Randomized, double-blind, placebo-controlled, dosed-finding study of the antiemetic effects and tolerability of ramosetron in adults undergoing middle ear surgery

BACKGROUND: Ramosetron is a selective serotonin receptor antagonist (SSRA) that is approved for the treatment of emetic symptoms induced by cytotoxic drugs in Japan. We have reported that ramosetron 0.3 mg had comparable efficacy to granisetron 3 mg, another SSRA, in preventing emetic symptoms in adults in the first 48 hours after the start of anesthesia for middle ear surgery. Although it has been shown that a high dose of ramosetron can cause adverse effects (AEs), such as severe headache, the minimal effective dose of ramosetron is unknown. OBJECTIVE: The aim of this study was to determine the minimum effective and tolerable dose of ramosetron needed to prevent postoperative emetic symptoms in adult patients undergoing middle ear surgery. METHODS: This randomized, double-blind, placebo-controlled, dose-finding study was conducted at the Department of Anesthesiology, Toride Kyodo General Hospital (Toride, Japan). Patients aged > or =20 years scheduled for middle ear surgery were randomized to receive either placebo or ramosetron at 1 of 3 doses (0.15, 0.3, or 0.6 mg), regardless of body weight, i.v. immediately before anesthesia induction. Emetic symptoms (nausea, retching, or vomiting) occurring from 0 to <24 and 24 to 48 hours after the start of anesthesia were recorded. Other AEs also were assessed. RESULTS: A total of 100 patients (55 women, 45 men; mean [SD] age, 44 [12] years; mean [SD] body weight, 56 [8] kg; mean [SD] height, 159 [8] cm) were enrolled. Each treatment group comprised 25 patients. The treatment groups were comparable with regard to demographic characteristics and type of surgery After the second 24 hour postanesthesia period, significantly more patients in the ramosetron 0.3-mg and 0.6-mg groups were emesis free than in the placebo group (both P<0.001). The number of emesis-free patients in the ramosetron 0.15-mg group and the placebo group were similar after both study periods. No significant difference in antiemetic efficacy was found between the ramosetron 0.3-mg and 0.6-mg groups. No relationship between body weight and the efficacy of ramosetron was observed. The incidence of AEs was similar in all 4 groups. CONCLUSIONS: Ramosetron 0.3 mg, regardless of body weight, was more effective than either ramosetron 0.15 mg or placebo and as effective as ramosetron 0.6 mg for the prevention of emetic symptoms in the first 48 hours after the start of anesthesia in this selected population of adult patients who underwent middle ear surgery.     

Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomized, double-blind, placebo-controlled, dose-ranging study

Background

Postoperative emetic symptoms (nausea, retching, and vomiting) frequently occur in women undergoing general anesthesia for abdominal hysterectomy. In a previous report by us, granisetron, a selective serotonin receptor antagonist, was more effective than the traditional antiemetics, droperidol and metoclopramide, for the treatment of postoperative emetic symptoms in this population.

Objective

The aim of this study was to determine the optimal dose of granisetron for the treatment of emetic symptoms following abdominal hysterectomy.

Methods

This randomized, double-blind, placebo-controlled, dose-ranging study was conducted at Toride Kyodo General Hospital (Toride, Japan). Female patients aged 33 to 66 years experiencing postoperative emetic symptoms after abdominal hysterectomy were eligible for the study. Patients received IV granisetron at 1 of 4 doses (10, 20, 40, or 100 μg/kg) or placebo; they were then observed for 24 hours. Emetic symptoms and the need for a rescue antiemetic were recorded by nursing staff, who were blinded to treatment assignment.

Results

A total of 100 patients (mean [SD] age, 45 [7] years [range, 33-66 years]) were enrolled (n = 20 in each group). No significant differences in patient demographic characteristics were observed between the groups. The number of patients in whom complete control of postoperative emetic symptoms, defined as being free of emetic symptoms and not needing rescue antiemetic medication for 24 hours after study drug administration, was established was significantly greater in 3 of the granisetron groups than in the placebo group (6 patients [30%]): granisetron 10 μg/kg, 7 patients (35%; P= NS); granisetron 20 μg/kg, 17 patients (85%; P = 0.001); granisetron 40 μg/kg, 17 patients (85%; P = 0.001); and granisetron 100 μg/kg, 16 patients (80%; P = 0.002). No clinically significant adverse events attributable to the study drug were observed in any group.

