Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery.

BACKGROUND: The neurokinin(1) antagonist aprepitant is effective for prevention of chemotherapy-induced nausea and vomiting. We compared aprepitant with ondansetron for prevention of postoperative nausea and vomiting. METHODS: Nine hundred and twenty-two patients receiving general anaesthesia for major abdominal surgery were assigned to receive a single preoperative dose of oral aprepitant 40 mg, oral aprepitant 125 mg, or i.v. ondansetron 4 mg in a randomized, double-blind trial. Vomiting episodes, use of rescue therapy, and nausea severity (verbal rating scale) were documented for 48 h after surgery. Primary efficacy endpoints were complete response (no vomiting and no use of rescue therapy) 0-24 h after surgery and no vomiting 0-24 h after surgery. The secondary endpoint was no vomiting 0-48 h after surgery. RESULTS: Aprepitant at both doses was non-inferior to ondansetron for complete response 0-24 h after surgery (64% for aprepitant 40 mg, 63% for aprepitant 125 mg, and 55% for ondansetron, lower bound of 1-sided 95% CI > 0.65), superior to ondansetron for no vomiting 0-24 h after surgery (84% for aprepitant 40 mg, 86% for aprepitant 125 mg, and 71% for ondansetron; P < 0.001), and superior for no vomiting 0-48 h after surgery (82% for aprepitant, 40 mg, 85% for aprepitant, 125 mg, and 66% for ondansetron; P < 0.001). The distribution of peak nausea scores was lower in both aprepitant groups vs ondansetron (P < 0.05). CONCLUSIONS: Aprepitant was non-inferior to ondansetron in achieving complete response for 24 h after surgery. Aprepitant was significantly more effective than ondansetron for preventing vomiting at 24 and 48 h after surgery, and in reducing nausea severity in the first 48 h after surgery. Aprepitant was generally well tolerated.

Speed of recovery and side-effect profile of sevoflurane sedation compared with midazolam.

BACKGROUND: Sedation for surgical procedures performed with regional or local anesthesia has usually been achieved with intravenous medications, whereas the use of volatile anesthetics has been limited. The use of sevoflurane for sedation has been suggested because of its characteristics of nonpungency, rapid induction, and quick elimination. The purpose of this investigation was to assess the quality, recovery, and side effects of sevoflurane sedation compared with midazolam. METHODS: One hundred seventy-three patients undergoing surgery with local or regional anesthesia were enrolled in a multicenter, open-label, randomized investigation comparing sedation with sevoflurane versus midazolam. Sedation level was titrated to an Observer's Assessment of Alertness--Sedation score of 3 (responds slowly to voice). Recovery was assessed objectively by Observer's Assessment of Alertness--Sedation, Digit Symbol Substitution Test (DSST), and memory scores, and subjectively by visual analog scales. RESULTS: Significantly more patients in the sevoflurane group had to be converted to general anesthesia because of excessive movement (18 sevoflurane and 2 midazolam; P = 0.043). Of remaining patients, 141 were assessable for efficacy and recovery data (93 sevoflurane and 48 midazolam). Sevoflurane and midazolam produced dose-related sedation. Sevoflurane patients had higher DSST and memory scores during recovery. Seventy-six percent (sevoflurane) compared with 35% (midazolam) returned to baseline DSST at 30 min postoperatively (P < 0.05). More frequent excitement-disinhibition was observed with sevoflurane (15 [16%] vs. midazolam; P = 0.008). CONCLUSIONS: Sevoflurane for sedation produces faster recovery of cognitive function as measured by DSST and memory scores compared with midazolam. However, sevoflurane for sedation is complicated by a high incidence of intraoperative excitement.

Dolasetron for the prevention of postoperative nausea and vomiting following outpatient surgery with general anaesthesia: a randomized, placebo-controlled study. The Dolasetron PONV Prevention Study Group.

In a multicentre, randomized, double-blind, placebo-controlled dose-ranging study, 1030 patients undergoing outpatient surgery with general anaesthesia received i.v. dolasetron mesylate (12.5, 25, 50, or 100 mg) or placebo. The principal outcome measure was the proportion of patients who were free of emesis or rescue medication for the 24-h period after the study drug was given; the subsidiary outcome measure was survival time without rescue medication. Effects on nausea were quantified using a visual analogue scale. Compared with placebo, a complete response was significantly higher when all four dolasetron doses were combined (49% vs. 58%, P =0.025). In females, dolasetron, 12.5-mg, dolasetron provided maximum clinical benefit (effectiveness compared with adverse events), with no additional benefit in complete response rates or nausea visual analogue scale scores at higher doses. No significant differences were observed in complete response for any dolasetron dose in males compared with placebo. The majority of adverse events reported were mild or moderate. Dolasetron provided well-tolerated, safe, and effective prophylaxis for post-operative nausea and vomiting with maximum effectiveness observed at a dose of 12.5 mg.

