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.

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.

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.

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.

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.

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.

A comparison of 3% hypertonic saline and mannitol for brain relaxation during elective supratentorial brain tumor surgery.

BACKGROUND: In this study, we compared the effects of 3% hypertonic saline (HTS) and 20% mannitol on brain relaxation during supratentorial brain tumor surgery, intensive care unit (ICU) stays, and hospital days. METHODS: This prospective, randomized, and double-blind study included patients who were selected for elective craniotomy for supratentorial brain tumors. Patients received either 160 mL of 3% HTS (HTS group, n = 122) or 150 mL of 20% mannitol infusion (M group, n = 116) for 5 minutes at the start of scalp incision. The PCO(2) in arterial blood was maintained within 35 to 40 mm Hg, arterial blood pressure was controlled within baseline values +/-20%, and positive fluid balance was maintained intraoperatively at a rate of 2 mL/kg/h. Outcome measures included fluid input, urine output, arterial blood gases, serum sodium concentration, ICU stays, and hospital days. Surgeons assessed the condition of the brain as "tight," "adequate," or "soft" immediately after opening the dura. RESULTS: Brain relaxation conditions in the HTS group (soft/adequate/tight, n = 58/43/21) were better than those observed in the M group (soft/adequate/tight, n = 39/42/35; P = 0.02). The levels of serum sodium were higher in the HTS group compared with the M group over time (P < 0.001). The average urine output in the M group (707 mL) was higher than it was in the HTS group (596 mL) (P < 0.001). There were no significant differences in fluid input, ICU stays, and hospital days between the 2 groups. CONCLUSIONS: Our results suggest that HTS provided better brain relaxation than did mannitol during elective supratentorial brain tumor surgery, whereas it did not affect ICU stays or hospital days.

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.

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.

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.

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.

Collateral meridian acupressure therapy effectively relieves postregional anesthesia/analgesia backache.

Epidural and spinal aesthesia may cause backache. In fact, the overall incidence of postneuraxial block backache is 9% to 50% and the incidence of back pain on the third postoperative day ranges from 5.91% to 22% after spinal anesthesia. Five patients suffering from postneuraxial block backache after regional anesthesia or analgesia are reported. Despite administering conventional treatment modalities including bed rest, cold/warm packing, physical therapy, and medications with nonsteroidal anti-inflammatory drugs (NSAIDs), strong analgesics, and opioids, the backache persisted and disturbed the patients' daily life. Surprisingly, utilization of a new acupressure technique, collateral meridian acupressure therapy (CMAT), relieved the backache dramatically.

Shoulder tip pain after laparoscopic surgery analgesia by collateral meridian acupressure (shiatsu) therapy: a report of 2 cases.

OBJECTIVES: This article describes 2 cases of collateral meridian acupressure (shiatsu) therapy (CMAT) for treatment of shoulder tip pain after laparoscopic cholecystectomy (LC). Both cases showed marked pain relief with reduction of skin temperature (1 degrees C) of the affected shoulder after CMAT. CLINICAL FEATURES: A 32- and a 53-year-old female presented with right shoulder tip pain after LC surgery. The repeated dose of intravenous ketorolac 30 mg and meperidine 50 mg did not improve the pain. Because of persistent pain and episodes of nausea and vomiting after intravenous nonsteroidal anti-inflammatory drugs and opioid medications, patients refused to take more analgesics, and we were consulted for pain management. INTERVENTION AND OUTCOME: After informed written consent obtained, CMAT was performed using acupoints located on the contralateral (left) kidney meridian to treat affected (right) shoulder pain. Postoperatively, patients' pain intensity was measured using a numeric pain scale. The infrared thermography of shoulder tip was obtained before and after the CMAT. Both patients reported immediate pain relief after the CMAT, with pain scores decreased from 5 to 1 of 10 and 5 to 0 of 10, respectively. Moreover, the local skin temperature of affected shoulders were significantly decreased in both patients after the CMAT. Similarly, the temperature difference between patients' affected and nonpainful shoulders were also significant after the CMAT. CONCLUSION: The results of these 2 cases suggest that the CMAT may be effective in reducing patients' post-LC shoulder tip pain without medication. An associated reduction of skin temperature of the painful shoulder with CMAT warrants further investigation.

Epidural clonidine for postoperative pain after total knee arthroplasty: a dose-response study.

