Exploration of beauvericin's toxic effects and mechanisms in human astrocytes and N-acetylcysteine's protective role.

Beauvericin (BEA) is a newly identified mycotoxin produced by various Fusarium species, and its contamination in food and animal feed is widespread globally. This mycotoxin demonstrates cytotoxic effects by inducing oxidative stress in multiple models. Furthermore, evidence indicates that BEA possesses diverse toxic activities, making it a promising candidate for toxicological research. Recent studies have highlighted the ability of BEA to traverse the blood-brain barrier, suggesting its potential neurotoxicity. However, limited information is available regarding the neurotoxic effects of BEA on human astrocytes. Therefore, this study aimed to assess the neurotoxic effects of BEA on the Gibco® Human Astrocyte (GHA) cell line and elucidate the underlying mechanisms. Additionally, the study aimed to investigate the protective effects of the antioxidant N-acetylcysteine (NAC) against BEA-induced toxicity. The data show that exposure to BEA within the 2.5-15 µM concentration range resulted in concentration-dependent cytotoxicity. BEA-treated cells exhibited significantly increased levels of reactive oxygen species (ROS), while intracellular glutathione (GSH) content was significantly reduced. Western blot analysis of cells treated with BEA revealed altered protein levels of Bax, cleaved caspase-9, and caspase-3, along with an increased Bax/Bcl-2 ratio, indicating the induction of apoptosis. Additionally, BEA exposure triggered antioxidant responses, as evidenced by increased protein expression of Nrf2, HO-1, and NQO1. Significantly, pretreatment with NAC partially attenuated the significant toxic effects of BEA. In conclusion, our findings suggest that BEA-induced cytotoxicity in GHA cells involves oxidative stress-associated apoptosis. Furthermore, NAC demonstrates potential as a protective agent against BEA-induced oxidative damage.

Optimizing nonintubated laryngeal microsurgery: The effectiveness and safety of superior laryngeal nerve block with high-flow nasal oxygen-A prospective cohort study.

BACKGROUND: Laryngeal microsurgery (LMS) typically requires intubated general anesthesia (ITGA). Although nonintubated general anesthesia (NIGA) with high-flow nasal oxygen (HFNO) can be applied with LMS, a muscle relaxant is required, which can cause apnea and hypercapnia. This study evaluated the effectiveness of a superior laryngeal nerve block (SLNB) in improving safety during LMS. METHODS: This prospective cohort study enrolled a cumulative total of 61 adult patients received LMS under intravenous general anesthesia and allocated to three groups: ITGA group (n = 18), which patients performed intubation; neuromuscular blocking (NMB) group (n = 21), which patients administrated muscle relaxant without intubation and superior laryngeal nerve block (NB) group (n = 22), which patients performed SLNB without intubation or muscle relaxant. RESULTS: The average (SD) values of PaCO 2 after surgery in ITGA, NMB, and NB group were 50.8 (7.5), 97.5 (24.9), and 54.8 (8.8) mmHg, respectively. The mean postoperative pH values were 7.33 (0.04), 7.14 (0.07), and 7.33 (0.04), respectively. The results were all p < 0.001, and the average pH value of the NMB group was lower than that of the ITGA and NB groups. During the LMS, the mean heart rate (HR) (93.9 [18.1] bpm) and noninvasive blood pressure systolic (NBPs) (143.5 [28.2] mmHg) in the NMB group were higher than those in the ITGA group (HR = 77.4 [13.5] bpm and NBPs = 132.7 [20.8] mmHg) and NB group (HR = 82.3 [17.4] bpm and NBPs = 120.9 [25.0] mmHg). The results of p value by HR and NBPs are p < 0.001. The PaCO 2 and pH values are similar between ITGA group and NB group. CONCLUSION: Our approach of using HFNO with SLNB was successful for performing nonintubated LMS, enabling the patients to maintain spontaneous breathing and effectively eliminate CO 2 . This approach reduces the risks of hypercapnia and acidosis even when the duration of LMS exceeds 30 minutes.

Hyperlactatemia is associated with increased risks of long-term mortality and major adverse cardiovascular events in sepsis survivors.

