Effects of preemptive intravenous lornoxicam on the analgesic efficacy of epidural morphine and expression of chemokines in women undergoing hysterectomy

Background: It is believed that preemptive IV lornoxicam treatment can reduce the consumption of other analgesics, improve analgesic efficacy, and ameliorate immune function during patient-controlled IV analgesia. However, the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of patient-controlled epidural analgesia (PCEA) with morphine and on chemokine expression remain unknown.Objective: The aim of this prospective, randomized, controlled study was to observe the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of PCEA with morphine and on the expression of monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1α (SDF-1α) in women undergoing hysterectomy.Methods: Patients undergoing elective hysterectomy with combined spinal and epidural anesthesia were randomized to 1 of 3 groups to receive IV lornoxicam 8 mg before anesthesia (group 1), lornoxicam 16-mg injection before anesthesia (group 2), or isotonic saline (control) before anesthesia. PCEA was used to treat postoperative pain, and a visual analog scale (VAS) and the Bruggemann Comfort Scale (BCS) were used to evaluate analgesic efficacy. Morphine consumption was recorded. To measure plasma concentrations of MCP-1 and SDF-1α via enzyme-linked immunosorbent assay, venous blood samples were obtained from patients at 4 separate times: before anesthesia (baseline); 0 (immediately after anesthesia administration); and 24 and 48 hours after surgery.Results: Forty-five patients (mean [SD] age, 41 [5] years; mean [SD] weight, 54 [6] kg) undergoing elective hysterectomy were included in the study. There were no significant differences in VAS scores, BCS scores, or morphine consumption between the 3 groups. Compared with baseline values, MCP-1 and SDF-1α concentrations were increased significantly immediately after surgery in all 3 groups (all, P < 0.01) and returned to near-baseline values at 24 hours postsurgery in groups 1 and 2, and by 48 hours postsurgery in the control group. MCP-1 and SDF-1α concentrations in groups 1 and 2 were significantly lower than those in the control group immediately (all, P < 0.01) and 24 hours postsurgery (all, P < 0.05).Conclusion: Preemptive IV lornoxicam treatment was associated with attenuation of the plasma concentrations of MCP-1 and SDF-1α immediately after and 24 hours after hysterectomy and was associated with more rapid resolution to near-baseline concentrations of both cytokines in these patients compared with controls; however, it was not associated with significantly reducing epidural morphine consumption.     

Efficacy of Preventive Analgesia with Tramadol or Lornoxicam for Percutaneous Nephrolithotomy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

Background: Prevention of postoperative pain provides better and more rapid convalescence for patients.Objective: The aim of this study was to compare the preventive analgesic effect of tramadol and lornoxicam in the early postoperative period in patients undergoing percutaneous nephrolithotomy (PCNL).Methods: Patients who were scheduled for elective PCNL at the Cumhuriyet University Hospital, Sivas, Turkey, were enrolled in this prospective, double-blind, placebo-controlled study. The patients were randomly assigned to 1 of 3 groups: tramadol, lornoxicam, and normal saline (NS). Ten minutes before induction of anesthesia, the tramadol group received tramadol 100 mg IV, the lornoxicam group received lornoxicam 8 mg IV, and the NS group received NS 2 mL IV. Anesthesia was induced using fentanyl 1 μg/kg and thiopental sodium 4 to 7 mg/kg. Vecuronium 0.1 mg/kg was used for muscle relaxation. Desflurane 4% to 6% and 50%:50% oxygen/nitrous oxide were used for maintenance. Oxygen saturation, heart rate, and mean blood pressure were recorded before induction and during the postoperative period. During the postoperative period, visual analogue scale O/AS) scores, time to first analgesic (TFA), total analgesic consumption (TAC), and patient satisfaction scores were determined. Data about postoperative nausea and vomiting and other adverse events and complications were also collected.Results: Seventy-three patients were assessed for enrollment and 60 (33 women, 27 men; mean [SD] age, 44.69 [11.27] years; age range, 20-62 years) were included in the study. The baseline demographic characteristics and duration of surgery were similar in all 3 groups. The mean (SD) VAS scores in the tramadol group were significantly lower than in the NS group at 15 and 30 minutes and 1, 2, 4, and 12 hours after surgery (all, P < 0.05). The VAS scores in the lornoxicam group were significantly lower than in the NS group at 15 and 30 minutes and 1 hour (all, P < 0.05). The VAS score at 1 hour after surgery was significantly lower in the tramadol group than in the lornoxicam group (18 [8] vs 32 [16]; P < 0.05); however, there were no other significant differences in VAS scores between the active groups. A significantly shorter TFA was associated with the NS group when compared with the tramadol and lornoxicam groups (46 [27] vs 354 [187] and 180 [118], respectively; both, P < 0.05). TFA was significantly shorter in the lornoxicam group when compared with the tramadol roup (180 [118] vs 354 [187]; P < 0.05). TAC was significantly higher in the NS group than in the tramadol and lornoxicam groups (270 [47] vs 115 [74] and 145 [72], respectively; both, P < 0.05). Patient satisfaction score (range) was significantly lower in the NS group when compared with the tramadol and lornoxicam groups (0 [0-1] vs 3 [0-3] and 2 [0-3], respectively; both, P < 0.05). There were no other significant between-group differences observed.Conclusions: Tramadol and lornoxicam were more effective than NS in preventing early postoperative pain. The preventive analgesic effect of tramadol was comparable with that of lornoxicam, except at 1 hour when tramadol was more effective among these patients undergoing PCNL. Both drugs were well tolerated.     