BACKGROUND: Combinations of epidural clonidine, local anesthetics, and opioids have improved postoperative analgesia after total knee arthroplasty. In this study we sought to determine the optimal epidural bolus dose of clonidine, which provides the best analgesia and fewest side effects. METHODS: Eighty ASA I-III patients, who underwent total knee arthroplasty were randomly assigned to one of four groups of 20 patients each. Identical epidural anesthesia procedures were used for all groups. After surgery, groups C0, C1, C2, and C4 received patient-controlled epidural analgesia (PCEA) with clonidine (0, 1.0, 2.0, or 4.0 mug/mL, respectively) and morphine (0.1 mg/mL) in 0.2% ropivacaine. The analgesia effect was estimated by PCEA consumption volume and visual analog pain scale at rest and with movement at 1, 2, 4, 12, 24, 48, and 72 h after surgery. Systolic blood pressure, heart rate, sedation, and sensory and motor blockade were also recorded for 72 h after surgery. RESULTS: The PCEA consumption volume for groups C0, C1, C2, and C4 were 71.8 +/- 19.5 mL, 49.6 +/- 12.3 mL, 48.1 +/- 9.3 mL, and 39.4 +/- 9.0 mL, respectively. The clonidine groups experienced less postoperative pain (P = 0.002). In the C4 group, four patients had prolonged sensory blockade and one patient had both severe sedation and prolonged sensory motor blockade. No significant statistical difference in analgesic consumption (P = 0.78) and pain intensity (P = 0.66) between groups C1 and C2 were noted. CONCLUSIONS: The optimal amount of epidural clonidine in a solution of morphine and ropivacaine for postoperative pain management is 1.0 microg/mL.

Premedication with intravenous low-dose ketamine suppresses fentanyl-induced cough.

STUDY OBJECTIVE: To evaluate the effect of low-dose ketamine on fentanyl-induced cough. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING: Medical center hospital. PATIENTS: 360 ASA physical status I-II patients aged 18 to 65 years, weighing between 40 and 80 kg, and scheduled for elective surgery during general anesthesia. INTERVENTIONS AND MEASUREMENTS: Patients were randomly assigned to receive either ketamine 0.15 mg/kg or placebo (equal volume of 0.9% saline) given intravenously over 10 seconds, one minute before administration of fentanyl (1.5 microg/kg IV, injected within 5 seconds), during induction of general anesthesia. Any episode of cough was classified as coughing and the onset time of cough (the time of the first episode of cough) was observed for one minute after fentanyl administration by a blinded observer. Severity of coughing was graded based on the number of episodes of coughing (mild, 1-2; moderate, 3-5; and severe, >5). Blood pressure, heart rate, and pulse oximetry oxygen saturation (Spo2) were recorded before giving ketamine or 0.9% saline and 1 minute after fentanyl injections. MAIN RESULTS: After the intravenous injection of fentanyl bolus, patients in the placebo group showed significantly higher frequency cough than those in the ketamine pretreatment group (21.6% vs 7.2%, P<0.05), and onset time of the ketamine group was significantly longer than that of the control group (20+/-8 vs 15+/-10 seconds, P<0.01). However, no difference in cough severity was observed between the two groups. CONCLUSION: Low-dose ketamine (0.15 mg/kg IV) effectively reduces fentanyl-induced cough and delays the onset time of cough.

Hyaluronic acid attenuates osteoarthritis development in the anterior cruciate ligament-transected knee: Association with excitatory amino acid release in the joint dialysate.

We previously reported increased release of the excitatory amino acid (EAA) neurotransmitters, glutamate and aspartate, during the early stage of experimental osteoarthritis (OA). Our present objective was to study the effect of intraarticular injection of hyaluronic acid (HA) on OA development, and to analyze concomitant changes in EAA levels in dialysates of anterior cruciate ligament-transected (ACLT) knee joints. OA was induced in Wistar rats by ACLT of one hindlimb; the knee of the other hindlimb was used as the sham-operated control. HA group (n = 12) were injected intraarticularly in the ACLT knee with 1 mg of HA once a week for 5 consecutive weeks, starting at 8 weeks after surgery. Saline group (n = 12) were injected as above with normal saline. The sham-operated group, underwent arthrotomy, but not ACLT, and received no treatment (n = 14). Twenty weeks after surgery, knee joint dialysates were collected by microdialysis and EAA levels assayed by high-performance liquid chromatography, and gross morphological examination and histopathological evaluation were performed on the medial femoral condyles and synovia. Rats receiving intraarticular HA injections showed a significantly lower degree of cartilage degeneration on the medial femoral condyle at both the macroscopic level and on the Mankin grading scale than rats receiving saline injections. Intraarticular HA treatment also suppressed synovitis. Moreover, glutamate and aspartate levels were significantly reduced in the HA group compared to the saline group. Intraarticular injection of HA limits articular cartilage and synovium damage and OA formation, and, in parallel, reduces EAA levels in ACLT joint dialysates. This study suggests that the underlying mechanism of the anti-inflammatory effect of HA is to inhibit glutamate and aspartate release in ACLT knee joints, which attenuates the early development of OA.

