Rs11726196 Single-Nucleotide Polymorphism of the Transient Receptor Potential Canonical 3 (TRPC3) Gene Is Associated with Chronic Pain.

Chronic pain is reportedly associated with the transient receptor potential canonical 3 (TRPC3) gene. The present study examined the genetic associations between the single-nucleotide polymorphisms (SNPs) of the TRPC3 gene and chronic pain. The genomic samples from 194 patients underwent linkage disequilibrium (LD) analyses of 29 SNPs within and around the vicinity of the TRPC3 gene. We examined the associations between the SNPs and the susceptibility to chronic pain by comparing the genotype distribution of 194 patients with 282 control subjects. All SNP genotype data were extracted from our previous whole-genome genotyping results. Twenty-nine SNPs were extracted, and a total of four LD blocks with 15 tag SNPs were observed within and around the TRPC3 gene. We further analyzed the associations between these tag SNPs and chronic pain. The rs11726196 SNP genotype distribution of patients was significantly different from the control subjects even after multiple-testing correction with the number of SNPs. The TT + TG genotype of rs11726196 is often carried by chronic pain patients, suggesting a causal role for the T allele. These results contribute to our understanding of the genetic risk factors for chronic pain.

Single-Nucleotide Polymorphisms of the PAR2 and IL-17A Genes Are Significantly Associated with Chronic Pain.

Patients with chronic pain are affected psychologically and socially. There are also individual differences in treatment efficacy. Insufficient research has been conducted on genetic polymorphisms that are related to individual differences in the susceptibility to chronic pain. Autoimmune disorders can lead to inflammation and chronic pain; therefore, we focused on the autoimmune-related protease-activated receptor 2 (PAR2/F2RL1) and interleukin 17A (IL-17A/IL17A) genes. PAR2 and IL-17A are associated with autoimmune diseases that lead to chronic pain, and PAR2 regulates T-helper (Th) cell activation and differentiation. We hypothesized that the PAR2 and IL-17A genes are associated with chronic pain. The present study used a case-control design to statistically examine associations between genetic polymorphisms and the vulnerability to chronic pain. The rs2243057 polymorphism of the PAR2 gene and rs3819025 polymorphism of the IL-17A gene were previously reported to be associated with pain- or autoimmune-related phenotypes. Thus, these polymorphisms were investigated in the present study. We found that both rs2243057 and rs3819025 were significantly associated with a susceptibility to chronic pain. The present findings revealed autoimmune-related genetic factors that are involved in individual differences in chronic pain, further aiding understanding of the pathomechanism that underlies chronic pain and possibly contributing to future personalized medicine.

Heparan sulfate 3-O-sulfotransferase 4 is genetically associated with herpes zoster and enhances varicella-zoster virus-mediated fusogenic activity.

Acute pain that is associated with herpes zoster (HZ) can become long-lasting neuropathic pain, known as chronic post-herpetic neuralgia (PHN), especially in the elderly. HZ is caused by the reactivation of latent varicella-zoster virus (VZV), whereas PHN is not attributed to ongoing viral replication. Although VZV infection reportedly induces neuronal cell fusion in humans, the pathogenesis of PHN is not fully understood. A genome-wide association study (GWAS) revealed significant associations between PHN and the rs12596324 single-nucleotide polymorphism (SNP) of the heparan sulfate 3-O-sulfotransferase 4 (HS3ST4) gene in a previous study. To further examine whether this SNP is associated with both PHN and VZV reactivation, associations between rs12596324 and a history of HZ were statistically analyzed using GWAS data. HZ was significantly associated with the rs12596324 SNP of HS3ST4, indicating that HS3ST4 is related to viral replication. We investigated the influence of HS3ST4 expression on VZV infection in cultured cells. Fusogenic activity after VZV infection was enhanced in cells with HS3ST4 expression by microscopy. To quantitatively evaluate the fusogenic activity, we applied cytotoxicity assay and revealed that HS3ST4 expression enhanced cytotoxicity after VZV infection. Expression of the VZV glycoproteins gB, gH, and gL significantly increased cytotoxicity in cells with HS3ST4 expression by cytotoxicity assay, consistent with the fusogenic activity as visualized by fluorescence microscopy. HS3ST4 had little influence on viral genome replication, revealed by quantitative real-time polymerase chain reaction. These results suggest that HS3ST4 enhances cytotoxicity including fusogenic activity in the presence of VZV glycoproteins without enhancing viral genome replication.