INTRODUCTION: Serum lactate is a potentially valuable biomarker for risk assessment for patients with sepsis, as hyperlactatemia is associated with elevated short-term mortality risks. However, the associations between hyperlactatemia and long-term clinical outcomes in sepsis survivors remain unknown. The objective of this study was to investigate whether hyperlactatemia at the time of hospitalisation for sepsis was associated with worse long-term clinical outcomes in sepsis survivors. METHODS: In total, of 4983 sepsis survivors aged ≥ 20 years were enrolled in this study between January 1, 2012, and December 31, 2018. They were divided into low (≤18 mg/dL; n = 2698) and high (>18 mg/dL; n = 2285) lactate groups. The high lactate group was then matched 1:1 by propensity-score method to the low lactate group. The outcomes of interest were all-cause mortality, major adverse cardiac events (MACEs), ischaemic stroke, myocardial infarction, hospitalisation for heart failure, and end-stage renal disease. RESULTS: After propensity score matching, the high lactate group had greater risks of all-cause mortality (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.41-1.67), MACEs (HR 1.53, 95% CI 1.29-1.81), ischaemic stroke (HR 1.47, 95% CI 1.19-1.81), myocardial infarction (HR 1.52, 95% CI 1.17-1.99), and end-stage renal disease (HR 1.42, 95% CI 1.16-1.72). Subgroup analyses stratified by baseline renal function revealed almost similarity across groups. CONCLUSION: We found that hyperlactatemia is associated with long-term risks of mortality and MACEs in sepsis survivors. Physicians may consider more aggressive and prompter management of sepsis in patients who present with hyperlactatemia to improve long-term prognoses.

Low Versus High Stroke Volume Variation-Guided and Reduction of Postoperative Complications After Liver Resection: A Randomized Clinical Trial.

BACKGROUND: Liver surgery is a major abdominal operation associated with a dramatic change in intraoperative hemodynamics; thus, the infusion strategy is challenging for anesthesiologists. Studies have demonstrated that stroke volume variation (SVV) can be used to predict fluid responsiveness during major abdominal surgery. SVV can be used as a guide for the administration of intraoperative fluids to improve postoperative prognosis. In the present study, we planned to investigate whether high- or low-SVV in liver surgery is associated with fewer postoperative complications. METHODS: This study was a prospective randomized trial of 74 patients who underwent hepatectomy. The patients were divided into two groups for SVV-guided infusion during tumor resection surgery using a low-SVV (≤ 10%, n = 37) or high-SVV (> 10%, n = 37) strategy. The primary outcome was postoperative complications, namely infection, pleural effusion, and atelectasis. The secondary outcomes were differences in perioperative physiological variables and postoperative pain. RESULTS: No differences in postoperative complications within 30 days of surgery were observed between the low-SVV and high-SVV groups. However, we observed lower estimated glomerular filtration rates (eGFRs) and higher alanine transaminase (ALT) levels in the high-SVV group after surgery. CONCLUSION: Patients who underwent major liver tumor resection with the low-SVV or high-SVV strategy exhibited no differences in postoperative complications (48.6% vs. 45.9%; P > 0.999). However, in the high-SVV group, postoperative eGFRs were lower and ALT levels were higher.

Effects of Renin-Angiotensin-Aldosterone System Inhibitors on Long-Term Major Adverse Cardiovascular Events in Sepsis Survivors.

Background Sepsis is known to increase morbidity and duration of hospital stay and is a common cause of mortality worldwide. Renin-angiotensin-aldosterone system inhibitors (RAASis) are commonly used to treat hypertension but are usually discontinued during hospitalization for sepsis because of concerns about renal hypoperfusion. The aim of our study was to investigate whether RAASis should be continued after discharge in sepsis survivors and to identify the effects on the clinical outcomes. Methods and Results A total of 9188 sepsis survivors aged 20 years and older who were discharged from January 1, 2012 to December 31, 2019 were included in our analyses. We further divided sepsis survivors into RAASi users and nonusers. These groups were matched by propensity scores before the outcomes of interest, including all-cause mortality and major adverse cardiac events (MACE), were examined. After propensity score matching, 3106 RAASi users and 3106 RAASi nonusers were included in our analyses. Compared with RAASi nonusers, RAASi users had lower risks of all-cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.62-0.75), MACEs (HR, 0.87; 95% CI, 0.81-0.94), ischemic stroke (HR, 0.85; 95% CI, 0.76-0.96), myocardial infarction (HR, 0.74; 95% CI, 0.61-0.90), and hospitalization for heart failure (HR, 0.84; 95% CI, 0.77-0.92). Subgroup analyses stratified by admission to the ICU and the use of inotropes showed similar results. Conclusions In our study, we found that RAASi users had reduced risks of all-cause mortality and MACEs. These findings suggested a beneficial effect of RAASi use by sepsis survivors after discharge.

