Depth of Hypnosis and Postoperative Nausea and Vomiting During Xenon Anaesthesia (XABP)

RWTH Aachen University

Status and phase: Completed; Phase 4

Conditions: Anaesthetics Volatile, Sevoflurane; Postoperative Vomiting; Postoperative Nausea; Anaesthetics Gases, Xenon; Depth of Anaesthesia

Treatments: Drug: Ondansetron; Drug: NaCl; Drug: Xenon; Drug: Dexamethasone; Drug: Sevoflurane

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00793663

2008-004132-20

Version V3 Date: 20.10.2008;

EudraCT-number:

Protocol version:

ALS-8-08-A-401

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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220 participants in 6 patient groups, including a placebo group

1

Experimental group

Description:

The effect of xenon as an anaesthetic on the depth of hypnosis.

Treatment:

Drug: Xenon

2

Active Comparator group

Description:

The effect of sevoflurane as an anesthetic on the depth of hypnosis

Treatment:

Drug: Sevoflurane

3

Experimental group

Description:

Dexamethasone as prevention of postoperative nausea and vomiting after xenon or sevoflurane anesthesia

Treatment:

Drug: Dexamethasone

4

Placebo Comparator group

Treatment:

Drug: NaCl

Drug: NaCl

5

Experimental group

Description:

Ondansetron, to determine the onset-time of ondansetron when used as rescue medication for postoperative nausea and vomiting

Treatment:

Drug: Ondansetron

6

Placebo Comparator group

Treatment:

Drug: NaCl

Drug: NaCl