Antiemetic effects of midazolam added to fentanyl-ropivacaine patient-controlled epidural analgesia after subtotal gastrectomy: A prospective, randomized, double-blind, controlled trial

Background: Nausea and vomiting are frequent adverse effects of patient-controlled epidural analgesia (PCEA) with opioids.Objective: This study was designed to assess the antiemetic effect of midazolam added to fentanyl—ropivacaine PCEA.Methods: In a prospective, randomized, double-blind, controlled trial, smoking patients with gastric cancer undergoing elective subtotal gastrectomy were evenly allocated to 1 of 2 treatment groups to manage postoperative pain: 0.2% ropivacaine mixed with fentanyl 4 μg/mL and midazolam 0.2 mg/mL (test group) or 0.2% ropivacaine mixed with fentanyl 4 μg/mL (control group). The PCEA infusion was set to deliver 4 μL/h of the study solution, with a bolus of 2 mL per demand and a 15-minute lockout time. The incidence of postoperative nausea and vomiting (PONV), pain intensity, sedation score, usage of rescue analgesia and rescue antiemetic, respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, 48, and 72 hours after surgery. Total infused volume of PCEA at 72 hours after surgery was measured.Results: A total of 60 patients were approached and randomized to treatment. No patients were excluded by exclusion criteria and all enrolled patients completed this study. Incidence of nausea (7% vs 33%; P = 0.02) in the test group was significantly lower than in the control group. The overall frequency of PONV in the test group was significantly less than that of the control group (7% vs 40%; P = 0.006). In addition, the mean (SD) infused volume of PCEA in the test group was significantly lower than that in the control group (392.3 [68.9] vs 351.2 [49.8] mL; P = 0.01). However, there were no significant differences in pain intensity, usage of rescue antiemetics and rescue analgesics, and mild pruritus between groups. No patient reported moderate or severe sedation, respiratory depression, or hypoxemia. In addition, there were no severe adverse events.Conclusions: Midazolam added to fentanyl-ropivacaine PCEA was associated with a significant reduction in the incidence of PONV compared with fentanyl-ropivacaine alone, and a significant decrease in the amount of PCEA administered without a significant increase in adverse events in these patients who underwent subtotal gastrectomy.     

Effect of Dexmedetomidine IV on the Duration of Spinal Anesthesia with Prilocaine: A Double-Blind, Prospective Study in Adult Surgical Patients

Background: The duration of spinal anesthesia with prilocaine has been poorly documented and no English-language study has been published regarding the effects of dexmedetomidine on the duration of anesthesia with spinal prilocaine.Objective: The aim of this study was to assess the effects of dexmedetomidine IV on the duration of action of prilocaine and its associated adverse events (AEs) in spinal anesthesia.Methods: In this double-blind, prospective study, patients classified as American Society of Anesthesiologists grade I to II who were to undergo lower abdominal, anorectal, or extremity surgery with a spinal anesthetic were assigned to 1 of 2 groups. All patients were administered prilocaine 2% for spinal anesthesia. Within 10 minutes after spinal anesthesia was initiated, group 1 received a loading dose of dexmedetomidine 1 μg/kg IV, followed by a maintenance dose of 0.4 μg/kg · h for 50 minutes; group 2 (control) received the same amount of physiologic saline in the same time frame. Mean arterial pressure (MAP), heart rate (HR), duration of sensory and motor blockade, and sedation scores were tracked. Patients were observed for 4.5 hours after surgery, with follow-ups occurring up to 96 hours after surgery.Results: Eighty-three patients were assessed for study inclusion, 23 of whom were excluded. Sixty patients (42 men, 18 women; mean [SD] age, 40.56 [16.86] years) were included in the study. MAP was similar in the 2 groups throughout the study. Mean (SD) HR was significantly lower in group 1 compared with group 2 at 20 minutes (70.43 [19.28] vs 77.63 [18.14] beats per minute, respectively; P = 0.02). The mean (SD) duration of the persistence of sensory anesthesia (ie, the time required for the maximal level of anesthesia to regress 2 dermatomes) was significantly longer in group 1 compared with group 2 (148.33 [21.18] vs 122.83 [18.73] minutes; P < 0.001). The mean (SD) time to complete abolishment of motor blockade was also significantly longer in group 1 than in group 2 (215.16 [25.10] vs 190.83 [18.57] minutes; P < 0.001). The average sedation score in group 1 was significantly higher than in group 2 (P < 0.001) during anesthesia. Significantly more patients in group 1 required atropine than those in group 2 (9 vs 2 patients; P < 0.001) to treat bradycardia. There was no significant between-group difference in the number of patients who received ephedrine to treat hypotension. One patient in each group reported waist and back pain; 2 patients in each group reported nausea. Shivering occurred in 0 and 5 patients in groups 1 and 2, respectively; the between-group difference in AEs was not statistically significant. Paresthesia, postdural puncture headache, allergic reactions, total spinal anesthesia, urinary retention, or vomiting—AEs commonly associated with spinal anesthesia—were not observed or reported by either group.Conclusions: The results of this study suggest that dexmedetomidine IV significantly prolonged the duration of spinal anesthesia and provided a significantly higher level of sedation compared to placebo in this group of adult surgical patients. The treatment was generally well tolerated in all patients.     

Comparative assessment of the effectiveness and tolerability of lornoxicam 8 mg BID and diclofenac 50 mg TID in adult indian patients with osteoarthritis of the hip or knee: A 4-week, double-blind, randomized, comparative, multicenter study

