A double-blind, randomized, placebo-controlled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy. Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Comparative effects of lidocaine, esmolol, and nitroglycerin in modifying the hemodynamic response to laryngoscopy and intubation. Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine in patients undergoing abdominal hysterectomy during spinal anesthesia. Postoperative analgesia and antiemetic efficacy after subarachnoid neostigmine in orthopedic surgery. Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study. Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus. Effects of intravenous lidocaine and/or esmolol on hemodynamic responses to laryngoscopy and intubation: a double-blind, controlled clinical trial. Neostigmine 50 microg kg(-1) with glycopyrrolate increases postoperative nausea in women after laparoscopic gynaecological surgery.
The purpose of this study was to investigate the safety and efficacy of alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in patients who undergo simple total abdominal hysterectomy.
                Women (n = 519) were randomized (4:1) to receive alvimopan 12 mg (n = 413) or placebo (n = 106) > or = 2 hours before the operation then twice daily for 7 days (hospital and home). Adverse events were monitored up to 30 days after the last dose of study drug was administered. Efficacy was assessed for 7 postoperative days.
                Overall, the most common adverse events were nausea, vomiting, and constipation; < 5% of patients discontinued use because of adverse events. Alvimopan significantly accelerated the time to first bowel movement (hazard ratio, 2.33; P <.001). Average time to first bowel movement was reduced by 22 hours, with more frequent bowel movement and better bowel movement quality found in the treatment cohort.
                Alvimopan has a safety profile that is similar to that of placebo and provides significantly improved lower gastrointestinal recovery in women who undergo simple total abdominal hysterectomy. Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus.
                Patients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive alvimopan 6 mg (n = 152), alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study.
                Mean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group.
                In patients undergoing major abdominal surgery, alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated. To compare the safety and efficacy of lidocaine, esmolol, and nitroglycerin in modifying the hemodynamic response to laryngoscopy and intubation.
                Randomized, placebo-controlled, double-blind study.
                University-affiliated VA medical center.
                40 ASA physical status I and II patients undergoing electric surgery with general endotracheal anesthesia.
                Anesthesia was induced with thiopental sodium 5 mg/kg, and intubation was facilitated with vecuronium 0.15 mg/kg. Isoflurane (0.5% to 1%) and 50% nitrous oxide in oxygen were used for maintenance of anesthesia. In addition, patients received one of the following four study drugs intravenously (i.v.) prior to laryngoscopy: Group 1 (control) = saline 5 ml; Group 2 = lidocaine 1.5 mg/kg; Group 3 = esmolol 1.4 mg/kg; Group 4 = nitroglycerin 2 micrograms/kg.
                Mean arterial pressure (MAP) and heart rate (HR) were recorded every minute for 20 minutes following induction of anesthesia. Following laryngoscopy and intubation, MAP increased significantly in all four treatment groups (control 49% +/- 19%, lidocaine 55% +/- 26%, esmolol 25% +/- 11%, nitroglycerin 45% +/- 21%) compared with preinduction baseline values. In the esmolol-pretreated patients, the increase in HR was significantly lower (20% +/- 3%) compared with the nitroglycerin (37% +/- 8%), lidocaine (52% +/- 8%), and control (29% +/- 4%) groups.
                Lidocaine 1.5 mg/kg i.v. and nitroglycerin 2 micrograms/kg i.v. were ineffective in controlling the acute hemodynamic response following laryngoscopy and intubation. Esmolol 1.4 mg/kg i.v. was significantly more effective than either lidocaine or nitroglycerin in controlling the HR response to laryngoscopy and intubation (p < 0.05). Esmolol also was significantly more effective than lidocaine in minimizing the increase in MAP (25% vs. 55%). Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine were investigated in a randomized, double-blind, placebo-controlled trial of 100 patients undergoing abdominal hysterectomy.
                The patients were assigned to one of five groups (n = 20), and received intravenous prior to the spinal block the antiemetic test drug (except propofol) and 0.05 mg/kg midazolam. The control group (group C), the neostigmine group (group N), and the propofol group (group P) received saline as the test drug. The droperidol group (group D) received 0.5 mg intravenous droperidol, and the metoclopramide group (group M) 10 mg intravenous metoclopramide. Group P was single-blinded and had an intravenous continuous propofol infusion (2-4 mg/kg/h) turned on 10 minutes after the spinal injection. The intrathecal drugs administered were 20 mg hyperbaric bupivacaine (0.5%) associated with either 100 microg neostigmine or saline (for group C). Nausea, emetic episodes, and the need for rescue medication were recorded for the first 24 hours postoperative and scored by the Visual Analog Scale (VAS).
