XABP: Depth of Hypnosis and Postoperative Nausea and Vomiting During Xenon Anaesthesia

Sponsor

RWTH Aachen University (Other)

Overall Status

Completed

CT.gov ID

NCT00793663

Collaborator

Air Liquide Santé International (Industry)

220

Enrollment

Location

Arms

28.9

Duration (Months)

7.6

Patients Per Site Per Month

Study Details

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 Drug: NaCl	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated 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 :

Nov 1, 2008

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

Apr 1, 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 Names: 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 Names: 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 Names: 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 Names: Zofran
Placebo Comparator: 6	Drug: NaCl Intravenous use; single shot

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Heart rate and blood pressure [During anesthesia]
Observer´s assessment of alertness and sedation scales [Recovery from anesthesia]
Sensitivity and specificity characteristics for both the BIS and the cAAI. [During anesthesia]
Awareness after anesthesia assessed by the Brice questionnaire at 2 and 24 hours after anesthesia. [24 hours after anaesthesia]
Occurrence of postoperative vomiting and the respective time-points will be recorded. Postoperative vomiting is defined as vomiting or retching. [24 hours postoperative]
Usage of rescue medication, time and dosage [24 hours postoperative]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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