AnesthesiaNCT06303518
End Tidal Carbon Dioxide Concentration and Depth of Anesthesia in Children
A study testing High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg) and Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg) in people with Anesthesia and Hypercapnia, run by University of British Columbia at 1 site in Canada.
Trial summary
Carbon Dioxide (CO2) is a by-product of metabolism and is removed from the body when we breathe out. High levels of CO2 can affect the nervous system and cause us to be sleepy or sedated. Read more about this study
- Who is it for?
- Ages 3 to 11 yearsHealthy volunteers can take part
- Conditions the study is for
- Anesthesia, Hypercapnia, Hypocapnia
- What is being tested?
- High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg) and Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- 25 Jun 2024to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 11 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Children aged 3 - 11 years undergoing non- or minimally-stimulating elective procedures, defined as anesthesia without skin incision or painful manipulation (e.g., non-invasive imaging, auditory brainstem response testing), middle ear surgery, surgery with effective local or regional anesthesia before surgical incision (e.g dental procedures with local anesthetic infiltration, urology with regional block).
- American Society of Anesthesiologists (ASA) physical status I and II
- TIVA technique appropriate throughout induction and maintenance of anesthesia
- Controlled ventilation via endotracheal tube
- Anticipated surgical time ≥ 90 minutes: to allow time for anesthetic induction and subsequent testing and washout periods at all three EtCO2 levels.
Who cannot join
- Need for inhalational induction of anesthesia
- Sedative premedication
- Use of ketamine intraoperatively
- Unable to place BIS electrodes due to surgical site or other contraindications (e.g., MRI)
- Allergy to study drugs (propofol, remifentanil, lidocaine)
- Depression of conscious level for any reason
Show all 10Show fewer
- BMI <5th or >95th centile for age
- History of obstructive or central sleep apnea
- Known or suspected raised intracranial pressure
- Recent or historical traumatic brain injury
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
BC Children's Hospital
Vancouver, British Columbia, V6H 3N1
Steffanie Fisher, 604 875 2000 ext. 1989, steffanie.fisher@bcchr.ca
About this study
Official title: Effects of End Tidal Carbon Dioxide Concentration on Depth of Anesthesia in Children Undergoing Total Intravenous Anesthesia
Carbon Dioxide (CO2) is a by-product of metabolism and is removed from the body when we breathe out. High levels of CO2 can affect the nervous system and cause us to be sleepy or sedated. Research suggests that high levels of CO2 may benefit patients who are asleep under anesthesia, such as by reducing infection rates, nausea, or recovery from anesthesia . CO2 may also reduce pain signals or the medication required to keep patients asleep during anesthesia; this has not been researched in children.
During general anesthesia, anesthesiologists keep patients asleep with anesthetic gases or by giving medications into a vein. These drugs can depress breathing; therefore, an anesthesiologist will control breathing (ventilation) with an artificial airway such as an endotracheal tube. Changes in ventilation can alter the amount of CO2 removed from the body. The anesthesiologist may also monitor a patient's level of consciousness using a 'Depth of Anesthesia Monitor' such as the Bispectral Index (BIS), which analyzes a patient's brain activity and generates a number to tell the anesthesiologist how asleep they are.
The investigator's study will test if different levels of CO2 during intravenous anesthesia are linked with different levels of sedation or sleepiness in children, as measured by BIS. If so, this could reduce the amount of anesthetic medication the child receives. Other benefits may be decreased medication costs, fewer side effects, and a positive environmental impact by using less disposable anesthesia equipment.
Read the detailed description
Purpose: Carbon dioxide (CO2) is a major end-product of metabolism and can have marked effects on central nervous system function. It can also be easily manipulated during general anesthesia via controlled ventilation. High levels of carbon dioxide (hypercapnia) are associated with sedation and have been shown to produce selective suppression of thermal and ischaemic pain in animals and humans. This effect was attenuated by dexamethasone and naloxone, indicating that stress pathways and endogenous opioids may be implicated. Hypercapnia during anesthesia may have additional benefits, including reduced levels of wound infection due to improved tissue oxygenation reduced incidence of postoperative nausea and vomiting and reduced recovery time from volatile anesthetic.