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia.

BACKGROUND: Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain. RESULTS: Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain (p ≥ 1.858 × 10-7), the GWAS of PHN patients revealed that the rs4773840 SNP within the ABCC4 gene region was significantly associated with PHN in the trend model (nominal p = 1.638 × 10-7). In the additional gene-based analysis, one gene, PRKCQ, was significantly associated with chronic pain in the trend model (adjusted p = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models. CONCLUSIONS: These results suggest that the PRKCQ gene and rs4773840 SNP within the ABCC4 gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.

[Device for quantitative analysis of perception and pain sensation].

The article describes an analysing device that measures the perception and intensity of pain quantitatively. While it is not necessarily true that psychological aspect is totally irrelevant to pain measurement, this device is remarkable in that it is capable of measuring the intensity of pain felt by the patient more objectively by using electric stimuli. The feature of this device is that it uses a non-pain heteresthesia for measuring the intensity of pain. The device is compact, light-weight, and portable. Unlike VAS that requires only a scale, the device requires a person to carry out the measurement. Nevertheless, as the National Health Insurance (NHI) coverage has been approved, introduction of the device may be facilitated in terms of budget for the purchase and labor. The device is useful to better understand not only the intensity of pain but also the pathological conditions, resulting in more appropriate treatment, by (1) comparing degree of pain or VAS values taken by a multicenter study with those of a patient; (2) using both degree of pain and VAS; and (3) multiple measurements of degree of pain and VAS in one case.

Appearance of burning abdominal pain during cesarean section under spinal anesthesia in a patient with complex regional pain syndrome: a case report.

INTRODUCTION: The mechanism of complex regional pain syndrome (CRPS) was reported as being related to both the central and peripheral nervous systems. Recurrence of CRPS was, reportedly, induced by hand surgery in a patient with upper limb CRPS. However, there is no documentation of mechanical allodynia and burning abdominal pain induced by Cesarean section under spinal anesthesia in patients with upper limb CRPS. CASE: We report the case of a patient who suffered from burning abdominal pain during Cesarean section under spinal anesthesia 13 years after the occurrence of venipuncture-induced CRPS of the upper arm. The patient's pain characteristics were similar to the pain characteristics of her right arm during her previous CRPS episode 13 years earlier. In addition, mechanical allodynia around the incision area was confirmed after surgery. We provided ultrasound-guided rectus sheath block using 20 mL of 0.4% ropivacaine under ultrasound guidance twice, which resulted in the disappearance of the spontaneous pain and allodynia. DISCUSSION: The pain relief was probably related to blockade of the peripheral input by this block, which in turn would have improved her central sensitization. CONCLUSION: Our report shows that attention should be paid to the appearance of neuropathic pain of the abdomen during Cesarean section under spinal anesthesia in patients with a history of CRPS.

Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.

