Incidence of akathisia after postoperative nausea and vomiting prophylaxis with droperidol and ondansetron in outpatient surgery: A multicentre controlled randomised trial.

BACKGROUND: Akathisia, a distressing movement disorder induced by butyrophenones, has been described with low doses of droperidol used for postoperative nausea and vomiting (PONV) prophylaxis, but the incidence remains unclear. OBJECTIVES: To determine the incidence of akathisia after PONV prophylaxis with two doses of droperidol in comparison with ondansetron, in patients undergoing ambulatory surgery. We hypothesised that the incidence of akathisia is higher with droperidol than that with ondansetron. DESIGN: Randomised controlled double blind trial. SETTING: Two University Hospital Centres and two private Clinics from January to September 2014. PATIENTS: Patients (n=297) undergoing general anaesthesia for ambulatory surgery were randomly allocated to receive PONV prophylaxis with droperidol (0.625 or 1.25 mg) or ondansetron 4 mg; patients of the three groups also received 4 mg of dexamethasone. Exclusion criteria were contraindication to droperidol and ondansetron, use of psychotropic medications or benzodiazepines or history of psychotic illness. INTERVENTIONS: Participants received droperidol (0.625 or 1.25 mg) or ondansetron 4 mg during general anaesthesia. After discharge from the postanaesthesia care unit presence and severity of akathisia were assessed using the Barnes Akathisia Rating Scale at 4 h postoperatively. MAIN OUTCOME MEASURES: Score of the Global Clinical Assessment of Akathisia of Barnes Akathisia Rating Scale. RESULTS: The number of akathisia observed was 1/118 (0.8%) in the ondansetron group, 1/84 (1.2%) in droperidol 0.625 mg group, and 3/87 (3.4%) in droperidol 1.25 mg group. The akathisia rate difference among the three groups was not significant (P = 0.52). We could not demonstrate significant differences in the incidence of akathisia between the two doses of droperidol. The only case of marked akathisia treated with benzodiazepines was observed after droperidol 1.25 mg. CONCLUSION: The use of droperidol or ondansetron for PONV prophylaxis is associated to a low incidence of akathisia (0.8 to 3.4%) after general anaesthesia for ambulatory surgery. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01942343.

Should the wheel be reinvented in a human study?

Recently, Zimmer and colleagues reported a lack of analgesic efficacy from intraperitoneal nebulization of bupivacaine using the Insuflow device for patients undergoing laparoscopic cholecystectomy. This is not surprising. An in vitro study in 2008 showed that hot evaporation-based devices, similar to Insuflow, are unable to transport drug molecules dissolved in a water solvent. These results are in keeping with the physical principle that hot evaporation enables only evaporation of the solvent (e.g., water) and not of the solute (e.g., bupivacaine). Although this well-conducted human study has a defendable medical justification and a high theoretical interest, it is not acceptable to choose a human model for an experimental study that attempts to explore a question whose answer has already been published years before in a bench setting.

Changes in core temperature during peritoneal insufflation: comparison of two CO2 humidification devices in pigs.

BACKGROUND: Various modifications of the physical status of CO2 have been used to reduce hypothermia caused by flow of insufflating gas. This animal study aimed to investigate the effects on core temperature, of insufflation with CO2 using two different humidification devices: unheated, humidified CO2 using the Modified-Aeroneb system (Nektar, San Carlos, CA) and warmed, humidified CO2 using the HME-Booster (Medisize, Hillegom, The Netherlands). METHODS: We undertook a prospective four-session study on a homogeneous group of four pigs. After general anesthesia, all animals were treated successively with the following protocols in a randomized order at 8-d intervals: Control (no pneumoperitoneum), Standard (unheated, unhumidified CO2), Modified-Aeroneb (unheated, humidified CO2 by cold nebulization), HME-Booster (heated, humidified CO2). The core temperature of the animals was recorded every 10 min. RESULTS: The temperature decrease is significantly influenced by time (P=0.0001; ANOVA), by the insufflation method (P=0.01), and by the interaction between time and the insufflation method (P=0.0001). The method of contrasts showed the following results:--The temperature decrease in the Standard group and HME-Booster group became greater than in the Control group after 40 min (P=0.02)--The temperature decrease in the Modified-Aeroneb group became greater than in the Control group after 100 min (P=0.04)--The temperature decrease in the Modified-Aeroneb group was less than in the HME-Booster group after 40 min (P=0.04) and less than in the Standard group after 60 min (P=0.01)--The temperature decrease in the Standard group was greater than in the HME-Booster group after 160 min (P=0.005). CONCLUSIONS: Compared with the HME-Booster system, the Modified-Aeroneb is at least as effective in limiting the drop in core temperature during laparoscopic insufflation.