Background: Reports of cardiovascular adverse events (AEs) associated with the use of cyclooxygenase-2 inhibitors for the treatment of osteoarthritis (OA) have prompted the quest for a better-tolerated NSAID.Objective: The aim of this study was to compare the effectiveness and tolerability of lornoxicam 8 mg BID and diclofenac 50 mg TID in adult Indian patients with OA of the hip or knee.Methods: This 4-week, double-blind, randomized, comparative, multicenter study was undertaken to compare oral lornoxicam and diclofenac in patients with OA. Patients who met the selection criteria were enrolled consecutively from the outpatient clinics of each of the participating hospitals in India. Participants completed the Western Ontario and McMasters Individual Osteoarthritis Index (WOMAC-OA), WOMAC Composite Index (WOMAC-CI) (for pain, stiffness, and physical function), and a 10-cm visual analog scale (VAS) (0-10 where 0 = no pain and 10 = worst possible pain or severe or excruciating pain) at each study visit (weeks 0 [baseline], 2, and 4 [or at early termination]). Patients' and physicians' global assessments of arthritis control were measured at each study visit when laboratory and clinical AEs were also monitored. The primary end points were the WOMAC-OA, the WOMAC-CI, and VAS scores for pain among the patients who completed the study.Results: Of the 273 patients (159 men, 114 women; mean [SD] age, 44.73 [10.72] years; range, 28-68 years) enrolled in the study, 13 (7 in the lornoxicam group and 6 in the diclofenac group) were lost to follow-up and their effectiveness and tolerability results were not included in the study analysis. Over the 4-week study period, both drugs provided significant (P < 0.05) sustained relief of OA symptoms compared with baseline. Compared with baseline, the mean pain score (WOMAC-CI) decreased 90.6% (13.88 [4.47] vs 1.30 [1.49]; P < 0.05) in the lornoxicam group and 88.9% (14.15 [4.56] vs 1.57 [1.49]; P < 0.05) in the diclofenac group after 4 weeks of treatment. After 4 weeks of treatment, the VAS pain score decreased from baseline 83.1% (8.04 [2.70] vs 1.36 [1.43]; P < 0.05) in the lornoxicam group and 79.3% (7.98 [2.98] vs 1.65 [1.47]; P < 0.05) in the diclofenac group. Compared with baseline, the improvement rated at 2 weeks was not significantly different between the 2 groups. Lornoxicam and diclofenac were well tolerated. The rate of mild to moderate adverse gastrointestinal events was not significantly different in the lornoxicam group compared with the diclofenac group (14.6% vs 18.4%). Similarly, overall tolerability between the 2 groups was not significantly different. None of the patients experienced cardiovascular AEs (eg, edema or increased blood pressure).Conclusion: The results of the present study suggest that lornoxicam was comparable to diclofenac in effectiveness and tolerability after 4 weeks of treatment in these adult Indian patients with OA of the hip or knee who completed the study.     

Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A parallel controlled study

Background: Clozapine has been associated with metabolic adverse events (AEs) (eg, elevated body weight, blood glucose concentrations, cholesterol, triglycerides [TG]), all of which have deleterious effects on health and medication compliance. However, little focus has been directed toward finding a suitable experimental model to study the metabolic AEs associated with clozapine.Objective: The aim of this study was to assess the effects of clozapine administration for 28 days on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in C57BL/6 mice.Methods: C57BL/6 mice were grouped and treated with clozapine 2 or 10 mg/kg or vehicle intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin (calculated by insulin resistance index [IRI]), and plasma lipids (including total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol) were assessed on day 29.Results: Sixty 10-week-old, male C57BL/6 mice were included in the study and were divided into 3 groups (20 mice per group). The body weight significantly decreased in the clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 30, 60, and 120 minutes after glucose administration compared with the vehicle group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had significant increases in plasma insulin concentrations compared with the vehicle group (12.70 [5.27] vs 7.62 [4.54] μIU/mL; P < 0.05) and IRI (3.01 [1.26] vs 1.51 [0.96]; P < 0.05). Plasma HDL-C concentration also significantly decreased in the clozapine 10-mg/kg group compared with the vehicle group (1.23 [0.25] vs 1.47 [0.16]; P < 0.05).Conclusion: Clozapine 10 mg/kg was associated with significant decreases in body weight and significant increases in fasting blood glucose and glucose tolerance in these male C57BL/6 mice.     

Controlled hypotension with desflurane combined with esmolol or dexmedetomidine during tympanoplasty in adults: A double-blind, randomized, controlled trial

Background: Controlled hypotension is a technique that is used to limit intraoperative blood loss to provide the best possible surgical field during surgery.Objective: The aim of this double-blind, randomized, controlled study was to compare the effects of desflurane combined with esmolol or dexmedetomidine on the amount of blood in the surgical field, recovery time, and tolerability in adult patients undergoing tympanoplasty.Methods: Turkish patients aged 18 to 60 years, classified as American Society of Anesthesiologists physical status I or II, who were scheduled for tympanoplasty were randomly divided into 2 groups: the esmolol group or the dexmedetomidine group. After the anesthesia induction in the esmolol group, a loading dose of esmolol was infused intravenously over 1 minute at 1 mg/kg, followed by a maintenance rate of 0.4 to 0.8 mg/ kg/h. In the dexmedetomidine group, a loading dose of dexmedetomidine was infused intravenously over 10 minutes at a rate of 1 μg/kg, followed by a maintenance rate of 0.4 to 0.8 μg/kg/h. The infusion rates were then titrated to maintain mean arterial pressure (MAP) of 65 to 75 mm Hg. General anesthesia was maintained with desflurane 4% to 6%. Heart rate (HR) and MAP were recorded during anesthesia. The following 6-point scale was used to assess the amount of bleeding in the operative field: 0 = no bleeding, a virtually bloodless field; 1 = bleeding that was so mild that it was not a surgical nuisance; 2 = moderate bleeding that was a nuisance but did not interfere with accurate dissection; 3 = moderate bleeding that moderately compromised surgical dissection; 4 = bleeding that was heavy but controllable and that significantly interfered with surgical dissection; and 5 = massive bleeding that was uncontrollable and made dissection impossible. Scores ≤2 were considered to be optimal surgical conditions. The sedation score was determined at 15, 30, and 60 minutes after tracheal extubation using the following scale: 1 = anxious, agitated, or restless; 2 = cooperative, oriented, and tranquil; 3 = responsive to commands; 4 = asleep, but with brisk response to light, glabellar tap, or loud auditory stimulus; 5 = asleep, sluggish response to glabellar tap or auditory stimulus; and 6 = asleep, no response. Time to extubation and to total recovery from anesthesia (Aldrete score ≥9 on a scale of 0-10), adverse effects (eg, intraoperative hypotension [blood pressure <65 mm Hg], bradycardia [HR <50 beats/min]), intraoperative fentanyl consumption, and postoperative nausea and vomiting were recorded. Arterial blood gas analysis and kidney and liver function tests were conducted. All patients were evaluated by the same attending surgeon and anesthesiologist, both of whom were blinded to the administered study drugs.Results: Fifty-two consecutive white patients undergoing tympanoplasty were identified. Two patients had to be excluded because of hypertension and 2 refused to participate. Forty-eight patients were equally randomized to either the esmolol group (n = 24 [16 women, 8 men]; mean [SD] age, 38.4 [10.5] years) or the dexmedetomi-dine group (n = 24 [17 women, 7 men]; mean age, 35.5 [14.7] years). Sedation scores were not collected for 1 patient in the esmolol group; therefore, analysis was conducted for 23 patients. The median (range) of the scores for the amount of blood in the surgical field in the esmolol and dexmedetomidine groups was 1 (0-3) and 1 (0-2), respectively (P = NS). Mean intraoperative fentanyl consumption in the esmolol group was significantly higher than in the dexmedetomidine group (50.0 [3.0] vs 25.0 [2.5] μg/min; P = 0.002). In the esmolol group, the mean times to extubation and to recovery from anesthesia were significantly shorter than those of the dexmedetomidine group (7.0 [1.4] vs 9.1 [1.9] minutes, respectively; 5.9 [2.1] vs 7.9 [2.3] minutes; both, P = 0.001). The mean sedation scores were significantly lower in the esmolol group (n = 23, because of intent-to-treat analysis) compared with the dexmedetomidine group at 15 minutes (2.5 [0.6] vs 3.6 [0.5]; P = 0.001) and 30 minutes (2.6 [0.6] vs 3.3 [0.6]; P = 0.001) postoperatively. No significant differences were found between the study groups in regard to blood urea nitrogen or creatinine concentration, aspartate aminotransferase or alanine aminotransferase activities, pH, partial pressure of carbon dioxide, or bicarbonate, before or after the operation.Conclusions: Both esmolol and dexmedetomidine, combined with desflurane, provided an effective and well-tolerated method of achieving controlled hypotension to limit the amount of blood in the surgical field in these adult patients undergoing tympanoplasty. Esmolol was associated with significantly shorter extubation and recovery times and significantly less postoperative sedation compared with dexmedetomidine.     

