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. Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. Establishing intravenous access: a study of local anesthetic efficacy. Safety and efficacy of intracameral injections of unpreserved lidocaine to reduce intraocular sensation. Effect of local medical opinion leaders on quality of care for acute myocardial infarction: a randomized controlled trial. Neostigmine with glycopyrrolate does not increase the incidence or severity of postoperative nausea and vomiting in outpatients undergoing gynaecological laparoscopy. [Experiences with adjuvant prostaglandin therapy in vascular surgery interventions]. Intrathecal neostigmine for postoperative analgesia after orthopedic surgery. Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction--a 21-day treatment-randomized clinical trial. A multi-center study of intrathecal neostigmine for analgesia following vaginal hysterectomy. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Clinical studies with computer-assisted initial lidocaine therapy. Alkalinization of intracuff lidocaine: efficacy and safety. Antiemetic prophylaxis for office-based surgery: are the 5-HT3 receptor antagonists beneficial? [Neostigmine added to bupivacaine in axillary plexus block: which benefit?]. Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study. Intra-articular lidocaine versus intravenous meperidine/diazepam in anterior shoulder dislocation: a randomised clinical trial. [Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test]. Caudal neostigmine, bupivacaine, and their combination for postoperative pain management after hypospadias surgery in children. Prospective, randomized trial comparing effect of oral versus intravenous pantoprazole on rebleeding after nonvariceal upper gastrointestinal bleeding: a pilot study. Efficacy of alkalinized lidocaine for reducing pain on intravenous and epidural catheterization. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Comparative study of intra-articular lidocaine and intravenous meperidine/diazepam for shoulder dislocations. Impact of a patient decision aid on care among patients with nonvalvular atrial fibrillation: a cluster randomized trial. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma. The effect of intraoperative use of esmolol and nicardipine on recovery after ambulatory surgery. Lidocaine: the optimal timing of intravenous administration in attenuation of increase of intraocular pressure during tracheal intubation. A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia.
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. The local anesthetic sodium-channel blockers lidocaine and mexiletine reduce spontaneous and evoked activity in experimental neuroma models and have been reported to relieve a variety of clinical neuropathic pain conditions. The predictive value of relief from an intravenous lidocaine infusion (IVL) for subsequent relief from a 4-week trial of oral mexiletine was assessed in a prospective study of nine subjects with chronic neuropathic pain of peripheral origin. Subjects received IVL, 2 mg/kg and 5 mg/kg, over 45 min during separate sessions in random order under double-blind conditions. One week later, a 4-week titrating trial of oral mexiletine was initiated. Both doses of IVL significantly reduced pain visual analogue scores (VAS) scores. Although IVL 5 mg/kg produced significantly higher pain relief scores than IVL 2 mg/kg, subjects responded in a highly consistent manner to the two IVL. Subsequent response to oral mexiletine was significantly correlated with the average response to the two IVL. Mexiletine dose and blood levels were not correlated with pain relief. The results suggest that IVL may be a valuable tool in selecting patients for oral therapy with analogous drugs. We performed a double-blind, randomized, prospective study to determine the local anesthetic that provided the best analgesia for insertion of an 18-gauge intravenous (i.v.) catheter and to determine whether alkalinization of lidocaine decreases the pain of intradermal injection. There were 280 healthy adult patients assigned randomly to seven different groups: benzyl alcohol 0.9% in normal saline, 2-chloroprocaine 3%, lidocaine 1%, lidocaine 1% with preservative, alkalinized lidocaine 1% with preservative, normal saline, and a control group that received i.v. catheter placement without previous drug injection. A 10-cm visual analog pain scale (VAPS) was used to obtain pain scores after pre-i.v. drug injection and after iv catheter insertion. Benzyl alcohol in normal saline (0.61 +/- 0.11) and alkalinized lidocaine (0.69 +/- 0.10) had the lowest mean pain scores for drug injection and these were significantly different from other drugs (P < 0.05). Alkalinized lidocaine (0.7 +/- 0.18) had the lowest mean pain score for i.v. catheter insertion with nothing (no previous drug injected) (3.47 +/- 0.38) and normal saline (3.97 +/- 0.18) had the highest mean pain scores (P < 0.05). We conclude that alkalinized lidocaine decreased the pain associated with its injection. Alkalinized lidocaine was the best local anesthetic for i.v. catheter placement. Benzyl alcohol in normal saline was also effective. To determine the safety and efficacy of intracameral injections of unpreserved lidocaine to reduce intraocular sensation.
                Carolina Eye Associates, Southern Pines, North Carolina, USA.
                In this prospective study, 100 patients having phacoemulsification under topical anesthesia were randomly assigned to receive an intracameral injection of unpreserved lidocaine (0.5 cc of a 1% unpreserved solution) or balanced salt solution.