BACKGROUND: In Japan, routine clinical care does not normally involve the use of a monitoring device to guide the administration of neuromuscular blocking drugs or their antagonists. Although most previous reports demonstrate that sugammadex offers more rapid and reliable antagonism from rocuronium-induced neuromuscular blockade, this advantage has not been confirmed in clinical settings when no neuromuscular monitoring is used. In this multicenter observational study, we sought to determine whether sugammadex reduces the incidence of postoperative residual weakness compared with neostigmine when the administration of rocuronium and its antagonists is not guided by neuromuscular monitoring. METHODS: This study was conducted in two 5-month periods that preceded and followed the introduction of sugammadex into clinical practice in Japan. Five university-affiliated teaching hospitals participated in this study. Neostigmine was used to antagonize rocuronium-induced neuromuscular blockade in the first phase, and sugammadex was used in the second phase. The timing and doses of rocuronium, neostigmine, and sugammadex were determined by the attending anesthesiologists without the use of neuromuscular function monitoring devices. To ascertain the incidence of postoperative residual neuromuscular weakness, the train-of-four ratio (TOFR) was determined acceleromyographically after tracheal extubation. Since our practice also does not usually involve calibration and normalization of accelerographic responses, both TOFR <0.9 and TOFR <1.0 were used as the criteria for defining postoperative residual weakness. RESULTS: In the first phase, 109 patients received neostigmine (average dose 33 µg/kg) and 23 patients were considered (by clinical criteria) to have adequate recovery and did not receive neostigmine (spontaneous recovery group). In the second phase, 117 patients received sugammadex (average dose 2.7 mg/kg) for antagonism of rocuronium-induced blockade. The incidence (95% confidence interval) of TOFR <0.9 under spontaneous recovery, after neostigmine, and after sugammadex, was 13.0% (2.8%-33.6%), 23.9% (16.2%-33.0%), and 4.3% (1.7%-9.4%), respectively. The incidence (95% confidence interval) of TOFR <1.0 in these groups was 69.6% (47.1%-86.6%), 67.0% (57.3%-75.7%), and 46.2% (36.9%-55.6%), respectively. The use of sevoflurane in the neostigmine group and the short interval between the administration of the last doses of rocuronium and sugammadex were associated with a higher incidence of postoperative residual weakness. CONCLUSIONS: This study demonstrated that the risk of TOFR <0.9 after tracheal extubation after sugammadex remains as high as 9.4% in a clinical setting in which neuromuscular monitoring (objective or subjective) was not used. Our finding underscores the importance of neuromuscular monitoring even when sugammadex is used for antagonism of rocuronium-induced neuromuscular block.

Effect of spinal anesthesia for elective cesarean section on cerebral blood oxygenation changes: comparison of hyperbaric and isobaric bupivacaine.

We used near-infrared spectroscopy (NIRS) to evaluate cerebral blood oxygenation changes in subjects undergoing cesarean section under spinal anesthesia (SP) with hyperbaric bupivacaine (group H, 27 subjects) or isobaric bupivacaine (group I, 15 subjects). In group H, total-Hb, oxy-Hb, and mean blood pressure (MBP) within 20 min after SP were significantly lower than the baseline values. In contrast, there was no significant change from baseline in total-Hb, oxy-Hb, or MBP in group I after SP. Total-Hb and MBP in group H were significantly lower than those in group I within 10 min after SP. There was no significant change of deoxy-Hb, tissue oxygen index, or heart rate from baseline in either of the groups. These results suggest that isobaric bupivacaine may be superior to hyperbaric bupivacaine for preventing a decrease of maternal cerebral blood flow after SP for cesarean section.

Incidence and prognosis of persistent pain induced by venipuncture for blood sampling: an observational study over a 5-year period.

OBJECTIVE: The purpose of this study was to determine the incidence and prognosis of persistent and neuropathic pain induced by venipuncture for blood sampling in clinical practice. DESIGN & SETTING: We investigated the incidence of persistent and neuropathic pain after venipuncture for blood sampling and evaluated the prognosis of patients with neuropathic pain at Nihon University Itabashi Hospital, Japan, based on an observational study. SUBJECTS: Outpatients who required venipuncture for blood sampling at the laboratory room of Nihon University Itabashi Hospital between 2004 and 2008 were included as study subjects. RESULTS: In the present study, of the 587,551 venipunctures performed at our hospital between 2004 and 2008, the incidences of persistent and neuropathic pain after venipuncture were 1 in every 4,418 venipunctures (133/587,551) and 1 in every 30,923 venipunctures (19/587,551), respectively. All the 19 patients who were identified as having neuropathic pain recovered completely. CONCLUSIONS: We demonstrated that the incidence of persistent pain after venipuncture for blood sampling is low and that its prognosis is good.

Rocuronium and sugammadex used effectively for electroconvulsive therapy in a patient with Brugada syndrome.

We report the successful anesthetic management of a patient with Brugada syndrome who underwent electroconvulsive therapy to treat bipolar disorder. Suxamethonium and neostigmine were contraindicated to avoid the vagotonic effects that can precipitate ventricular fibrillation during anesthesia in patients with Brugada syndrome. The combination of 1.2 mg/kg rocuronium and 10 mg/kg sugammadex was effectively and safely used to induce and antagonize neuromuscular block for 8 consecutive electroconvulsive therapy sessions in this patient.

The effect of dexmedetomidine on arterial-cardiac baroreflex function assessed by spectral and transfer function analysis.

PURPOSE: The α(2)-adrenergic receptor agonist dexmedetomidine reportedly weakens heart rate (HR) responses to 'rapid' (during a few seconds) reduction in arterial pressure, but does not affect HR responses to 'gradual' (during 60 s) reduction in arterial pressure. As the speed of neurotransmission along the parasympathetic nerve is relatively rapid, alteration of parasympathetic-mediated arterial-cardiac baroreflex function plays a more important role in HR responses to 'rapid' changes in arterial pressure. We therefore hypothesized that dexmedetomidine attenuates parasympathetic-mediated arterial-cardiac baroreflex function. METHODS: Twelve healthy men received placebo, low-dose (loading, 3 µg/kg/h for 10 min; maintenance, 0.2 µg/kg/h for 60 min) (low-DEX), or moderate-dose (loading, 6 µg/kg/h for 10 min; maintenance, 0.4 µg/kg/h for 60 min) (moderate-DEX) dexmedetomidine infusions in a randomized, double-blind, crossover study. Before and after 70 min of infusion, arterial-cardiac baroreflex function was assessed by spectral and transfer function analysis between arterial pressure variability and HR variability. RESULTS: The high-frequency power of systolic arterial pressure (SAP) variability increased significantly with low-DEX and moderate-DEX infusions (significant interaction effects, P = 0.005), whereas the high-frequency power of R-wave-R-wave interval (RRI) variability (as an index of cardiac parasympathetic activity) did not change significantly at any dose infusions. Then, transfer function gain in the high-frequency range (as an index of parasympathetic arterial-cardiac baroreflex) decreased significantly with low-DEX and moderate-DEX infusions (significant interaction effects, P = 0.007). CONCLUSIONS: The present results suggest that dexmedetomidine attenuates parasympathetic-mediated arterial-cardiac baroreflex function, implying weakened HR response to 'rapid' reduction in arterial pressure.

Cauda equina syndrome following combined spinal and epidural anesthesia: a case report.

PURPOSE: To describe a case of complete neurological recovery from cauda equina syndrome lasting ten months following spinal anesthesia with 0.5% hyperbaric bupivacaine and epidural anesthesia with ropivacaine, and to discuss the possible mechanisms involved. CLINICAL FINDINGS: A 79-yr-old man with Paget's disease was scheduled for surgery to remove a skin tumour below his scrotum. He had no history of radicular pain or back pain and no pre-existing neurologic disorder. Surgery was performed with the patient in the supine position. He received 0.5% hyperbaric bupivacaine intrathecally for the procedure and ropivacaine through an epidural catheter for postoperative pain management. After catheter removal, the patient developed urinary retention, fecal incontinence, and perianal hypoesthesia. A lumbosacral magnetic resonance imaging (MRI) revealed no tumour, infarction, degeneration, spinal stenosis, or compression on the cauda equina nerve roots. A diagnosis of cauda equina syndrome was made, and the etiology was thought to be toxicity of bupivacaine either alone or in combination with ropivacaine. After three months, the patient reported some return of sensation at the perianal area, with complete resolution at four months. At the ten-month follow-up visit, the patient had recovered from his urinary retention and fecal incontinence. CONCLUSION: This case suggests that spinal anesthesia, even with an ordinary dose of hyperbaric 0.5% bupivacaine, might induce cauda equina syndrome in older patients.

A randomized trial to identify optimal precurarizing dose of rocuronium to avoid precurarization-induced neuromuscular block.

