PURPOSE: We evaluated the incidence and risk factors of postoperative nausea and vomiting (PONV) in patients with fentanyl-based intravenous patient-controlled analgesia (IV-PCA) and single antiemetic prophylaxis of 5-hydroxytryptamine type 3 (5 HT3)-receptor antagonist after the general anesthesia. MATERIALS AND METHODS: In this retrospective study, incidence and risk factors for PONV were evaluated with fentanyl IV-PCA during postoperative 48 hours after various surgeries. RESULTS: Four hundred-forty patients (23%) of 1878 had showed PONV. PCA was discontinued temporarily in 268 patients (14%), mostly due to PONV (88% of 268 patients). In multivariate analysis, female, non-smoker, history of motion sickness or PONV, long duration of anesthesia (>180 min), use of desflurane and intraoperative remifentanil infusion were independent risk factors for PONV. If one, two, three, four, five, or six of these risk factors were present, the incidences of PONV were 18%, 19%, 22%, 31%, 42%, or 50%. Laparoscopic surgery and higher dose of fentanyl were not risk factors for PONV. CONCLUSION: Despite antiemetic prophylaxis with 5 HT3-receptor antagonist, 23% of patients with fentanyl-based IV-PCA after general anesthesia showed PONV. Long duration of anesthesia and use of desflurane were identified as risk factors, in addition to risk factors of Apfel's score (female, non-smoker, history of motion sickness or PONV). Also, intraoperative remifentanil infusion was risk factor independent of postoperative opioid use. As the incidence of PONV was up to 50% according to the number of risk factors, risk-adapted, multimodal or combination therapy should be applied.
Adult ; Aged ; Analgesia, Patient-Controlled/*adverse effects ; Analgesics, Opioid/*adverse effects/therapeutic use ; Antiemetics/administration & dosage/therapeutic use ; Female ; Fentanyl/*adverse effects/therapeutic use ; Humans ; Incidence ; Isoflurane/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Piperidines/*adverse effects/therapeutic use ; Postoperative Nausea and Vomiting/chemically induced/*epidemiology ; Retrospective Studies ; Risk Factors

PURPOSE: Endoscopic submucosal dissection (ESD) is a technically difficult and lengthy procedure requiring optimal depth of sedation. The bispectral index (BIS) monitor is a non-invasive tool that objectively evaluates the depth of sedation. The purpose of this prospective randomized controlled trial was to evaluate whether BIS guided sedation with propofol and remifentanil could reduce the number of patients requiring rescue propofol, and thus reduce the incidence of sedation- and/or procedure-related complications. MATERIALS AND METHODS: A total of 180 patients who underwent the ESD procedure for gastric adenoma or early gastric cancer were randomized to two groups. The control group (n=90) was monitored by the Modified Observer's Assessment of Alertness and Sedation scale and the BIS group (n=90) was monitored using BIS. The total doses of propofol and remifentanil, the need for rescue propofol, and the rates of complications were recorded. RESULTS: The number of patients who needed rescue propofol during the procedure was significantly higher in the control group than the BIS group (47.8% vs. 30.0%, p=0.014). There were no significant differences in the incidence of sedation- and/or procedure-related complications. CONCLUSION: BIS-guided propofol infusion combined with remifentanil reduced the number of patients requiring rescue propofol in ESD procedures. However, this finding did not lead to clinical benefits and thus BIS monitoring is of limited use during anesthesiologist-directed sedation.
Aged ; Anesthetics, Intravenous/*administration & dosage/therapeutic use ; *Consciousness Monitors ; Endoscopy/methods ; Female ; Humans ; Intraoperative Complications/*prevention & control ; Male ; Middle Aged ; Monitoring, Physiologic/methods ; Piperidines/*administration & dosage/adverse effects/therapeutic use ; Propofol/*administration & dosage/adverse effects/therapeutic use

PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Adult ; Aged ; Androstanols/adverse effects/pharmacology ; Anesthetics/adverse effects/pharmacology ; Anesthetics, Inhalation/adverse effects/*pharmacology ; Blood Pressure/drug effects ; Etomidate/adverse effects/pharmacology ; Female ; Heart/*drug effects ; Heart Rate/drug effects ; Humans ; Isoflurane/adverse effects/*analogs & derivatives/pharmacology ; Male ; Middle Aged ; Piperidines/adverse effects/*therapeutic use ; Protective Agents/adverse effects/*therapeutic use

BACKGROUNDThe authors found no study to compare the efficacy of bolus dose fentanyl and remifentanil blunting the cardiovascular intubation response in children, so they designed this randomized, double-blind clinical study to assess the effects of remifentanil 2 microg/kg and fentanyl 2 microg/kg by bolus injection on the cardiovascular intubation response in healthy children.

METHODSOne hundred and two children, the American Society of Anesthesiologists (ASA) physical status 1-2 and scheduled for elective plastic surgery under general anesthesia, were randomly divided into one of two groups to receive the following treatments in a double blind manner: remifentanil 2 microg/kg (Group R) and fentanyl 2 microg/kg (Group F) when anesthesia was induced with propofol and vecuronium. The orotracheal intubation was performed using a direct laryngoscope. Blood pressure (BP) and heart rate (HR) were recorded before anesthesia induction (baseline values), immediately before intubation, at intubation and every minute for 5 minutes after intubation. The percent changes of systolic blood pressure (SBP) and HR relative to baseline values and the rate pressure product (RPP) at every observing point were calculated. The incidences of SBP and HR percent changes >30% of baseline values and RPP >22,000 during the observation were recorded.

RESULTSThere were no significant differences between groups in the demographic data, baseline values of BP and HR and the intubation time. As compared to baseline values, BP, HR and RPP at intubation and their maximum values during observation increased significantly in Group F, but they all decreased significantly in Group R. BP, HR and RPP at all observed points, and their maximum values during the observation, were significantly different between groups. There were also significant differences between groups in the percent change of SBP and HR relative to baseline values at all observed points and their maximum percent changes during the observation. The incidences of SBP and HR percent increased >30% of the baseline values and RPP >22,000 during the observation, were significantly higher in Group F than in Group R, but the incidences of SBP and HR percent decreased >30% of baseline values were significantly lower in Group F compared with Group R.

CONCLUSIONSWhen used as part of routine anesthesia induction with propofol and vecuronium in children, fentanyl 2 microg/kg by bolus injection fails to effectively depress the cardiovascular intubation response. Remifentanil 2 microg/kg by bolus injection can completely abolish the cardiovascular intubation response, but also cause more adverse complications of temporary significant cardiovascular depression.

Anesthetics, Intravenous ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Child ; Child, Preschool ; Double-Blind Method ; Female ; Fentanyl ; pharmacology ; therapeutic use ; Heart Rate ; drug effects ; Humans ; Intubation, Intratracheal ; adverse effects ; Male ; Piperidines ; pharmacology ; therapeutic use

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population. Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population. Clinical Trial Identifier NCT00856544 and NCT00413699.
Administration, Oral ; Adult ; Aged ; Arthritis, Rheumatoid ; drug therapy ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Middle Aged ; Piperidines ; adverse effects ; therapeutic use ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Pyrroles ; adverse effects ; therapeutic use ; Surveys and Questionnaires ; Young Adult