                Ninety-three patients completed the study. There were no significant between-group differences in cell density parameters or Kowa laser flare-cell meter measurements. Seventy-eight percent of lidocaine patients and 56% of controls reported no sensation (P = .048, Fisher's exact test).
                Intracameral injections of unpreserved lidocaine safely and effectively reduced intraocular sensation during phacoemulsification. The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood.
                To evaluate a guideline-implementation intervention of clinician education by local opinion leaders and performance feedback to (1) increase use of lifesaving drugs (aspirin and thrombolytics in eligible elderly patients, beta-blockers in all eligible patients) for acute myocardial infarction (AMI), and (2) decrease use of a potentially harmful therapy (prophylactic lidocaine).
                Randomized controlled trial with hospital as the unit of randomization, intervention, and analysis.
                Thirty-seven community hospitals in Minnesota.
                All patients with AMI admitted to study hospitals over 10 months before (1992-1993, N=2409) or after (1995-1996, N=2938) the intervention.
                Using a validated survey, we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussions, informal consultations, and revisions of protocols and clinical pathways. They focused on (1) evidence (drug efficacy), (2) comparative performance, and (3) barriers to change. Control hospitals received mailed performance feedback.
                Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug.
                Among experimental hospitals, the median change in the proportion of eligible elderly patients receiving aspirin was +0.13 (17% increase from 0.77 at baseline), compared with a change of -0.03 at control hospitals (P=.04). For beta-blockers, the respective changes were +0.31 (63% increase from 0.49 at baseline) vs +0.18 (30% increase from baseline) for controls (P=.02). Lidocaine use declined by about 50% in both groups. The intervention did not increase thrombolysis in the elderly (from 0.73 at baseline), but nearly two thirds of eligible nonrecipients were older than 85 years, had severe comorbidities, or presented after at least 6 hours.
                Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies (eg, aspirin, beta-blockers). Secular changes in knowledge and hospital protocols may extinguish outdated practices (eg, prophylactic lidocaine). However, it is more difficult to increase use of effective but riskier treatments (eg, thrombolysis) for frail elderly patients. We studied 100 healthy women undergoing outpatient gynaecological laparoscopy in a randomized, double-blind and placebo-controlled study to evaluate the effect of neostigmine on postoperative nausea and vomiting (PONV). After induction of anaesthesia with propofol, anaesthesia was maintained with sevoflurane and 66% nitrous oxide in oxygen. Mivacurium was used for neuromuscular block. At the end of anaesthesia, neostigmine 2.0 mg and glycopyrrolate 0.4 mg, or saline, was given i.v. The incidence of PONV was evaluated in the postanaesthesia care unit, on the ward and at home. The severity of nausea and vomiting, worst pain, antiemetic and analgesic use, times to urinary voiding and home readiness were recorded. During the first 24 h after operation, 44% of patients in the neostigmine group and 43% in the saline group did not have PONV. We conclude that neostigmine with glycopyrrolate did not increase the occurrence of PONV in this patient group. Two prospective randomized trials were referred. In the first study 50 patients with femorotibial greater saphenous vein in situ bypasses were treated intraarterially with 0.2 ng PGE 1/kg body weight/min and 15,000 i.U. of heparine continuously. The control group of 50 patients also got 15,000 i.U. of heparine and 3 x 0.5 g of Aspirin. We observed 2 (4%) immediate occlusions in the PGE 1 group and 7 (14%) immediate occlusions in the control group. This difference proved to be statistically significant. In the second study 83 patients with three level occlusions (ilio-femoro-tibial) in stage III and IV were treated with a profundaplasty. 42 patients received 60 micrograms PGE 1 in 250 ml saline twice daily. The control group of 41 patients only got twice 250 ml saline over a period of three weeks. In the PGE 1 group 26 patients (61%) showed disappearance of rest pain and healing of necrotic lesions, whereas in the control group this could only be achieved in 15 patients (35%). The difference proved to be statistically significant. To establish a dose-response curve for the analgesic effect of intrathecal neostigmine in patients undergoing below knee surgery with spinal anesthesia. To assess adverse effects, principally nausea and vomiting.
                Randomized, double-blind, prospective study.
                Teaching hospital.
                60 ASA physical status I and II premedicated patients undergoing orthopedic surgery (tibial or ankle reconstruction).
                Spinal anesthesia was performed at the sitting position, L3-L4 interspace, 4 ml final volume, injected at a rate of 1 ml/10 sec. The control group (CG) received 15 mg hyperbaric bupivacaine 0.5% plus saline. The 25 micrograms neostigmine group (25NG) received 15 mg hyperbaric bupivacaine plus 25 micrograms neostigmine; the 50 micrograms neostigmine group (50NG) received 15 mg hyperbaric bupivacaine plus 50 micrograms neostigmine; and the 100 micrograms neostigmine group (100NG) received 15 mg hyperbaric bupivacaine plus 100 micrograms neostigmine. Patients were placed supine after the spinal punction.