PURPOSE: The aim of this study was to examine the safe precurarizing dose of rocuronium required to avoid neuromuscular block after precurarization. METHODS: Twenty-four female patients were randomly allocated into two groups of 12 patients each. General anesthesia was induced and maintained with remifentanil and propofol, and a laryngeal mask was inserted without the aid of a neuromuscular blocking agent. Patients were randomized to receive either 0.03 or 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular block was monitored using acceleromyographic train-of-four (TOF) of the adductor pollicis muscle. Three minutes after the precurarization, all patients received suxamethonium 1.5 mg/kg and were graded on severity of fasciculations. RESULTS: The average TOF ratio was kept above 0.9 even 3 min after precurarization with 0.03 mg/kg rocuronium. In contrast, in patients who received 0.06 mg/kg rocuronium, the ratios significantly decreased to 0.72 (0.14) [mean (SD), P < 0.004] and 0.68 (0.18) (P < 0.006) 2 min and 3 min after the precurarization, respectively. No visible muscle movement was observed following suxamethonium injection, except that one patient who received 0.03 mg/kg rocuronium showed very fine muscle movements of the fingertips. CONCLUSION: Rocuronium at 0.06 mg/kg is an overdose for precurarization. The results of the present study demonstrate that a safe and effective precurarizing dose of rocuronium is 0.03 mg/kg.

Onset of rocuronium-induced neuromuscular block evaluated subjectively and accerelomyographically at the masseter muscle.

PURPOSE: The main aim of this study was to compare the onset times of rocuronium evaluated subjectively and by acceleromyography at the masseter muscle (MM). METHODS: Forty female patients were sequentially enrolled in this study. In the first 20 patients, neuromuscular block was evaluated subjectively. After induction of anesthesia with fentanyl and propofol, both the left masseter and ulnar nerves were stimulated in 2-Hz train-of-four (TOF) mode using peripheral nerve stimulators. Contractions of the MM were felt with an anesthesiologist's left hand holding an anesthesia facemask; those of the adductor pollicis (APM) were visually observed. All the patients received a bolus of rocuronium, 0.6 mg/kg. Onset times after rocuronium were defined as the duration until the contractions became impalpable at the MM or invisible at the APM. At the time contraction of the MM had not been felt, intubating conditions were assessed. In the next 20 patients, contractions of the MM and the APM were concurrently quantified using acceleromyography after induction of anesthesia and laryngeal mask insertion. Following 0.6 mg/kg rocuronium, onset of the action was recorded. RESULTS: Onset of the action of rocuronium at the MM evaluated subjectively [mean (SD), 70.3 (17.7) s] was similar to that monitored acceleromyographically [73.3 (27.6) s, P > 0.05], and significantly shorter than that at the APM acceleromyographically [111.0 (34.8) s, P = 0.016]. Intubating conditions of 20 patients were graded either excellent or good. CONCLUSION: Subjective evaluation of contractions of the MM by an anesthesiologist's hand may be reliable to determine faster timing for safe tracheal intubation.

[Comprehensive evaluation of the effect of triazolam on amnesia during the preoperative period].

BACKGROUND: Triazolam reportedly has greater amnesic potential than other benzodiazepines. The present study was designed to investigate whether this amnesic potential can be applied to surgical patients as premedication, thus relieving them from postoperatively remembering preoperative fears of anesthesia and surgery. METHODS: We prospectively evaluated the effect on amnesia of triazolam administered during the preoperative period in 80 patients between 20-64 years of age (mean, 43.1 +/- 14.3 years) who underwent surgeries for non-malignant diseases under general anesthesia maintained with sevoflurane and nitrous oxide in oxygen throughout the operation, or general anesthesia maintained with the same anesthetics combined with epidural or spinal anesthesia. Patients with diseases or factors influencing the effect of triazolam, such as a history of mental diseases, recent sedative or antihistamine usage, or current sleep disturbances, were excluded from this study. Triazolam was administered to the 80 patients orally at a dose of 0.375 mg 60 minutes prior to entering the operating room. During structured interviews on postoperative day 1, the patients were asked to state what they remembered of the preoperative period. Amnesia was classified based on the patients' last memory before the anesthetic induction as follows: loss of memory from immediately after taking triazolam, loss of memory at departure from the ward, loss of memory at the entrance to the operating room, loss of memory at the operating table and some recall of events at the operating table. RESULTS: Interviews revealed that 26.3% of the patients experienced loss of memory immediately after taking triazolam, this number increasing to 28.8% of the patients at departure from the ward, 35.0% at the entrance to the operating room and 67.5% on the operating table. The remaining patients (32.5%) had some memory of the operating room and table. Triazolam caused no respiratory depression at the operating table, although 2 of the patients experienced dizziness, 1 patient had nausea and 1 patient felt heavy-headed during the period between taking triazolam and the induction of anesthesia. Although 13 patients had delayed emergence from general anesthesia, these patients remaining anesthetized even 5 minutes after the concentration of sevoflurane in the expired gas decreased and remained below 0.1 percent, all these patients emerged immediately after intravenous administration of flumazenil. CONCLUSIONS: The use of triazolam as premedication produced a high incidence of amnesia for preoperative events without causing respiratory depression. Triazolam appears to be a useful premedicant for surgical patients who wish to have no memory at the operating room.