Effects of vitamins E and C supplementation on hepatic glutathione peroxidase activity and tissue injury associated with ethanol ingestion in malnourished rats

Background: Oxidative stress has been associated with tissue injury in alcoholic liver disease. Although this close association is well known, whether prevention of oxidative stress retards tissue injury has not been thoroughly investigated.Objective: The aim of this study was to determine the effects of supplementation with vitamins E and C on antioxidant enzyme status and histologic changes in hepatic tissue in a rat model of alcoholic liver disease.Methods: This 8-week, blinded, controlled study was conducted at the Department of Internal Medicine, Trakya University, Edirne, Turkey. Weanling albino female protein-deficient Wistar rats weighing ∼200 g were randomly assigned to 1 of 6 groups: (1) liquid diet+ethanol+vitamin E 15 mg/kg PO (LDetvitE); (2) liquid diet+ethanol+vitamin C 10 mg/kg PO (LDetvitC); (3) liquid diet+ethanol+vitamin E 15 mg/kg+vitamin C 10 mg/kg PO (LDetvitEC); (4) liquid diet+ethanol (LDet); (5) liquid diet+isocaloric sucrose (LDS); and (6) normal diet (control). The primary end point of the study was to determine whether antioxidant vitamin E/C combination therapy prevents development of hepatic fibrosis (ie, cirrhosis in a period of 1 year). After being euthanized at week 8, the rats were weighed, and their livers and spleens were weighed. Hepatic tissue specimens were histopathologically assessed according to the Brunt system. Hepatic tissue glutathione peroxidase, superoxide dismutase, and catalase activities were determined. Biochemical tissue collagen concentrations were measured to determine the presence of hepatic fibrosis.Results: Seventy-two rats were included in the study (mean [SE] weight, 205 [21] g) (12 rats per group). Initially planned to last 48 weeks, the study was terminated at 8 weeks due to the death of 3 rats in each group (except the LDS group and control group). The relative liver weight was significantly lower in the LDetvitEC group compared with that in the LDet group (mean [SE], 3.7% [0.5%] vs 4.8% [0.9%]; P<0.01). Mean (SE) hepatic tissue glutathione peroxidase activity was significantly reduced in the LDet-treated rats compared with controls (1.2 [0.2] vs 2.6 [0.3] U/mg protein; P<0.001). The groups that received supplementation with vitamin E, vitamin C, and vitamins E and C combined had significantly more hepatic glutathione peroxidase activity (mean [SE], 2.1 [0.5], 2.5 [0.2], and 2.6 [0.7] U/mg protein, respectively) compared with the LDet group (1.2 [0.2] U/mg protein) (all, P<0.001). No significant between-group differences in hepatic superoxide dismutase or catalase activities were found. Compared with controls (14.5 [1.9] μg collagen/mg protein), the mean (SE) histologic hepatic collagen concentration was significantly higher in all groups (19.2 [1.2], 19.5 [3.3], 18.5 [3.0], 25.9 [3.3], and 21.6 [1.5] μg collagen/mg protein in the LDetvitE, LDetvitC, LDetvitEC, LDet, and LDS groups, respectively; P<0.01, P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Compared with the LDet group, the mean hepatic collagen concentration was significantly lower in the LDetvitE, LDetvitC, and LDetvitEC groups (P<0.01, P<0.05, and P<0.01, respectively). The LDetvitEC group had a significantly lower mean (SE) hepatic inflammatory score compared with the LDet group (0.8 [0.1] vs 1.3 [0.2]; P<0.05). The LDetvitEC group had a significantly lower mean (SE) hepatic necrosis score compared with that in the LDet group (1.5 [0.2] vs 2.4 [0.3]; P<0.05).Conclusions: The results of this study in protein-deficient rats fed with a high-fat liquid diet suggest that supplementation with vitamin E, vitamin C, and a combination of vitamins E and C was associated with decreased ethanol-induced hepatic glutathione peroxidase activity and hepatic fibrosis, and that supplementation with vitamins E and C might have attenuated the development of hepatomegaly and hepatic necroinflammation, whereas this result was not found in the group given a liquid diet and ethanol in this 8-week study. (Curr Ther Res Clin Exp. 2006;67:118-137) Copyright © 2006 Excerpta Medica, Inc.     