                Time to first rescue analgesics, analgesia, and adverse effects at constant intervals were assessed using the 10 cm visual analog scale (VAS). Intrathecal neostigmine produced a dose-independent reduction in the postoperative rescue analgesic consumption (p < 0.0001). The time to first rescue analgesics was similar among groups (p > 0.05), and the overall 24-hour VAS pain scores were lowest for patients who had spinal neostigmine (p < 0.02). The 100NG group had the highest incidence of postoperative nausea and vomiting of all the groups (p < 0.05).
                Intrathecal neostigmine produced a dose-independent analgesia and a dose-dependent incidence of adverse effects with the doses studied. Alvimopan has been shown to reverse the inhibitory effect of opioids on gastrointestinal transit without affecting analgesia. We evaluated oral alvimopan, 0.5 or 1 mg, versus placebo, once daily for 21 days, in 168 patients with opioid-induced bowel dysfunction (OBD) who were receiving chronic opioid therapy (minimum, 1 month) for nonmalignant pain (n = 148) or opioid dependence (n = 20). The primary outcome was the proportion of patients having at least one bowel movement (BM) within 8 hours of study drug on each day during the 21-day treatment period. Averaged over the 21-day treatment period, 54%, 43%, and 29% of patients had a BM within 8 hours after alvimopan 1 mg, 0.5 mg, or placebo, respectively (P < .001). Secondary outcomes of median times to first BM were 3, 7, and 21 hours after initial doses of 1 mg, 0.5 mg, and placebo, respectively (P < .001; 1 mg vs placebo). Weekly BMs and overall patient satisfaction were increased after the 1-mg dose (P < .001 at weeks 1 and 2 vs placebo, and P = .046, respectively). Treatment-emergent adverse events were primarily bowel-related, occurred during the first week of treatment, and were of mild to moderate severity. Alvimopan was generally well tolerated and did not antagonize opioid analgesia. Patients treated with chronic opioid therapy often experience opioid-induced bowel dysfunction as a result of undesirable effects on peripheral opioid receptors located in the gastrointestinal tract. Alvimopan, a novel peripheral opioid mu-receptor antagonist, has demonstrated significant efficacy for the management of opioid-induced bowel dysfunction without compromise of centrally mediated opioid-induced analgesia. Intrathecal neostigmine injection produces analgesia in volunteers and reduces hypotension from intrathecal bupivacaine in animals. Initial clinical trials with neostigmine studied doses of more than 100 microg, but animal studies suggest that smaller doses may be effective. In addition, all controlled clinical trials of neostigmine have come from one Brazilian university. This multicenter, placebo-controlled trial investigated the effects of 25-75 microg intrathecal neostigmine on analgesia and blood pressure in women undergoing vaginal hysterectomy.
                After institutional review board approval was obtained at the three university centers, and after patients gave informed consent, 92 women scheduled for vaginal hysterectomy were randomized to receive an intrathecal injection of 2 ml bupivacaine, 0.75%, in dextrose plus either 1 ml saline or 25, 50, or 75 microg neostigmine. Blood pressure, heart rate, pain and nausea (both assessed by visual analog scale), and intravenous morphine use were recorded during surgery and at specified intervals afterward.
                Morphine use was reduced similarly by all doses of neostigmine. Only the 75-microg dose of neostigmine increased the nausea score in the recovery room. The incidence of treatment for nausea was greater in patients receiving neostigmine (61%) than in those receiving saline placebo (29%) and was unaffected by neostigmine dose. Neostigmine did not reduce the incidence of hypotension from bupivacaine.
                These data in patients after vaginal hysterectomy suggest that analgesia from intrathecal neostigmine may occur at doses less than 50 microg. In these doses, neostigmine does not reduce spinal bupivacaine-induced hypotension but may increase the need for treatment of nausea. Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP.
                117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740.
                During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33.5%, 95% CI 15.4-51.7; p=0.0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10.9 kPa, 4.6-17.2; p=0.0008) and the non-dominant hand (8.6 kPa, 2.6-14.6; p=0.005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0.011). The incidence of serious adverse events per infusion was 0.8% (9/1096) with IGIV-C versus 1.9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension.
