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

• ClinicalTrials.gov Identifier: NCT00793663
• Recruitment Status: Completed
• First Posted: November 19, 2008
• Last Update Posted: May 17, 2011
• Sponsor: RWTH Aachen University
• Collaborator: Air Liquide Santé International
• Information provided by: RWTH Aachen University

Study Description

Brief Summary:

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 or disease	Intervention/treatment	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 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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.
• Study Start Date: November 2008
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: April 2011

Arms and Interventions

Arm	Intervention/treatment
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
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

Outcome Measures

Primary Outcome Measures :

1. The average depths of hypnosis as assessed by the BIS and the cAAI between skin incision and start of closure. [ Time Frame: During anaesthesia ]
2. 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. ]
3. 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. ]

Secondary Outcome Measures :

1. Heart rate and blood pressure [ Time Frame: During anesthesia ]
2. Observer´s assessment of alertness and sedation scales [ Time Frame: Recovery from anesthesia ]
3. Sensitivity and specificity characteristics for both the BIS and the cAAI. [ Time Frame: During anesthesia ]
4. Awareness after anesthesia assessed by the Brice questionnaire at 2 and 24 hours after anesthesia. [ Time Frame: 24 hours after anaesthesia ]
5. 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 ]
6. Usage of rescue medication, time and dosage [ Time Frame: 24 hours postoperative ]
7. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fahlenkamp AV, Stoppe C, Cremer J, Biener IA, Peters D, Leuchter R, Eisert A, Apfel CC, Rossaint R, Coburn M. Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial. PLoS One. 2016 Apr 25;11(4):e0153807. doi: 10.1371/journal.pone.0153807. eCollection 2016.

• Responsible Party: Dr Mark Coburn, Principal Investigator, RWTH Aachen University; Department of Anesthesiology
• ClinicalTrials.gov Identifier: NCT00793663
• Other Study ID Numbers: ALS-8-08-A-401; EudraCT-number: 2008-004132-20; Protocol version: Version V3; Date: 20.10.2008
• First Posted: November 19, 2008
• Last Update Posted: May 17, 2011
• Last Verified: May 2011

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; Postoperative Complications; Pathologic Processes; Dexamethasone; Dexamethasone acetate; Ondansetron; Sevoflurane; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Platelet Aggregation Inhibitors; Anesthetics, Inhalation; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Antipruritics; Dermatologic Agents; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists