Inflammatory and Cerebrospinal Biochemical Markers in Blood After Trimix Diving
Condition: Diving Medicine; Inflammation; Central Nervous System Injury
MeSH terms: Trauma, Nervous System; Inflammation
Study type: Observational

Summary: 
      Research hypothesis

        -  Diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing
           gas will affect the central nervous system.

        -  Diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing
           gas will induce inflammatory changes.

      Objectives:

        -  To investigate the presence of cerebrospinal biochemical markers in blood after diving
           to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.

        -  To investigate the presence of inflammatory markers in blood after diving to depths up
           to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.

        -  To investigate the presence of venous gas emboli (VGE) in blood after diving to depths
           up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.
    

Detailed description: 
      When diving with compressed air as breathing gas, a continuous accumulation of nitrogen will
      take place in the body. The total uptake of nitrogen by the tissues is dependent on the
      duration and depth of the performed dive. Decompression at the end of a dive can cause
      accumulated nitrogen to form intravascular bubbles.

      Furthermore, at depths greater than 30 meters seawater (msw) the elevated partial pressure of
      nitrogen in the breathing gas will exert a direct effect on the nervous system. This is known
      as nitrogen narcosis and can cause altered cognitive function, confusion, behavioural
      disturbance and altered level of consciousness. The effect of nitrogen narcosis gets more
      pronounced with increasing diving depth. To avert nitrogen narcosis it is common to reduce
      the amount of nitrogen in the breathing gas being used. At the same time the amount of oxygen
      must also be reduced, as partial pressures of oxygen above 1,6kPa could induce seizures.
      Usually a breathing gas mixture containing helium, nitrogen and oxygen (TriMix) is used.

      It has long been considered that decompression sickness (DCS) is caused by bubble formation
      when dissolved nitrogen at the end of diving comes out of solution. Doppler ultrasound
      techniques have shown that intravascular gas bubbles could exist even after uneventful dives.
      Therefore, additional pathophysiological factors must be sought.

      There is evidence of an increased inflammatory activity in blood after diving. Signs of
      neutrophil activation is a common finding. It is not known if hyperbaric exposure in itself
      is enough to elicit these biochemical changes or if the presence of intravascular nitrogen
      bubbles is needed.

      Studies have shown that biochemical markers of central nervous system (CNS) injury can be
      detected in blood samples obtained from patients with DCS, metabolic and neurologic disease,
      during cardiac surgery and after traumatic brain injuries. Such markers can also be seen in
      blood after sport activities like boxing and breath hold diving. If biochemical markers of
      CNS injury will be present in blood after hyperbaric exposure is not known.

      The Swedish armed forces (SwAF) Diving and Naval Medicine Center (DNC) is responsible for
      education and training of divers for SwAF. The centre is also responsible for research and
      development and conduct tests for diving medicine, and tests of underwater equipment.

      SwAF DNC will during 2017 and 2018 be responsible for naval dive training including deep
      dives (up to 90 msw) using TriMix as breathing gas. The partial pressure of oxygen will be
      kept at 130kPa. The study "Inflammatory and cerebrospinal biochemical markers in blood after
      TriMix diving - an observational controlled study" will be followed out during these tests.
      It entails venous blood sampling and cardiac ultrasound.

      This is a prospective, controlled observational study (see addendum 08/03/19 below). The
      study aims to involve at least 16 study subjects. Half of the subjects (at least 8 persons),
      named the intervention group, dive to depths up to 90msw with an oxygen partial pressure of
      130kPa in the TriMix breathing gas. Half of the subjects (at least 8 persons), named the
      control group, do not dive. The dives are part of the Swedish navy´s training programme for
      TriMix diving.

      Blood samples are obtained from the intervention group before and after diving (two tubes and
      about 8mL of blood each time, in total 16mL of blood). If possible, a third blood sample are
      taken about 24 hours after the first sample. Blood samples are obtained from the control
      group at the same time points as from the intervention group.

      Immmediately after diving, cardiac ultrasound will be used to assess presence and duration of
      VGE in the intervention group.

      Signs of DCS will be actively sought.

      Addendum 08/03/19: A control group containing non-diving military divers was initially
      planned. However, difficulties in subject recruitment meant that an appropriate control group
      could not be formed. It was performed as an observational study without controls.
    

Intervention name(s): Exposure to oxygen partial pressure of 130 kPa; Exposure to ambient pressure of maximum 11 ATA
Intervention type(s): Other; Other
Intervention description(s): Open sea diving to a maximum depth of 100 msw while breathing Trimix.; Open sea diving to a maximum depth of 100 msw while breathing Trimix.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Military divers and individuals approved by the Swedish navy to dive or perform work in
        hyperbaric environment.
      
Biospecimen description: 
      Plasma, Serum.
    
Keywords: Diving medicine; Inflammation; Central nervous system injury; Trimix; Decompression sickness; Venous gas emboli