Conclusion

In this study of patients who experienced emetic symptoms after undergoing general anesthesia for abdominal hysterectomy, granisetron at doses ≥20 μg/kg was effective in the treatment of established postoperative emetic symptoms.     

Granisetron versus granisetron/dexamethasone combination for the treatment of nausea,retching, and vomiting after major gynecologic surgery: a randomized,double-blind study

BACKGROUND: Granisetron, a selective 5-hydroxytryptamine3 antagonist, is effective for the treatment of patients with postoperative nausea and vomiting. Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. OBJECTIVE: This study compared the efficacy of granisetron alone with granisetron/dexamethasone combination for the treatment of nausea and vomiting after major gynecologic surgery. METHODS: In this randomized, double-blind study, patients who were experiencing emetic symptoms during 0 to 3 hours after the end of anesthesia administration received granisetron 40 microg/kg i.v. either alone or in combination with dexamethasone 8 mg. Patients then were observed for 24 hours after study drug administration, with emetic episodes recorded and tolerability assessments performed by nursing staff blinded to treatment. RESULTS: A total of 120 women were enrolled (n = 60 in each treatment group; mean [SD] age in the granisetron group, 44 [9] years [range, 23-63 years]; combination group, 45 [8] years [range, 21-65 years]). No significant differences in patient demographic characteristics were found between the 2 treatment groups. However, the percentage of patients free of emetic symptoms (nausea, retching, vomiting) was higher in the granisetron/dexamethasone combination group than in the granisetron group (95.0% and 80.0%, respectively; P = 0.012). No clinically serious adverse events attributed to the study drugs were observed in either group. CONCLUSION: In this study, the granisetron/dexamethasone combination was more effective than was granisetron alone for the management of nausea and vomiting during 0 to 3 hours after anesthesia in women undergoing major gynecologic surgery.     

A randomized, double-blind comparison of granisetron alone and combined with dexamethasone for post-laparoscopic cholecystectomy emetic symptoms

Background

Granisetron hydrochloride, a selective serotonin receptor antagonist, has been used to treat established postoperative nausea and vomiting (PONV). Dexamethasone has been shown to reduce the incidence of chemotherapy-induced emesis when added to an antiemetic regimen.

Objective

The aim of this study was to examine the differences in efficacy and tolerability between the combination of granisetron plus dexamethasone and granisetron alone for the treatment of PONV.

Methods

This study was a randomized, double-blind trial conducted at Toride Kyodo General Hospital (Toride, Ibaraki, Japan). Men and women aged 25 to 65 years and experiencing emetic symptoms after laparoscopic cholecystectomy were eligible for the study. Patients received IV therapy with either granisetron 40 μg/kg alone or with dexamethasone 8 mg. Patients were observed for 24 hours. Emetic episodes and the need for a rescue antiemetic were recorded by nursing staff, who were blinded to treatment assignment.

Results

One hundred patients (63 women, 37 men; mean [SD] age, 47 [10] years; range, 25-65 years) were enrolled; 50 patients were randomized to each treatment group. No significant differences in baseline demographic or clinical characteristics were observed between the groups. Complete control of established PONV, defined as no emetic symptoms and no need for another rescue antiemetic medication, occurred in significantly more patients who received the combination (49/50 [98%]) than in those who received granisetron alone (41/50 [82%]) (P = 0.008). No clinically important adverse effects due to the study drugs were observed in either group.

Conclusion

In this study population of patients experiencing post-cholecystectomy emesis, the combination of granisetron plus dexamethasone was more efficacious than granisetron alone for the treatment of PONV. Tolerability between the 2 treatments was similar.     

Randomized, double-blind comparison of subhypnotic-dose propofol alone and combined with dexamethasone for emesis in parturients undergoing cesarean delivery

