An interventional study of High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg) and Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg) in Anesthesia, Hypercapnia and Hypocapnia, sponsored by University of British Columbia. Recruiting at 1 site in Canada. Open to participants aged 3 Years to 11 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-05-22.
Sponsored by University of British Columbia · Not applicable, Interventional, and Other
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.
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.
156 studies on the registry are indexed under Hypercapnia; 31 are open to participants now.
This study's planned enrollment of 100 is above the median of 36 across 120 interventional studies indexed under Hypercapnia.
Browse Hypercapnia studies →University of British Columbia is the lead sponsor of 1,339 studies on the registry; 259 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 1 (17%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
ASA physical status
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All patients will receive same interventions, in a randomised order.
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.
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.
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.
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.
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.
Other: High normal ETCO2: ETCO2 50 mmHg (+/- 3mmHg) · Other: Normal ETCO2: ETCO2 40 mmHg (+/- 3mmHg) · Other: Low Normal ETCO2: ETCO2 30 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.
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.
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.
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.
Time frame: Continually assessed throughout the general anesthetic, approximately 1.5-2 hours
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.
Time frame: Continually assessed throughout the general anesthetic, approximately 1.5-2 hours
Plan to share: No
Started Jun 2024 (actual). Primary completion is estimated for Dec 2026, 30 months after the start.
Of 50 non-industry interventional studies with no phase under Hypercapnia, half reached primary completion within 13 months of starting (the median), counting those still running; a quarter within 7 and three quarters within 32. This study's planned 30 months is above that.
Counting every sponsor, half of 54 studies reached it within 14 months; a quarter within 7 and three quarters within 32.
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