Randomized, Active-Controlled, Parallel-Group Clinical Study Assessing the Efficacy and Safety of FKScope® for Nasotracheal Intubation in Patients Scheduled for Oral and Maxillofacial Surgery Under General Anesthesia.

BACKGROUND: Most of the reports showed that videolaryngoscopy has better outcomes than direct laryngoscopy for nasotracheal intubation. The FKScope® comprises a semirigid and malleable stylet with a terminal camera and has been used to facilitate orotracheal intubation. However, its efficacy and safety for nasotracheal intubation remain unknown. This study compared FKScope® with Macintosh direct laryngoscopy for nasotracheal intubation. METHODS: Sixty-four patients scheduled for oral and maxillofacial surgery requiring nasotracheal intubation were enrolled and randomly assigned to FKScope® (n = 32) or Macintosh group (n = 32). The primary outcome was time to successful intubation during the first attempt. Secondary outcomes included modified nasal intubation difficulty scale (MNIDS) scores; percentage of glottic opening (POGO); immediate postintubation side effects such as mucosal bleeding, dental injury, and lip lacerations; and postoperative side effects including nasal pain, sore throat, hoarseness, dysphagia, and dyspnea. RESULTS: The rates of successful first-attempt intubation were 87.5% and 90.6% in the FKScope® and Macintosh group, respectively (P = 0.69). Mean (± standard deviation) total intubation time was 68.7 ± 34.8 s in the FKScope® group compared with 61.5 ± 21.9 s in the Macintosh group (P = 0.35), despite a higher POGO for the FKScope® group (77 ± 27 vs. 41 ± 31, P ＜ 0.01). The MNIDS scores of the FKScope® group were significantly lower (0.8 ± 1.0 vs. 2.8 ± 1.4, P ＜ 0.01). The groups did not differ significantly regarding most postoperative side effects, although the FKScope® group had fewer lip lacerations (P = 0.04). CONCLUSIONS: The use of FKScope® improves the view of the glottic opening and is safe for nasotracheal intubation with normal airways. However, secretions and blood can obstruct the camera, and therefore, to select the patient carefully is necessary.

Hypertension and Postoperative Pain: A Prospective Observational Study.

Objectives: The relationship between pain and hypertension is of great pathophysiological and clinical interest in the pain field, but the mechanism is poorly understood. This study used the postoperative patient-controlled analgesia (PCA) dose and the visual analysis scale (VAS) score to assess the relationship between pain and hypertension. Methods: In this prospective study in a single-center hospital, 200 participants were enrolled and divided into three groups: normotensive group, hypertension without treatment group, and hypertension with treatment group. The participants scheduled for elective inhalational general anesthesia were interviewed at hospital admission. Results: A significant difference was observed in analgesic dosage on postoperative days 1, 2, and 3 between the female normotensive group and female hypertension with treatment group (independent-samples, one-way analysis of covariance, age, and weight as covariates:P=0.021, 0.014, 0.032). No significant differences in the VAS scores and PCA dosages were observed between the male normotensive group and any one of the male hypertensive groups. Conclusion: We agree that hypertensive hypoanalgesia exists in some experimental settings. The mechanism linking postoperative pain and hypertension is far more complex than we initially believed. Therefore, more studies are required to investigate the roles that antihypertensive drugs, sex, and psychological stress play. Antihypertensive drugs may play a crucial role in mediating the relationship between pain and hypertension. Psychosocial factors were discussed but were not examined.

The Antinociceptive Effect of Light-Emitting Diode Irradiation on Incised Wounds Is Correlated with Changes in Cyclooxygenase 2 Activity, Prostaglandin E2, and Proinflammatory Cytokines.