It is a known phenomenon for high levels of CO2 to be associated with reduced levels of consciousness in humans, known as CO2 narcosis. A 1927 paper described narcosis of animals when breathing 30-40% CO2 in oxygen, with prompt recovery upon removal. The authors described a 'sharp sour taste' and associated hypertension when the same solution was administered to humans. However, few studies investigate the impact of carbon dioxide on anesthetic requirements. An animal study from 1967 demonstrated that very high levels of CO2 (>95 mmHg) offset halothane requirements in dogs. Most recently, increased carbon dioxide levels during surgery (40 - 45 mmHg) were shown to reduce the Minimal Alveolar Concentration to Blunt Adrenergic Response (skin incision; MAC-BAR) of sevoflurane in adult patients undergoing gastric carcinoma resection.
Total intravenous anesthesia (TIVA), an alternative to inhalational anesthesia, is a commonly used anesthetic technique in the investigator's institution. This is due to its many benefits, including reduced emergence delirium, reduced environmental impact and reduced post-operative nausea and vomiting. Administration can be guided by depth of anesthesia monitoring such as the Bispectral Index (BIS), which measures the patient's level of consciousness derived from electroencephalogram readings. BIS has been shown to help guide propofol dosing in children regardless of whether the TIVA technique was target controlled or a manual infusion regimen, and to correlate well with both modelled and measured propofol levels in children.
The investigator's study aims to determine whether differing levels of CO2 affect the anesthetic depth in anesthetized children, as measured by BIS.
Hypothesis: Hypercarbia is associated with a reduction in BIS readings, in anesthetized children.
Justification: The impact of EtCO2 on BIS has not been studied in children. If discovered, a correlation between the two could significantly change anesthetic practice. It is straightforward to increase EtCO2 levels in anesthetized patients, and if this was found to reduce their anesthetic requirements it could enable lower rates of anesthetic drug administration. This would benefit the patient by exposing them to less medication and fewer associated side effects, as well as benefitting the hospital and wider environment by reducing cost and use of disposable equipment such as ampoules, packaging and syringes.
Objectives: (1) To determine the effect of EtCO2 on the depth of anesthesia in children, as measured by BIS.
(2) Patient movement as detected clinically by the surgical or anesthetic team.
Research Design: The investigators plan to conduct a randomized, prospective, crossover trial. The within-subject design allows patients to act as their own controls. The order in which the EtCO2 levels are tested will be randomized between patients using sealed envelopes. The anesthesiologist in the room will be blinded to the BIS reading but will be informed by a research assistant if it reads persistently high (>60) for over one minute.
Statistical analysis: Physiological data will be collected in real-time using purpose-built software. Patient demographics and characteristics will be collected by a research assistant. Time-series plots of BIS and EtCO2 for each participant will be made in R (R Foundation for Statistical Computing, Vienna, Austria). Generalized estimating equations (GEE), using the geepack package, will be applied to estimate the effect of changes in target EtCO2 on serial BIS measurements during the anesthesia maintenance phase. Each participant will be considered their own data cluster to provide an appropriate grouping structure for the analysis. An independent correlation structure will be applied, and a robust (sandwich) estimator method will be used to obtain standard errors.
- Conditions
- Anesthesia, Hypercapnia, Hypocapnia
- Being tested
- High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg), Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)
- Medical subject headings
- Hypercapnia, Hypocapnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg)Other
BIS readings will be recorded continuously at 'High Normal ETCO2' (50 mmHg +/- 3 mmHg). Each patient will be tested at High normal, normal, and low normal ETCO2 levels in a randomized order.
Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg)Other
BIS readings will be recorded continuously at 'Normal ETCO2' (40 mmHg +/- 3 mmHg). Each patient will be tested at High normal, normal, and low normal ETCO2 levels in a randomized order.
Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)Other
BIS readings will be recorded continuously at 'Low Normal ETCO2' (30 mmHg +/- 3 mmHg). Each patient will be tested at High normal, normal, and low normal ETCO2 levels in a randomized order.
| Study group | Role | What they receive |
|---|---|---|
| High normal ETCO2, Normal ETCO2, Low normal ETCO2 | Experimental | All patients will receive same interventions, in a randomised order. Receives: Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg); Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg); Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg) |
| High normal ETCO2, Low normal ETCO2, Normal ETCO2 | Experimental | All patients will receive same interventions, in a randomised order. Receives: Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg); Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg); Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg) |
| Low normal ETCO2, Normal ETCO2, High normal ETCO2 | Experimental | All patients will receive same interventions, in a randomised order. Receives: Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg); Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg); Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg) |
| Low normal ETCO2, High normal ETCO2, Normal ETCO2 | Experimental | All patients will receive same interventions, in a randomised order. Receives: Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg); Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg); Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg) |
| Normal ETCO2, Low normal ETCO2, High normal ETCO2 | Experimental | All patients will receive same interventions, in a randomised order. Receives: Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg); Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg); Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg) |
| Normal ETCO2, High normal ETCO2, Low normal ETCO2 | Experimental | All patients will receive same interventions, in a randomised order. Receives: Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg); Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg); Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the effect of end-tidal carbon dioxide concentration (EtCO2) on the depth of anesthesia in children, as measured by BIS.