Effects of valsartan treatment on indicators of cardiovascular damage in newly diagnosed hypertensive patients: A prospective, twelve-month, open-label, pilot study

Background: Myocardial fibrosis and dysfunction can be detected in the early phases of organ damage associated with hypertension. Valsartan, an angiotensin-II receptor blocker, is efficacious in lowering blood pressure (BP) and reducing left ventricular mass in patients with hypertension. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and procollagen type I carboxy-terminal propeptide (PICP) are correlated with organ damage in patients with overt congestive heart failure; however, few data are available in patients with hypertension.Objective: The aim of this study was to assess the effects of 12 months of valsartan treatment on echocardiographic measures and indices of organ damage (NT-proBNP and PICP) in newly diagnosed patients with hypertension.Methods: This was a prospective, open-label, single-center, exploratory study. Patients with newly diagnosed, previously untreated hypertension were treated for 12 months with valsartan 160 mg/d and compared with an equal number of healthy, untreated control subjects. Baseline and follow-up visits at 3, 6, and 12 months included physical examination, systolic BP (SBP) and diastolic BP (DBP) measurements, ECG, echocardiography, and NT-proBNP and PICP determination.Results: A total of 20 patients (mean [SD] age, 48.05 [7.29] years) were enrolled and compared with 20 healthy controls (age, 49-6 [6.95] years). Compared with baseline, valsartan was associated with reduced BP in the group with hypertension after 12 months of treatment (mean SBP, 150.05 [11.15] vs 120.00 [8.43] mm Hg, P < 0.001; DBP, 97.80 [8.36] vs 79-50 [4.26] mm Hg, P < 0.001). Compared with the control group, at baseline, the group with hypertension had significantly higher mean left ventricular mass index (LVMI) (119.88 [22.86] vs 87.31 [15.77] g/m²; P < 0.001), relative wall thickness (thickness/radius [h/r] ratio: 0.45 [0.08] vs 0.35 [0.07]; P = 0.001), and NT-proBNP (50.00 [32.01] vs 25.47 [9.69] pg/dL; P = 0.002). PICP was higher, but the difference was not statistically significant (46.10 [15.69] vs 37.50 [7.20] μg/L). After 12 months, treatment with valsartan was associated with significant reductions in all measured parameters compared with baseline (LVMI, 106.51 [17.12] g/m², P = 0.004; h/r, 0.41 [0.07], P = 0.026; NT-proBNP, 22.55 [13.52] pg/dL, P = 0.001; PICP, 35.20 [9-19] μg/L, P < 0.008). At 12 months, patients with hypertension treated with valsartan achieved NT-proBNP and PICP levels not statistically different from those of the healthy controls (NT-proBNP, 22.55 [13-52] vs 25.24 [8.43] pg/dL; PICP, 35.20 [9.19] vs 36.90 [6.41] μg/L).Conclusion: Patients treated with valsartan for 12 months had significant reductions in BP, LVMI, and indices of subclinical organ damage (NT-proBNP and PICP) compared with baseline.     

Comparison of methimazole/hydrocortisone ointment with oral methimazole in patients with graves disease: A prospective, randomized, open-label, parallel-group, 18-month study

Background: Thionamide antithyroid drugs (ATDs) have certain disadvantages and are associated with some adverse events (AEs). To overcome the problems associated with ATDs, a compound antithyroid ointment (CATO) containing methimazole (MMI) and hydrocortisone has been developed for use as a local thyroid treatment (LTT).Objective: The aim of this study was to assess the clinical effectiveness and tolerability of CATO LTT in patients with Graves disease (GD).Methods: This was a prospective, randomized, open-label, parallel-group clinical trial conducted at the Provincial Hospital Affiliated to Shandong University (Jinan, China). Patients with GD aged 19 to 65 years were randomized to receive either CATO LTT 0.3 g/d or oral MMI 37.5 mg/d (control group) treatment for 18 months, with a 4-year follow-up period. Hyperthyroid symptoms, thyroid function, granulocyte count, liver function, and AEs were assessed at baseline and every 2 weeks until serum thyroid hormone (TH) concentration normalized, at which point patients were assessed monthly. The primary efficacy end points were the duration of treatment required for serum TH concentration to normalize and the remission rate after completing the 18-month treatment regimen.Results: A total of 154 patients (133 women, 21 men; mean [SD] age, 39.6 [11.8] years; all Han Chinese) participated in the study; all patients completed the 18-month treatment period. Compared with the MMI group (n 76), the CATO- treated group (n 78) had a significantly shorter median (range) time to restoration of normal serum thyroid hormone concentration (43 [12-150] vs 22 [7-60] days; P < 0.001), a significantly lower rate of recurrence of hyperthyroidism (309/1520 [20.3%] vs 193/1368 [14.1%] person-time; P < 0.001), a significantly lower drug hypothyroidism rate (185/1520 [12.2%] vs 54/1368 [3.9%] person-time; P < 0.001), and a higher remission rate (year 1:46/69 [66.7%] vs 65/72 [90.3%] patients, P 0.001; year 2:40/69 [58.0%] vs 60/72 [83.3%] patients, P - 0.001; year 3:34/69 [49.3%] vs 57/72 [79.2%] patients, P < 0.001; and year 4:30/69 [43.5%] vs 55/72 [76.4%] patients, P < 0.001). Systemic AEs occurred in 6 patients (7.9%) in the MMI group (drug neutropenia, 2 patients [2.6%]; epistaxis, 1 [1.3%]; hepatopathy, 1 [1.3%]; and other systemic AEs, 2 [2.6%]), while no systemic AEs were observed/reported in the CATO group.Conclusion: This study suggests that CATO LTT was well tolerated and more effective than oral MMI treatment in controlling thyrotoxicosis and promoting remission of GD in these Han Chinese patients.     

