Knowledge, attitude, and barriers regarding prescribing long-term opioids among Taiwan physicians treating officially registered patients with chronic noncancer pain.

BACKGROUND: Prescribing opioids for patients with chronic noncancer pain (CNCP) remains controversial. This study surveyed Taiwanese physicians who were clinically treating CNCP outpatients with long-term opioids. METHODS: Anonymous questionnaires investigating the clinical practices, opioid knowledge, attitude, and barriers regarding the prescription of long-term opioids were delivered to 66 physicians treating CNCP outpatients who were officially registered and monitored by the Taiwan Food and Drug Administration in 2011. RESULTS: All 66 (100%) physicians responded to the survey, comprising 41 (62%) board-certified pain specialists and 25 (38%) nonpain board-certified physicians. Pain specialists treated a greater number of CNCP outpatients and attended more CNCP training courses than nonpain board-certified physicians (97.6% vs. 56.0%, p < 0.001). Most of pain specialists stated that they were familiar with the Taiwan's narcotic regulations for CNCP patients (92.7% vs. 68.0%, p = 0.015). In addition, pain specialists were less likely to skip or reduce the dosage and duration of opioid prescriptions (22.0% vs. 36.0%, p < 0.001). By contrast, nonpain board-certified physicians had significantly less knowledge and a more negative attitude toward opioid prescription. The major perceived barriers were physician's reluctance to prescribe opioids (78% vs. 92%) and an inadequate knowledge of pain management (73% vs. 84%) among all physicians. CONCLUSION: Among the Taiwanese physicians treating the officially registered CNCP patients, nonpain board-certified physicians had fewer patients, less knowledge, and an increased negative attitude toward long-term opioid prescriptions. Better education on chronic pain management is needed for improvement of clinical practice.

Bilateral tension pneumothorax during colonoscopy in a patient with chronic obstructive pulmonary disease: a case report.

Colonoscopy is widely performed for the diagnosis and treatment of various colonic disorders and the screening and surveillance of colorectal neoplasia. According to research evidence, up to one-third of patients had at least 1 minor and transient gastrointestinal symptom after colonoscopy. Although severe complications developed uncommonly, they are potentially serious and life threatening. Here, we present the case of a 95-year-old man with chronic obstructive pulmonary disease who developed bilateral tension pneumothorax during therapeutic colonoscopy for sigmoid volvulus. In this case, air trapping resulting from the Valsalva maneuver under inadequate pain control may be the mechanism for fatal tension pneumothorax during colonoscopy.

Comparing complementary alternative treatment for chronic shoulder pain of myofascial origin: Collateral meridian therapy versus local tender area-related meridians therapy.

The aim of this study was to compare the short-term outcomes between 2 different treatments for unilateral chronic shoulder pain of myofascial origin, that is, local tender area related meridians (LTARMs) treatment and collateral meridian therapy (CMT), which were performed 6 times over a period of 4 weeks.Seventy patients with unilateral shoulder pain of chronic myofascial origin were enrolled. The patients were randomly assigned to 2 different treatment groups: 1 group received CMT (n = 35) and the other received LTARM (n = 35). Before and after the 2 treatment processes, all patients rated their overall pain intensity on a visual analogue scale (VAS) and a validated 13-question shoulder pain and disability index (SPADI) questionnaire was used to measure shoulder pain and functional impairment after therapy for 4 weeks.After CMT, the pain intensity was reduced after CMT. VAS score is reduced from 5.90 ±â€Š2.07 (a mean of 5.90 and standard deviation of 2.07) to 3.39 ±â€Š1.2. This was verified by the SPADI pain subscale scores (from 0.58 ±â€Š0.193 to 0.33 ±â€Š0.14). The pain-relief effect of CMT was significantly better than that of LTARM (VAS score from 5.78 ±â€Š1.64 to 4.58 ±â€Š1.40; P < 0.005; SPADI pain subscale score from 0.58 ±â€Š0.16 to 0.45 ±â€Š0.14, P < 0.001). In addition, the VAS scores of patients changed considerably in the CMT group after 4 weeks of treatment, where 63% of patients felt no or mild pain, whereas the VAS scores for moderate pain were even higher in the LTARM group in 75% of patients (P < 0.001). Moreover, the SPADI disability subscale scores improved significantly in the CMT group because of their greater mobility associated with shoulder impairment (disability score: from 0.58 ±â€Š0.20 to 0.35 ±â€Š0.14) than those in the LTARM group (disability score: from 0.55 ±â€Š0.17 to 0.44 ±â€Š0.14, P < 0.001).CMT may be more effective in reducing chronic shoulder pain of myofascial origin than the LTARM treatment, where treatment with the former resulted in better functional recovery after 4 weeks than the latter.