BACKGROUND: Nausea, retching, and vomiting are common in parturients undergoing cesarean delivery performed under regional anesthesia. Subhypnotic-dose propofol 1.0 mg/kg per hour has been used to reduce the incidence of these emetic symptoms. Dexamethasone has been shown to reduce chemotherapy-induced emesis when added to an antiemetic regimen. OBJECTIVE: The aim of this study was to examine the difference in efficacy and tolerability between subhypnoticdose propofol 1.0 mg/kg per hour alone and combined with dexamethasone 8 mg for reducing postdelivery emetic episodes in parturients undergoing cesarean delivery. METHODS: In a randomized, double-blind trial, parturients received IV placebo (saline) or dexamethasone 8 mg followed by a continuous infusion of propofol at subhypnotic dose (1.0 mg/kg per hour) immediately after clamping of the umbilical cord. Intraoperative, postdelivery emetic episodes and safety assessments were performed by an investigator. RESULTS: One hundred twenty parturients (mean [SD] age, 29 [5] years; age range, 21-38 years; mean [SD] height, 158 [7] cm; height range, 145-172 cm; mean [SD] body weight, 72 [8] kg; weight range, 54-90 kg) were enrolled in the study, 60 in each treatment group. The treatment groups were comparable with respect to maternal demographics and operative management. The rate of emetic symptoms (nausea, retching, and vomiting) in an intraoperative, postdelivery period was lower in patients who received the combination regimen than in those who received subhypnotic-dose propofol 1.0 mg/kg per hour alone (5% [3/60] vs 20% [12/60], respectively; P = 0.012). No clinically important adverse events attributable to the study drug were observed in either group. CONCLUSION: In the parturients undergoing cesarean delivery performed under spinal anesthesia in this study, the combination of subhypnotic-dose propofol 1.0 mg/kg per hour and dexamethasone 8 mg was more effective than propofol alone for reducing the incidence of postdelivery emetic symptoms.     

Benefits and risks of granisetron versus ramosetron for nausea and vomiting after breast surgery: a randomized, double-blinded, placebo-controlled trial

Women undergoing general anesthesia for breast surgery are at particular risk of postoperative nausea and vomiting. In a randomized, double-blinded, placebo-controlled trial, 90 patients scheduled for breast surgery, aged 33-63 years, received intravenously placebo, 3 mg granisetron, or 0.3 mg ramosetron (n = 30 of each) at the end of surgical procedure. A standard general anesthetic technique and postoperative analgesia were used. Emetic episodes and safety assessment were performed during 0-24 hours and 24-48 hours after anesthesia. The rate of patients experiencing emetic symptoms (nausea, retching, vomiting) 0-24 hours after anesthesia was 17% with granisetron (P = 0.013) and 10% with ramosetron (P = 0.002) compared with placebo (47%); the corresponding rate 24-48 hours after anesthesia was 27% (P = 0.032) and 7% (P = 0.001), compared with placebo (53%). In the 24-48 hours after anesthesia, there were fewer emetic episodes in patients who had received ramosetron than in those who had received granisetron (P = 0.039). The severity of nausea was less in patients receiving ramosetron than in those receiving granisetron (P = 0.044). Zero to 24 hours after anesthesia, no difference in the rate of patients having emetic symptoms and the severity of nausea was observed between the granisetron and ramosetron groups. The most common reported adverse events were headache and dizziness, and there were no difference in the incidence of adverse events due to the study drug among the 3 groups. In conclusion, prophylactic therapy with ramosetron is more effective than that with granisetron for the long-term prevention of postoperative nausea and vomiting in women undergoing general anesthesia for breast surgery.     

Effects of dexamethasone in preventing postoperative emetic symptoms after total knee replacement surgery: a prospective, randomized, double-blind, vehicle-controlled trial in adult Japanese patients

BACKGROUND: Postoperative emetic symptoms (nausea, retching, and vomiting) are common following total joint replacement, with an incidence as high as 83% when no prophylactic antiemetic is provided. However, most antiemetics currently used in Japan, such as antihistamines (eg, hydroxyzine), butyrophenones (eg, droperidol), and dopamine receptor antagonists (eg, metoclopramide), have been associated with adverse effects (AEs), such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal symptoms. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of 3 doses of intravenous dexamethasone monotherapy versus vehicle in preventing emetic symptoms after total knee replacement performed under combined general and epidural anesthesia. METHODS: This prospective, randomized, double-blind, vehicle-controlled trial was conducted at the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Japan. Adult Japanese patients scheduled to undergo total knee replacement were eligible. Patients were randomly assigned to 1 of 4 treatment groups: dexamethasone 4, 8, or 16 mg, or vehicle (control). Patients received combination anesthesia with sevoflurane and nitrous oxide in pure oxygen (general) and lidocaine (epidural). Study drugs were administered intravenously after the completion of surgery. An investigator blinded to treatment assignment monitored patients for emetic symptoms for 24 hours after the patient awoke. Patients rated their satisfaction with the study drug using a linear, 11-point scale (0 = complete satisfaction to 10 = complete dissatisfaction). Tolerability was assessed by the study investigator using spontaneous reporting and patient interview. RESULTS: A total of 80 patients were enrolled (58 women, 22 men; mean [SD] age, 59 [10] years; mean [SD] height, 154 [7] cm; mean [SD] body weight, 55 [7] kg; 20 patients per treatment group). The demographic, clinical, and surgical data were comparable between the 4 treatment groups. The rates of emesis-free patients were 35% (7 patients), 70% (14), and 75% (15) with dexamethasone 4, 8, and 16 mg, respectively, compared with 30% (6) with vehicle (P = NS, 0.013, and 0.005, respectively). Median (range) patient satisfaction scores were significantly higher in the groups receiving dexamethasone 8 and 16 mg (both, 0.0 [0-9]) compared with controls (6.0 [0-10]) (P = 0.013 and 0.008, respectively). This effect was not found with the 4-mg dose. No clinically serious AEs attributed to the study drug were observed in any of the 4 treatment groups. CONCLUSIONS: In this study of a small, select group of adult Japanese patients undergoing total knee replacement, the rates of emesis-free patients were higher with dexamethasone 8 and 16 mg compared with vehicle 24 hours after anesthesia induction. This effect was not found with the 4-mg dose. All treatments were well tolerated.     

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.     

A comparison of granisetron,droperidol, and metoclopramide in the treatment of established nausea and vomiting after breast surgery: a double-blind,randomized, controlled trial

BACKGROUND: Women undergoing breast surgery are at particular risk for post-operative nausea and vomiting (PONV), with an incidence of emesis as high as 50% when no prophylactic antiemetic is used.OBJECTIVE: This study compared the efficacy of the selective 5-hydroxytryptamine(3) receptor antagonist granisetron with that of the traditional antiemetics droperidol and metoclopramide in the treatment of established PONV after breast surgery. METHODS: In this prospective, randomized, double-blind trial, patients who had undergone breast surgery and were experiencing PONV during the first 3 hours after anesthesia received either granisetron 40 microg/kg IV, droperidol 20 microg/kg IV, or metoclopramide 0.2 mg/kg IV. Patients were observed for 24 hours after administration of study drug. Emetic episodes were recorded by nursing staff who were blinded to treatment assignment. RESULTS: Seventy-five patients were enrolled in the study, 25 in each treatment group. Their age ranged from 41 to 65 years. There were no significant between-group differences in patients' demographic or surgical characteristics at study entry. The number of patients who were emesis free (no nausea, retching, or vomiting) was significantly higher in patients who received granisetron (88% [2225]) than in those who received droperidol (64% [1625]; P = 0.047) or metoclopramide (56% [1425]; P = 0.013). In patients who experienced nausea (3, 8, and 9 patients in the granisetron, droperidol, and metoclopramide groups, respectively), the severity of nausea was significantly lower with granisetron compared with droperidol (P = 0.028) and metoclopramide (P = 0.025). No clinically serious adverse events were observed in any group. CONCLUSION: Granisetron was significantly more effective than the traditional antiemetics droperidol and metoclopramide for the treatment of PONV in this population of patients undergoing breast surgery.     

Results of a prospective, randomized, double-blind, placebo-controlled, dose-ranging trial to determine the effective dose of ramosetron for the prevention of vomiting after tonsillectomy in children

