Depth of Hypnosis and Postoperative Nausea and Vomiting During Xenon Anaesthesia

Condition(s) targeted: Anaesthetics Gases, Xenon; Anaesthetics Volatile, Sevoflurane; Depth of Anaesthesia; Postoperative Nausea; Postoperative Vomiting

Intervention: Xenon (Drug); Sevoflurane (Drug); Dexamethasone (Drug); NaCl (Drug); Ondansetron (Drug); NaCl (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: RWTH Aachen University

Official(s) and/or principal investigator(s):
Rolf Rossaint, MD, Study Chair, Affiliation: RWTH University Aachen; Department of Anesthesiology

Overall contact:
Mark Coburn, MD, Phone: +49-241-80, Ext: 88179, Email: mcoburn@ukaachen.de

The purpose of this study is ad 1) to measure the depth of hypnosis as assessed by BIS and cAAI during an average general anesthesia with xenon or sevoflurane and to establish a reliable monitoring system for measuring and documenting the actual depth of hypnosis for the volatile anesthetics investigated. Ad 2) the question is to be answered whether 4 mg dexamethasone i. v. is an effective prophylactic treatment against postoperative nausea and vomiting in case of xenon or sevoflurane anesthesia. Ad 3) it serves to gain evidence about the (non-)effectiveness and kinetics of ondansetron as antiemetic remedy after xenon or sevoflurane anesthesia.

Official title: 1) The Effect of Xenon and Sevoflurane on Hypnosis Monitors. 2) Prevention of Postoperative Nausea and Vomiting. 3) Rescue Treatment of Established Postoperative Nausea and Vomiting. Sevoflurane.

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome:

The average depths of hypnosis as assessed by the BIS and the cAAI between skin incision and start of closure.

Postoperative nausea as assessed by a verbal rating scale (VRS) ranging between 0 and 10.

Reduction of VRS nausea immediately at 2, 5, 7.5, 10, 15, 20 and 30 min after rescue treatment administration.

Secondary outcome:

Heart rate and blood pressure

Observer´s assessment of alertness and sedation scales

Sensitivity and specificity characteristics for both the BIS and the cAAI.

Awareness after anesthesia assessed by the Brice questionnaire at 2 and 24 hours after anesthesia.

Occurrence of postoperative vomiting and the respective time-points will be recorded. Postoperative vomiting is defined as vomiting or retching.

Usage of rescue medication, time and dosage

Time to discharge from post anesthetic care unit (Aldrete Score ≥ 9 equals the hypothetic discharge time from post anesthetic care unit)

Detailed description: 1. Patients included into the trial will randomly be allocated to either 0. 8-1. 1 minimum alveolar concentration (MAC) xenon in 30 % oxygen or 0. 8-1. 1 MAC sevoflurane (age adapted)/30 % oxygen. The MAC is defined and will therefore be applied according to the investigated subject`s age. Premedication will be performed with midazolam 7. 5 mg orally 45 min before induction (standard dose and application form for adults as clinical practice of our department). Anesthesia will be induced in both groups with propofol 2 mg/kg i. v. and remifentanil 0. 5 mcg/kg/min by infusion over 60 s. For tracheal intubation non-depolarizing neuromuscular blocking agents can be used (rocuronium 0. 6 mg/kg). Both groups will receive remifentanil at a base rate of 0. 2 mcg/kg/min. Xenon or sevoflurane can be titrated in the range from 0. 8-1. 1 MAC according to clinical needs based on the patient's hemodynamic, autonomic and somatic signs. Twenty minutes before the estimated cessation of all surgical procedures 0. 05 mg kg-1 piritramide for post anesthetic pain management will be administered intravenously, as well as a short infusion of metamizole 15 mg kg-1.

Depth of anesthesia (hypnosis) will be monitored with spontaneous EEG (BIS VISTA, Aspect Medical Systems, Newton, MA) and the mid latency auditory evoked potentials including a monitoring variable indicating the patients hypnotic state calculated from the MLAEP and the electroencephalogram, the composite A-Line ARX Index (cAAI) with the AEP Monitor/2 (Danmeter A/S, Odense, Denmark). Dosing will be conducted according to the current clinical standard without the monitoring, thus the anesthesia provider will be blinded towards both measurements.

2. After induction of anesthesia patients will be randomized to a second factor, i. e. 4 mg dexamethasone or placebo for the prevention of PONV. To avoid potential imbalances, this will be achieved using a factorial design. The application of dexamethasone or placebo will be blinded to the investigator assessing postoperative nausea and vomiting.

3. Patients who experience significant nausea will be randomized to receive either 4 mg ondansetron or placebo and the course of nausea will be assessed for > 32 min. Again, the application of ondansetron or placebo will be blinded to the investigator assessing postoperative nausea and vomiting. If the symptoms of postoperative nausea and vomiting persist for more than 32 min after treatment additional rescue treatment will be offered. Of note, all patients are able to receive further rescue treatment at any time point of the study on demand.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- patients ≥ 18 < 75 years

- ASA physical status I-II

- planned duration of anesthesia ≥ 60 minutes

- Apfel score ≥ 2-3

- elective (laparoscopic) surgery (abdominal, gynecological)

- women: with a highly effective contraception, defined as methods with a pearl index <

1 (i. e. hormonal contraceptives, IUD)

Exclusion Criteria:

- history of hypersensitivity to any used drugs or additive components used for

preparation and stabilization of the named drugs in this trial

- history or reasonable suspicion of malignant hyperthermia and/or degenerative

neuromuscular disease, in the subject observed or blood relatives

- history of liver function disorders, leucocytosis and unclear fever after usage of

halogenated anesthetics.

- any indisposition that may be aggravated by the use of the drugs investigated:

- liver and/or kidney function disorders

- severe acute or chronic infectious disease (i. e. viral, bacterial, fungal)

- elevated intracranial pressure

- history of gastrointestinal ulcer(s) or inflammatory bowel disease

- severe metabolic disorders

- hematoporphyria

- glaucoma

- hearing disorders

- any disease including air-filled closed cavities, such as pneumothorax, ileus

- pregnancy and lactation period

- subjects under the age of 18 years

- ambulatory surgery

- any disease that is associated with the requirement of a high oxygen yield and/or

- risk of high oxygen consumption:

- severe lung and/or airway disease

- coronary heart disease and/or seriously impaired cardiac function

- severe psychiatric disorder

Mark Coburn, MD, Phone: +49-241-80, Ext: 88179, Email: mcoburn@ukaachen.de

RWTH Aachen University; Department of Anesthesiology, Aachen D-52074, Germany; Recruiting
Mark Coburn, MD, Phone: +49-241-80, Ext: 88179, Email: mcoburn@ukaachen.de
Mark Coburn, MD, Principal Investigator

Starting date: November 2008
Ending date: March 2010
Last updated: November 24, 2008