Difference in time until onset of symptoms and recovery between hypobaric and normobaric hypoxia

When flying at altitude, aircrew of the Royal Netherlands Air Force (RNLAF),
are dependent on either a pressurized cabin and/or an oxygen delivery system
for protection against the effects of hypoxia. In the event of oxygen delivery
equipment failure or cabin depressurization, it is essential for aircrew to
recognize their hypoxia symptoms and initiate emergency procedures. Inability
of aircrew to initiate emergency procedures can lead to impairment of cognitive
functioning (McMorris 2017, Aebi 2020) and at extreme altitudes (>18,000 ft)
may eventually lead to loss of consciousness with fatal results (Cable 2002).
The Time of Useful Consciousness (TUC) is the duration a person can function
effectively in a hypoxic environment. During a hypoxic event a decrease in the
partial pressure of oxygen in the ambient air (PO2) causes a decrease in the
inspired partial pressure of oxygen (PiO2) and alveolar oxygen pressure (PAO2),
this results in a lower partial pressure of oxygen in arterial blood (PaO2)
(Dehart 2002). The TUC depends on the altitude, the rate of decompression and
the individual*s reaction to hypoxia, and can range from seconds to minutes
(Dehart 2002). After this point, a person may still be conscious, but would be
unable to initiate and follow the proper emergency procedures due to cognitive
impairment (Dehart 2002, Leinonen 2021, Hohenauer 2022). These procedures are
to descend the aircraft to a safe flying altitude <10000 ft (;3048 m) and if
available, switch the onboard oxygen system to high pressure breathing.

Aircrew of the RNLAF receive hypoxia training every five years in accordance
with NATO standards. The purpose of this training is to teach aircrew to
recognize their hypoxia symptoms such as tingling, warm sensations, fatigue
(Dehart 2002) and initiate *recovery* within their TUC using standardized
emergency procedures (Cable 2010). Normally, aircrew is encouraged to initiate
recovery after recognizing their third hypoxia symptom. Currently, in this
training, altitude is simulated in a hypobaric chamber (HC) by reducing the
atmospheric pressure within the chamber. This induces hypobaric hypoxia (HH).
This training is costly, time-consuming, and has a risk of decompression
sickness (Rice 2003, Smart 2004). To limit the risk of decompression sickness,
subjects denitrogenate by breathing 100% oxygen, for the duration of 30 minutes
before exposure (Rice 2003, Dehart 2002). In addition, during this training,
aircrew do not perform flight-related tasks, making it difficult for them to
translate their experiences during training to the effects hypoxia may have on
their performance during flight.

The Reduced Oxygen Breathing Device (ROBD) was introduced in RNLAF for hypoxia
training purposes to solve these issues. The ROBD was designed to induce
normobaric hypoxia (NH), by lowering the fraction of inspired oxygen (FiO2),
without changing the ambient pressure. One of the advantages of the ROBD over
HC, is that it can be integrated with a flight simulator. This allows aircrew
to train hypoxia recognition and recovery in a realistic environment. Another
advantage of the ROBD is that there is no risk for decompression sickness and
doesn*t require any pre-breathing/denitrogenation. Furthermore, it is
transportable, which makes it possible to train air crew at their own air force
base.

For the ROBD training to be able to replace the HC training effectively, the
time until onset of hypoxia symptoms should be the same. It should also offer
the same symptom severity to allow the aircrew to initiate recovery within
their TUC. The severity of hypoxia symptoms is dependent on the magnitude of
changes in O2 and CO2 content in the blood (Leinonen 2021, Drechsler 2023).
Several studies show that respiratory parameters differ between HH and NH
during acute exposure (Self 2011, Savourey 2003 and 2007). They reported lower
O2 content (PaO2 (Savourey 2003) or SpO2 (Savourey 2003 and 2007) in HH
compared to NH. In addition, Self (2011) showed that the decrease in O2 content
was faster in HH compared to NH. Savourey (2003 and 2007) found a higher
respiratory rate (RR) in HH compared to NH. Self (2011) also showed a steeper
rate of decline in cerebral O2 saturation in HH vs NH measured with a forehead
sensor. Furthermore, lower partial pressure of CO2 in arterial blood pressure
(PaCO2) (Self 2011) and partial pressure of end tidal CO2 (PETCO2) (Savourey
2007) values were reported in HH compared to NH. The results of these studies
may indicate an earlier onset of symptoms and more severe symptoms in HH
compared to NH, leading to an earlier initiation of recovery.

Self (2011) investigated the difference in the number of hypoxia symptoms
reported between HH and NH at a simulated altitude of 25000 ft. He found that
subjects reported more symptoms in the first minute of exposure to HH, compared
to NH but not after three and four minutes. To the best of our knowledge, there
are no studies comparing the until onset of hypoxia symptoms or the time until
initiation of recovery between HH and NH. In addition, the effect of
differences in ventilatory parameters between HH and NH and their relation to
time to the until onset of hypoxia symptoms, has also not been studied

The results of this study will offer a better understanding of the
physiological and subjective differences between HH and NH. It may be used to
assess effectiveness of ROBD training compared to HC training. In addition, it
may be used to improve ROBD hypoxia training.
More realistic training offers air crew a better chance of successful recovery
in a real-world scenario.

This study aims to answer the following questions:
1. Is there a difference in the time to onset of the first symptom between HH
and NH?
2. Is there a difference in the severity of symptoms between HH and NH?
3. Is there a difference in the time to recovery between HH and NH?
4. Are there differences in ventilatory parameters between HH and NH?
5. What is the correlation between ventilatory parameters and the time to the
onset of symptoms?
6. What is the correlation between ventilatory parameters and the time to
recovery?

This will be a randomised crossover research. We will use a repeated within
subject measure design where every test subject will follow a hypobaric and a
normobaric hypoxia session. During the sessions, altitude up to 18000ft will be
simulated with either hypobaric hypoxia or normobaric hypoxia. There will be a
minimum of three days between the two sessions. Symptoms will be registered
continuously as well as ventilatory and oxygenation parameters.

Each test subject will undergo a hypobaric hypoxia- and a normobaric hypoxia
session

Subjects will participate in both hypoxia sessions taking approximately two
hours each (including pre-flight and post-flight briefing). There will be a
minimum of three days between the sessions. Subjects will be exposed to
hypobaric and normobaric hypoxia which may cause hypoxia symptoms such as
paraesthesia, shortness of breath, dizziness, nausea and headache. This will
last for the duration of the exposure to hypoxia. The subject might feel tired
after exposure. Subjects will be continuously monitored, and an instructor will
be available to administer additional 100% oxygen to those who want it or
neglect to do so in accordance with the guidelines. There is always a flight
surgeon readily available on site during all hypoxia training sessions for
medical questions and emergencies. Subjects have access to the flight surgeon
on call 24/7.