Pooled analysis of three large clinical trials to determine the optimal dose of dolasetron mesylate needed to prevent postoperative nausea and vomiting. The Dolasetron Prophylaxis Study Group.

STUDY OBJECTIVE: To identify the maximally effective dolasetron dose (i.e., maximum efficacy with minimum adverse events) for prevention of postoperative nausea and vomiting (PONV) using the statistical power generated in a pooled patient sample from three large, nearly identical clinical trials. DESIGN: Three randomized, multicenter, placebo-controlled, double-blinded trials. SETTING: Trials 1, 2, and 3 enrolled patients at 10, 25, and 17 hospitals and/or surgical centers, respectively. PATIENTS: A total of 1,946 ASA physical status, I, II, and III patients. Trials 1 and 2 enrolled only female patients (n = 916) undergoing gynecologic surgery. Trial three enrolled 722 females (approximately 70% gynecologic surgeries) and 308 males (approximately 46% orthopedic surgeries) undergoing a variety of surgical procedures. INTERVENTIONS: All surgical procedures used balanced general anesthesia. Patients received 12.5, 25, 50, or 100 mg of the antiemetic, dolasetron, near the end of anesthesia. MEASUREMENTS AND MAIN RESULTS: Efficacy endpoints were identical and measured for 24 hours: complete response (no vomiting or rescue medication) and maximum nausea, reported using a 100-mm visual analog scale (VAS). Safety was assessed using adverse event reports, laboratory and electrocardiographic data, and vital signs. All four dolasetron doses produced significant increases in complete response and decreases in maximum VAS nausea compared with placebo (p < 0.01). No increased efficacy was observed with dolasetron doses higher than 12.5 mg. Safety was similar between each dolasetron dose and placebo. CONCLUSION: Dolasetron 12.5 mg, given near the end of anesthesia, is the maximally effective dose studied for preventing postoperative nausea and vomiting.

Comparison of vital capacity induction with sevoflurane to intravenous induction with propofol for adult ambulatory anesthesia.

UNLABELLED: We compared vital capacity inhaled induction (VC) with sevoflurane with i.v. induction with propofol for adult ambulatory anesthesia. Patients were randomly assigned to receive either 8% sevoflurane in 75% N2O/O2 from a primed circuit (VC, 32 patients) or propofol 2-mg/kg bolus (i.v., 24 patients). Times to loss of consciousness (response to command) and induction side effects (airway, hemodynamic, motor) were assessed. Anesthesia was maintained with sevoflurane/N2O via a face mask for both groups. At the end of surgery, recovery times were measured and psychomotor function tests were performed. Patients were also asked to assess the quality of their anesthesia. Of the VC patients, 59% lost responsiveness in one breath, taking 39 +/- 3 s. All VC patients completed the induction, and all measures of induction time were significantly shorter for VC than for i.v. Induction side effects were different in the two groups (cough and hiccough for VC versus movement and blood pressure changes for i.v.), but overall incidences were similar. There were no significant differences in any index of early or intermediate recovery. Mild nausea occurred more often with VC, but no antiemetics were needed, and discharge was not delayed. Patients' assessments of the quality of induction or wake up were not significantly different between VC and i.v. Thus, VC induction with sevoflurane is an acceptable alternative to propofol i.v. induction of general anesthesia for adult ambulatory surgical patients. IMPLICATIONS: A vital capacity induction with sevoflurane produced a faster loss of consciousness and had side effects, recovery times, and patient satisfaction similar to that of a propofol induction in adults undergoing ambulatory surgery.

A comparison of recovery after sevoflurane or desflurane in ambulatory anesthesia.

STUDY OBJECTIVE: To determine if there is a difference between sevoflurane and desflurane when used as part of a balanced anesthetic technique in terms of time to discharge from an ambulatory surgery unit. DESIGN: Randomized, double blind study. SETTING: Ambulatory surgery unit of a large, metropolitan teaching hospital. PATIENTS: 60 ASA physical status I and II adult women undergoing laparoscopic tubal ligation on an outpatient basis. INTERVENTIONS: Patients were randomized to receive either sevoflurane or desflurane as a component of a balanced anesthetic technique. Visual analog scores (VAS) for discomfort, nausea, and wakefulness, and digit-symbol substitution tests (DSST) were completed preoperatively and at specified intervals after extubation. MEASUREMENTS AND MAIN RESULTS: Time to eye opening, command response, orientation, sitting in bed, sitting with legs dangling, standing, walking, discharge, and departure were measured for all patients. VAS and DSST scores were compared with preoperative baseline scores. CONCLUSIONS: Recovery indices and psychomotor function are marginally but not significantly better with sevoflurane than desflurane.

Friendliness of OR staff is top determinant of patient satisfaction with outpatient surgery.

Two hundred patients (151 women) undergoing outpatient surgery at a university hospital were asked to complete a questionnaire at the time of discharge. Listing 12 factors related to preoperative intraoperative, and postoperative care, the questionnaire asked each respondent to rank the five most important factors from 1 to 5. The most important factor, ranked among the top five by 67% of the patients, was friendliness of the operating room staff. The other four (and, parenthetically, the percentage of patients ranking the factor among the top five) were as follows: surgeons's postoperative visit (63%); management of postoperative pain (62%); starting i.v. smoothly (53%); and avoidance of delays (45%).

Remifentanil compared with alfentanil for ambulatory surgery using total intravenous anesthesia. The Remifentanil/Alfentanil Outpatient TIVA Group.

The purpose of this study was to test the hypothesis that using a 1:4 ratio of remifentanil to alfentanil, a remifentanil infusion would provide better suppression of intraoperative responses and comparable recovery profiles after ambulatory laparoscopic surgery than an alfentanil infusion, as part of total intravenous anesthesia. Two hundred ASA physical status I, II, or III adult patients participated in this multicenter, double-blind, parallel group study. Patients were randomly assigned 2:1 to either the remifentanil-propofol or alfentanil-propofol regimens. The anesthesia sequence was propofol (2 mg/kg intravenously [IV] followed by 150 micrograms.kg-1.min-1), and either remifentanil (1 microgram/kg IV followed by 0.5 microgram.kg-1.min-1)of alfentanil (20 micrograms/kg IV followed by 2 micrograms.kg-1.min-1), and vecuronium. After trocar insertion, infusion rates were decreased (propofol to 75 micrograms.kg-1.min-1; remifentanil to 0.25 microgram.kg-1.min-1; alfentanil to 1 microgram.kg-1.min-1). Alfentanil and propofol were discontinued at 10 and 5 min, respectively, before the anticipated end of surgery (last surgical suture); remifentanil was discontinued at the end of surgery. Recovery times were calculated from the end of surgery. The median duration of surgery was similar between groups (39 min for remifentanil versus 34 min for alfentanil). A smaller proportion of remifentanil patients than alfentanil patients had any intraoperative responses (53% vs 71%, P = 0.029), had responses to trocar insertion (11% vs 32%, P < 0.001), or required dosage adjustments during maintenance (24% vs 41%, P < 0.05). Early awakening times were similar. Remifentanil patients qualified for Phase 1 discharge later and were given postoperative analgesics sooner than alfentanil patients (P < 0.05). Actual discharge times from the ambulatory center were similar between groups (174 min for remifentanil versus 204 min for alfentanil) (P = 0.06). In conclusion, remifentanil can be used for maintenance of anesthesia in a 1:4 ratio compared with alfentanil, for total IV anesthesia in ambulatory surgery. This dose of remifentanil provides more effective suppression of intraoperative responses and does not result in prolonged awakening.

New approaches to anesthesia for day case surgery.

Anesthesia for day case or ambulatory surgery must be specifically tailored to meet its specialized goals, and the use of sevoflurane helps to meet these goals. Maintenance of sevoflurane anesthesia is associated with good titratability and short early recovery times. The rapidity and quality of recovery after sevoflurane anesthesia are as good or better than other available agents. Clinically more important are the new inhalation induction options possible with sevoflurane. These include vital capacity induction of general anesthesia in adult patients, intubation without neuromuscular blocking drugs, and management of selected patients with difficult airways. Anesthesia by facemask or LMA is easily performed without agent-related irritative side effects. The cost of induction with sevoflurane is significantly less than the standard agent propofol, and is even less when sevoflurane is used for both induction and intubation. The costs of maintenance with sevoflurane are more than isoflurane but less than propofol, and can be reduced to low money amounts by the use of N2O and low fresh gas flows, as well as elimination of the anesthetic adjuvant drugs. These new, cost effective anesthetic techniques are useful additions to the spectrum of anesthetic choices for ambulatory surgery.

A multicenter comparison of maintenance and recovery with sevoflurane or isoflurane for adult ambulatory anesthesia. The Sevoflurane Multicenter Ambulatory Group.

Sevoflurane was compared with isoflurane in 246 adult ASA class I-III patients undergoing ambulatory surgery. After administration of midazolam 1-2 mg and fentanyl 1 microgram/kg, anesthesia was induced with propofol 2 mg/kg and maintained with either sevoflurane or isoflurane in 60% nitrous oxide to maintain arterial blood pressure at +/- 20% of baseline. Fresh gas flows were 10 L/min during induction and 5 L/min during maintenance. Times to eye opening, command response, orientation, and ability to sit without nausea and/or dizziness were significantly faster after sevoflurane. Significantly more sevoflurane patients met Phase 1 of postanesthesia care unit (PACU) Aldrete recovery criteria (> or = 8) at arrival, 95% vs 81%. Also, significantly more sevoflurane patients were able to complete psychomotor recovery tests during the first 60 min postanesthesia. Discharge times were not different. Sevoflurane patients had significantly lower incidences of postoperative somnolence (15% vs 26%) and of nausea both in the PACU (36% vs 51%) and in the 24-h postdischarge period (9% vs 24%). Patient satisfaction was high overall (sevoflurane 97%, isoflurane 93%). We conclude that sevoflurane is a useful inhaled anesthetic for maintenance of ambulatory anesthesia.