Predicting Neuroinflammation in Morphine Tolerance for Tolerance Therapy from Immunostaining Images of Rat Spinal Cord.

Long-term morphine treatment leads to tolerance which attenuates analgesic effect and hampers clinical utilization. Recent studies have sought to reveal the mechanism of opioid receptors and neuroinflammation by observing morphological changes of cells in the rat spinal cord. This work proposes a high-content screening (HCS) based computational method, HCS-Morph, for predicting neuroinflammation in morphine tolerance to facilitate the development of tolerance therapy using immunostaining images for astrocytes, microglia, and neurons in the spinal cord. HCS-Morph first extracts numerous HCS-based features of cellular phenotypes. Next, an inheritable bi-objective genetic algorithm is used to identify a minimal set of features by maximizing the prediction accuracy of neuroinflammation. Finally, a mathematic model using a support vector machine with the identified features is established to predict drug-treated images to assess the effects of tolerance therapy. The dataset consists of 15 saline controls (1 µl/h), 15 morphine-tolerant rats (15 µg/h), and 10 rats receiving a co-infusion of morphine (15 µg/h) and gabapentin (15 µg/h, Sigma). The three individual models of astrocytes, microglia, and neurons for predicting neuroinflammation yielded respective Jackknife test accuracies of 96.67%, 90.00%, and 86.67% on the 30 rats, and respective independent test accuracies of 100%, 90%, and 60% on the 10 co-infused rats. The experimental results suggest that neuroinflammation activity expresses more predominantly in astrocytes and microglia than in neuron cells. The set of features for predicting neuroinflammation from images of astrocytes comprises mean cell intensity, total cell area, and second-order geometric moment (relating to cell distribution), relevant to cell communication, cell extension, and cell migration, respectively. The present investigation provides the first evidence for the role of gabapentin in the attenuation of morphine tolerance from phenotypic changes of astrocytes and microglia. Based on neuroinflammation prediction, the proposed computer-aided image diagnosis system can greatly facilitate the development of tolerance therapy with anti-inflammatory drugs.

Grand mal seizure induced by low-dose fentanyl and lidocaine in a young child.

Surgical procedures require general anesthesia using combinations of drugs including fentanyl and/or lidocaine. Because many of these drugs have bimodal anticonvulsant/proconvulsant effects, they must be administered carefully. We herein report a case of seizure attack during anesthesia induction with low-dose fentanyl and lidocaine in a young child with no history of seizures. A 10-year-old girl was scheduled to receive an elective tenectomy. After a few seconds of fentanyl and lidocaine administration for anesthesia induction, she developed generalized tonic-clonic seizures. Seizures subsided spontaneously after 3 minutes. The patient's blood sugar, serum electrolytes, and arterial blood gas analysis were normal immediately after the event. She remained hemodynamically stable; however, the surgery was postponed after communication and discussion with the surgeon. Postoperatively, there was no evidence of postictal phase, and serum electrolytes and magnetic resonance imaging of the brain were normal. The patient had an uneventful recovery. However, electroencephalogram showed that hyperventilation stimulation test induced isolated epileptiform spikes over O1, suggesting a potential paroxysmal disorder over the left occipital area. This report is on a rare complication likely caused by fentanyl or lidocaine, which suggests that these drugs should be used cautiously in children whose clinical epileptic activities have been verified or are strongly suspected.

Minocycline and fluorocitrate suppress spinal nociceptive signaling in intrathecal IL-1ß-induced thermal hyperalgesic rats.