                This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP. A randomized prospective study compared achievement and maintenance of therapeutic plasma concentrations in patients receiving computer-assisted (CA) initial lidocaine hydrochloride therapy, designed pharmacokinetically to achieve and maintain a chosen plasma concentration, v conventional lidocaine therapy (CT). A separate audit of outcome was also conducted. The CA regimens provided more effective concentrations in the first hour than did CT, 2.65 v 1.5 micrograms/mL average. In the audit, ventricular fibrillation occurred in two of 78 CA v eight of 78 CT patients. Dosage adjustments were required in two CA patients v 33 CT patients. The CA therapy improved therapeutic precision, reduced dosage adjustments, and may have improved safety during initial lidocaine therapy before fitting to plasma concentration data for subsequent feedback. An improved clinical computer program now also fits to plasma concentration data. It is accessed and used routinely by hospitals over an international time-sharing network. When alkalinized lidocaine instead of air is used to fill the endotracheal tube (ETT) cuff, coughing, and bucking are decreased during extubation when ventilation is controlled with N2O. However, sodium bicarbonate (NaHCO3) used to transform lidocaine hydrochloride (L-HCl) to lidocaine base induces a pH increase that could be irritating for mucosa in the case of cuff rupture. Therefore, we determined, in a randomized controlled study with controlled patient ventilation without N2O, whether the smallest concentrations of NaHCO3 (1.4% versus 8.4%) reduced diffusion (in vitro evaluation) and other secondary clinical benefits. After pH determination of different solutions (2 mL of 2% L-HCl and 2 to 6 mL of 8.4%, or 1.4% NaHCO3), an in vitro lidocaine diffusion through the ETT cuffs was evaluated (2 mL of 2% L-HCl and 3 mL of 8.4% or 1.4% NaHCO3). Then, adult patients scheduled for total thyroidectomy surgery were consecutively enrolled (n = 20 for each group). The ETT cuff was filled with air (group air) or with alkalinized lidocaine (2 mL of 2% L-HCl) using 8.4% (group large dose) or 1.4% (group small dose) of NaHCO3. After tracheal extubation, sore throat was evaluated by visual analog scale as the main end-point of the study. Hoarseness, bucking, dysphonia, dysphagia, cough, restlessness, and postoperative nausea and vomiting were also evaluated. There was a slight tendency toward a slower release when a small concentration of NaHCO3 was used (i.e., 1.4%). Compared with group air, the alkalinized-lidocaine groups had a significant reduction in sore throat during the 24-h postoperative period (P < 0.0001). The difference was not significant between the two alkalinized lidocaine groups. This increase in ETT tolerance was confirmed by the analysis of secondary end-points. No laryngospasm, rupture of ETT cuff, or depression of the swallowing reflex were recorded. A decrease in sore throat during the postoperative period was recorded when the cuff was inflated with a small dose of alkalinized lidocaine (i.e., 40 mg of L-HCl and 1.4% of NaHCO3) rather than with air when ventilation was controlled without N2O. Office-based surgery has become increasingly popular because of its cost-saving potential. However, the occurrence of postoperative nausea and vomiting (PONV) can delay patient discharge. Prophylaxis using a combination of antiemetic drugs has been suggested as an effective strategy for minimizing PONV. The authors designed this randomized, double-blinded, placebo-controlled study to assess the efficacy of ondansetron and dolasetron when administered in combination with droperidol and dexamethasone for routine antiemetic prophylaxis against PONV in the office-based surgery setting.
                Following institutional review board approval, 135 consenting outpatients with American Society of Anesthesiologists physical status I-III who were undergoing superficial surgical procedures lasting 20-40 min were randomly assigned to one of three antiemetic treatment groups. Propofol was administered for induction of anesthesia, followed by 2-4% desflurane with 67% nitrous oxide in oxygen. Desflurane was subsequently adjusted to maintain a clinically adequate depth of anesthesia with an electroencephalographic Bispectral Index value between 50 and 60. All patients received 0.625 mg intravenous droperidol and 4 mg intravenous dexamethasone after induction of anesthesia. The study medication, containing normal saline (control), 12.5 mg intravenous dolasetron, or 4 mg intravenous ondansetron, was administered prior to the end of surgery. All patients received local anesthetics at the incisional site and 30 mg intravenous ketolorac to minimize postoperative pain. Recovery profiles, incidence of PONV, requirement for rescue antiemetic drugs, complete response rates, and patient satisfaction were assessed.
                The recovery times to patient orientation, oral intake, ambulation, and actual discharge did not differ among the three groups. The incidence of PONV, nausea scores, and requirement for rescue antiemetics were also similar in all three groups during the 24-h study period. In addition, the complete response rates to the prophylactic antiemetics (96-98%) and percentages of very satisfied patients (93-98%) were equally high in all three groups. However, the antiemetic drug acquisition costs were US $2.50, $15.50, and $18.50 in the control, dolasetron, and ondansetron groups, respectively.