Resistance to fluid flow in veins.

We evaluated the resistance to fluid infusion in the veins of 118 adult patients after intravenous catheter insertion prior to elective surgery. Hydraulic resistance in veins was defined as the slope of the pressure-flow relationship obtained by measuring venous pressure at several fluid flow rates. A resistance unit (RU) was defined as 1 mmHg/L/hr. Resistance in veins ranged from -12.1 to 732 RU, with 50th and 95th percentiles being 22 and 198 RU, respectively. Venous resistance was not significantly affected by site of catheter insertion, tissue characteristics at the insertion site, age, sex, patient anxiety, American Society of Anesthesiologists physical status, or catheter size. This report provides a distribution of resistance to fluid infusion in arm veins of adult patients.

Detection of intravenous fluid extravasation using resistance measurements.

Resistance to fluid infusion can be derived from measurements of pressure at two or more flow rates. We measured resistance in 31 patients using a pressure-monitoring infusion pump (Model 560, IVAC) by recording pressure at five flow rates (0, 50, 100, 200, and 300 mL/hr), and computing resistance as the slope of the pressure versus flow curve. Resistance was measured subcutaneously (Rtissue) and intravenously (Rvein) immediately after unsuccessful or successful IV catheter placement. In all patients, Rtissue was always greater than Rvein. The difference ranged from 23 resistance units (RU) to 4166 RU, with a mean difference of 1147 RU (p < 0.0001, Student's t-test). Unpaired analysis of the data was performed to assess the ability of resistance to indicate extravasation in the absence of prior Rvein measurement. The median value for Rvein was 62 RU (range -13.6 to 420 RU), and for Rtissue, 544 RU (range 65.7 to 4170 RU). Receiver operating characteristic (ROC) analysis revealed that a 200-RU threshold detected infiltration with 0.90 sensitivity and 0.91 specificity. We conclude that elevated resistance during fluid infusion is an important early and easily measurable finding in fluid extravasation.

Practical cost-effective choices: ambulatory general anesthesia.

To determine cost-effectiveness, we need to determine the value obtained for the price paid. Several points emerge. We need to identify specific recovery goals as our benefits, looking at early, intermediate, and late phases of recovery. Benefits such as effects on nausea may be specific to the procedure, duration, and site of practice. Time savings in the OR or recovery areas do not generate cost savings unless utilization actually increases or staffing actually decreases. Recovery care protocols that mandate a specific duration of stay in the PACU can negate any intraoperative or postoperative benefit differences generated by an anesthetic agent. Most of all, it is difficult to assign a dollar value to a very important benefit: patient satisfaction. Each of us, in our practices, must identify cost-effective choices for ambulatory anesthesia. Determining prices is simple. This we can and should do. Determining value, however, is more complicated and it is in this direction our work must lie.

Patients' assessment of ambulatory anesthesia and surgery.

STUDY OBJECTIVE: To obtain patients' assessments of ambulatory anesthesia and surgery using a return-mail questionnaire postcard. DESIGN: Return-mail questionnaire given to consecutive ambulatory surgery patients. SETTING: Adult ambulatory surgery unit of a university hospital. PATIENTS: The questionnaire was given to 3,722 patients. Responses were returned by 1,511 patients (41%). Among the respondents, 95% had gynecologic procedures and 5% had general surgical procedures. MEASUREMENTS AND MAIN RESULTS: Eighty-six percent of respondents reported at least one minor sequela persisting after discharge. Laparoscopy patients experienced significantly more aches, drowsiness, dizziness, sore throat, nausea, and vomiting. For all patients, sequelae lasted 1 day for 59% of all patients, 2 days for 28%, and 3 or more days for 14%. Different sequelae had different durations. Thirty-eight percent of respondents were able to return to their usual activities the day after surgery; the remainder required 3.2 +/- 2.0 additional days. The main reasons for delayed recovery included general malaise (57%) and surgical discomfort (38%). Assessing their overall satisfaction, 97% would choose day surgery again. CONCLUSIONS: Return-mail questionnaires can be used for patient follow-up after ambulatory surgery, with limitations characteristic of unselected-patient methods. Patients' assessments of their anesthesia and surgery can identify common sequelae that ambulatory patients should realistically expect to experience.