Gas narcosis in hyperbaric environments

In this prospective intervention study a total of 72 participants are needed. There are four parts in this study. Participants can choose to participate in a single part, all four parts or in any combination of the four parts in this study. This will lower the total number of participants needed. Objective 1 - Developing the qEEG algorithm for narcosis Nitrous oxide is an anaesthetic gas, which is already narcotic at atmospheric pressure. Therefore, normobaric nitrous oxide is a good substitute for hyperbaric exposure to air during the development of the sensitive qEEG method and the optimization of this measurement method. Increasing doses of nitrous oxide produce a similar pattern of EEG change to nitrogen under hyperbaric conditions. 36 divers will individually breathe 20%, 30% and 40% nitrous oxide in oxygen mixture in the hospital. The mixtures will be administered in a random order. To reduce the possibility of vomiting and nausea caused by the nitrous oxide, participants will be asked to fast 4 hours before the measurement, which commence at 9 am. Dexamethasone can be administered as an anti-emetic. After baseline measurements, the participant starts breathing the nitrous oxide in oxygen mixture from the anaesthetic machine. After 5 minutes of nitrous oxide mixture breathing the EEG, psychometric, CFFF and pupillometry measurements are repeated. Thereafter the participant will breathe 100% oxygen again for 5 minutes to wash out the nitrous oxide. After the measurement the participant will be asked to fill in the Karolinska Sleepiness Scale (KSS) and the Mental Effort Scale (MES). The same measurement will be repeated after 20 minutes of breathing air with a second and third concentration of nitrous oxide. At the end the baseline measurement is repeated. Objective 2 - Benchmark the algorithm with nitrogen narcosis In the second objective I will validate the algorithm, developed in objective 1, in the hyperbaric situation. I will do this by comparing the algorithm to the psychometric performance, which will measure known functional deficits. The psychometric tests will measure changes in short-term memory and effects on comprehension of the information processing of the brain. Both are higher cognitive functions that are more affected by gas narcosis. In this part of the study 12 divers will individually have two exposures in a hyperbaric chamber. On one exposure the participant will breathe air, and on the other a heliox mixture of 21% oxygen and balance helium will be breathed. Both gases will be breathed from a built-in breathing mask of the hyperbaric chamber. Each exposure will pause at 25 meters of seawater (msw) equivalent (3.5 ATA) and 50 msw (6 ATA) depths. The two exposures will be performed on different days. After baseline measurements, the participant will be compressed at a rate of 18 meters a minute, to 3.5 ATA. At 3.5 ATA a next block of measurements will be done beginning with 10 minutes of EEG measurement with the eyes closed, followed by 10 minutes of psychometric and CFFF tests. Next, the participant will be compressed to 6 ATA to repeat the EEG, psychometric and CFFF measurements. After each measurement the participant will be asked to complete the Karolinska Sleepiness Scale (KSS) and the Mental Effort Scale (MES). The decompression will be controlled (including oxygen stops) according to the schedule prescribed by the Canadian Navy decompression tables. Objective 3 - Measuring oxygen narcosis Next, I will investigate the narcotic effect of oxygen. I will compare the three different levels of oxygen pressure to evaluate its narcotic potency. Further, I will compare oxygen narcosis to nitrogen narcosis. The measurements obtained in objective 2 while breathing air at 3.5 ATA, have a partial pressure of nitrogen of 2.8 ATA. By comparing the results from these dives where the inspired PO2 is 2.8 ATA (objective 3) and the inspired PN2 is 2.8 ATA (objective 2) the supposed similar narcotic effect can be evaluated. To do this 12 divers will breathe 100% oxygen at the surface (1.0 ATA), 4 msw (1.4 ATA) and 18 msw (2.8 ATA). 1.4 ATA is the operational limit of oxygen for recreational divers. 2.8 ATA is a commonly accepted maximal partial pressure of oxygen in a dry hyperbaric chamber. After baseline measurements, the participant will breathe 100% oxygen from a demand valve mask in the hyperbaric chamber. The EEG and CFFF measurements are repeated. At a rate of 18 meters a minute the diver will be compressed to 1.4 ATA. At 1.4 ATA a next block of measurements will be done; first with 10 minutes of EEG measurement with the eyes closed followed by the CFFF test. The participant will then be compressed to 2.8 ATA to repeat the EEG and CFFF. The diver will be decompressed at 10 meters per minute. Any decompression stops will be based on the needs of the air-breathing investigator as prescribed by the Canadian Navy decompression tables. After each measurement the participant will be asked to fill in the Karolinska Sleepiness Scale (KSS) and the Mental Effort Scale (MES). Objective 4 – Investigate the magnitude and the physiological mechanism of carbon dioxide narcosis For this part 12 divers will visit the facility 3 times. Each time they will breath air or heliox (21% oxygen) with three increasing levels of inspired CO2. The increased end-tidal CO2 concentrations will be achieved with prepared gas mixtures with CO2. The CO2 fractions in the gas mixtures are chosen to inflict end-tidal CO2 values that fall within the ranges of 35-45 mmHg (normal range for end-tidal CO2 with no inspired CO2), 45-50 mmHg and 55-60 mmHg. End-tidal CO2 is measured using a sampling line to a gas analyser outside the hyperbaric chamber. Between the two CO2¬-containing breathing mixtures, there will be a 10-minute recovery. At each exposure the participant will undergo the following measurements: • 2 minute Psychometric tests (EEG and fNIRS will be recorded simultaneously) • 1 minute EEG and fNIRS eyes open • 1 minute EEG and fNIRS eyes closed • Breath hold (as long as possible at end of exposure) • Effort and sleepiness questionnaire • Breathing frequency and flow during exposure and recovery phase During the normobaric carbon dioxide measurements participants will be breathing air (no added CO2) as baseline measurement. Followed by a heliox mixture (20% oxygen, balance helium) at 1 ATA with subsequently 0% CO2 resulting in end-tidal CO2 between 35-45 mmHg and elevated inspired CO2 levels resulting in end-tidal CO2 values between respectively 45-50 mmHg and 55-60 mmHg. There will be two hyperbaric exposures in random order. In one session the participant will breathe air at the surface (1.0 ATA) (baseline), air at 50 meter (6 ATA), followed by two air mixtures with elevated levels of inspired CO2. In the other session they will breathe air at the surface (1.0 ATA) (baseline), heliox 20/80 at the surface, heliox 20/80 at 50 meter (6 ATA) and two mixtures with increasing levels of inspired CO2 in heliox, resulting in end-tidal CO2 levels between 45-50 mmHg and 55-60 mmHg. Each elevated inspired CO2¬ exposures is followed by a 10-minute recovery period. The two dives will be at least 48 hours apart. After baseline measurements, the participant will be compressed to 6 ATA at a rate of 10 meters/minute. The diver will be decompressed at 10 meters per minute. Any decompression stops will be prescribed by the Canadian Navy decompression tables. After each measurement the participant will be asked to fill in the Karolinska Sleepiness Scale (KSS) and the Mental Effort Scale (MES).