The investigator's study aims to determine whether differing levels of CO2 affect the anesthetic depth in anesthetized children, as measured by BIS. The investigators will determine a significant change in BIS to be at least a 5 point difference. Patients will act 'as their own controls', and be tested across three ETCO2 levels in a randomized order.
Measured: Continually assessed throughout the general anesthetic, approximately 1.5-2 hours
Secondary outcomes (1)
Patient movement as detected clinically by the surgical or anesthetic team.
Clinical indicators of inadequate aesthetic depth, to be recorded on data collection team if observed by any member of the clinical team.
Measured: Continually assessed throughout the general anesthetic, approximately 1.5-2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start25 Jun 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for AnesthesiaStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The investigators plan to conduct a randomized, prospective, crossover trial. The six arms will be as below: 1. Normal ETCO2 -\> High Normal ETCO2 -\> Low Normal ETCO2 2. Normal ETCO2 -\> Low Normal ETCO2 -\> High Normal ETCO2 3. High Normal ETCO2 -\> Low Normal ETCO2 -\> Normal ETCO2 4. High Normal ETCO2 -\> Normal ETCO2 -\> Low Normal ETCO2 5. Low Normal ETCO2 -\> High Normal ETCO2 -\> Normal ETCO2 6. Low Normal ETCO2 -\> Normal ETCO2 -\> High Normal ETCO2
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christopher Chin, University of British Columbia
- Investigators
- Christopher A Chin, MBBS, FRCA, FRCP, MA, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06303518
- Sponsor's protocol ID
- H23-03546
- Status last verified
- May 2026
- First submitted
- 26 Feb 2024
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
WOODBURY DM, KARLER R. The role of carbon dioxide in the nervous system. Anesthesiology. 1960 Nov-Dec;21:686-703. doi: 10.1097/00000542-196011000-00012. No abstract available.
PubMed 13786527Fukuda T, Hisano S, Toyooka H. Moderate hypercapnia-induced anesthetic effects and endogenous opioids. Neurosci Lett. 2006 Jul 31;403(1-2):20-3. doi: 10.1016/j.neulet.2006.04.026. Epub 2006 May 15.
PubMed 16701947Gronroos M, Pertovaara A. A selective suppression of human pain sensitivity by carbon dioxide: central mechanisms implicated. Eur J Appl Physiol Occup Physiol. 1994;68(1):74-9. doi: 10.1007/BF00599245.
PubMed 8162926Akca O, Liem E, Suleman MI, Doufas AG, Galandiuk S, Sessler DI. Effect of intra-operative end-tidal carbon dioxide partial pressure on tissue oxygenation. Anaesthesia. 2003 Jun;58(6):536-42. doi: 10.1046/j.1365-2044.2003.03193.x.
PubMed 12846617Saghaei M, Matin G, Golparvar M. Effects of intra-operative end-tidal carbon dioxide levels on the rates of post-operative complications in adults undergoing general anesthesia for percutaneous nephrolithotomy: A clinical trial. Adv Biomed Res. 2014 Feb 28;3:84. doi: 10.4103/2277-9175.127997. eCollection 2014.
PubMed 24761392Katznelson R, Djaiani G, Naughton F, Wasowicz M, Ragoonanan T, Duffin J, Fedorko L, Murphy J, Fisher JA. Post-operative hypercapnia-induced hyperpnoea accelerates recovery from sevoflurane anaesthesia: a prospective randomised controlled trial. Acta Anaesthesiol Scand. 2013 May;57(5):623-30. doi: 10.1111/aas.12093. Epub 2013 Mar 3.
PubMed 23452265Yamaguchi J, Kinoshita K, Hosokawa T, Ihara S. "The eyes are the windows of the soul": Portable automated pupillometry to monitor autonomic nervous activity in CO2 narcosis: A case report. Medicine (Baltimore). 2023 May 12;102(19):e33768. doi: 10.1097/MD.0000000000033768.