Preoperative cotreatment with dextromethorphan and ketorolac provides an enhancement of pain relief after laparoscopic-assisted vaginal hysterectomy.

OBJECTIVES: Both N-methyl-D-aspartate receptor antagonists and nonsteroidal anti-inflammatory drugs have been demonstrated to produce better postoperative pain relief. The concept of multimodal analgesia has also been used for clinical pain management. The aim of the present study was to examine the analgesic effect of preoperative cotreatment with dextromethorphan (DM) and ketorolac on postoperative pain management after laparoscopic-assisted vaginal hysterectomy (LAVH). METHODS: Eighty ASA physical status I or II patients scheduled for LAVH were included and randomly assigned to 1 of 4 groups. Patients received intramuscular (IM) chorpheniramine 20 mg+ intravenous (IV) 2 mL of normal saline, IM DM 40 mg+IV 2 mL of normal saline, IM chorpheniramine 20 mg+IV 60 mg (2 mL) of ketorolac, and IM DM 40 mg+IV ketorolac 60 mg as the groups C, DM, Keto, and DM+Keto, respectively. All patients were given a patient-controlled analgesia (PCA) with morphine for pain relief postoperatively. Analgesic effects were evaluated using Visual Analog Scale pain scores at rest and during coughing, time to first PCA request for pain relief, total morphine consumption, bed rest time, and the time to first passage of flatus for 48 hours after surgery. RESULTS: Patients in DM and Keto groups had significantly better pain relief than patients in group C. Patients in DM+Keto group exhibited the best postoperative pain relief among groups in the following several categories: time to first trigger of PCA, total morphine consumption, the worst Visual Analog Scale, bed rest time, and the time to first passage of flatus, demonstrating an enhanced effect between DM and ketorolac. Neither synergistic nor antagonistic interaction was observed between DM and ketorolac. DISCUSSION: Preoperative treatment with both DM and ketorolac diminish postoperative pain. Our results suggest that the N-methyl-D-aspartate antagonist-DM and the nonsteroidal anti-inflammatory drugs-ketorolac cotreatment provide an enhancement of analgesia for postoperative pain management in patients after LAVH surgery.

Correlation between changes in regional cerebral blood flow and pain relief in complex regional pain syndrome type 1.

OBJECTIVE: Analyzing changes in regional cerebral blood flow (rCBF) with SPECT in complex regional pain syndrome type 1 (CRPS 1), formerly known as reflex sympathetic dystrophy, is an optimal method for evaluating effective pain relief. We attempted to investigate the correlation of changes in rCBF with pain relief during treatments of sympathetic blockade and multimodal epidural pain control. CASE REPORT: We describe a patient with severe CRPS 1 in whom conventional treatment failed to relieve the pain. Combined repeated lumbar sympathetic blocks and long-term epidural morphine, bupivacaine, and ketamine administration provided satisfactory pain relief and functional activity recovery. Six normal control subjects having one Tc-99m HMPAO scan each and the patient with CRPS having 3 Tc-99m HMPAO scans (once before treatment and twice at 4 months and 6 months after treatment, respectively). The patient with CRPS showed lower rCBF than normal controls in the left thalamus and higher rCBF than normal controls in the right parietal lobe and left frontal lobe. After subsequent treatment, the subtraction images showed increased rCBF in the left thalamus and decreased rCBF in the right parietal and left frontal lobes. CONCLUSIONS: Tc-99m HMPAO SPECT showed a relationship of rCBF in the thalamus, parietal lobe, and frontal lobe with pain relief. rCBF alterations may provide an indicator for the quality of pain management for neuropathic pains. Subtraction analysis between pre- and posttreatment, by using statistical parametric mapping (version 2), can be used as an objective indicator for the effectiveness of therapy.

Anesthetic management of an AAI pacemaker patient with paroxysmal atrial fibrillation during colorectal surgery.

Perioperative management of patients with cardiac pacemakers may be challenging because of the increasing sophistication of these devices. We report a case of a patient with paroxysmal atrial fibrillation (PAF) and with a permanent AAIR (bipolar atrial-inhibited adaptive rate) pacemaker who suffered life-threatening episodes of arrhythmias during operation. The first episode was vagally induced PAF during bowel manipulation; the second, induced by the increased pacing threshold from the external electric cardioversion and hyperkalemia. Transcutaneous pacing provided cardiac pacing and stabilized the patient during the second episode. Thorough preoperative evaluation and prophylactic placement of temporary pacing or at least transcutaneous pacing are important for the avoidance and minimization of intraoperative complications in patients with sick sinus syndrome and with an AAI (atrial inhibited) pacemaker.