CO2 (Carbon Dioxide) - Cerebral Oxygenation

Anesthesia vs Aviation: Does Added Carbon Dioxide in Normobaric Hypoxia Have the Same Effect on Cerebral Oxygenation as in Hypobaric Hypoxia?

Several projects in high altitude research in environments with a low oxygen partial pressure (hypobaric hypoxia) leading to hypoxemia showed, that cerebral perfusion and cerebral performance could be improved by adding C02 (cabon dioxide).

The investigators hypothesize that adding 5% C02 to 02 (Oxygen) also under normobaric conditions increases the time until a significant cerebral hyopxia is measured by near infrared spectroscopy (NIRS) compared to the administration of 95% 02.

lf this hypothesis proves to be true, this approach might be used in situations in which individuals are prone to cerebral hypoxia. In bariatric surgery, patients that experience an apnea phase are more prone to (cerebral) hypoxia due to the fact, that they have a higher body mass index (BMI) leading to a reduced functional residual capacity (FRC), which serves as the oxygen reserve in the body.

Study Overview

• Status: Completed
• Conditions: Hypoxia, Brain
• Intervention / Treatment: Drug: Oxycarbon (5% CO2+ 95% O2)

Detailed Description

On the day of surgery patients will be randomized. After induction of anesthesia and endotracheal intubation patients will be managed by the study team to perform the intervention and the measurements.

According to randomization, investigational medical product (IMP) or comparator will be administrated by ventilator 1/ventilator 2.

At time point 1 apnea will be performed by disconnecting the ventilator from the endotracheal tube until the NIRS value has dropped by 20% from baseline. After that, re-ventilation will be resumed immediately, until parameters have returned to baseline.

During apnea time NIRS and vital signs will be recorded permanently, blood samples will be drawn at definite time points.

Application of IMP (or comparator) will be performed in this cross-over study design in the same manner after the baseline level is reached again.

At the end of the study procedure, after the baseline level of end-expiratory CO2 is reached again, patient will be taken over by the clinical anesthesia team and surgeons.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are designated for bariatric surgery at the University Hospital Zurich (USZ)
• Informed Consent as documented by signature
• BMI >35 kg/m2

Exclusion Criteria:

• Severe end-organ damage: chronic obstuctive pulmonary disease (COPD) GOLD (cassification) III and IV, known hepatic insufficiency or elevated liver enzymes, renal creatinine clearance <30ml/min
• Severe cardiovascular disease (NYHA classification III and IV)
• Known pulmonary Hypertension
• Cerebrovascular disease
• Pregnancy and lactation
• Cardiac dysrhythmias
• acidosis, chronic pulmonary disease
• Known or suspected non-compliance, drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxycarbon (5% CO2 + 95% O2); Patients will be mechanical ventilated with Oxycarbon (5%CO2 +95% O2) after normocapnia is reached until FeO2 is stable for at least 1 min ≥ 80%. At timepoint 1 immediately prior apnea NIRS and vital parameters will be registered and an bloodsample will be drawn.	Drug: Oxycarbon (5% CO2+ 95% O2); Oxycarbon will be administered by mechanical ventilation
Placebo Comparator: Control (95% O2); Same procedure as arm "active comparator"	Drug: Oxycarbon (5% CO2+ 95% O2); Oxycarbon will be administered by mechanical ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to decrease of tissue oxygenation index by 20 %	Parameter will be measured by NIRS	1 Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PaO2 (Oxygen partial pressure)	Parametere will be measured by arterial bloodgas	1 Day
SpO2 (oxygen saturation)	Parametere will be measured by arterial bloodgas	1 Day
PCO2 ( partial pressure of carbon)	Parametere will be measured by arterial bloodgas	1Day

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Martin Schläpfer, MD, M.Sc., University of Zurich

Publications and helpful links

General Publications

• Kety SS, Schmidt CF. THE EFFECTS OF ALTERED ARTERIAL TENSIONS OF CARBON DIOXIDE AND OXYGEN ON CEREBRAL BLOOD FLOW AND CEREBRAL OXYGEN CONSUMPTION OF NORMAL YOUNG MEN. J Clin Invest. 1948 Jul;27(4):484-92. doi: 10.1172/JCI101995. No abstract available.
• Karl AA, McMillan GR, Ward SL, Kissen AT, Souder ME. Effects of increased ambient CO2 on brain tissue oxygenation and performance in the hypoxic rhesus. Aviat Space Environ Med. 1978 Aug;49(8):984-9.
• Brzecka A. Role of hypercapnia in brain oxygenation in sleep-disordered breathing. Acta Neurobiol Exp (Wars). 2007;67(2):197-206.
• Kronenberg RS, Drage CW. Attenuation of the ventilatory and heart rate responses to hypoxia and hypercapnia with aging in normal men. J Clin Invest. 1973 Aug;52(8):1812-9. doi: 10.1172/JCI107363.
• Hannay DR, Maddox EJ. Symptom prevalence and referral behaviour in Glasgow. Soc Sci Med (1967). 1976 Mar-Apr;10(3-4):185-9. doi: 10.1016/0037-7856(76)90046-9. No abstract available.
• Ainslie PN, Poulin MJ. Ventilatory, cerebrovascular, and cardiovascular interactions in acute hypoxia: regulation by carbon dioxide. J Appl Physiol (1985). 2004 Jul;97(1):149-59. doi: 10.1152/japplphysiol.01385.2003. Epub 2004 Mar 5.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Actual): October 26, 2018
• Study Completion (Actual): February 12, 2019

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): February 20, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: hypoxia; CO2; cerebral perfusion; cerebral hypoxia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia; Hypoxia, Brain
• Other Study ID Numbers: 2017-01790

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Ist not planned to share data with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No