PubMed 37171322Leake CD, Waters RM. Leake CD, Waters RM (1928) The anaesthetic properties of carbon dioxide. J Pharmacol Exp Ther 33:280-281. In.
Eisele JH, Eger EI 2nd, Muallem M. Narcotic properties of carbon dioxide in the dog. Anesthesiology. 1967 Sep-Oct;28(5):856-65. doi: 10.1097/00000542-196709000-00019. No abstract available.
PubMed 6035017Wu Z, Yu J, Zhang T, Tan H, Li H, Xie L, Lin W, Shen D, Cao L. Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial. Anesth Analg. 2022 Jul 1;135(1):62-70. doi: 10.1213/ANE.0000000000005784. Epub 2022 Jun 16.
PubMed 34744156Chandler JR, Myers D, Mehta D, Whyte E, Groberman MK, Montgomery CJ, Ansermino JM. Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia. Paediatr Anaesth. 2013 Apr;23(4):309-15. doi: 10.1111/pan.12090.
PubMed 23464658Narayanan H, Raistrick C, Tom Pierce JM, Shelton C. Carbon footprint of inhalational and total intravenous anaesthesia for paediatric anaesthesia: a modelling study. Br J Anaesth. 2022 Aug;129(2):231-243. doi: 10.1016/j.bja.2022.04.022. Epub 2022 Jun 18.
PubMed 35729012Biallas R, Rusch D, de Decker W, Wulf H, Siebrecht D, Scholz J. [Prophylaxis of postoperative nausea and vomiting (PONV) in children undergoing strabismus surgery. Sevoflurane/N2O plus dimenhydrinate vs.propofol/remifentanil plus dimenhydrinate]. Anaesthesist. 2003 Jul;52(7):586-95. doi: 10.1007/s00101-003-0516-9. Epub 2003 Jun 18. German.
PubMed 12898043Marchant N, Sanders R, Sleigh J, Vanhaudenhuyse A, Bruno MA, Brichant JF, Laureys S, Bonhomme V. How electroencephalography serves the anesthesiologist. Clin EEG Neurosci. 2014 Jan;45(1):22-32. doi: 10.1177/1550059413509801. Epub 2014 Jan 10.
PubMed 24415399Louvet N, Rigouzzo A, Sabourdin N, Constant I. Bispectral index under propofol anesthesia in children: a comparative randomized study between TIVA and TCI. Paediatr Anaesth. 2016 Sep;26(9):899-908. doi: 10.1111/pan.12957.
PubMed 27461767
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of End Tidal Carbon Dioxide Concentration on Depth of Anesthesia in Children Undergoing Total Intravenous Anesthesia
- ClinicalTrials.gov ID
- NCT06303518
- Acronym / sponsor ID
- H23-03546
- Conditions
- Anesthesia, Hypercapnia, Hypocapnia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 25 Jun 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 12 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Carbon Dioxide (CO2) is a by-product of metabolism and is removed from the body when we breathe out. High levels of CO2 can affect the nervous system and cause us to be sleepy or sedated. Research suggests that high levels of CO2 may benefit patients who are asleep under anesthesia, such as by reducing infection rates, nausea, or recovery from anesthesia . CO2 may also reduce pain signals or the medication required to keep patients asleep during anesthesia; this has not been researched in children.
During general anesthesia, anesthesiologists keep patients asleep with anesthetic gases or by giving medications into a vein. These drugs can depress breathing; therefore, an anesthesiologist will control breathing (ventilation) with an artificial airway such as an endotracheal tube. Changes in ventilation can alter the amount of CO2 removed from the body. The anesthesiologist may also monitor a patient's level of consciousness using a 'Depth of Anesthesia Monitor' such as the Bispectral Index (BIS), which analyzes a patient's brain activity and generates a number to tell the anesthesiologist how asleep they are.
The investigator's study will test if different levels of CO2 during intravenous anesthesia are linked with different levels of sedation or sleepiness in children, as measured by BIS. If so, this could reduce the amount of anesthetic medication the child receives. Other benefits may be decreased medication costs, fewer side effects, and a positive environmental impact by using less disposable anesthesia equipment.
