Depth of Hypnosis and Postoperative Nausea and Vomiting During Xenon Anaesthesia - Full Text View

Sponsor:	RWTH Aachen University
Collaborator:	Air Liquide Santé International
Information provided by:	RWTH Aachen University
ClinicalTrials.gov Identifier:	NCT00793663

Purpose

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.

Condition	Intervention	Phase
Anaesthetics Gases, Xenon Anaesthetics Volatile, Sevoflurane Depth of Anaesthesia Postoperative Nausea Postoperative Vomiting	Drug: Xenon Drug: Sevoflurane Drug: Dexamethasone Drug: NaCl Drug: Ondansetron	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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.

Resource links provided by NLM:

MedlinePlus related topics: Gas Nausea and Vomiting

Drug Information available for: Dexamethasone Sevoflurane Dexamethasone acetate Doxiproct plus Ondansetron hydrochloride Ondansetron Dexamethasone Sodium Phosphate Xenon

U.S. FDA Resources

Further study details as provided by RWTH Aachen University:

Primary Outcome Measures:

The average depths of hypnosis as assessed by the BIS and the cAAI between skin incision and start of closure. [ Time Frame: During anaesthesia ] [ Designated as safety issue: No ]
Postoperative nausea as assessed by a verbal rating scale (VRS) ranging between 0 and 10. [ Time Frame: After anesthesia at 5, 10, 15, 30, 45, 60, and 90 min. At 2, 6 and 24 h after anesthesia the maximum nausea will be rated for the 30-120 min, 2-6 h, and 6-24 h interval. ] [ Designated as safety issue: Yes ]
Reduction of VRS nausea immediately at 2, 5, 7.5, 10, 15, 20 and 30 min after rescue treatment administration. [ Time Frame: Maximum nausea will be rated at 2, 6 and 24 hours after treatment for the 30-120 min, 2-6 h and 6-24 h interval. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Heart rate and blood pressure [ Time Frame: During anesthesia ] [ Designated as safety issue: Yes ]
Observer´s assessment of alertness and sedation scales [ Time Frame: Recovery from anesthesia ] [ Designated as safety issue: No ]
Sensitivity and specificity characteristics for both the BIS and the cAAI. [ Time Frame: During anesthesia ] [ Designated as safety issue: No ]
Awareness after anesthesia assessed by the Brice questionnaire at 2 and 24 hours after anesthesia. [ Time Frame: 24 hours after anaesthesia ] [ Designated as safety issue: No ]
Occurrence of postoperative vomiting and the respective time-points will be recorded. Postoperative vomiting is defined as vomiting or retching. [ Time Frame: 24 hours postoperative ] [ Designated as safety issue: Yes ]
Usage of rescue medication, time and dosage [ Time Frame: 24 hours postoperative ] [ Designated as safety issue: No ]
Time to discharge from post anesthetic care unit (Aldrete Score ≥ 9 equals the hypothetic discharge time from post anesthetic care unit) [ Time Frame: Time in the post anesthetic care unit ] [ Designated as safety issue: No ]

Estimated Enrollment:	220
Study Start Date:	November 2008
Study Completion Date:	April 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 The effect of xenon as an anaesthetic on the depth of hypnosis.	Drug: Xenon Inhalational gas; maximum dose allowed: 70 % Xenon; the duration of the treatment will be defined through anesthesia-time. Other Name: LENOXe
Active Comparator: 2 The effect of sevoflurane as an anesthetic on the depth of hypnosis	Drug: Sevoflurane Inhalation gas; age adapted MAC-values; the duration of the treatment will be defined through anesthesia-time Other Name: Sevorane
Experimental: 3 Dexamethasone as prevention of postoperative nausea and vomiting after xenon or sevoflurane anesthesia	Drug: Dexamethasone Intravenous use, 4 mg, single shot Other Name: Fortecortin Inject
Placebo Comparator: 4	Drug: NaCl Intravenous use; single shot Other Name: NaCL
Experimental: 5 Ondansetron, to determine the onset-time of ondansetron when used as rescue medication for postoperative nausea and vomiting	Drug: Ondansetron Intravenous use; 4 mg; single shot Other Name: Zofran
Placebo Comparator: 6	Drug: NaCl Intravenous use; single shot Other Name: NaCl

Detailed Description:

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.
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.
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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00793663

Locations

Germany
RWTH Aachen University; Department of Anesthesiology
Aachen, Germany, D-52074

Sponsors and Collaborators

RWTH Aachen University

Air Liquide Santé International

Investigators

Study Chair:

Rolf Rossaint, MD

RWTH University Aachen; Department of Anesthesiology

More Information

No publications provided

Responsible Party:	Dr Mark Coburn, Principal Investigator, RWTH Aachen University; Department of Anesthesiology
ClinicalTrials.gov Identifier:	NCT00793663 History of Changes
Other Study ID Numbers:	ALS-8-08-A-401, EudraCT-number:, 2008-004132-20, Protocol version:, Version V3; Date: 20.10.2008
Study First Received:	November 18, 2008
Last Updated:	May 16, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by RWTH Aachen University:

Xenon
Sevoflurane
Postoperative Nausea and vomiting
Depth of anaesthesia

Additional relevant MeSH terms:

Nausea
Vomiting
Postoperative Nausea and Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Postoperative Complications
Pathologic Processes
Anesthetics
Xenon
Sevoflurane
Dexamethasone acetate
Dexamethasone
Ondansetron
Dexamethasone 21-phosphate
BB 1101

Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012