We previously demonstrated that intrathecal IL-1ß caused thermal hyperalgesia in rats. This study was conducted to examine the effects and cellular mechanisms of glial inhibitors on IL-1ß-induced nociception in rats. The effects of minocycline (20 µg), fluorocitrate (1 nmol), and SB203580 (5 µg) on IL-1ß (100 ng) treatment in rats were measured by nociceptive behaviors, western blotting of p38 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthase (iNOS) expression, cerebrospinal fluid nitric oxide (NO) levels, and immunohistochemical analyses. The results demonstrated that intrathecal IL-1ß activated microglia and astrocytes, but not neurons, in the dorsal horn of the lumbar spinal cord, as evidenced by morphological changes and increased immunoreactivity, phosphorylated p38 (P-p38) MAPK, and iNOS expression; the activation of microglia and astrocytes peaked at 30 min and lasted for 6 h. The immunoreactivities of microglia and astrocytes were significantly increased at 30 min (6.6- and 2.7-fold, respectively) and 6 h (3.3- and 4.0-fold, respectively) following IL-1ß injection, as compared with saline controls at 30 min (all P < 0.01). IL-1ß induced P-p38 MAPK and iNOS expression predominantly in microglia and less in astrocytes. Minocycline, fluorocitrate, or SB203580 pretreatment suppressed this IL-1ß-upregulated P-p38 MAPK mainly in microglia and iNOS mainly in astrocytes; minocycline exhibited the most potent effect. Minocycline and fluorocitrate pretreatment abrogated IL-1ß-induced NO release and thermal hyperalgesia in rats. In conclusion, minocycline, fluorocitrate, and SB203580 effectively suppressed the IL-1ß-induced central sensitization and hyperalgesia in rats.

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.

Priming dose of intravenous rocuronium suppresses fentanyl-induced coughing.

OBJECTIVES: An intravenous bolus of fentanyl often induces a cough reflex. This study investigates whether priming with rocuronium can effectively attenuate fentanyl-induced coughing. METHODS: The study involved 260 participants, aged between 18 and 80 years of age, who were undergoing various elective surgeries. They were randomly assigned to two groups. Patients in the study group (the rocuronium group) were treated with intravenous (IV) 0.06 mg/kg rocuronium, whereas those in the control group were treated with the same volume of normal saline. Fentanyl (1.5 µg/kg IV, given over 2 seconds) was administered 30 seconds after the injection of rocuronium or normal saline. We recorded the number of coughs for 1 minute after the fentanyl injection. RESULTS: Patients in the rocuronium group showed a significantly lower incidence of coughing (8.5% vs. 23.1%, in the control group; p < 0.05) and a milder severity of cough in comparison with the patients in the control group. CONCLUSION: Pretreatment with IV rocuronium (0.06 mg/kg) suppressed the cough reflex induced by fentanyl. Therefore, priming with rocuronium may be a clinically useful method for preventing fentanyl-induced cough.

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.

Intrathecal etanercept partially restores morphine's antinociception in morphine-tolerant rats via attenuation of the glutamatergic transmission.

BACKGROUND: Long-term exposure to morphine leads to analgesic tolerance. In addition to an opioid receptor conformational change, enhancing the glutamatergic signal transmission is also involved in morphine tolerance. Tumor necrosis factor-α has been demonstrated to correlate with neuronal plasticity via activation of glutamatergic transmission. We examined the effect of etanercept, a tumor necrosis factor-α inhibitor on morphine tolerance in rats. METHODS: Male Wistar rats were implanted with 2 intrathecal (IT) catheters, and 1 IT catheter was connected to a mini-osmotic pump, used for either morphine infusion (15 µg/h) or saline (1 µL/h) infusion for 5 days. On day 5, either etanercept (50 µg) or saline (10 µL) was injected after discontinued morphine infusion. Three hours later, acute morphine (15 µg/10 µL, IT) treatment was given and all rats received a nociceptive tail-flick test. RESULTS: The results showed that acute etanercept (50 µg) treatment caused a significant antinociceptive effect of morphine in morphine-tolerant rats. Western blotting indicated that etanercept attenuated the downregulation of membrane glutamate transporters GLT-1 and GLAST in morphine-tolerant rats. Etanercept also inhibited the upregulation of surface AMPA-receptor and N-methyl-d-aspartate-receptor subunits, including GluR1/GluR2 and NR1/NR2A. CONCLUSIONS: These results demonstrate that etanercept partially restores the antinociceptive effect of morphine in morphine tolerance after a morphine challenge. Etanercept has potential for use in the clinical management of pain, particularly in patients who require long-term opioid treatment, and the effectiveness of which can be hampered by tolerance.

