Inflammatory and Cerebrospinal Biochemical Markers in Blood After Trimix Diving

Inflammation Clinical Trial

— TriMix17-18  

Official title:

Biokemiska förändringar Vid förhöjt Partialtryck för Syrgas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03190252
• Other study ID #: EPN 292-17
• Status: Completed
• Start date: June 12, 2017
• Est. completion date: January 30, 2019

Study information

• Verified date: March 2019
• Source: Sahlgrenska University Hospital, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 30, 2019
• Est. primary completion date: January 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Military diver or individual approved by the Swedish navy to dive or perform work in hyperbaric environments

Exclusion Criteria:

• As this is a highly selected population there is no exclusion criteria

Related Conditions & MeSH terms

• Central Nervous System Injury
• Diving Medicine
• Inflammation
• Trauma, Nervous System

Intervention

Other:
• Exposure to oxygen partial pressure of 130 kPa
Open sea diving to a maximum depth of 100 msw while breathing Trimix.
• Exposure to ambient pressure of maximum 11 ATA
Open sea diving to a maximum depth of 100 msw while breathing Trimix.

Locations

Country	Name	City	State
Sweden	Gothenburg University	Gothenburg

Sponsors (4)

Lead Sponsor	Collaborator
Sahlgrenska University Hospital, Sweden	Göteborg University, KTH Royal Institute of Technology, Swedish Armed Forces Diving and Naval Medicine Centre

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of cerebrospinal and inflammatory biochemical markers in blood	E.g. GFAP, Tau, NfL, JCHL-1, VCAM-1, ICAM-1	Three months
Secondary	Presence of Venous Gas Emboli (VGE)	Kisman-Masurel grading	Five days
Secondary	Decompression Sickness (DCS)	Clinical diagnosis	Five days