Abstract 4: Acupuncture analgesia and electromyography

Objectives: To evaluate the analgesic effect of a simple acupuncture protocol with needle electromyography and to validate independently a telescopic sham acupuncture needle. Design: Randomized, double-blinded, controlled study. Setting: University-based electrodiagnostics laboratory. Participants: 38 subjects referred for electrodiagnostic evaluation. Intervention: Before the electromyographic examination, an independent provider applied either real acupuncture needles or telescopic sham needles to the acupuncture points Large Intestine 4 and Liver 3 bilaterally. Main Outcome Measures: 100-mm visual analog scale (VAS) of the subjects’ pain before electromyography as well as pain and unpleasantness related to electromyography after 3 muscles were examined. Subjects were also asked if they thought they had received true acupuncture or sham needles. Pretest pain was subtracted from electromyography-related pain to give a measurement of pain attributable to the electromyography. Results: 21 subjects were randomized to the treatment group and 17 to the sham group. The subjects in the two treatment arms did not differ by age (P=0.9) or gender (P=0.4). The pain attributable to electromyography in the treatment group (mean, −5.38±27.6) was significantly less than the pain attributable to electromyography in the control group (mean, 11.3±17.3) (P=.037; 95% CI, −32.3 to −1.1) The percentage of subjects who thought they had received real needles in the acupuncture group (67%) did not differ from the proportion in the control group (53%) (Fisher exact test, P=.51). Conclusion: Acupuncture may represent an effective form of analgesia for electromyography. This is the first study of which we are aware that independently validates the telescopic sham acupuncture needle as an effective control.     

多模式镇痛对老年人腹腔镜快通道术后应激反应的影响*

目的探讨多模式镇痛对老年人腹腔镜快通道手术后应激反应的影响,比较不同镇痛模式的术后镇痛效果。方法选择2014年3月-2015年8月60岁以上的择期手术患者80例,随机分为A、B两组(n=40):A、B组患者均于术前给予凯纷(氟比洛芬酯注射液)2.00 mg/kg行超前镇痛;A组患者术后行硬膜外自控镇痛(PCEA),B组患者术后行静脉自控镇痛(PCIA)。A组与B组术后镇痛均于术毕拔除气管导管后5 min开始使用。比较两组手术前后平均动脉压(MAP)、心率(HR)、血糖值和皮质醇浓度等指标,以及术后视觉模拟疼痛评分(VAS)与不良反应的发生情况。结果在术后6及24 h,A组VAS疼痛评分明显低于B组(P0.05);与B组比较,A组的血糖、皮质醇、MAP以及HR水平在术后6 h明显较低(P0.05),且在术后24 h,A组的血皮质醇水平仍明显低于B组(P0.05);此外,A组老年病患在术后呕吐、头晕和嗜睡等不良反应发生情况明显低于B组(P0.05)。结论凯纷超前镇痛复合硬膜外术后镇痛模式比复合静脉术后镇痛模式更适用于老年腹腔镜快通道患者术后镇痛,值得临床推广和应用。     

Comparison of beraprost and ticlopidine in Chinese patients with chronic peripheral arterial occlusion: a multicenter, single-blind, randomized, controlled study

Background: Chronic peripheral arterial occlusion (CPAO) is a progressive disease that is associated with a variety of symptoms, the 4 most common being a sensation of coolness in the limbs, intermittent claudication (in which pain occurs on walking), limb pain (which occurs spontaneously at rest), and ischemic leg ulcers. Beraprost sodium is an oral prostaglandin I₂ analogue that may ameliorate these symptoms.Objective: The aim of this study was to compare the efficacy and tolerability of beraprost sodium and ticlopidine hydrochloride in the treatment of patients with CPAO in China.Methods: In this multicenter, single-blind, controlled study, patients with CPAO were randomly assigned to receive beraprost 120-μg tablet TID or ticlopidine 500-mg tablet BID, both administered orally. The clinical efficacy of the drugs was assessed using the 4 main symptoms of CPAO. Ankle-brachial index (ABI) also was measured as a clinical pharmacologic procedure. Adverse events were assessed throughout the study.Results: A total of 124 patients (96 men, 28 women; mean [SD] age, 65 [12] years) were enrolled in 3 hospitals. Data from 119 patients (93 men, 26 women; mean [SD] age, 65 [12] years) were included in the efficacy analysis (64 and 55 patients in the beraprost and ticlopidine groups, respectively). Although all 4 symptoms of CPAO were ameliorated after 3 and 6 weeks of treatment with both drugs, only the cool sensation was significantly improved with beraprost compared with ticlopidine at 6 weeks (P<0.05). ABI was significantly increased with both beraprost and ticlopidine at 6 weeks versus baseline (P<0.001 and P<0.01, respectively), suggesting that this pharmacologic action may have led to their beneficial effect on various symptoms. The tolerability analysis included 123 patients (65 and 58 patients in the beraprost and ticlopidine groups, respectively). The numbers of patients who (1) experienced adverse events (AEs), (2) experienced adverse drug reactions, and (3) withdrew due to AEs were significantly smaller in the beraprost group than in the ticlopidine group (P<0.001, P<0.05, and P<0.05, respectively).Conclusions: In this study population of patients with CPAO, beraprost ameliorated cool sensation in the limbs, intermittent claudication, limb pain, and ischemic/leg ulcers. Beraprost was more efficacious in relieving CPAO symptoms and was better tolerated than ticlopidine. Beraprost may be useful for the treatment of patients with CPAO, but more studies are needed.     

Effects of dibutyryl cyclic adenosine monophosphate on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs

Background: Hypercapnia is associated with diaphragm muscle dysfunction that causes a reduction of diaphragmatic force generated for a constant elective myographic activity. No published data are available concerning hypercapnic depression of diaphragmatic contractility during dibutyryl cyclic adenosine monophospate (DBcAMP) administration.Objective: The aim of this study was to assess the effects of DBcAMP on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs.Methods: This experimental study was conducted from July to December 2008 at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Adult (aged >5 years) mongrel dogs weighing 10 to 15 kg were randomly divided into 3 equal groups. Hypercapnia (80-90 mm Hg) was induced with 10% carbon dioxide added to the inspired gas. When hypercapnia was established, group 1 was infused with low-dose DBcAMP (0.05 mg/kg/min); group 2 was infused with high-dose DBcAMP (0.2 mg/kg/min); and group 3 received placebo (saline). Study drug was administered intravenously for 60 minutes. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at baseline, induction of hypercapnia, and study drug administration.Results: Twenty-one dogs were divided into 3 groups of 7. There were no significant differences observed at baseline. In the presence of hypercapnia, Pdi (mean [SD], cm H₂O) at low- (20-Hz) and high-frequency (100-Hz) stimulation was significantly decreased from baseline in each group (all, P = 0.001). In groups 1 and 2, Pdi at both stimuli was significantly increased during DBcAMP administration compared with hypercapnia-induced values (group 1: 20-Hz, 13.5 [2.2] vs 15.0 [2.4], respectively, P = 0.001, 100-Hz, 21.2 [1.6] vs 22.5 [1.6], P = 0.001; group 2: 20-Hz, 13.7 [1.4] vs 19.2 [1.7], P = 0.001, 100-Hz, 21.0 [2.4] vs 27.2 [2.5], P = 0.001). The Pdi at both stimuli during DBcAMP administration was significantly higher in group 2 than in group 1 (20-Hz, 19.2 [1.7] vs 15.0 [2.4], P = 0.001, 100-Hz, 27.2 [2.5] vs 22.5 [1.6], P = 0.003). In group 3, Pdi did not significantly change in regard to either stimulus from hypercapnia-induced values.Conclusion: DBcAMP, in a dose-dependent manner, was associated with improved hypercapnic depression of diaphragmatic contractility in these pentobarbital-anesthetized dogs.     