Background. Light-emitting diode (LED) phototherapy has been reported to relieve pain and enhance tissue repair through several mechanisms. However, the analgesic effect of LED on incised wounds has never been examined. Objectives. We examined the analgesic effect of LED therapy on incision pain and the changes in cyclooxygenase 2 (COX-2), prostaglandin E2 (PGE2), and the proinflammatory cytokines interleukin 6 (IL-6), IL-1ß, and tumor necrosis factor α (TNF-α). Methods. Rats received LED therapy on incised skin 6 days before incision (L-I group) or 6 days after incision (I-L group) or from 3 days before incision to 3 days after incision (L-I-L group). Behavioral tests and analysis of skin tissue were performed after LED therapy. Results. LED therapy attenuated the decrease in thermal withdrawal latency in all the irradiated groups and the decrease in the mechanical withdrawal threshold in the L-I group only. The expression levels of COX-2, PGE2, and IL-6 were significantly decreased in the three LED-treated groups, whereas IL-1ß and TNF-α were significantly decreased only in the L-I group compared with their levels in the I groups (p < 0.05). Conclusions. LED therapy provides an analgesic effect and modifies the expression of COX-2, PGE2, and proinflammatory cytokines in incised skin.

Reversal of Progressive Conscious Disturbance with Epidural Blood Patch for Cerebrospinal Fluid Leakage at C2 Level.

Intracranial hypotension syndrome (IHS) is generally caused by cerebrospinal fluid (CSF) leakage. Complications include bilateral subdural hygroma or haematoma and herniation of the cerebellar tonsils. Epidural blood patch (EBP) therapy is indicated if conservative treatment is ineffective. We reported the case of a 46-year-old man with a history of postural headache and dizziness. The patient was treated with bed rest and daily hydration with 2000 mL of fluid for 2 weeks. However, dizziness and headache did not resolve, and he became drowsy and disoriented with incomprehensible speech. Magnetic resonance imaging demonstrated diffuse dural enhancement on the postcontrast study, sagging of the midbrain, and CSF leakage over right lateral posterior thecal sac at C2 level. We performed EBP at the level of T10-T11. We injected 14 mL of autologous blood slowly in the Trendelenburg position. Within 30 minutes, he became alert and oriented to people, place, and time. We chose thoracic EBP as first line treatment in consideration of the risk of cervical EBP such as spinal cord and nerve root compression or puncture, chemical meningitis. Also we put our patient in Trendelenburg position to make blood travel towards the site of the leak. Untreated IHS may delay the course of resolution and affect the patient's consciousness. Delivery of EBP via an epidural catheter inserted from the thoracic spine is familiar with most of anesthesiologists. It can be a safe and effective treatment for patients with IHS caused by CSF leak even at C2.Key words: Anaesthetic techniques, regional, thoracic; cerebrospinal fluid leakage; epidural blood patch; heavily T2-weighted magnetic resonance myelography; intracranial hypotension syndrome; Trendelenburg position.

Lentiviral vector-encoded microRNA-based shRNA-mediated gene knockdown of N-methyl-D-aspartate receptors in skin reduces pain.

BACKGROUND AND PURPOSE: RNA polymerase II promoters that drive the expression of rationally designed primary microRNA-based shRNA, for example, shRNAmir, can produce more potent gene knockdown than RNA polymerase III promoters. Antagonists of peripheral N methyl-D-aspartate (NMDA) receptors that do not interfere with central glutamate processing would prevent the development of adverse central nervous system effects. Thus, in this study, we examined the effects of gene silencing and antinociception on formalin- and Complete Freund's adjuvant (CFA)-induced pain in rats by subcutaneously injecting a lentiviral vector encoding a shRNAmir that targets the NR1 subunit of the NMDA receptor. METHODS: Rats received intradermal injections of different doses of NR1 shRNAmir at different time points before injection of formalin. Pain behavior was assessed by monitoring the paw flinch response, paw withdrawal threshold, and thermal withdrawal latency. We then analyzed NR1 messenger RNA and protein expression in skin and the L5 dorsal root ganglion (DRG). RESULTS: We found that intradermal injection of 1, 5, and 10 µg of shRNAmir significantly inhibited flinch responses (p < .05). Administration of 5 µg of shRNAmir resulted in the attenuation of CFA-induced mechanical allodynia, but did not affect the time spent on the rotarod. Real-time polymerase chain reaction and western blotting revealed that NR1 mRNA and protein levels were significantly lower in all NR1 shRNAmir1 groups than in controls (p < .05). There was a significant reduction in the percentage of NR1- and pERK-positive neurons in the DRG ipsilateral to shRNAmir treated paws (p < .05). The effect of antinociception and inhibition of NR1 expression by NR1 shRNAmir was evident on day 3 and persisted for 7 days after injection of 5 µg of vector. CONCLUSION: Peripheral administration of the vector-encoded NR1 shRNAmir is a promising therapy for persistent inflammatory pain.