                The addition of dolasetron (12.5 mg) or ondansetron (4 mg) failed to improve the antiemetic efficacy of droperidol (0.625 mg intravenous) and dexamethasone (4 mg intravenous) when they were used for routine prophylaxis in the office-based surgery setting. Recent study showed that neostigmine (500 microg) by intra-articular produces postoperative analgesia without adverse effect. The author's goal was to determine whether 500 microg of neostigmine added to bupivacaine in axillary plexus block could prolonged postoperative analgesia without increasing the incidence of side effects.
                Ninety patients scheduled for orthopedic or plastic surgery with axillary plexus block were randomly assigned to one of 3 groups : group 1 (TGr n = 30) received saline solution (1 ml) in the axillary plexus, group 2 (NAGr n = 30) received 500 microg (1 ml) neostigmine in the axillary plexus and group 3.500 microg neostigmine subcutaneously (NSGr n = 30). We evaluated visual analog pain scores (VAS), the consumption of the ketoprofene, nausea and vomiting incidence during the first 24 h. ANOVA, Kruskall Wallis and Fisher tests were used for statistical analysis. A p value of <0.05 was considered significant.
                The VAS score was lower in NAGr (21 +/- 18) vs NSGr (31 +/- 14) and control group TGr (45 +/- 2) (p < 0.05). The consumption of the ketoprofene is 127 +/- 65 mg in NAGr vs 150 +/- 53 mg in NSGr and 200 +/- 50 mg in group TGr (p = 0.02). Incidence of nausea and vomiting was 3.5% in NAGr vs 6.8% in NSGr and 0% for TGr.
                Neostigmine combined to a mixture of lidocaine and bupivacaine prolongs postoperative analgesia after axillary plexus block. The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD).
                VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects.
                NCT00099216.
                710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p< or = 0.05, intent-to-treat population [ITT]), but not other outcomes. Predominant adverse events were nausea and vomiting. Exploratory analyses indicated that older patients (> or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance.
                Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have concomitant Alzheimer pathology. This is supportive of an existing argument that the putative cholinergic deficit in VaD reflects the presence of concomitant Alzheimer pathology. Anterior shoulder dislocation is one of the most common complaints of patients referred to emergency departments. Intravenous opiates and benzodiazepines are traditionally prescribed in order to relieve the pain in this group of patients; however, complications always pose a problem.
                To compare the pain relief and complications following intra-articular lidocaine and intravenous meperidine/diazepam in patients with anterior shoulder dislocation.
                48 patients with non-habitual traumatic anterior dislocation of the glenohumoral joint admitted to Imam Khomeini hospital emergency department were enrolled in this randomised clinical trial. They were divided into two groups: one group of patients received intra-articular lidocaine 1%, while the other received intravenous meperidine and diazepam. Closed reduction using the countertraction-traction method was performed by a single person in all the patients. Utilising a 100 mm visual analogue scale, each patient's pain was recorded before injection, before reduction, and after reduction.
                Mean pain (mm) recorded before injection, before reduction, and after reduction in the intra-articular lidocaine group was 84.3 (95% confidence interval (CI) 79.8 to 88.8), 52.6 (95% CI 45.2 to 60.1), and 27.3 (95% CI 19.9 to 34.7), respectively. The corresponding rates in the intravenous meperidine/diazepam group were 83.2 (95% CI 79.2 to 87.2), 57.9 (95% CI 53.8 to 62.0), and 23.9 (95% CI 18.9 to 28.8), respectively. Both groups demonstrated a similar significant decline in pain after injection (p<0.005). No severe complications were reported in either of the groups.
                Intra-articular injection of lidocaine before closed reduction of anterior shoulder dislocation produces the same pain relief as intravenous meperidine and diazepam. Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy. In a randomized, double-blinded study, we examined the analgesic efficacy of caudal neostigmine, bupivacaine, or a mixture of both drugs in 60 children. After the induction of general anesthesia, children were allocated randomly into three groups (n = 20) to receive a caudal injection of either 0.25% bupivacaine 1 mL/kg, with or without neostigmine 2 micro g/kg, or neostigmine 2 micro g/kg in normal saline 1 mL/kg. Intraoperatively, children receiving caudal bupivacaine or a bupivacaine/neostigmine mixture maintained hemodynamic stability, required less inhaled anesthetics, and had a shorter recovery time compared with the caudal neostigmine alone. Postoperatively, the caudal bupivacaine/neostigmine mixture resulted in superior analgesia compared with the other two groups. Recovery to first rescue analgesic times were (mean +/- SD) 22.8 +/- 2.9 h, 8.1 +/- 5.9 h, and 5.2 +/- 2.1 h in the bupivacaine/neostigmine, bupivacaine, and neostigmine groups, respectively (P < 0.001). In addition, the bupivacaine and neostigmine groups received more doses of paracetamol than the bupivacaine/neostigmine group to maintain adequate analgesia in the first 24 postoperative h. Postoperative vomiting occurred in 25%, 10%, and 30% in the caudal bupivacaine/neostigmine, bupivacaine, and neostigmine groups, respectively (P < 0.01). We conclude that caudal neostigmine 2 micro g/kg provides postoperative analgesia comparable to caudal bupivacaine in children undergoing hypospadias repair surgery.
                Caudal neostigmine 2 micro g/kg provides postoperative analgesia comparable to caudal bupivacaine in children undergoing hypospadias repair surgery. Co-administration of the two drugs is associated with extended postoperative analgesia and reduced need for supplementary analgesics. Proton pump inhibitors (PPIs) reduce the rate of rebleeding in patients with nonvariceal upper GI bleed (NVGIB). Oral (PO) and intravenous (IV) pantoprazole are equipotent in raising gastric pH. We conducted a pilot study comparing the efficacy of PO vs. IV pantoprazole for reducing rebleeding after NVGIB. Patients with NVGIB were randomized to receive PO (80 mg BID for 3 days) or IV (80-mg IV bolus and 8 mg/hr infusion for 3 days) pantoprazole followed by pantoprazole, 40 mg PO BID, for 30 days. All patients underwent endoscopy within 24 hr and endotherapy was applied where necessary. Twelve patients randomized to the PO and 13 to the IV pantoprazole group were comparable in age, hematocrit, Rockall scores, ulcer characteristics, and endoscopic interventions. Two patients in the IV arm rebled and another in the IV arm developed reversible renal failure. No patient in the PO arm rebled, had organ failure, or had to be changed to IV pantoprazole. We conclude that in this pilot study, the effect of PO pantoprazole on 30-day rebleeding rate in patients with NVGIB was similar to that of IV pantoprazole. To investigate whether increasing the pH of lidocaine could reduce the pain caused by its skin infiltration as well as that caused by intravenous and epidural needle insertion.
                A randomized, double-blind trial was undertaken in patients who were allocated to receive topical anesthesia with either plain (plain group; n = 25) or alkalinized lidocaine (alkalinized group; n = 25). An alkalinized lidocaine solution was prepared by adding 8.4% sodium bicarbonate to a plain 1% lidocaine solution at a ratio of 1 : 10. Pain was assessed using the verbal analog scale (VAS).
                In the alkalinized group, the VAS scores on skin infiltration in the hand (2.5 +/- 1.4) and the back (2.7 +/- 1.4) were significantly lower than the respective scores in the plain group (3.5 +/- 1.4, and 4.9 +/- 1.9). Although the VAS score on intravenous needle insertion did not differ between the two groups, the VAS score on epidural needle insertion was significantly lower in the alkalinized group (1.3 +/- 1.0) than in the plain group (3.6 +/- 1.3).
                Alkalinization of lidocaine was effective in attenuating pain on skin infiltration and on epidural needle insertion. To investigate the effects of systemic administration of lidocaine on different components of neuropathic central pains by quantitative sensory testing.
                The efficacy of systemic lidocaine (5 mg/kg IV over 30 minutes) was evaluated in a double-blind, placebo-controlled, and cross-over fashion, on both spontaneous ongoing pain and evoked pains (allodynia and hyperalgesia) in 16 patients with chronic poststroke (n = 6) or spinal cord injury (n = 10) related pain.
                Lidocaine was significantly superior to the placebo (saline) in reducing the intensity of spontaneous ongoing pain for up to 45 minutes after the injection: 10 of 16 patients (62.5%) receiving lidocaine showed a significant reduction in spontaneous pain, whereas only six patients showed this after the placebo. Lidocaine also significantly reduced the intensity of brush-induced allodynia and mechanical hyperalgesia, but was no better than the placebo against thermal allodynia and hyperalgesia. In general, the side effects were moderate and consisted mainly of lightheadedness (44%).
                Systemic lidocaine can induce a significant and selective reduction of several components of pain caused by CNS injuries. The observed preferential antihyperalgesic and antiallodynic effects of this drug suggest a selective central action on the mechanisms underlying these evoked pains. The purpose of this study was to compare the analgesic effectiveness of intra-articular lidocaine versus intravenous meperidine and diazepam during the reduction of anterior shoulder dislocations. Patients were randomized to one of the two methods before the reduction of shoulder dislocations. Patients marked a visual analog pain scale at baseline, after anesthesia just before reduction, and at the time of discharge. Interference with the procedure caused by pain or lack of muscle relaxation, perception of adequacy of analgesia by the patient, adverse effects, and time to discharge from the Emergency Department (ED) were measured. Differences of outcomes, relative risks (RR), and 95% confidence intervals (CIs) were derived. Fifty-four patients with anterior shoulder dislocations presenting from May 21, 1998 through January 21, 1999 were included in this study; 29 were randomly assigned to receive intra-articular lidocaine (IAL) and 25 to receive intravenous meperidine/diazepam (IVMD). IAL was less effective than IVMD in relieving pre-reduction pain (p = 0.045) but equally effective in overall pain relief (p = 0.98). IAL was more effective than IVMD in shortening recovery time (p = 0.025). There was an indication favoring IVMD in terms of physician-perceived muscle relaxation and patient's perception of analgesia adequacy. In conclusion, although the IVMD method appears to have some clinically and statistically significant advantages, IAL possesses some favorable features that render it to be an analgesia alternative in shoulder dislocation reduction. Too few patients with nonvalvular atrial fibrillation (NVAF) receive appropriate antithrombotic therapy. We tested the short-term (primary outcome) and long-term (secondary outcome) effect of a patient decision aid on the appropriateness of antithrombotic therapy among patients with NVAF.
                We conducted a cluster randomized trial with blinded outcome assessment involving 434 NVAF patients from 102 community-based primary care practices. Patients in the intervention group received a self-administered booklet and audiotape decision aid tailored to their personal stroke risk profile. Patients in the control group received usual care. The primary outcome measure was change in antithrombotic therapy at 3 months. Appropriateness of therapy was defined using the American College of Chest Physicians (ACCP) recommendations.
                The mean patient age was 72 years, and the median duration of NVAF was 5 years. In the control group, there was a 3% decrease over 3 months in the number of patients receiving therapy appropriate to their risk of stroke (40% [85/215] at baseline v. 37% [79/215] at 3 months). In the intervention group, the number of patients receiving therapy appropriate to their stroke risk increased by 9% (32% [69/219] at baseline v. 41% [89/219] at 3 months). Although the proportion of patients whose therapy met the ACCP treatment recommendations did not differ between study arms at baseline (p = 0.11) or 3 months (p = 0.44), there was a 12% absolute improvement in the number of patients receiving appropriate care in the intervention group compared with the control group at 3 months (p = 0.03). The beneficial effect of the decision aid did not persist (p = 0.44 for differences between study arms after 12 months).
                There was short-term improvement in the appropriateness of antithrombotic care among patients with NVAF who were exposed to a decision aid, but the improvement did not persist. Age is an important prognostic parameter, especially in patients with advanced high-grade non-Hodgkin's lymphoma (HG-NHL) who require more intensive and extensive therapy for any possible chance of cure. We investigated the potential of granulocyte colony-stimulating factor (G-CSF) for reducing myelotoxicity, which is the most important dose-limiting factor for chemotherapy. Between March 1993 and June 1995, 158 previously untreated patients 60 years and older with HG-NHL were included in a cooperative randomized comparative trial and treated with a combination therapy including VNCOP-B (cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone) with or without G-CSF. G-CSF was administered at 5 microg/kg/d throughout the treatment starting on day 3 of every week for 5 consecutive days. Of the 158 patients registered for the trial, 149 patients were evaluable: 77 received VNCOP-B plus G-CSF and 72 received VNCOP-B alone. The overall response rate was 81.5%, with complete response in 59%: 60% in the VNCOP-B plus G-CSF group, and 58% in the VNCOP-B group. At 30 months (median 24 months), 68% of all complete responders were alive without disease in the G-CSF group and 65% in the control group. Neutropenia occurred in 18 out of 77 (23%) of the G-CSF treated patients and in 40 out of 72 (55.5%) of the controls (P = .00005). Clinically relevant infections occurred in 4 out of 77 (5%) of the G-CSF group and in 15 out of 72 (21%) of the controls (P = .004). The delivered dose intensity was higher in patients receiving G-CSF (95% v 85%), but the difference was not statistically significant. Our data show that VNCOP-B is a feasible and effective regimen in elderly HG-NHL patients, and that the use of G-CSF reduces infection and neutropenia rates without producing any significant modifications to the dose intensity, CR rate, and relapse-free survival curve. There