Effects of doxycycline on intestinal ischemia reperfusion injury induced by abdominal compartment syndrome in a rat model

Background: Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema.Objective: The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS.Methods: Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and β-cell lymphoma 2 (βcl-2) expression were assessed immunohistochemically.Results: Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1β, IL-6, TNF-α, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of βcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively).Conclusion: Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.     

Preemptive analgesia with epidural bupivacaine plus fentanyl in gynaecological surgery—effects on serum interleukin-6 concentrations

Purpose: The aim of this study was to evaluate preemptive analgesia and its influence on interleukin-6 (IL-6) levels.Methods: Thirty patients scheduled for hysterectomy were randomised in two groups to receive 13 ml bupivacaine 0.25% plus fentanyl (100 μg) before incision and 15 ml of saline after incision (group I, GI), or 15 ml of saline before incision and 13 ml bupivacaine 0.25% plus fentanyl (100 μg) after incision (group II, GII). General anaesthesia was performed using propofol/pancuronium/O₂/isoflurane. Postoperative analgesia consisted of epidural bolus doses of 4 ml bupivacaine 0.25% plus fentanyl (50 μg) or dipyrone i.v. on demand. Pain was assessed by visual analogue scale (VAS). IL-6 levels were quantified during the study.Results: Patients in group I had significantly less pain only at arrival in recovery room. The requirements for rescue analgesia were similar in both groups and there were no significant differences in IL-6 concentrations.Conclusions: This study showed no preemptive effect of epidural fentanyl plus bupivacaine on postoperative pain and stress response as measured by IL-6 concentrations.     

Effects of Ondansetron and Granisetron on Postoperative Nausea and Vomiting in Adult Patients Undergoing Laparoscopic Cholecystectomy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Postoperative nausea and vomiting (PONV) are common and potentially distressing adverse events (AEs) associated with surgery and anesthesia. In patients undergoing laparoscopic cholecystectomy (LC) without antiemetic prophylaxis, the incidence of PONV can be as high as 72%.Objective: The aim of this study was to investigate the prophylactic antiemetic effects of ondansetron and granisetron in patients undergoing LC when these agents are administered before the end of surgery.Methods: Patients classified by the American Society of Anesthesiologist's physical status as I or II who were scheduled for elective LC were included in this randomized, double-blind, placebo-controlled study. Anesthesia was induced with thiopental 5 mg/kg and fentanyl 2 μg/kg, and was maintained with isoflurane 1% to 3% in 50% oxygen and 50% nitrous oxide and fentanyl as needed. Approximately 20 to 30 minutes before the end of the surgery, the patients randomly received either IV ondansetron 100 μg/kg (group O), IV granisetron 40 μg/kg (group G), or normal saline (group P). Plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined preoperatively and 24 hours postoperatively. The patients were observed for 24 hours for PONV and other possible AEs. Postoperative pain intensity was determined using a 10-cm visual analogue scale. Four-point satisfaction scores were determined at 24 hours.Results: Ninety patients (69 women, 21 men) participated in the study. Demographic characteristics and operative data (duration of surgery and anesthesia and amount of intraoperative fentanyl) were similar in the 3 groups. The only AE reported by patients during the 24-hour observation period was nonsevere headache. The number of patients experiencing headache was similar in group P, group O, and group G (10 [33%] patients, 6 [20%], and 10 [33%], respectively). No significant changes were found in presurgical and postsurgical plasma levels of ALT and AST in any group. The mean (SD) satisfaction scores in group O and group G (3.0 [0.4] and 3.0 [0.6], respectively) were significantly higher than those in group P (2.5 [0.5]; both, P < 0.01). Immediately after surgery (period 0), significantly more patients in the placebo group (21 [70%]) experienced PONV compared with those in the ondansetron group (9 [30%]; P < 0.05) and the granisetron group (7 [23%]; P < 0.01). During the 24-hour observation period, a significantly greater number of patients in group P (18 [60%]) required a single dose of a rescue antiemetic drug compared with those in groups O and G (9 [30%] and 6 [20%], respectively; both, P < 0.01).Conclusions: Patients administered ondansetron 100 μg/kg or granisetron 40 μg/kg 20 to 30 minutes before the end of LC had significantly higher PONV control during the 24-hour postoperative observation period than patients receiving placebo. However, there were no significant differences between the active treatment groups in the incidence of PONV, patient satisfaction, or AEs.     