The Implications of Tobacco Smoking on Acute Postoperative Pain: A Prospective Observational Study.

Background. The clinical importance of cigarette smoking on acute postoperative pain perception is not fully understood. Methods. To determine whether smokers who underwent major surgery need more postoperative opiate than do nonsmokers. We prospectively enrolled 407 male and 441 female participants who underwent in-hospital surgery. Current-smokers were compared with nonsmokers and past-smokers about opiate use during the first 72 h after surgery. Results. A greater proportion of males had more smoking history than females. The average age of male current-smokers is smaller than both nonsmokers and past-smokers. The surgical type (upper abdomen, lower abdomen, extremities, spine, and others) and duration of surgery have no differences between current-smokers, past-smokers, and nonsmokers. Statistically, the male current-smokers required more opiate analgesics during the first 72 h following surgery compared with the male nonsmokers and past-smokers; furthermore, the male current-smokers reported higher pain intensity when moving and at rest on day 1 after surgery. Conclusions. In this study, the male current-smokers required more morphine in the first 72 h after surgery than did the nonsmokers and past-smokers. Furthermore, smoking was more prevalent among the males than the females. Health care providers must be aware of the potential for increased narcotic requirements in male current-smokers.

Risk of Chronic Low Back Pain Among Parturients Who Undergo Cesarean Delivery With Neuraxial Anesthesia: A Nationwide Population-Based Retrospective Cohort Study.

To investigate the risk of chronic low back pain (LBP) in parturients undergoing cesarean delivery (CD) with neuraxial anesthesia (NA). LBP is common during pregnancy and also after delivery, but its etiology is poorly understood. Previous studies that investigated the correlation between epidural labor analgesia and chronic low back pain were inconclusive. These studies lacked objective diagnostic criteria for LBP and did not exclude possible confounders. We performed this nationwide population-based retrospective cohort study to explore the relationship between CD with NA and subsequent LBP. From the Taiwan National Health Insurance Research Database (NHIRD), we identified all primiparas who had given birth between January 1, 2000 and December 31, 2013. Using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes, we identified the women who had vaginal delivery (VD) and those who had CD. The mode of anesthesia was ascertained by the NHI codes. Multivariable logistic regression was used to estimate the odds of postpartum LBP in women undergoing CD with NA compared with those having VD. The outcome was a diagnosis of LBP according to the first ICD-9-CM diagnosis code. The patients were observed for 3 years after delivery or until diagnosis of postpartum LBP, withdrawal from the NHI system, death, or December 31, 2013. Of the 61,027 primiparas who underwent delivery during the observation period, 40,057 were eligible for inclusion in the study. Of these women, 27,097 (67.6%) received VD, 8662 (21.6%) received CD with spinal anesthesia, and 4298 (10.7%) received CD with epidural anesthesia (EA). Women who received CD with EA were found to have higher risk of LBP than did women who received VD, with the adjusted OR being 1.26 (95% CI: 1.17-1.34). CD with EA might increase the risk of subsequent chronic LBP.

Single-injection femoral nerve block lacks preemptive effect on postoperative pain and morphine consumption in total knee arthroplasty.