BACKGROUND: Postoperative vomiting (POV) is an important adverse effect of anesthesia and surgery, and children undergoing tonsillectomy may be particularly at risk. OBJECTIVE: The aim of this study was to determine the effective dose of ramosetron, a 5-hydroxytryptamine type 3 receptor antagonist, for prophylaxis of severe POV (> or =2 episodes) in children undergoing general anesthesia for tonsillectomy. METHODS: Standard general anesthetic technique and postoperative analgesia were used in this prospective, randomized, double-blind, placebo-controlled, dose-ranging trial of pediatric patients. Patients who had experienced POV, had taken an antiemetic medication within 24 hours before surgery of had a history of motion sickness were excluded. Only patients aged 4 to 10 years were included, because of their ability to answer questions. Patients received a single administration of either i.v. placebo or i.v. ramosetron at 3, 6, or 12 microg/kg immediately after the end of surgery. During the first 48 hours after anesthesia, episodes of retching, vomiting, and adverse events were recorded by nursing staff blinded to treatment assignment. RESULTS: Eighty children (20 in each group)--42 girls and 38 boys--were enrolled. There were no differences in patient demographic characteristics among the treatment groups. The rates of complete response (no vomiting, retching, or need for another antiemetic medication) from 0 to 24 hours after anesthesia were 35% (7/20) with ramosetron 3 microg/kg, 90% (18/20) with ramosetron 6 micro/kg, and 90% (18/20) with ramosetron 12 microg/kg compared with placebo (30% [620], P=NS, P=0.001, and P=0.001 vs placebo, respectively); the corresponding rates from 24 to 48 hours after anesthesia were 35% (7/20), 90% (18/20), and 95% (19/20) compared with placebo (35% [7/20]; P=NS, P=0.001, and P=0.001 vs placebo, respectively). No difference in antiemetic efficacy was observed between ramosetron 6 and 12 microg/kg. No clinically serious adverse events attributable to the study drug were observed in any group. CONCLUSIONS: In the pediatric population studied, ramosetron 6 microg/kg was effective for the prevention of vomiting after tonsillectomy from 0 to 48 hours after anesthesia. Increasing the dose to 12 microg/kg did not appear to provide further benefit.     

Comparison of granisetron with granisetron plus droperidol combination prophylaxis in post-operative nausea and vomiting after laparoscopic cholecystectomy

The aim of this study was to evaluate the effects of granisetron and granisetron plus droperidol combination therapy on post-operative nausea and vomiting (PONV) in 60 patients who had undergone elective laparoscopic cholecystectomy. Induction of anaesthesia was achieved using 5 mg/kg thiopentone, 2 micrograms/kg fentanyl and 0.5 mg/kg atracurium, and anaesthesia was maintained with 2-2.5% sevoflurane. The patients were randomly assigned to two groups: group G (granisetron) (n = 30) patients received 3 mg granisetron and group GD (granisetron plus droperidol) (n = 30) patients received 3 mg granisetron and 1.25 mg droperidol shortly before the induction of anaesthesia. PONV incidence was recorded post-operatively at 15 min, 30 min, 60 min, 2 h, 4 h, 12 h and 24 h. While PONV prophylaxis provided almost complete emetic control in patients who received the granisetron plus droperidol combination, patients who received granisetron prophylaxis alone experienced PONV more frequently at 30 min and 60 min post-operatively. We conclude that addition of a low dose of droperidol to granisetron prophylaxis is more effective than granisetron prophylaxis alone for successful control of PONV.     

A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain

Safety and efficacy data from a study of slow intrathecal (IT) ziconotide titration for the management of severe chronic pain are presented. Patients randomized to ziconotide (n = 112) or placebo (n = 108) started IT infusion at 0.1 microg/hour (2.4 microg/day), increasing gradually (0.05-0.1 microg/hour increments) over 3 weeks. The ziconotide mean dose at termination was 0.29 microg/hour (6.96 microg/day). Patients' baseline Visual Analogue Scale of Pain Intensity (VASPI) score was 80.7 (SD 15). Statistical significance was noted for VASPI mean percentage improvement, baseline to Week 3 (ziconotide [14.7%] vs. placebo [7.2%; P = 0.036]) and many of the secondary efficacy outcomes measures. Significant adverse events (AEs) reported in the ziconotide group were dizziness, confusion, ataxia, abnormal gait, and memory impairment. Discontinuation rates for AEs and serious AEs were comparable for both groups. Slow titration of ziconotide, a nonopioid analgesic, to a low maximum dose resulted in significant improvement in pain and was better tolerated than in two previous controlled trials that used a faster titration to a higher mean dose.     

Pain on injection of propofol: the effect of granisetron pretreatment

OBJECTIVE: To assess the effect of granisetron pretreatment in alleviating propofol injection pain. STUDY DESIGN: A randomized, controlled, double-blind study, using venous retention with a tourniquet. MATERIALS AND METHODS: One hundred fifty adult patients were randomly assigned to one of three groups: group 1 (who received 5 mL of 0.9% saline pretreatment), group 2 (who received 5 mL lidocaine [40 mg in 0.9% saline] pretreatment), and group 3 (who received 5 mL granisetron [2 mg in 0.9% saline] pretreatment). Injections were given in the largest vein on the dorsum of the hand. After 2 minutes, the tourniquet was released and one fourth of the total calculated dose of propofol (2.5 mg/kg body weight) was administered and pain assessment was made. RESULTS: Lidocaine and granisetron significantly reduced the incidence and severity of propofol injection pain more than placebo (P < 0.001). The efficacy of granisetron in alleviating the pain on injection of propofol was no different from lidocaine. CONCLUSIONS: Granisetron pretreatment may be used to reduce the incidence of pain on injection of propofol, an advantage added to the useful prevention of postoperative nausea and vomiting.     