Etanercept restores the antinociceptive effect of morphine and suppresses spinal neuroinflammation in morphine-tolerant rats.

BACKGROUND: In the present study we examined the effect of the tumor necrosis factor (TNF)-α antagonist etanercept on the antinociceptive effect of morphine in morphine-tolerant rats. METHODS: Male Wistar rats were implanted with 2 intrathecal catheters, and 1 was connected to a mini-osmotic pump for either morphine (15 µg/h) or saline (1 µL/h) infusion for 5 days. On day 5, either etanercept (5 µg, 25 µg, and 50 µg/10 µL) or saline (10 µL) was injected via the other catheter after morphine infusion was discontinued. Three hours later, morphine (15 µg/10 µL, intrathecally) was given and tail-flick latency was measured to evaluate the antinociceptive effect of morphine. Rats were then killed and their spinal cords were removed for quantitative real-time polymerase chain reaction and immunohistochemistry to measure proinflammatory cytokines expression. RESULTS: We found that acute etanercept (50 µg) treatment preserved a significant antinociceptive effect of morphine in morphine-tolerant rats. In addition, the expression of TNFα mRNA was increased by 2.5-fold, interleukin (IL)-1ß mRNA increased by 13-fold and IL-6 mRNA by 111-fold in the dorsal spinal cord of morphine-tolerant rats. The increase in TNFα, IL-1ß, and IL-6 mRNA expression was blocked by 50 µg etanercept pretreatment. The immunohistochemistry analysis revealed that 50 µg etanercept suppressed proinflammatory cytokines expression and neuroinflammation in the microglia. CONCLUSIONS: The present study demonstrates that etanercept restores the antinociceptive effect of morphine in morphine-tolerant rats by inhibition of proinflammatory cytokine TNF-α, IL-1ß, and IL-6 expression and spinal neuroinflammation. The results suggest that etanercept could also be an adjuvant therapy for morphine tolerance, which extends the effectiveness of opioids in clinical pain management.

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.

Co-administration of ultra-low dose naloxone attenuates morphine tolerance in rats via attenuation of NMDA receptor neurotransmission and suppression of neuroinflammation in the spinal cords.

Although mechanisms underlying ultra-low dose naloxone-induced analgesia have been proposed, possible interactions with glutamatergic transmission and glial cell activation have not been addressed. In the present study, we examined the effect of ultra-low dose naloxone on spinal glutamatergic transmission and glial cell activity in rats chronically infused with morphine. In male Wistar rats, intrathecal morphine infusion (15microg/h) for 5days induced (1) antinociceptive tolerance, (2) downregulation of glutamate transporters (GTs) GLT-1, GLAST, and EAAC1, (3) increasing of NMDA receptor (NMDAR) NR1 subunit expression and phosphorylation, (4) upregulation of protein kinase C gamma (PKCgamma) expression, and (5) glial cell activation. On day 5, morphine challenge (15microg/10microl) caused a significant increase in the concentration of the excitatory amino acids (EAAs) aspartate and glutamate in the spinal CSF dialysates of morphine-tolerant rats. Intrathecal co-infusion of ultra-low dose naloxone (15pg/h) with morphine attenuated tolerance development, reversed GTs expression, inhibited the NMDAR NR1 subunit expression and phosphorylation, and PKCgamma expression, inhibited glial cell activation, and suppressed the morphine-evoked EAAs release. These effects may result in preservation of the antinociceptive effect of acute morphine challenge in chronic morphine-infused rats. Ultra-low dose naloxone infusion alone did not produce an antinociceptive effect. These findings demonstrated that attenuation of glutamatergic transmission and neuroinflammation by ultra-low dose naloxone co-infusion preserves the lasting antinociceptive effect of morphine in rats chronically infused with morphine.

Ultra-low dose naloxone upregulates interleukin-10 expression and suppresses neuroinflammation in morphine-tolerant rat spinal cords.