is controversy regarding the optimal technique for maintaining hemodynamic stability during anesthesia. We designed this prospective, randomized, double-blinded study to test the hypothesis that the technique used for maintaining hemodynamic stability during general anesthesia can influence recovery after ambulatory surgery. Forty-five healthy consenting women undergoing gynecologic laparoscopy procedures were randomly assigned to 1 of 3 treatment groups: Group 1 (control, n = 15) received normal saline 5 mL and 1 mL, followed by a saline infusion at a rate of 0.005 mL x kg(-1) x min(-1); Group 2 (n = 15) received esmolol 50 mg and saline 1 mL, followed by an esmolol infusion 5 microg x kg(-1) x min(-1); and Group 3 (n = 15) received esmolol 50 mg and nicardipine 1 mg, followed by an esmolol infusion 5 microg x kg(-1) x min(-1). The study drugs were administered after the induction of anesthesia with fentanyl 1.5 microg/kg, and propofol 2 mg/kg I.V. Tracheal intubation was facilitated with vecuronium 0.12 mg/kg I.V. Anesthesia was initially maintained with desflurane 2% end-tidal and N(2)O 67% in oxygen in all 3 groups. During surgery, the mean arterial blood pressure (MAP) was maintained within +/-15% of the baseline value by varying the study drug infusion rate and the inspired concentration of desflurane. In addition to MAP and heart rate values, electroencephalogram bispectral index values were recorded throughout the perioperative period. Recovery times and postoperative side effects were assessed. Compared with the control group, adjunctive use of esmolol and nicardipine attenuated the increase in heart rate (in Group 2) and MAP (in Group 3) after tracheal intubation. Furthermore, the use of an esmolol infusion as an adjunct to desflurane to control the acute autonomic responses during the maintenance period significantly decreased emergence times (4 +/- 2 versus 7 +/- 4 min), decreased the need for postoperative opioid analgesics (43% versus 80%), and reduced the time to discharge (209 +/- 89 versus 269 +/- 100 min). We conclude that the adjunctive use of esmolol alone or in combination with nicardipine during the induction of anesthesia reduced the hemodynamic response to tracheal intubation. Furthermore, use of an esmolol infusion as an adjuvant to desflurane-N(2)O anesthesia for controlling the acute hemodynamic responses during the maintenance period improved the recovery profile after outpatient laparoscopic surgery.
                The adjunctive use of the beta-adrenergic blocker esmolol to control the acute sympathetic responses during desflurane-based anesthesia provided a more rapid awakening from anesthesia, reduced the postoperative opioid analgesic requirement, and decreased the time to discharge home after ambulatory laparoscopic surgery. This study was designed to examine the optimal timing of intravenous lidocaine in attenuation of increase of intraocular pressure in response to laryngoscopy and tracheal intubation during induction of anesthesia.
                One hundred and thirty five adult patients of ASA class I, aged between 20-35 years, undergoing surgical procedures irrelevant to ophthalmology were enrolled for study. Patients were randomly assigned to one of five groups. In group II, III, IV and V the patients received intravenous injection of lidocaine (2 mg/kg), 1, 3, 5, 10 min before tracheal intubation, respectively. Group I in which patients did not receive lidocaine served as the control group.
                In patients of groups I, IV and V, the intraocular pressure increased significantly after intubation, whereas in those of groups II and III, the intraocular pressure did not. All patients in the five groups showed concomitantly a surge of blood pressure, but the magnitude of increase was smallest in group III in comparison with the other groups. The values of systolic and diastolic pressures 1 min after intubation were significantly less in groups III and IV than in the control group.
                In healthy patients aged between 20 and 35 the most optimal time of administration of intravenous lidocaine to attenuate the increase of intraocular pressure seemed to be the space between 1 to 3 min before laryngoscopy and tracheal intubation. This study investigated the effect of intravenous lidocaine at two doses (1 mg/kg and 5 mg/kg over 2 hours) and an intravenous saline placebo on the pain and allodynia of postherpetic neuralgia (PHN). Twenty-four patients were studied using a randomized, double-blind, within-patient crossover design. Each patient received normal saline, lidocaine 0.5 mg/kg/h, and lidocaine 2.5 mg/kg/h for a 2-h period. The McGill Pain Questionnaire Short Form, visual analogue scores (VAS), and area of allodynia were measured at intervals during the infusions. Free plasma lidocaine levels were also measured. The results were statistically analyzed using Student's t-test for paired data. The VAS for ongoing pain showed a significant reduction after all the infusions (P < 0.05). For dynamic pressure-provoked pain, the VAS was unaffected by placebo but showed a reduction at an equal level of significance with both lidocaine infusions (P < 0.05). The area of allodynia of PHN, as mapped by brush stroke, declined in association with intravenous lidocaine (0.5 mg/kg/h = P < 0.05; 2.5 mg/kg/h = P < 0.001). Placebo had no significant effect on the area of allodynia. These findings demonstrate a positive effect on pain and allodynia following a brief intravenous infusion of lidocaine. The higher dose infusion may produce plasma levels in the toxic range, with no significant clinical increase in response.
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.