[Effects of the induction of anesthesia with propofol on hemodynamics in patients with Parkinson's disease].

BACKGROUND: Patients with Parkinson's disease frequently suffer from impaired autonomic nervous function. To elucidate the effects of the induction of anesthesia with propofol on cardiovascular hemodynamics has become important, since the number of patients with Parkinson's disease undergoing deep brain stimulation under general anesthesia has increased recently. METHODS: Effects of induction with propofol in patients with Parkinson's disease on cardiovascular hemodynamics and autonomic nervous activity were compared with those of the control patients. Moreover, possible different effect on hemodynamics between the propofol alone and the combination of propofol and fentanyl for the induction were examined in patients with Parkinson's disease. RESULTS: Although heart rate or blood pressure was not different between patients with Parkinson's disease and the control patients before the induction, sympathetic vasomotor activity was lower in patients with Parkinson's disease than the control patients. The induction of anesthesia significantly decreased blood pressure in patients with Parkinson's disease. However the decreasing systolic blood pressure after the induction of anesthesia was more marked in patients with Parkinson's disease than the control patients. We did not find differences in the changes of blood pressure between the propofol alone and the combination of propofol and fentanyl in patients with Parkinson's disease. CONCLUSIONS: No abnormal responses to the induction of anesthesia with propofol were found in the patients with Parkinson's disease.

The different effects of midazolam and propofol sedation on dynamic cerebral autoregulation.

BACKGROUND: Although midazolam and propofol reduce cerebral blood flow (CBF) similarly, they generate different effects on the autonomic nervous system and endothelium-induced relaxation. Midazolam induces sympathetic dominance, whereas propofol induces parasympathetic dominance. Midazolam has no effect on endothelium-dependent relaxation, whereas propofol suppresses endothelium-dependent relaxation. Moreover, midazolam apparently constricts cerebral arterioles. We therefore hypothesized that midazolam and propofol have different effects on dynamic cerebral autoregulation. METHODS: Ten healthy male subjects received midazolam, propofol, and placebo administrations in a randomized, single-blind, crossover study. The modified Observer's Assessment of Alertness/Sedation scale was used to assess sedation depth. After reaching a target depth of sedation (Observer's Assessment of Alertness/Sedation scale score 3, responds only after name is called loudly and/or repeatedly) or after 15 minutes of normal saline administration as placebo, dynamic cerebral autoregulation was evaluated by spectral and transfer function analyses between mean arterial blood pressure variability in the radial artery measured by tonometry, and CBF velocity variability in the middle cerebral artery measured by transcranial Doppler ultrasonography. RESULTS: Steady-state CBF velocity decreased significantly with midazolam and propofol administration (significant interaction effects, P = 0.024). However, transfer function gain in the low-frequency range decreased significantly only with midazolam administration (significant interaction effects, P = 0.015), suggesting a reduced magnitude of transfer from mean arterial blood pressure oscillations to CBF fluctuations during midazolam sedation. CONCLUSION: Our results suggest that midazolam and propofol sedation have different effects on dynamic cerebral autoregulation despite causing equivalent decreases in steady-state CBF velocity. Only midazolam sedation is likely to improve dynamic cerebral autoregulation.

Monitoring masseter muscle evoked responses enables faster tracheal intubation.

