Physiological Effects of Nitrous Oxide on Anaesthesia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dr Philip Peyton, Austin Health
ClinicalTrials.gov Identifier:
NCT01092923
First received: March 10, 2010
Last updated: September 11, 2012
Last verified: September 2012
  Purpose

Nitrous oxide is the oldest anaesthetic agent still in routine use today. Despite huge changes in the pharmacology of volatile anaesthetic agents and intravenous anaesthetics, the unique properties of nitrous oxide have maintained its place in modern practice, where it is used in combination with other, more powerful inhaled agents, such as sevoflurane. It has useful analgesic properties, unlike the other agents used today, and its inclusion reduces the concentration of other agents required to maintain an adequate depth of anaesthesia for surgery.

In particular, its low solubility in body tissues gives it a unique pharmacokinetic profile, with rapid washin and washout from the body. It has been shown to have a similar effect on the speed of uptake of accompanying agents like sevoflurane (the "second gas effect"), which have much slower pharmacokinetics. A recent study by us suggested that this promotes faster and smoother onset of anaesthesia, as measured using the standard monitor of depth of anaesthesia (the BIS monitor). This finding requires confirmation prospectively in a larger group of patients. The investigators further hypothesise that a similar effect also exists on washout of sevoflurane at the end of the procedure, promoting quicker recovery (emergence) from anaesthesia. This has never been previously demonstrated. This information will help better define the place of nitrous oxide in achieving optimal outcomes in modern anaesthetic practice. The investigators propose to conduct a simple study to measure the effects of nitrous oxide washin and washout on exhaled concentrations of accompanying sevoflurane during both induction of anaesthesia and emergence, and identify any accompanying effect on the rate of change in depth of anaesthesia using BIS. The investigators hypothesise that the rate of fall of exhaled sevoflurane concentration at the end of anaesthesia will be more rapid in the group of patients breathing a gas mixture containing nitrous oxide, and that the rate of fall of BIS on induction and the rate of rise of BIS on emergence will be faster in the nitrous oxide group.


Condition Intervention Phase
Anesthesia
Drug: sevoflurane on air/O2
Drug: sevoflurane in N2O/O2
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Nitrous Oxide and Inhalational Agent Pharmacokinetics During Anaesthetic Induction and Emergence

Resource links provided by NLM:


Further study details as provided by Austin Health:

Primary Outcome Measures:
  • Pa t/Pa0 Sevo (Arterial Partial Pressure of Sevoflurane), t=Time(Minutes) [ Time Frame: Baseline, 2 minutes, 5 minutes, and 30 minutes after emergence ] [ Designated as safety issue: No ]
    Rate of fall in the arterial partial pressure of sevoflurane relative to baseline at 2 minutes (Pa 2/Pa0 Sevo), 5 minutes (Pa 5/Pa0 Sevo, and 30 minutes (Pa 30/Pa0 Sevo)

  • PA t/PA0 Sevo (End Tidal Partial Pressure of Sevoflurane), t=Time (Minutes) [ Time Frame: Baseline, 2 minutes, and 5 minutes after emergence ] [ Designated as safety issue: No ]
    Rate of fall in the end-tidal partial pressure of sevoflurane relative to baseline at 2 minutes (PA2/PA0 sevo) and 5 minutes (PA5/PA0 sevo)


Secondary Outcome Measures:
  • Time to Eye Opening [ Time Frame: 20 Minutes ] [ Designated as safety issue: No ]
    The time to eye opening to command after cessation of inhalational anaesthetic administration


Enrollment: 20
Study Start Date: October 2009
Study Completion Date: October 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Air/Oxygen
Sevoflurane with Air/Oxygen Mix
Drug: sevoflurane on air/O2
sevoflurane on air/O2
Experimental: sevoflurane in N2O/O2 Drug: sevoflurane in N2O/O2
sevoflurane in N2O/O2

Detailed Description:

Nitrous oxide is the oldest anaesthetic agent still in routine use today. Despite huge changes in the pharmacology of volatile anaesthetic agents and intravenous anaesthetics, the unique properties of nitrous oxide have maintained its place in modern practice, where it is used in combination with other, more powerful inhaled agents, such as sevoflurane. It has useful analgesic properties, unlike the other agents used today, and its inclusion reduces the concentration of other agents required to maintain an adequate depth of anaesthesia for surgery. In particular, its low solubility in body tissues gives it a unique pharmacokinetic profile, with rapid washin and washout from the body. It has been shown to have a similar effect on the speed of uptake of accompanying agents like sevoflurane (the "second gas effect"), which have much slower pharmacokinetics.

A recent study by us suggested that this promotes faster and smoother onset of anaesthesia, as measured using the standard monitor of depth of anaesthesia (the BIS monitor). This finding requires confirmation prospectively in a larger group of patients.

We further hypothesise that a similar effect also exists on washout of sevoflurane at the end of the procedure, promoting quicker recovery (emergence) from anaesthesia. This has never been previously demonstrated. This information will help better define the place of nitrous oxide in achieving optimal outcomes in modern anaesthetic practice.

We propose to conduct a simple study to measure the effects of nitrous oxide washin and washout on exhaled concentrations of accompanying sevoflurane during both induction of anaesthesia and emergence, and identify any accompanying effect on the rate of change in depth of anaesthesia using BIS.

Consenting adult participants will be recruited who are undergoing general anaesthesia for elective surgery anticipated to take a minimum of 1 hour and where an arterial line is considered appropriate for monitoring of blood pressure.

As, in normal practice, the decision whether to include of nitrous oxide in the anaesthetic mixture is largely discretionary on the part of the anaesthetist, and therefore allocation to either arm of the protocol is consistent with routine practice, it is intended that the patients will be approached for consent on admission to hospital for their surgery. Standard patient monitoring will be used including BIS and a 2 mL sample of blood will be taken to assess blood gas content lung function and optimise lung ventilation.

Following induction of anaesthesia, participants will receive an inhaled gas mixture containing standard concentrations of sevoflurane. They will be randomised to a treatment group where a standard concentration of nitrous oxide is included in this mixture, or a control group where nitrous oxide is not included. Monitoring and recording of exhaled gas concentrations will be made by continuous sampling of gas from the breathing circuit and computer storage. We hypothesise that the rate of fall of exhaled sevoflurane concentration at the end of anaesthesia will be more rapid in the group of patients breathing a gas mixture containing nitrous oxide, and that the rate of fall of BIS on induction and the rate of rise of BIS on emergence will be faster in the nitrous oxide group.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult patients undergoing elective general or orthopaedic surgery under relaxant general anaesthesia anticipated to take >1 hour

Exclusion Criteria:

  • Age under 18 years
  • Morbid obesity BMI > 35
  • Severe or moderately severe lung disease (FEV1 < 1.0L, FEV1/FVC < 50%)
  • Past history of severe post-operative nausea and vomiting
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092923

Locations
Australia, Victoria
Austin Health
Melbourne, Victoria, Australia, 3084
Sponsors and Collaborators
Austin Health
Investigators
Principal Investigator: Phil Peyton, MBBS Austin Health
  More Information

No publications provided

Responsible Party: Dr Philip Peyton, Staff Anaesthetist, Austin Health
ClinicalTrials.gov Identifier: NCT01092923     History of Changes
Other Study ID Numbers: 03749
Study First Received: March 10, 2010
Results First Received: February 16, 2012
Last Updated: September 11, 2012
Health Authority: Australia: National Health and Medical Research Council

Keywords provided by Austin Health:
Nitrous Oxide
washin
washout
second gas effect
sevoflurane
induction
emergence

Additional relevant MeSH terms:
Nitrous Oxide
Sevoflurane
Analgesics
Analgesics, Non-Narcotic
Anesthetics
Anesthetics, General
Anesthetics, Inhalation
Central Nervous System Agents
Central Nervous System Depressants
Hematologic Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014