Co-infusion of ultra-low dose naloxone and morphine attenuates morphine tolerance through the prevention of mu opioid receptor-Gs protein coupling. We previously demonstrated that chronic intrathecal infusion of morphine leads to tolerance and spinal neuroinflammation. The aim of present study was to examine the possible mechanisms by which ultra-low dose naloxone modulates spinal neuroinflammation, particularly the role of anti-inflammatory cytokine interleukin 10 (IL-10). Morphine tolerance was induced in male Wistar rats by intrathecal infusion of morphine (15 microg/h) for 5 days, and co-infusion of naloxone (15 pg/h) was used to evaluate the impact on spinal cytokine expression. Recombinant rat IL-10 (rrIL-10) or anti-rat IL-10 antibody was injected to elucidate the effect of IL-10 on morphine tolerance. Our results showed that co-infusion of naloxone (15 pg/h) with morphine not only attenuated tolerance, shifting the AD(50) from 89.2 to 11.7 microg but also inhibited the increased expression of pro-inflammatory cytokine (TNF-alpha, IL-1beta, and IL-6) caused by chronic intrathecal morphine infusion. The increase of IL-10 protein and mRNA were 1.5- and 3-fold, respectively, compared to that in morphine-infused rat spinal cords. A combination of daily rrIL-10 (1 microg) injection with morphine infusion produced, in a less potent, preservative antinociception and inhibited pro-inflammatory cytokine production compared to ultra-low dose naloxone co-infusion, and the effect of ultra-low dose naloxone co-infusion was inhibited by daily intrathecal anti-rat IL-10 antibody injection. These results demonstrate that IL-10 contributes to the attenuation of pro-inflammatory cytokine expression caused by ultra-low dose naloxone/morphine co-infusion and thus the attenuation of morphine tolerance.

Amitriptyline suppresses neuroinflammation-dependent interleukin-10-p38 mitogen-activated protein kinase-heme oxygenase-1 signaling pathway in chronic morphine-infused rats.

BACKGROUND: This study explores the underlying mechanism of the antiinflammatory effect of amitriptyline in chronic morphine-infused rats. METHODS: Male Wistar rats were implanted with two intrathecal catheters. One catheter was for the continuous infusion of saline, amitriptyline (15 microg/h), morphine (15 microg/h), p38 mitogen-activated protein kinase inhibitor SB203580 (0.5 microg/h), morphine plus amitriptyline, or morphine plus amitriptyline plus SB203580 for 5 days. The other catheter was used for daily intrathecal injection of anti-interleukin-10 (IL-10) antibody or heme oxygenase-1 inhibitor zinc protoporphyrin for 5 days. RESULTS: Amitriptyline/morphine coinfusion upregulated IL-10 protein expression in microglia; this was not observed in morphine-infused rats. Anti-IL-10 antibody effectively neutralized the amitriptyline-induced IL-10 expression in chronic morphine-infused rats. In addition, coinfusion of amitriptyline restored the antinociceptive effect of morphine (a 4.8-fold right-shift of the morphine dose-response curve compared to a 77.8-fold right-shift in its absence), and the injection of anti-IL-10 antibody or coinfusion of SB203580 partially reversed the effect of amitriptyline on the antinociceptive effect of morphine in morphine-infused rats (a 17.9-fold and 15.1-fold right-shift in morphine dose-response curves). Anti-IL-10 antibody and SB203580 significantly inhibited the amitriptyline-induced p38 mitogen-activated protein kinase and heme oxygenase-1 expression and the associated antiinflammatory effect of amitriptyline. Daily injection of zinc protoporphyrin also demonstrated that it reverses the effect of amitriptyline in morphine's antinociception and antiinflammation in chronic morphine-infused rats. CONCLUSIONS: These results suggest that the antiinflammatory effect of amitriptyline on morphine tolerance, probably acting by increasing IL-10 expression, is mediated by p38 mitogen-activated protein kinase heme oxygenase-1 signal transduction cascade.

Ultra-low-dose naloxone restores the antinociceptive effect of morphine and suppresses spinal neuroinflammation in PTX-treated rats.