PURPOSE: The aim of this study was to investigate whether monitoring neuromuscular block at the masseter muscle (MM) would allow faster tracheal intubation when compared with that at the adductor pollicis muscle (APM). METHODS: Twenty female patients undergoing gynecological surgery were enrolled into this study. Immediately after inducing anesthesia with fentanyl and propofol, both the left masseter and ulnar nerves were stimulated in a 2 Hz train-of-four (TOF) mode using peripheral nerve stimulators. Contractions of the MM were felt with the anesthesiologist's left hand lifting the patient's jaw and holding an anesthesia facemask, while those of the APM were visually observed. Immediately after the contracting responses of the muscles were confirmed, all of the patients received an iv bolus of vecuronium 0.1 mg kg(-1). Onset times after vecuronium were defined as the duration until the contractions became impalpable at the MM or invisible at the APM. When the contraction of the MM could no longer be felt, the conditions for laryngoscopy and tracheal intubation were assessed. RESULTS: Onset time evaluated tactually at the MM (mean +/- SD, 108.4 +/- 27.7 s) was significantly shorter than that evaluated visually at the APM (181.2 +/- 32.1 s, P < 0.0001). The intubating conditions for all patients were graded as either excellent or good. CONCLUSION: Tactual evaluation of muscle paralysis of the MM during induction of anesthesia is clinically useful since it leads to faster tracheal intubation.

Effectiveness of the timing principle with high-dose rocuronium during rapid sequence induction with lidocaine, remifentanil and propofol.

PURPOSE: The main purpose of this study was to examine the effectiveness of the timing principle with 1 mg kg(-1) rocuronium for rapid sequence intubation. As secondary outcomes, propofol and lidocaine with or without remifentanil were examined to note their effects on the cardiovascular responses to laryngoscopy and intubation. METHODS: Thirty patients were randomly allocated to one of two groups of 15 patients each: a lidocaine-treated group (L) and a lidocaine/remifentanil-treated group (LR). Thirty seconds after lidocaine 1 mg kg(-1) with or without infusion of remifentanil 1 microg kg(-1) min(-1), all patients received a bolus of rocuronium 1 mg kg(-1). Shortly afterwards, patients were given propofol 2-2.5 mg kg(-1). Intubating conditions and cardiovascular responses were observed 60 s after rocuronium. The time to spontaneous recovery of visible train-of-four (TOF) counts of 4 was observed at the thumb during 1.0-1.5% end-tidal sevoflurane and remifentanil anesthesia. RESULTS: All patients had excellent or good intubating conditions. Hypertension and tachycardia during laryngoscopy were well prevented in group LR, whereas they were significantly observed in group L. The times to reappearance of TOF counts of 4 were comparable in all groups [mean (SD); 63.6 (8.6) min in group L and 63.5 (11.6) min in group LR]. CONCLUSION: Application of the timing principle with 1 mg kg(-1) rocuronium is beneficial for rapid tracheal intubation. Co-administered lidocaine, remifentanil and propofol can definitely suppress cardiovascular responses during laryngoscopy and intubation.

[Long-term efficacy and safety of pregabalin in patients with postherpetic neuralgia: results of a 52-week, open-label, flexible-dose study].

BACKGROUND: The efficacy of pregabalin was demonstrated in a randomized double-blind placebo-controlled 13-week trial in 371 Japanese patients with postherpetic neuralgia (PHN). In this study, we evaluated the long-term efficacy and safety of pregabalin for relief of PHN. METHODS: 126 patients were enrolled from the preceding double-blind study into the 52-week open-label study. Patients were given pregabalin 150 to 600 mg x day(-1). Pain intensity was measured using the Short-Form McGill Pain Questionnaire (SF-MPQ: total score, visual analogue scale and present pain intensity). RESULTS: The efficacy parameter SF-MPQ showed a decrease over the treatment-term. The changes of visual analogue scale and present pain intensity at the endpoint were -28.3 mm and -1.1 score, respectively. The commonly reported adverse events were dizziness, somnolence, peripheral edema and weight gain, and most of them were mild to moderate in intensity. No new adverse events were observed due to long-term pregabalin administration. CONCLUSIONS: These results suggest that long-term treatment of pregabalin may be beneficial in patients with PHN.