Detailed description
Purpose: Carbon dioxide (CO2) is a major end-product of metabolism and can have marked effects on central nervous system function. It can also be easily manipulated during general anesthesia via controlled ventilation. High levels of carbon dioxide (hypercapnia) are associated with sedation and have been shown to produce selective suppression of thermal and ischaemic pain in animals and humans. This effect was attenuated by dexamethasone and naloxone, indicating that stress pathways and endogenous opioids may be implicated. Hypercapnia during anesthesia may have additional benefits, including reduced levels of wound infection due to improved tissue oxygenation reduced incidence of postoperative nausea and vomiting and reduced recovery time from volatile anesthetic.
It is a known phenomenon for high levels of CO2 to be associated with reduced levels of consciousness in humans, known as CO2 narcosis. A 1927 paper described narcosis of animals when breathing 30-40% CO2 in oxygen, with prompt recovery upon removal. The authors described a 'sharp sour taste' and associated hypertension when the same solution was administered to humans. However, few studies investigate the impact of carbon dioxide on anesthetic requirements. An animal study from 1967 demonstrated that very high levels of CO2 (>95 mmHg) offset halothane requirements in dogs. Most recently, increased carbon dioxide levels during surgery (40 - 45 mmHg) were shown to reduce the Minimal Alveolar Concentration to Blunt Adrenergic Response (skin incision; MAC-BAR) of sevoflurane in adult patients undergoing gastric carcinoma resection.
Total intravenous anesthesia (TIVA), an alternative to inhalational anesthesia, is a commonly used anesthetic technique in the investigator's institution. This is due to its many benefits, including reduced emergence delirium, reduced environmental impact and reduced post-operative nausea and vomiting. Administration can be guided by depth of anesthesia monitoring such as the Bispectral Index (BIS), which measures the patient's level of consciousness derived from electroencephalogram readings. BIS has been shown to help guide propofol dosing in children regardless of whether the TIVA technique was target controlled or a manual infusion regimen, and to correlate well with both modelled and measured propofol levels in children.
The investigator's study aims to determine whether differing levels of CO2 affect the anesthetic depth in anesthetized children, as measured by BIS.
Hypothesis: Hypercarbia is associated with a reduction in BIS readings, in anesthetized children.
Justification: The impact of EtCO2 on BIS has not been studied in children. If discovered, a correlation between the two could significantly change anesthetic practice. It is straightforward to increase EtCO2 levels in anesthetized patients, and if this was found to reduce their anesthetic requirements it could enable lower rates of anesthetic drug administration. This would benefit the patient by exposing them to less medication and fewer associated side effects, as well as benefitting the hospital and wider environment by reducing cost and use of disposable equipment such as ampoules, packaging and syringes.
Objectives: (1) To determine the effect of EtCO2 on the depth of anesthesia in children, as measured by BIS.
(2) Patient movement as detected clinically by the surgical or anesthetic team.
Research Design: The investigators plan to conduct a randomized, prospective, crossover trial. The within-subject design allows patients to act as their own controls. The order in which the EtCO2 levels are tested will be randomized between patients using sealed envelopes. The anesthesiologist in the room will be blinded to the BIS reading but will be informed by a research assistant if it reads persistently high (>60) for over one minute.
Statistical analysis: Physiological data will be collected in real-time using purpose-built software. Patient demographics and characteristics will be collected by a research assistant. Time-series plots of BIS and EtCO2 for each participant will be made in R (R Foundation for Statistical Computing, Vienna, Austria). Generalized estimating equations (GEE), using the geepack package, will be applied to estimate the effect of changes in target EtCO2 on serial BIS measurements during the anesthesia maintenance phase. Each participant will be considered their own data cluster to provide an appropriate grouping structure for the analysis. An independent correlation structure will be applied, and a robust (sandwich) estimator method will be used to obtain standard errors.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (care provider)
- Number of arms
- 6
- Model description
- The investigators plan to conduct a randomized, prospective, crossover trial. The six arms will be as below: 1. Normal ETCO2 -> High Normal ETCO2 -> Low Normal ETCO2 2. Normal ETCO2 -> Low Normal ETCO2 -> High Normal ETCO2 3. High Normal ETCO2 -> Low Normal ETCO2 -> Normal ETCO2 4. High Normal ETCO2 -> Normal ETCO2 -> Low Normal ETCO2 5. Low Normal ETCO2 -> High Normal ETCO2 -> Normal ETCO2 6. Low Normal ETCO2 -> Normal ETCO2 -> High Normal ETCO2
| Arm | Type | Receives |
|---|---|---|
| High normal ETCO2, Normal ETCO2, Low normal ETCO2 | Experimental | Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg), Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)All patients will receive same interventions, in a randomised order. |
| High normal ETCO2, Low normal ETCO2, Normal ETCO2 | Experimental | Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg), Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)All patients will receive same interventions, in a randomised order. |
| Low normal ETCO2, Normal ETCO2, High normal ETCO2 | Experimental | Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg), Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)All patients will receive same interventions, in a randomised order. |
| Low normal ETCO2, High normal ETCO2, Normal ETCO2 | Experimental | Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg), Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)All patients will receive same interventions, in a randomised order. |
| Normal ETCO2, Low normal ETCO2, High normal ETCO2 | Experimental | Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg), Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)All patients will receive same interventions, in a randomised order. |
| Normal ETCO2, High normal ETCO2, Low normal ETCO2 | Experimental | Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg), Other: Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)All patients will receive same interventions, in a randomised order. |
Who may qualify
- Ages
- 3 to 11 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Children aged 3 - 11 years undergoing non- or minimally-stimulating elective procedures, defined as anesthesia without skin incision or painful manipulation (e.g., non-invasive imaging, auditory brainstem response testing), middle ear surgery, surgery with effective local or regional anesthesia before surgical incision (e.g dental procedures with local anesthetic infiltration, urology with regional block).