格拉斯琼预防全麻后寒战的临床观察

目的：探讨同哌替啶和曲马多比较,格拉斯琼预防全麻后寒战的临床效果。方法：120例ASAI～II级,在全麻下拟行择期手术患者,随机分为四组,每组30例：T组（曲马多1mg/kg）,G组（格拉斯琼40μg/kg）,M组（哌替啶0.4mg/kg）和P组（0.9%生理盐水）。各组药物在手术结束时通过静脉给予。记录术后寒战评分和麻醉恢复时间及镇静程度。结果：同对照组比较,格拉斯琼明显减少麻醉后寒战的发生（P〈0.01）,但同哌替啶和曲马多组比较无统计学差异（P〉0.05）。哌替啶组和曲马多组的麻醉恢复时间（20.58±3.56和16.45±4.13min）较对照组（12.61±3.31min）和格拉斯琼组（13.58±3.41min）明显延长（P〈0.05）。结论：使用40μg/kg格拉司琼同使用曲马多1mg/kg和哌替啶0.4mg/kg一样可有效地预防麻醉后寒战。     

Tolerability and safety profile of 12- to 28-week treatment with interferon beta-1b 250 and 500 microg QOD in patients with relapsing-remitting multiple sclerosis: a multicenter, randomized, double-blind, parallel-group pilot study

BACKGROUND: It is not known whether the currently available treatment regimen of interferon beta-1b (IFNbeta-1b) 250 microg provides the maximum benefit possible in the treatment of relapsing-remitting multiple sclerosis (RRMS), or whether higher doses of IFNbeta-1b will prove to be more beneficial. OBJECTIVE: The objective of the present study was to evaluate the tolerability and safety profile of IFNbeta-1b 500 microg compared with the currently approved 250-microg dose. METHODS: A multicenter, randomized, double-blind, parallel-group pilot study was carried out to compare IFNbeta-1b 250 microg with IFNbeta-1b 500 microg, both self-administered SC QOD for >or=12 weeks in patients with RRMS. Patients in both groups started with 25% (0.25 mL) of their final dose and were scheduled to increase the dose by 0.25 mL every 2 weeks, so that the full dose (1.0 mL, 250 microg or 500 microg) would be reached by week 7. The primary outcome measure was the percentage of patients experiencing each of the following adverse events (AEs): influenza-like symptoms (general term used to code the presence of >1 symptom typical of influenza), fever, myalgia, asthenia, headache, injection-site reactions, injection-site pain, or liver or hematologic abnormalities. All patients underwent a priori magnetic resonance imaging (MRI) with 0.1 mmol/kg gadolinium (Gd)-diethylenetriaminepentaacetic acid as contrast medium at screening and at week 12. MRI evaluation was included as a safety measure to monitor for excessive new disease not visible through clinical symptoms. RESULTS: Seventy-seven patients were assessed for inclusion in the study. Of these, 6 patients were screening failures and the remaining 71 were randomized to treatment (38-250 and 33-500 microg IFNbeta-1b). The uneven numbers in the groups were a consequence of the randomization process. Two patients in the 250-microg group (withdrawal of consent) and 1 in the 500-microg group (not completing follow-up visit) prematurely discontinued medication. The demographic characteristics were not significantly different between the 250-microg (n=38; mean [SD] age, 37.9 [8.3] years; weight, 83.5 [19.0] kg; height, 168.4 [9.3] cm) and 500-microg (n=33; mean [SD] age, 37.8 [7.7] years; weight, 82.3 [19.5] kg; height, 169.9 [10.5] cm) treatment groups. The patients in both groups were mostly white (87% and 73%, respectively). Baseline Expanded Disability Status Scale scores also were not significantly different between the 2 groups (mean [SD] score, 2.8 [1.4] vs 2.0 [1.4], respectively). In the IFN(2)-1b 250-microg group, 97% of the patients titrated to the full dose at some point during the course of the study, compared with 91% of the 500-microg group (P=NS). A dose-response effect was observed in some of the more frequent AEs (no. [%]) that included influenza-like syndrome (250-microg group, 13 [34] vs 500-microg group, 16 [48]), asthenia (13 [34] vs 16 [48], respectively), headache (12 [32] vs 12 [36]), myalgia (10 [26] vs 13 [39]), hypesthesia (10 [26] vs 11 [33]), nausea (6 [16] vs 8 [24]), paresthesia (6 [16] vs 8 [24]), myasthenia (4 [11] vs 8 [24]), chills (3 [8] vs 6 [18]), depression (3 [8] vs 5 [15]), back pain (2 [5] vs 5 [15]), increased liver enzymes (4 [11] vs 6 [18]), lymphopenia (4 [11] vs 3 [9]), fever (2 [5] vs 4 [12]), and pain in extremities (1 [3] vs 4 [12]). The between-group incidence of injection-site reactions was not significantly different. No new or unexpected AEs were recorded. Changes in MRI parameters between screening and 12 weeks were not significantly different between dose groups; these included median T2 lesion volume, median Gd-enhanced lesion volume, median Gd-enhanced lesion number, and mean number of newly active lesions. CONCLUSIONS: IFNbeta-1b 500 microg administered SC QOD was generally well tolerated in these patients with RRMS. Large, randomized controlled studies are needed to determine if there are significant differences in MRI end points between the 250- and 500-microg doses.     