OBJECTIVE: Postoperative pain is severe after total knee arthroplasty (TKA). Therefore, femoral nerve block (FNB) is commonly used as an adjuvant to spinal anesthesia for TKA. Some anesthesia providers perform this preoperatively, while others perform it postoperatively. To our knowledge, no study has compared the relative benefits of the timing of performing the procedure. In this study, we investigated whether preoperative FNB would provide better analgesic effects than postoperative FNB in patients undergoing unilateral TKA. METHODS: In this double-blind, randomized, controlled trial, we divided 82 patients (ASA physical status I-III) undergoing unilateral TKA into four groups: (1) a pre-treatment group, in which FNB was performed with 0.4 mL/kg 0.375% bupivacaine plus 1:200,000 epinephrine after spinal anesthesia but before the operation; (2) a post-treatment group, in which FNB was performed with the same drugs at similar dosages immediately after the operation; (3) a pre-control group, in which FNB was performed with normal saline in the same volume as the tested drugs before the operation; and (4) a post-control group, in which FNB was performed with normal saline in the same volume as the tested drug after the operation. At 2, 4, 6, 24, 48 and 72 postoperative hours, we recorded cumulative morphine consumption, visual analog pain scales (VAS), the time of first request for morphine and its side effects. We also measured knee maximum flexion range of motion once a day for 3 days. Our primary aim was to obtain cumulative morphine consumption in 24 hours. RESULTS: Within the postoperative 24 hours, we found significant differences in cumulative morphine consumption between patients who received true FNB and those who did not (at 24 hours, treatment groups = 45.6 ± 31.7 and 33.5 ± 20.6 mg vs. controls = 70.8 ± 31.2 and 78.8 ± 37.7 mg, p < 0.001). We also found significant differences in VAS (at 24 hours, p < 0.001) and time to first request of morphine (p = 0.005) between the treatment group and the sham group. However, there were no significant differences in these values between the pre-surgical treatment group and the post-surgical treatment group. Beyond 24 hours, there were no significant differences in morphine consumption or maximum flexion range on day 2 and day 3 among the four groups. CONCLUSION: Patients who received FNB used for total knee arthroplasty consumed significantly less postoperative morphine and had significant relief of post-TKA pain on postoperative day 1 than those who did not have FNB. However, at follow-up we found no significant differences in these values between those receiving FNB before surgery and those receiving it after surgery.

Effects of postoperative background PCA morphine infusion on pain management and related side effects in patients undergoing abdominal hysterectomy.

STUDY OBJECTIVE: To examine the effects of background morphine infusion via patient-controlled intravenous analgesia (PCA) device. DESIGN: Randomized, controlled, double-blinded study. SETTING: University-affiliated hospital. PATIENTS: 60 ASA physical status 1 and 2 patients scheduled for abdominal hysterectomy. INTERVENTIONS: Patients were randomly allocated to either the PCA group without continuous background morphine infusion (Group 1; n = 30) or the PCA group with continuous background morphine infusion (Group 2; n = 30). MEASUREMENTS: Pain intensity during movement and at rest, morphine consumption at indicated time intervals, and related side effects were evaluated and recorded for three postoperative days at 12-hour intervals. The degree of patient satisfaction with PCA pain management was elicited and recorded. MAIN RESULTS: Pain intensity during movement (VASC) at 12 and 36 hours postoperatively and pain intensity at rest from 12 to 60 hours were significantly higher in Group 2 than Group 1. PCA morphine consumption for three days postoperatively in Group 2 was significantly higher. The frequency of vomiting, nausea, and dizziness were higher in Group 2. The frequency of pruritus, urinary retention, and allodynia was similar for both groups. The degree of patient satisfaction with pain management was generally equivalent between the groups. CONCLUSION: A continuous background morphine infusion of 0.5 mg/hr did not lower pain intensity during movement or at rest, but induced higher pain intensity, higher opioid usage, and more complications such as vomiting, nausea, and dizziness.

Gene knockdown of the N-methyl-D-aspartate receptor NR1 subunit with subcutaneous small interfering RNA reduces inflammation-induced nociception in rats.