                Time-to-first-rescue medication and rescue medications in 24 hours were similar among the groups (P = .2917 and P = .8780, respectively). Intrathecal 100 microg neostigmine was associated with a high incidence of nausea and vomiting perioperative, leading to a high consumption of antiemetics (P < .002). None of the antiemetic test drugs were effective in preventing nausea and vomiting after 100 microg neostigmine.
                Intrathecal neostigmine (100 microg) was ineffective for postoperative analgesia after abdominal hysterectomy due to side effects of nausea and vomiting. The efficacy of operatively administered spinal neostigmine to provide analgesia and that of different antiemetics to prevent neostigmine-related nausea and vomiting were evaluated in patients undergoing tibial or ankle reconstruction.
                One hundred patients were randomized to five groups (n = 20). The intravenous antiemetic test drug (except propofol) was given as premedication in the holding room, after intravenous midazolam, 0.05 mg/kg. The subarachnoid drugs administered were 20 mg bupivacaine (0.5%) in conjunction with 100 micrograms neostigmine, except for the saline group (S group), which received bupivacaine and saline. The S group, the neostigmine group (N group), and the propofol group (P group) received saline as the intravenous test drug. The droperidol group (D group) received intravenous droperidol 0.5 mg, and the metoclopramide group (M group) received intravenous metoclopramide 10 mg. The P group had a continuous intravenous propofol infusion (2-4 mg/kg/hr), started 10 minutes after the spinal injection. Nausea, emetic episodes, and the need for analgesic (disclofenac) or antiemetic medication were recorded for the first 24 hours following surgery and scored by a 10-cm visual analog scale (VAS).
                Subarachnoid neostigmine 100 micrograms did not affect subarachnoid bupivacaine analgesia as measured by time to first rescue analgesic in most patients, but it decreased the overall 24-hour visual analog scale (VAS) scores and the need for postoperative analgesics in 24 hours (P < .001). The incidence of intraoperative nausea and vomiting was higher in the N, D, and M groups than in the S group (P < .001). Following surgery, the 3-hour VAS assessment for emesis was higher for the N, P, and M groups than for the S group (P < .05). The overall 24-hour assessment was similar among groups.
                Subarachnoid neostigmine reduced postoperative pain scores and analgesic requirements. Whether it prolonged the duration of action of diclofenac or enhanced the mechanisms involved in spinal analgesia cannot be determined from these data. Although propofol and droperidol appeared to be more effective during and after surgery, respectively, all neostigmine groups were associated with a high consumption of antiemetics. Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist for accelerating gastrointestinal recovery after surgery.
                Patients undergoing open laparotomy (bowel resection, n = 418; hysterectomy, n = 197) were randomized to receive alvimopan 6 or 12 mg or placebo orally > or = 2 h before surgery and then b.i.d. until hospital discharge (up to 7 days). The primary efficacy endpoint was time to gastrointestinal (GI) recovery (measured by toleration of solid food and passage of flatus/stool; GI-3). Secondary endpoints included time to GI-2 recovery (toleration of solid food and passage of stool) and hospital discharge order written (DCO).
                Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015). Adverse events were similar between groups.
                Alvimopan (6 or 12 mg) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy. To demonstrate that alvimopan (6 or 12 mg) accelerates recovery of gastrointestinal (GI) function in patients undergoing laparotomy for bowel resection or radical hysterectomy.
                Postoperative ileus (POI) following laparotomy may increase morbidity and extend hospitalization. Opioids can contribute to the duration of POI. Alvimopan is a novel opioid receptor antagonist in development for the management of POI.
                A total of 510 patients scheduled for bowel resection or radical hysterectomy were randomized (1:1:1) to receive alvimopan 6 mg, alvimopan 12 mg, or placebo orally > or =2 hours before surgery, then twice a day (b.i.d.) until hospital discharge or for up to 7 days. The primary efficacy end point was a composite of time to recovery of upper and lower GI function. An associated secondary end point was time to hospital discharge order written.