舒芬太尼和芬太尼对腹腔镜胆囊切除术患者全麻苏醒质量的比较

[目的]比较舒芬太尼和芬太尼对腹腔镜胆囊切除术全麻苏醒质量的影响.[方法]将110例择期行腹腔镜胆囊切除手术的患者随机分为舒芬太尼（S）组和芬太尼（F）组,每组55例.S组以咪达唑仑0.1 mg/kg、舒芬太尼0.4 μg/kg、丙泊酚2 mg/kg、维库溴胺0.12 mg/kg诱导插管;F组,以咪达唑仑0.1 mg/kg、芬太尼4 μg/kg、丙泊酚2 mg/kg、维库溴胺0.12 mg/kg诱导插管.以丙泊酚0.5 mg/（kg·h）和瑞芬太尼0.25 mg/h维持麻醉.比较两组术后患者的呼吸恢复时间、呼唤睁眼时间、气管导管拔出时间及术后的疼痛语言（VRS）分级评分和镇静（SS）评分及苏醒期内不良反应的发生情况.[结果]F组患者术后呼吸恢复时间、呼唤睁眼时间、气管导管拔出时间均长于S组,且两组相比较差异有显著性（P〈0.05）,F组术后躁动发生率、疼痛发生率显著高于S组（P〈0.01）,S组镇静强度显著强于F组（P〈0.01）.[结论]与芬太尼全身麻醉相比,使用舒芬太尼的患者苏醒期更平稳     

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.     

A double-blind comparison of granisetron and placebo for the treatment of acute migraine in the emergency department

Three hundred and ninety-seven patients who presented to the emergency department were screened for a randomized, double-blind, placebo-controlled study of iv granisetron (40 micrograms/kg or 80 micrograms/kg) in acute migraine. Twenty-eight patients fulfilled the stringent eligibility criteria and completed the study. Rescue medication was required 2 h post-infusion in 8 of 10 patients receiving granisetron 40 micrograms/kg, 5 of 10 patients receiving granisetron 80 micrograms/kg, and 6 of 8 patients receiving placebo. Significant improvement (p less than 0.05) in headache pain (on a visual analogue scale and categorical scale) was observed in the 80-micrograms/kg group. Headache pain evaluated with the Hunter headache scale indicated improvement for the sensory and affective components of headache pain in both granisetron groups. Except for more nausea at 30 min in the placebo group, no significant differences were noted between treatments. All three treatments were well tolerated. Granisetron may be effective for acute migraine headache; however, further studies with increased patient numbers are required.     