The pharmacokinetics of ropivacaine after intraperitoneal administration: instillation versus nebulization.

BACKGROUND: Intraperitoneal local anesthetic administration provides perioperative analgesia during laparoscopic procedures. We compared the pharmacokinetics of intraperitoneal ropivacaine administered by instillation or nebulization. METHODS: A crossover study was performed on 5 pigs under standardized general anesthesia with a carbon dioxide pneumoperitoneum of 12 mm Hg for 1 hour. Each animal, acting as its own control, was studied twice with an 8-day interval and received, in a randomized sequence, 3 mg/kg ropivacaine either by intraperitoneal instillation at the time of pneumoperitoneum exsufflation or by continuous nebulization in the carbon dioxide insufflation tubing. Arterial blood samples were taken every 10 minutes up to 120 minutes, and then hourly up to 6 hours. Ropivacaine concentrations were measured using high-performance liquid chromatography with ultraviolet-visible detection. The plasma-free fraction was evaluated after plasma ultracentrifugation. Pharmacokinetic parameters were calculated using both noncompartmental and compartmental analysis. The mean values were compared using the Student t test, or Wilcoxon test for paired series. RESULTS: The data were described by a 1-compartment model for both ropivacaine administration techniques, with a delay of 10 minutes for the nebulization group. The maximal ropivacaine concentrations were 0.96 µg/mL for the nebulization group and 0.92 µg/mL for the instillation group (P = 0.66). The ropivacaine absorption constant was lower in the nebulization group (0.043 vs 0.083 min(-1), P = 0.02). There were no differences in the elimination half-life, elimination constant, mean total body clearance, distribution volume, mean area under the curve, and mean residence time. The free fraction of ropivacaine was also similar in the 2 groups. CONCLUSIONS: The pharmacokinetic profile of ropivacaine nebulization is similar to direct intraperitoneal instillation, but with a lower absorption rate.

An evaluation of gas humidifying devices as a means of intraperitoneal local anesthetic administration for laparoscopic surgery.

BACKGROUND: Intraperitoneal local anesthetic administration has been reported to provide perioperative analgesia during laparoscopic procedures. The aim of this in vitro study was to assess the efficiency of commercially available humidification devices to deliver ropivacaine and to determine the effects of modifying the device's position between the insufflator and the Veress needle on the amount of ropivacaine delivered. METHODS: In the first experiment, four humidification devices filled with ropivacaine (0.20% and 0.75%) were placed at the outlet of a laparoscopic insufflation system delivering a constant carbon dioxide flow. A catheter was connected to the humidifier's outlet and the other end submerged in a calibrated vial containing 25 mL of 50% methanol in water. The concentration of ropivacaine collected in the methanol-water solution was measured using high performance liquid chromatography. In the second experiment, the clinical situation was imitated by placing 3 m of silicone tubing between the humidifier and the collection vial to evaluate its influence on the amount of ropivacaine delivered. Only one humidifier was tested in the second experiment because the other three tested humidification devices did not efficiently deliver ropivacaine. RESULTS: The evaporation-based humidifiers delivered very small or nonmeasurable quantities of ropivacaine. In contrast, the microvibration-based aerosol humidification device delivered significant amounts (89.1%-94.3%) of the drug. The insertion of silicone tubing between the humidifier and the collecting vial reduced the amount of delivered ropivacaine to 62.3%. CONCLUSIONS: The microvibration-based aerosol humidification device may be used to deliver local anesthetics during laparoscopic procedures. Further research is necessary to confirm these results in clinical practice and to provide effective humidification that does not blur the surgeon's view.