Effects of fenofibrate on albuminuria in patients with hypertriglyceridemia and/or hyperuricemia: a multicenter, randomized, double-blind, placebo-controlled, crossover study

Background: A slight increase in albuminuria (urinary albumin excretion [UAE] ≥30 mg/d) is associated with hypertension, type 2 diabetes mellitus, dyslipidemia (high triglyceride [TG] and low high-density lipoprotein cholesterol [HDL-C] concentrations), and hyperuricemia. Although antihypertensive and antidiabetic therapies have been reported to reduce UAE, an association between improvement in dyslipidemia and/or hyperuricemia and a reduction in UAE has not been reported.Objective: The aim of this study was to investigate the efficacy and tolerability of fenofibrate on albuminuria in patients with hypertriglyceridemia and/or hyperuricemia.Methods: Patients with hypertriglyceridemia and/or hyperuricemia were recruited from general clinics and lipid clinics in Japan; they received fenofibrate (300 mg once daily) in this randomized, double-blind, placebo-controlled, crossover study. Patients in group A received fenofibrate for 8 weeks followed by placebo for an additional 8 weeks, whereas those in group B received placebo for 8 weeks followed by fenofibrate for 8 additional weeks. UAE was measured at baseline and at the end of each 8-week period. Blood tests were performed at baseline and every 4 weeks until study end. Each physician who participated in the study was to record adverse events at each study visit.Results: A total of 43 patients entered this study (38 men, 5 women; mean [SE] age, 57.1 [1.4] years; mean [SE] body mass index, 24.3 [0.4] kg/m²). Twenty-one patients (18 men, 3 women) were randomly assigned to group A and 22 (20 men, 2 women) to group B. In group A, serum TG (P<0.001) and apolipoprotein (apo) C2, C3, and E (all P<0.01) concentrations decreased significantly with fenofibrate, and HDL-C and apo A1 and A2 increased significantly (all P<0.001). All of these parameters returned to near-baseline levels after placebo administration. In group B, serum TG, HDL-C, or apo A1, A2, B, C2, C3, and E concentrations did not change significantly with placebo, but TG (P<0.01), apo C3 (P<0.05), and apo E (P<0.05) were significantly decreased with fenofibrate. In addition, HDL-C (P<0.05), apo A1 (P<0.001), and apo A2 (P<0.01) were significantly increased with fenofibrate. Serum concentrations of TG (group A, P<0.001; group B, P<0.001); apo C2 (group A, P<0.01), C3 (group A, P<0.01; group B, P<0.05), and E (group A, P<0.01; group B, P<0.05); and uric acid (group A, P<0.001; group B, P<0.01) were significantly decreased with fenofibrate compared with placebo. HDL-C and apo A1 and A2 were significantly increased with fenofibrate compared with placebo (all P<0.001 in both groups). Fenofibrate treatment was associated with significant reductions in UAE (group A, P<0.05; group B, P<0.01). Spearman rank correlation analysis showed that changes in UAE were associated with changes in apo C2 (ρ = 0.43; P = 0.02) and apo C3 (ρ = 0.49; P = 0.01) concentrations. Multiple regression analysis revealed that a decrease in apo C3 concentration was independently and significantly associated with reductions in albuminuria (ρ = 0.48; P = 0.01). At the end of the study, neither drug-related nor clinical adverse events were evident in any of the patients, except for an increase in serum creatinine concentration above the upper limit of normal (1.40 mg/dL) in 3 patients (14.3%) in group A and 1 patient (4.5%) in group B.Conclusions: In our study population of patients with hypertriglyceridemia and/or hyperuricemia, fenofibrate-induced ameliorations of impaired TG-rich lipoprotein metabolism were associated with reductions in albuminuria.     

Glucagon-like peptide-1 receptor agonists versus insulin glargine for type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of hypoglycemic drugs, including exenatide, liraglutide, albiglutide, lixisenatide, and taspoglutide. Insulin glargine is a standard agent used to supplement basal insulin in type 2 diabetes mellitus (T2DM).Objective: The aim of this study was to review the efficacy and safety profiles of GLP-1 receptor agonists versus insulin glargine in type 2 diabetic patients who have not achieved treatment goals with oral hypoglycemic agents.Methods: The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and the database of ongoing trials were searched from inception through April 2010. Additional data were sought from relevant Web sites, the American Diabetes Association, reference lists of included trials and related (systematic) reviews, and industry. Randomized controlled trials (RCTs) were selected if they were ≥3 months in duration, compared GLP-1 receptor agonists with insulin glargine in patients with T2DM, and included ≥1 of the following outcomes: mortality, complications of T2DM, glycemie control, weight, lipids, blood pressure, adverse effects, and health-related quality of life. Quasirandomized controlled trials were excluded. The quality of the eligible studies was assessed on the basis of the following aspects: randomization procedure, allocation concealment, blinding, incomplete outcome data (intent-to-treat [ITT] analysis), selective outcome reporting, and publication bias.Results: A total of 410 citations were retrieved; 5 multicenter RCTs that met the inclusion criteria were identified. They were all open-label designs with an insulin glargine arm, predefined outcomes reported, and ITT analysis. One trial had an unclear randomization procedure and allocation concealment. Publication bias was not able to be determined. No data wete found with regard to mortality or diabetes-associated complications, and few data were found on quality of life. The results of the metaanalysis suggest that insulin glargine was significantly better in reducing the fasting blood glucose (mean difference [MD] [95% CI], 1.31 [1.04 to 1.58]; P < 0.001), but exhibits greater incidence of nocturnal hypoglycemia (risk ratio [RR] [95% CI], 0.40 [0.23 to 0.71]; P = 0.002) and influenza (RR [95% CI], 0.56 [0.32 to 0.98]; P = 0.04). GLP-1 receptor agonists are more conducive to reducing weight (MD [95% CI], −3.96 [−5.14 to -2.77]; P < 0.001), postprandial blood glucose (after breakfast, P < 0.001; after dinner, P < 0.001), and LDL-C (MD [95% CI], −0.18 [−0.28 to −0.08]; P < 0.001), but have significantly more gastrointestinal adverse effects (eg, nausea/ vomiting, P < 0.001). There were no significant differences between GLP-1 receptor agonists and insulin glargine in reducing glycosylated hemoglobin (HbA_1c) levels (MD [95% CI], −0.03 [−0.13 to 0.08]) and the overall incidence of hypoglycemia (RR [95% CI], 0.69 [0.42 to 1.14]).Conclusions: Compared with insulin glargine, GLP-1 receptor agonists did not have a significant difference in regard to reducing HbA1c levels and they were significantly associated with decreased weight but increased gastrointestinal adverse events. It remains unclear whether GLP-1 receptor agonists influence mortality or diabetes-associated complications in patients with T2DM. More trials with longer follow-up are needed to determine the exact long-term efficacy and safety profiles of this new class of hypoglycemic drugs.