Inflammatory and Cerebrospinal Biochemical Markers in Blood After Trimix Diving (TriMix17-18)

Biokemiska förändringar Vid förhöjt Partialtryck för Syrgas

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Central Nervous System Injury; Diving Medicine
• Intervention / Treatment: Other: Exposure to oxygen partial pressure of 130 kPa; Other: Exposure to ambient pressure of maximum 11 ATA

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.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, S-405 30
    • Gothenburg university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Military divers and individuals approved by the Swedish navy to dive or perform work in hyperbaric environment.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Trimix; Exposure to ambient pressure of maximum 11 ATA breathing Trimix. Exposure to oxygen partial pressure of 130 kPa breathing Trimix.	Other: Exposure to oxygen partial pressure of 130 kPa; Open sea diving to a maximum depth of 100 msw while breathing Trimix.; Other: Exposure to ambient pressure of maximum 11 ATA; Open sea diving to a maximum depth of 100 msw while breathing Trimix.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of cerebrospinal and inflammatory biochemical markers in blood	E.g. GFAP, Tau, NfL, JCHL-1, VCAM-1, ICAM-1	Three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Venous Gas Emboli (VGE)	Kisman-Masurel grading	Five days
Decompression Sickness (DCS)	Clinical diagnosis	Five days

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Collaborators: Göteborg University; KTH Royal Institute of Technology; Swedish Armed Forces Diving and Naval Medicine Centre

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2017
• Primary Completion (Actual): January 30, 2019
• Study Completion (Actual): January 30, 2019

Study Registration Dates

• First Submitted: June 14, 2017
• First Submitted That Met QC Criteria: June 14, 2017
• First Posted (Actual): June 16, 2017

Study Record Updates

• Last Update Posted (Actual): March 12, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Inflammation; Diving medicine; Central nervous system injury; Trimix; Decompression sickness; Venous gas emboli
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Wounds and Injuries; Inflammation; Trauma, Nervous System
• Other Study ID Numbers: EPN 292-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No