A 2-week, multicenter, randomized, double-blind, double-dummy, add-on study of the effects of titration on tolerability of tramadol/acetaminophen combination tablet in Korean adults with knee osteoarthritis pain

BACKGROUND: Combined tramadol/acetaminophen is used to treat pain related to osteoarthritis. However, adverse events (AEs) leading to discontinuation can occur. Dose titration may decrease the risk for AEs. OBJECTIVE: The aim of this study was to assess the effect of tramadol/acetaminophen titration on the development of AEs leading to treatment discontinuation in patients with knee osteoarthritis. METHODS: This 2-week, multicenter, randomized, double-blind, double-dummy, add-on study was conducted at 12 tertiary referral university hospitals in the Republic of Korea. Patients aged 35 to 75 years with knee osteoarthritis receiving a stable dose of NSAIDs and with a daily mean pain-intensity score of > or = 4 on a numeric rating scale (NRS) (0 = no pain to 10 = worst pain) during the 48 hours prior to enrollment were eligible. Patients were randomly assigned to receive 1 tablet of tramadol/acetaminophen 37.5/325 mg QD and 1 placebo BID for 3 days, followed by 1 active tablet BID and 1 placebo QD for 4 days, followed by 1 active tablet TID for 7 days (titration group) or 1 tablet of combined tramadol 37.5 mg/acetaminophen 325 mg TID for 14 days (nontitration group). The primary outcome measure was the rate of treatment discontinuation due to AEs. Secondary outcome measures were time to discontinuation due to AEs, prevalences and characteristics of AEs, decrease from baseline in pain intensity as measured on the NRS, and change in the Korean version of the Western Ontario and McMaster Universities (K-WOMAC) index score (scale: 0 = best to 100 = worst). RESULTS: A total of 250 patients were enrolled (92.0% female; mean [SD] age, 60.2 [7.8] years; mean [SD] weight, 60.0 [9.2] kg [range, 37.5-90.7 kg]; all Korean). The discontinuation rate was significantly lower in the titration group than in the nontitration group (10.5% vs 26.2%; P < 0.001). The Kaplan-Meier survival curve showed that the rates of discontinuation due to AEs were similar in the 2 groups up to day 2, but thereafter the discontinuation rate was significantly lower in the titration group. The most common AEs were nausea (12.1% and 24.6% in the titration and nontitration groups, respectively; P = 0.008), vomiting (4.0% and 17.2%; P < 0.001), and dizziness (9.7% and 22.1%; P = 0.005). No serious AEs were reported in either group. Tramadol/acetaminophen use was associated with a similar decrease from baseline in pain in both the titration and nontitration groups (mean [SD] Delta: NRS, -1.60 [1.62] vs -1.68 [1.58]; total K-WOMAC, -12.86 [13.73] vs -12.52 [16.58]). CONCLUSIONS: In this population of Korean patients with knee osteoarthritis pain managed with a stable dose of NSAIDs, titration of tramadol/acetaminophen over 12 days was associated with improved tolerability and a significantly lower discontinuation rate compared with nontitration. Both regimens significantly reduced from baseline associated with osteoarthritis.     

Efficacy and safety of different doses of granisetron for the prophylaxis of cisplatin-induced emesis

The purpose of this study was to evaluate the efficacy and safety of four different doses of granisetron when administered as a single intravenous (i.v.) dose for prophylaxis of cisplatin-induced emesis in a multicenter, randomized, parallel-group, double-blind investigation. A total of 353 chemotherapy-naive patients were enrolled, stratified according to cisplatin dose (moderate dose: 50–80 mg/m²,n = 169; high dose: 81–120 mg/m²,n = 184) and randomized to one of four granisetron doses: 5, 10, 20, or 40 µ/kg. Control of emesis was evaluated by the percentages of patients attainingcomplete response (no vomiting or retching, and no rescue medication) andmajor response (2 episodes of vomiting or retching, and no rescue medication). Patients were assessed on an inpatient basis for 18–24 h. Safety analyses consisted of adverse events and laboratory parameter changes. Complete response rates over 24 h after chemotherapy were 23%, 48%, 48%, and 44% for granisetron doses of 5, 10, 20, and 40 µg/kg, respectively, in the combined patient population (P=0.011 for linear trend); 29%, 56%, 58%, and 41%, respectively, in the moderate-dose cisplatin stratum (P=0.278 for linear trend); and 18%, 41%, 40%, and 47%, respectively, in the high-dose cisplatin stratum (P = 0.011 for linear trend). Transient headache was the most frequently reported adverse event (19%). There was no evidence of association between increased dose and headache. A single 10-, 20- or 40-µg/kg dose of granisetron is comparably effective in controlling nausea and vomiting associated with moderateor high-dose cisplatin chemotherapy. Granisetron was safe and well tolerated at all doses.