BACKGROUND: Spinal N-methyl-D-aspartate receptors have been demonstrated to play an important role in the facilitation and maintenance of nociception. To avoid adverse effects of blocking N-methyl-D-aspartate receptors in the central nervous system, blocking N-methyl-D-aspartate receptor in peripheral nervous system is an ideal alternative. Transfection of small interfering RNAs (siRNAs) into cells has been revealed to provide potent silencing of specific genes. In this study, the authors examined the effect of subcutaneous injection of siRNA targeting the NR1 subunit of the N-methyl-D-aspartate receptor on silencing NR1 gene expression and subsequently abolishing inflammatory nociception in rats. METHODS: Male Sprague-Dawley rats received intradermal injection of NR1 siRNA and underwent injection of formalin or complete Freund's adjuvant. The flinch response and mechanical hypersensitivity by von Frey filaments were assessed. Then the messenger RNA and protein of NR1 in skin and dorsal root ganglion were analyzed. RESULTS: The results revealed that subcutaneous injection of 1 nmol NR1 siRNA effectively diminished the nociception induced by formalin and complete Freund's adjuvant stimuli and attenuated the level of NR1 messenger RNA and protein in skin and ipsilateral dorsal root ganglion. The antinociception effect and the inhibition of NR1 expression persisted for about 7 days after administration of NR1 siRNA. CONCLUSIONS: The data of this study suggest that NR1 siRNA has potential therapeutic value in the treatment of inflammatory pain induced or maintained by peripheral nociceptor activity and support the potential application of this method to the study of nociceptive processes and target the validation of pain-associated genes.

Optimal duration of urinary catheterization after thoracotomy in patients under postoperative patient-controlled epidural analgesia.

BACKGROUND: Epidural analgesia is widely used for efficient pain relief after major surgery. However, it may cause urinary retention, leading to delayed removal of bladder catheters with prolonged patient discomfort. Using a specific regimen in patient controlled epidural analgesia (PCEA), we examined the optimal duration of urinary catheterization in patients undergoing major thoracic surgery. METHODS: Seventy-eight patients scheduled for elective thoracotomy were prospectively randomized into two groups: Group 1, removal of the transurethral catheter on the first postoperative day (n = 38); Group 2, removal of the catheter after discontinuation of PCEA (n = 40). The PCEA regimen was a mixture containing low-dose morphine, bupivacaine and neostigmine and was given for 3 days after surgery in all subjects. Micturition problems, pain scores assessed by the visual analog scale (VAS), and side effects were evaluated during and after PCEA treatment. RESULTS: The average duration of urinary drainage after surgery was 30.2 + or - 5.1 hours and 78.5 + or - 7.3 hours in Groups 1 and 2, respectively. After removal of the bladder catheter, no patient in either group required re-catheterization for urinary retention or encountered catheter-related infection. VAS scores were significantly lower in Group 1 at rest and at 24, 36 and 48 hours after cessation of PCEA. VAS scores were significantly higher in Group 2 patients, possibly due to catheter-induced pain related to prolonged catheterization. CONCLUSION: Routine continuous bladder catheterization may not necessarily be required after thoracotomy in patients with ongoing continuous thoracic epidural analgesia.

Sevoflurane with or without antiemetic prophylaxis of dexamethasone in spontaneously breathing patients undergoing outpatient anorectal surgery.

STUDY OBJECTIVE: To evaluate the prophylactic use of dexamethasone with sevoflurane in outpatient anorectal surgery. DESIGN: Randomized, controlled study. SETTING: Operating room and Postanesthesia Care Unit of a general hospital. PATIENTS: 60 adult, ASA physical status I and II outpatients undergoing anorectal surgery. INTERVENTIONS: Patients were randomized to receive either dexamethasone 5 mg intravenously (IV; Group D; n = 30) or an equal volume of saline (Group S; n = 30) before anesthesia induction. Anesthesia was induced with propofol 2.5 mg.kg(-1), fentanyl two microg.kg(-1), and 2% lidocaine one mg.kg(-1) followed by placement of a Laryngeal Mask Airway. MEASUREMENTS: Frequency of postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, and patient satisfaction were recorded. MAIN RESULTS: Frequency of PONV and VAS pain scores were significantly lower in Group D than Group S (P < 0.05). The time required for "home readiness" was significantly shorter in Group D than Group S (P < 0.05). CONCLUSIONS: The prophylactic administration of 5 mg dexamethasone IV can reduce the frequency of PONV, lower VAS pain scores, facilitate recovery to home readiness, and improve satisfaction in outpatients undergoing anorectal surgery.

