence and severity of POST.