- American Society of Anesthesiologists (ASA) physical status I and II
- TIVA technique appropriate throughout induction and maintenance of anesthesia
- Controlled ventilation via endotracheal tube
- Anticipated surgical time ≥ 90 minutes: to allow time for anesthetic induction and subsequent testing and washout periods at all three EtCO2 levels.
Key exclusion criteria (10 listed)
- Need for inhalational induction of anesthesia
- Sedative premedication
- Use of ketamine intraoperatively
- Unable to place BIS electrodes due to surgical site or other contraindications (e.g., MRI)
- Allergy to study drugs (propofol, remifentanil, lidocaine)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg)BIS readings will be recorded continuously at 'High Normal ETCO2' (50 mmHg +/- 3 mmHg). Each patient will be tested at High normal, normal, and low normal ETCO2 levels in a randomized order. | Other | High normal ETCO2, Low normal ETCO2, Normal ETCO2, High normal ETCO2, Normal ETCO2, Low normal ETCO2, Low normal ETCO2, High normal ETCO2, Normal ETCO2, Low normal ETCO2, Normal ETCO2, High normal ETCO2, Normal ETCO2, High normal ETCO2, Low normal ETCO2, Normal ETCO2, Low normal ETCO2, High normal ETCO2 |
| Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg)BIS readings will be recorded continuously at 'Normal ETCO2' (40 mmHg +/- 3 mmHg). Each patient will be tested at High normal, normal, and low normal ETCO2 levels in a randomized order. | Other | High normal ETCO2, Low normal ETCO2, Normal ETCO2, High normal ETCO2, Normal ETCO2, Low normal ETCO2, Low normal ETCO2, High normal ETCO2, Normal ETCO2, Low normal ETCO2, Normal ETCO2, High normal ETCO2, Normal ETCO2, High normal ETCO2, Low normal ETCO2, Normal ETCO2, Low normal ETCO2, High normal ETCO2 |
| Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg)BIS readings will be recorded continuously at 'Low Normal ETCO2' (30 mmHg +/- 3 mmHg). Each patient will be tested at High normal, normal, and low normal ETCO2 levels in a randomized order. | Other | High normal ETCO2, Low normal ETCO2, Normal ETCO2, High normal ETCO2, Normal ETCO2, Low normal ETCO2, Low normal ETCO2, High normal ETCO2, Normal ETCO2, Low normal ETCO2, Normal ETCO2, High normal ETCO2, Normal ETCO2, High normal ETCO2, Low normal ETCO2, Normal ETCO2, Low normal ETCO2, High normal ETCO2 |
Primary outcome
To determine the effect of end-tidal carbon dioxide concentration (EtCO2) on the depth of anesthesia in children, as measured by BIS.
Time frame: Continually assessed throughout the general anesthetic, approximately 1.5-2 hours
The investigator's study aims to determine whether differing levels of CO2 affect the anesthetic depth in anesthetized children, as measured by BIS. The investigators will determine a significant change in BIS to be at least a 5 point difference. Patients will act 'as their own controls', and be tested across three ETCO2 levels in a randomized order.
1 secondary outcome
Patient movement as detected clinically by the surgical or anesthetic team.
Time frame: Continually assessed throughout the general anesthetic, approximately 1.5-2 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Background: PubMed 13786527WOODBURY DM, KARLER R. The role of carbon dioxide in the nervous system. Anesthesiology. 1960 Nov-Dec;21:686-703. doi: 10.1097/00000542-196011000-00012. No abstract available.
- Background: PubMed 16701947Fukuda T, Hisano S, Toyooka H. Moderate hypercapnia-induced anesthetic effects and endogenous opioids. Neurosci Lett. 2006 Jul 31;403(1-2):20-3. doi: 10.1016/j.neulet.2006.04.026. Epub 2006 May 15.
- Background: PubMed 8162926Gronroos M, Pertovaara A. A selective suppression of human pain sensitivity by carbon dioxide: central mechanisms implicated. Eur J Appl Physiol Occup Physiol. 1994;68(1):74-9. doi: 10.1007/BF00599245.
- Background: PubMed 12846617Akca O, Liem E, Suleman MI, Doufas AG, Galandiuk S, Sessler DI. Effect of intra-operative end-tidal carbon dioxide partial pressure on tissue oxygenation. Anaesthesia. 2003 Jun;58(6):536-42. doi: 10.1046/j.1365-2044.2003.03193.x.
- Background: PubMed 24761392Saghaei M, Matin G, Golparvar M. Effects of intra-operative end-tidal carbon dioxide levels on the rates of post-operative complications in adults undergoing general anesthesia for percutaneous nephrolithotomy: A clinical trial. Adv Biomed Res. 2014 Feb 28;3:84. doi: 10.4103/2277-9175.127997. eCollection 2014.
- Background: PubMed 23452265Katznelson R, Djaiani G, Naughton F, Wasowicz M, Ragoonanan T, Duffin J, Fedorko L, Murphy J, Fisher JA. Post-operative hypercapnia-induced hyperpnoea accelerates recovery from sevoflurane anaesthesia: a prospective randomised controlled trial. Acta Anaesthesiol Scand. 2013 May;57(5):623-30. doi: 10.1111/aas.12093. Epub 2013 Mar 3.
- Background: PubMed 37171322Yamaguchi J, Kinoshita K, Hosokawa T, Ihara S. "The eyes are the windows of the soul": Portable automated pupillometry to monitor autonomic nervous activity in CO2 narcosis: A case report. Medicine (Baltimore). 2023 May 12;102(19):e33768. doi: 10.1097/MD.0000000000033768.
- BackgroundLeake CD, Waters RM. Leake CD, Waters RM (1928) The anaesthetic properties of carbon dioxide. J Pharmacol Exp Ther 33:280-281. In.
- Background: PubMed 6035017Eisele JH, Eger EI 2nd, Muallem M. Narcotic properties of carbon dioxide in the dog. Anesthesiology. 1967 Sep-Oct;28(5):856-65. doi: 10.1097/00000542-196709000-00019. No abstract available.
- Background: PubMed 34744156Wu Z, Yu J, Zhang T, Tan H, Li H, Xie L, Lin W, Shen D, Cao L. Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial. Anesth Analg. 2022 Jul 1;135(1):62-70. doi: 10.1213/ANE.0000000000005784. Epub 2022 Jun 16.
- Background: PubMed 23464658Chandler JR, Myers D, Mehta D, Whyte E, Groberman MK, Montgomery CJ, Ansermino JM. Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia. Paediatr Anaesth. 2013 Apr;23(4):309-15. doi: 10.1111/pan.12090.
- Background: PubMed 35729012Narayanan H, Raistrick C, Tom Pierce JM, Shelton C. Carbon footprint of inhalational and total intravenous anaesthesia for paediatric anaesthesia: a modelling study. Br J Anaesth. 2022 Aug;129(2):231-243. doi: 10.1016/j.bja.2022.04.022. Epub 2022 Jun 18.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christopher A Chin, MBBS, FRCA, FRCP, MA principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg), Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg) and Low Normal ETCO2: ETCO2 30 mmHg (+/- 3mmHg) in people with Anesthesia and Hypercapnia, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Victoria Buswell (604-875-1989, victoria.buswell@cw.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the effect of end-tidal carbon dioxide concentration (EtCO2) on the depth of anesthesia in children, as measured by BIS. (time frame: Continually assessed throughout the general anesthetic, approximately 1.5-2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06303518, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.