Depth of Hypnosis and Postoperative Nausea and Vomiting During Xenon Anaesthesia

Postoperative Nausea Clinical Trial

— XABP  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00793663
• Other study ID #: ALS-8-08-A-401
• Secondary ID: EudraCT-number:2
• Status: Completed
• Phase: Phase 4
• First received: November 18, 2008
• Last updated: May 16, 2011
• Start date: November 2008
• Est. completion date: April 2011

Study information

• Verified date: May 2011
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Anaesthetics Gases, Xenon
• Anaesthetics Volatile, Sevoflurane
• Depth of Anaesthesia
• Nausea
• Postoperative Nausea
• Postoperative Nausea and Vomiting
• Postoperative Vomiting
• Vomiting

Intervention

Drug:
• Xenon
Inhalational gas; maximum dose allowed: 70 % Xenon; the duration of the treatment will be defined through anesthesia-time.
• Sevoflurane
Inhalation gas; age adapted MAC-values; the duration of the treatment will be defined through anesthesia-time
• Dexamethasone
Intravenous use, 4 mg, single shot
• NaCl
Intravenous use; single shot
• Ondansetron
Intravenous use; 4 mg; single shot
• NaCl
Intravenous use; single shot

Locations

Country	Name	City	State
Germany	RWTH Aachen University; Department of Anesthesiology	Aachen

Sponsors (2)

Lead Sponsor	Collaborator
RWTH Aachen University	Air Liquide Santé International

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The average depths of hypnosis as assessed by the BIS and the cAAI between skin incision and start of closure.		During anaesthesia	No
Primary	Postoperative nausea as assessed by a verbal rating scale (VRS) ranging between 0 and 10.		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.	Yes
Primary	Reduction of VRS nausea immediately at 2, 5, 7.5, 10, 15, 20 and 30 min after rescue treatment administration.		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.	Yes
Secondary	Heart rate and blood pressure		During anesthesia	Yes
Secondary	Observer´s assessment of alertness and sedation scales		Recovery from anesthesia	No
Secondary	Sensitivity and specificity characteristics for both the BIS and the cAAI.		During anesthesia	No
Secondary	Awareness after anesthesia assessed by the Brice questionnaire at 2 and 24 hours after anesthesia.		24 hours after anaesthesia	No
Secondary	Occurrence of postoperative vomiting and the respective time-points will be recorded. Postoperative vomiting is defined as vomiting or retching.		24 hours postoperative	Yes
Secondary	Usage of rescue medication, time and dosage		24 hours postoperative	No
Secondary	Time to discharge from post anesthetic care unit (Aldrete Score = 9 equals the hypothetic discharge time from post anesthetic care unit)		Time in the post anesthetic care unit	No