PURPOSE: The incidence of pain induced withdrawal movement following intravenous injection of rocuronium is high. This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of pretreatment of remifentanil on the withdrawal movements due to intravenous injection of rocuronium during anesthetic induction. MATERIALS AND METHODS: Ninety adult female patients undergoing thyroidectomy were randomly allocated to three groups. Each patient intravenously received one of three solutions of equal volume (4 mL): normal saline (Group I, n=30), 0.5 microgram/kg remifentanil (Group II, n=30) or 1 microgram/kg remifentanil (Group III, n=30). Thirty seconds after remifentanil administration, anesthesia was induced with 5 mg/kg IV thiopental. Twenty seconds after thiopental injection, 0.6 mg/kg IV rocuronium was administered (injection rate of 0.5 mL/sec) and patients' withdrawal movements were assessed. Mean arterial pressure (MAP) and heart rate were assessed on arrival in the operation room, before the tracheal intubation and immediately, 1 and 2 min after the tracheal intubation. RESULTS: The incidence of withdrawal movements was significantly lower in both of the remifentanil groups (3 and 0% in Group II and III, respectively) than in the saline group (70%). Remifentanil attenuated the increase of heart rate and MAP immediately and 1 min after the tracheal intubation. CONCLUSION: The pretreatment with 0.5 and 1.0 microgram/kg remifentanil of bolus doses prevented the withdrawal movements caused by rocuronium injection, and effectively blunted cardiovascular activation following tracheal intubation.
Adult ; Aged ; Analgesics, Opioid/administration & dosage/therapeutic use ; Androstanols/administration & dosage/*adverse effects ; Female ; Humans ; Injections, Intravenous/adverse effects ; Middle Aged ; Pain/etiology/*prevention & control ; Piperidines/administration & dosage/*therapeutic use

BACKGROUND/AIMS: The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA). METHODS: A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches. RESULTS: Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. CONCLUSIONS: Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile.
Antirheumatic Agents/administration & dosage/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Humans ; Janus Kinases/antagonists & inhibitors ; Methotrexate/therapeutic use ; Piperidines/administration & dosage/adverse effects/*therapeutic use ; Protein Kinase Inhibitors/administration & dosage/adverse effects/therapeutic use ; Pyrimidines/administration & dosage/adverse effects/*therapeutic use ; Pyrroles/administration & dosage/adverse effects/*therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome

PURPOSE: In this randomized, double-blind study, we investigated the analgesic efficacy and side effects of continuous constant-dose infusions of remifentanil after total abdominal hysterectomy and compared it to fentanyl. MATERIALS AND METHODS: Fifty-six adult female patients scheduled for elective total abdominal hysterectomy were enrolled in this study. Patients were randomly assigned to two groups according to fentanyl (group F, n=28) or remifentanil (group R, n=28) for postoperative analgesia. Patients in group F were given fentanyl intravenously with an infusion rate of fentanyl 0.5 microgram/kg/hr; group R was given remifentanil with an infusion rate of remifentanil 0.05 microgram/kg/min for 2 days. Pain intensity at rest, occurrence of postoperative nausea and vomiting (PONV), dizziness, pruritus, and respiratory depression were assessed 1 hr after arrival at the post-anesthesia care unit, at 6; 12; 24; and 48 hr post-operation and 6 hr post-infusion of the study drug. Pain was evaluated by using visual analogue scale (VAS; 0-10). The time that patients first requested analgesics was recorded as well as additional analgesics and antiemetics. RESULTS: There were no significant differences in VAS, time to first postoperative analgesics, and additional analgesics between the 2 groups. The incidences and severities of PONV and opioid related side effects were not different between the groups; however, there were 3 episodes (10.7%) of serious respiratory depression in group R. CONCLUSION: Continuous infusion technique of remifentanil did not reveal any benefits compared to fentanyl. Furthermore, it is not safe for postoperative analgesia in the general ward.
Adolescent ; Adult ; Aged ; Analgesics, Opioid/administration & dosage/therapeutic use ; Drug Administration Schedule ; Female ; Fentanyl/administration & dosage/*therapeutic use ; Humans ; Hysterectomy/*adverse effects ; Infusions, Intravenous ; Middle Aged ; Pain, Postoperative/*drug therapy/etiology ; Piperidines/administration & dosage/*therapeutic use ; Treatment Outcome

PURPOSE: Target-controlled infusion (TCI) of remifentanil can suppress coughing during emergence from general anesthesia; nevertheless, previous studies under different clinical conditions recommend significantly different effective effect-site concentrations (effective Ce) of remifentanil for 50% of patients (EC50). The differences among these studies include type of surgery and patient sex. In recent years, study of sex differences in regards to anesthetic pharmacology has drawn greater interest. Accordingly, we attempted to determine the effective Ce of remifentanil for preventing cough for each sex under the same clinical conditions. MATERIALS AND METHODS: Twenty female and 25 male ASA physical status I-II grade patients between the ages of 20 and 46 years who were undergoing thyroidectomy were enrolled in this study. The effective Ce of remifentanil for preventing cough was determined for each sex using the isotonic regression method with a bootstrapping approach, following Dixon's up-and-down method. RESULTS: Isotonic regression with a bootstrapping approach revealed that the estimated EC50 of remifentanil for preventing coughing during emergence was significantly lower in females {1.30 ng/mL [83% confidence interval (CI), 1.20-1.47 ng/mL]} than in males [2.57 ng/mL (83% CI, 2.45-2.70 ng/mL)]. Mean EC50 in females was also significantly lower than in males (1.23+/-0.21 ng/mL vs. 2.43+/-0.21 ng/mL, p<0.001). Mean arterial pressure, heart rate, and respiratory rate over time were not significantly different between the sexes. CONCLUSION: When using remifentanil TCI for cough prevention during anesthetic emergence, patient sex should be a considered for appropriate dosing.
Adult ; Anesthesia, General/*adverse effects ; Cough/*prevention & control ; Female ; Humans ; Male ; Middle Aged ; Piperidines/*administration & dosage/*therapeutic use ; Sex Factors ; Young Adult

PURPOSE: Although the presence of cannabinoid type 1 (CB1) receptor in islets has been reported, the major contributor to the protective effect of rimonabant on islet morphology is unknown. We determined whether the protective effect of rimonabant on pancreatic islet morphology is valid in established diabetes and also whether any effect was independent of decreased food intake. MATERIALS AND METHODS: After diabetes was confirmed, Otsuka Long-Evans Tokushima Fatty rats, aged 32 weeks, were treated with rimonabant (30 mg/kg/d, rimonabant group) for 6 weeks. Metabolic profiles and islet morphology of rats treated with rimonabant were compared with those of controls without treatment (control group), a pair-fed control group, and rats treated with rosiglitazone (4 mg/kg/d, rosiglitazone group). RESULTS: Compared to the control group, rats treated with rimonabant exhibited reduced glycated albumin levels (p<0.001), islet fibrosis (p<0.01), and improved glucose tolerance (p<0.05), with no differences from the pair-fed control group. The retroperitoneal adipose tissue mass was lower in the rimonabant group than those of the pair-fed control and rosiglitazone groups (p<0.05). Rimonabant, pair-fed control, and rosiglitazone groups showed decreased insulin resistance and increased adiponectin, with no differences between the rimonabant and pair-fed control groups. CONCLUSION: Rimonabant had a protective effect on islet morphology in vivo even in established diabetes. However, the protective effect was also reproduced by pair-feeding. Thus, the results of this study did not support the significance of islet CB1 receptors in islet protection with rimonabant in established obesity-associated type 2 diabetes.
Adiponectin/metabolism ; Adiposity/drug effects ; Animals ; Cell Proliferation/drug effects ; Diabetes Mellitus, Type 2/diet therapy/*drug therapy ; Eating/*drug effects ; Glucose Intolerance/diet therapy/*drug therapy ; Insulin Resistance ; Insulin-Secreting Cells/*drug effects/pathology ; Male ; Piperidines/adverse effects/*therapeutic use ; Pyrazoles/adverse effects/*therapeutic use ; Rats ; Rats, Inbred OLETF ; Receptor, Cannabinoid, CB1/physiology ; Thiazolidinediones/*therapeutic use