                The modified intent-to-treat population included 469 patients (451 bowel resection and 18 radical hysterectomy patients). Time to recovery of GI function was accelerated for the alvimopan 6 mg (hazard ratio [HR] = 1.28; P < 0.05) and 12 mg (HR = 1.54; P < 0.001) groups with a mean difference of 15 and 22 hours, respectively, compared with placebo. The time to hospital discharge order written was also accelerated in the alvimopan 12 mg group (HR = 1.42; P = 0.003) with a mean difference of 20 hours compared with placebo. The incidence of adverse events was similar among treatment groups.
                Alvimopan accelerated GI recovery and time to hospital discharge order written compared with placebo in patients undergoing laparotomy and was well tolerated. To evaluate the efficacy of intravenous lidocaine and two doses of esmolol for attenuating the cardiovascular responses to laryngoscopy and intubation, and to assess whether a combination of both drugs is more effective than either drug alone.
                Randomized, prospective, double-blind, placebo-controlled study.
                University hospital.
                90 ASA status I and II normotensive women scheduled for elective gynecologic procedures with general anesthesia.
                Induction of anesthesia was standardized for all patients. The first group received lidocaine 1.5 mg/kg (Group LID); the second and third groups received esmolol 1 mg/kg and 2 mg/kg, respectively (Groups E1 and E2, respectively); the fourth group received lidocaine 1.5 mg/kg and esmolol 1 mg/kg (Group LID-E1); the fifth group received lidocaine 1.5 mg/kg and esmolol 2 mg/kg (Group LID-E2); the sixth group received saline as a placebo (Group PLAC).
                Systolic blood pressure and heart rate (HR) were recorded before induction, before injection of the first test drug, immediately before laryngoscopy, and 1, 2, and 5 minutes following intubation. Duration of laryngoscopy was recorded. Only patients receiving placebo had increased HR values after intubation compared with baseline values (p < 0.05). The proportion of patients with a maximum HR exceeding 90 beats/min was significantly higher in the placebo group (8 of 15 patients) than in both esmolol groups (E1 2 of 15; E2 2 of 15) (p < 0.05). Systolic blood pressure values after tracheal intubation did not differ among groups except for those receiving the combinations of lidocaine and esmolol, and they had significantly lower blood pressure (BP) values compared with placebo (p < 0.05).
                Esmolol 1 to 2 mg/kg is reliably effective in attenuating HR response to tracheal intubation. Neither of the two doses of esmolol tested nor that of lidocaine affected the BP response. Only the combination of lidocaine and esmolol attenuated both HR and BP responses to tracheal intubation. Neostigmine, used for reversal of neuromuscular block, has been implicated in the development of postoperative nausea and vomiting (PONV). The use of mivacurium, which does not require neostigmine reversal due to its metabolism by plasma cholinesterase, has made it possible to study the effect of neostigmine on PONV in a randomised, double-blind, placebo-controlled manner.
                Ninety healthy women scheduled for laparoscopic gynaecological surgery were randomly allocated to two groups in a double-blind manner. One group was given neostigmine (50 microg kg(-1)) and glycopyrrolate (10 microg kg(-1)) (group NG), the other NaCl i.v. as placebo (group P) at the end of surgery when all the patients were spontaneously reversed to at least 75% of full muscle power. The risk of PONV was reduced by using low doses of opioids and ondansetron prophylaxis. All the patients were monitored and assessed for 24 h with regard to pain, nausea, vomiting and overall satisfaction.
                There was a statistically significant difference (P=0.03) in the occurrence of nausea during the first 6 h postoperatively between NG group (30%) and P group (11%), resulting in the more extensive use of antiemetic drugs in the NG group (28%) than in P group (7%) (P=0.01) in this period. There was no difference between the groups in the frequency of vomiting; seven nauseated patients had vomiting, four in group NG, three in group P. Total number of patients with PONV during the observation period of 24 h, usage of antiemetic rescue medication and overall patient satisfaction did not differ significantly between the groups.
                The results suggest that antagonism of neuromuscular block with a high dose of neostigmine increases postoperative nausea and the use of antiemetic drugs during the first 6 h after administration.
Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.