The aim of the present study was to examine the effect of ultra-low-dose naloxone on pertussis toxin (PTX)-induced thermal hyperalgesia in rats and its underlying mechanisms. Male Wistar rats, implanted with an intrathecal catheter with or without a microdialysis probe, received a single intrathecal injection of PTX (1 microg in 5 microl saline). Four days after PTX injection, they were randomly given a different dose of naloxone (either 15 microg or 15 ng in 5 microl saline), followed by a morphine injection (10 microg in 5 microl saline) after 30 min. The results found that PTX injection induced thermal hyperalgesia and increasing excitatory amino acid (EAA; L-glutamate and L-aspartate) concentration in the spinal CSF dialysates. Ultra-low-dose naloxone not only preserved the antinociceptive effect of morphine but also suppressed the PTX-evoked EAA release as well. Moreover, ultra-low-dose naloxone plus morphine administration inhibited the downregulation of L-glutamate transporters (GTs) and the L-glutamate-metabolizing enzyme glutamine synthetase (GS), and, moreover, inhibited microglial activation and suppressed cytokine expression in PTX-treated rat spinal cords. These results show that ultra-low-dose naloxone preserves the antinociceptive effect of morphine in PTX-treated rats. The mechanisms include (a) inhibition of pro-inflammatory cytokine expression, (b) attenuation of PTX-evoked EAA release, and (c) reversion of the downregulation of GT expression.

Closed-circuit isoflurane-based anesthesia provides better fast-tracking anesthesia than fentanyl/propofol-based anesthesia for off-pump coronary artery bypass graft surgery.

BACKGROUND: In recent years, low-dose fentanyl combined with short-acting hypnotic drug has been thought to be better than traditional high-dose fentanyl in cardiac anesthesia. On the other hand, the practice of closed-circuit inhaled anesthesia offers many advantages, including hemodynamic stability, maintenance of adequate anesthesia depth and early recovery. This study sought to evaluate the effect of closed-circuit isoflurane-based anesthesia (CIA) and fentanyl/propofol-based anesthesia (FPA) on off-pump coronary artery bypass graft (OPCABG) surgery. METHODS: Fifty patients scheduled for elective OPCABG surgery were enrolled and randomly assigned to receive either CIA (n = 25) or FPA (n = 25). In the CIA group, anesthesia was induced with fentanyl 2 microg/kg and midazolam 0.05 mg/kg, followed by 2% isoflurane in oxygen (oxygen flow rate = 3 L/min) via mask ventilation for 30 min. Pancuronium 0.1-0.15 mg/kg was given thereafter to facilitate endotracheal intubation. Anesthesia was maintained by isoflurane in a minimal oxygen flow of 300 mL/min, with the vaporizer adjusted to deliver 3%-5% concentration. In the FPA group, anesthesia was induced with fentanyl 10-15 microg/kg and midazolam 0.05 mg/kg; and pancuronium 0.1-0.15mg/kg was used for endotracheal intubation. Anesthesia was maintained by propofol 2-6 mg/kg/hr and fentanyl 1-2 microg/kg/hr, and an incremental bolus of i.v. propofol 20 mg was given if the patient's mean blood pressure (MBP) exceeded 85 mmHg. An inotropic agent was given if the patient's MBP dropped below 65 mmHg or if the patient experienced a decrease in MBP greater than 20% of the preinduction value. The time of extubation, length of stay in the intensive care unit, and inotropic requirements were recorded. RESULTS: The patients in the CIA group were extubated earlier than those in the FPA group (281.3 +/- 32.5 min versus 311.3 +/- 38.5 min, respectively; P < 0.05), although there was no statistical difference in the length of stay in the intensive care unit (29.6 +/- 4.8 hr versus 30.1 +/- 7.6 hr, respectively; P = 0.4). The use of inotropic agent in the CIA group was less than in the FPA group (16% vs. 56%, P < 0.01). Dopamine requirement was less in the CIA group than in the FPA group (0.8 +/- 0.3 vs. 3.7 +/- 0.4 microg/kg/min, respectively; P < 0.01). CONCLUSIONS: These results suggest that CIA, as compared with FPA, provides a significant reduction in the time to extubation after OPCABG surgery with less use of inotropic agents.

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.