Bedside ultrasonic detection of massive hemothorax due to superior vena cava perforation after hemodialysis catheter insertion.

Hemothorax resulting from perforation of a great vessel is an uncommon but life-threatening complication which may occur during central venous insertion of a hemodialysis catheter. We describe a 78-year-old uremic female who developed unexplained and refractory shock on the completion of percutaneous placement of a hemodialysis catheter in the right subclavian vein under general anesthesia. Bedside transthoracic ultrasound revealed a large anechoic area above the right hemidiaphragm, suggestive of the presence of extensive hemothorax. The diagnosis was further confirmed by prompt drainage of fresh blood from the right thoracostomy tube. Emergent thoracotomy was performed and perforation of the superior vena cava was identified. Hemodynamic stability was restored after surgical repair of the injured vessel, aggressive volume resuscitation and inotropic/vasopressor treatment. This case suggests that portable ultrasonography is an invaluable bedside tool which allows anesthesiologists to made reliable and prompt diagnosis of potentially fatal complications, such as perforation of great central vein due to inadvertent cannulation.

Propofol causes less postoperative pharyngeal morbidity than thiopental after the use of a laryngeal mask airway.

The insertion of a laryngeal mask airway (LMA) may result in postoperative sore throat. The choice of induction drug on airway morbidity after LMA insertion may be important. We performed this study to compare the incidence of postoperative pharyngeal morbidity after the insertion of a LMA in 340 patients administered either 2 mg/kg propofol (group P) or thiopental 5 mg/kg (group T) for induction of anesthesia. Patients were maintained at 1-2 minimum alveolar anesthetic concentration sevoflurane in 50% oxygen/air. Spontaneous or assisted spontaneous ventilation was maintained. An investigator blinded to group allocation visited patients at 2, 12, and 24 h postoperatively. Adverse responses were noted (yes/no) at each time point including sore throat, sore mouth, sore jaw, hoarseness, dysphonia, and dysphagia. At 2 h postoperatively, the incidence of sore throat, dysphagia, and postoperative nausea and vomiting in group T was higher than in group P (24% vs 13% for sore throat, 15% vs 3% for dysphagia, 20% vs 11% for nausea, 14% vs 6% for vomiting, P < 0.05). The number-needed-to-treat to prevent sore throat and dysphagia was 10 and 8, respectively (95% confidence intervals, 5-43). We concluded that, when propofol, rather than thiopental, is used for the induction of anesthesia, it results in a lower incidence of early pharyngeal morbidity and postoperative nausea and vomiting after the insertion of a LMA.

The efficacy of thoracic epidural neostigmine infusion after thoracotomy.

Few anesthesia studies have explored perioperative continuous epidural infusion of neostigmine. We examined such a regimen in thoracotomy patients. Ninety patients were randomized to one of three groups in this double-blind trial. Before anesthesia induction, an epidural catheter was inserted in all patients at T5-8 levels under local anesthesia. Pre-neo patients received bolus 500-microg epidural neostigmine before anesthesia induction followed by infusion of 125 microg/h until the end of surgery. Post-neo patients received epidural saline during the same time periods plus bolus 500-microg epidural neostigmine at end of surgery. Patients in the control group received saline placebo during all three periods. Patients in the neostigmine groups postoperatively received patient-controlled epidural analgesia with morphine 0.02 mg/mL, bupivacaine 0.08 mg/mL, and neostigmine 7 microg/mL. Control patient-controlled epidural analgesia excluded neostigmine. Data were recorded for 6 postoperative days. Daily patient-controlled epidural analgesia consumption (mL) for Pre-neo patients was significantly less than that of post-neo and control group patients for postoperative days 1-6 (at least 10% and 16% less, respectively; P < 0.05). There was a modest decrease in pain intensity on postoperative days 3-6 for pre-neo patients versus other groups (P < 0.05). These results suggest that continuous thoracic epidural neostigmine started before anesthesia provided preemptive, preventive analgesia and an analgesic-sparing effect that improved postoperative analgesia for these patients without increasing the incidence of adverse effects.