1st InnovaSpace Journal Club...

Author: Lucas Rehnberg

NHS Doctor - Anaesthetics & Intensive Care | MSc Space Physiology & Health

Extremely pleased to report on the 1st InnovaSpace Journal Club meeting that had the participation of a very international audience, with attendees from Belgium, Brazil, India, Israel, Italy, Romania, and UK! Thank you to all those who attended and look forward to future talks and discussions.

For those who couldn’t attend, or are interested in the Space Journal Club, I have created a ‘one page’ summary of the paper we discussed. I have also added in the discussion points raised after the critical appraisal of the paper, together with links to additional reading material for anyone wishing to learn more.
​PAPER PRESENTED & DISCUSSED:

HEADLINE:
After 50+ years of spaceflight, the first documented venous thrombus in an astronaut identified - highlighting a new pathology, not previously diagnosed in astronauts.

Who are the authors?
Experts in this field from several space agencies => NASA, IBMP (Russia), ESA
Funding => NASA, under the Human research program. Part of the multi-institution international fluid shifts study.

What is interesting about this paper/ Why would the medical space community be interested in this?
New pathology, not diagnosed before. Potentially massive implications for future long duration missions. LBNP could potentially be a countermeasure to enhance venous blood flow or improve cerebral venous outflow.

The research question.
Loss of hydrostatic gradient and variation on Earth, sustained fluid redistribution. Effect on cerebral venous drainage/blood flow. Possible mechanism linked to SANS? Increased risk of clot formation due to static/retrograde flow?
Aims:

1. Characterise cerebral venous outflow during spaceflight vs. +1Gz (in left IJV)
2. Evaluate effect of LBNP on cerebral venous outflow

Why is this research question important?
Static/stagnant flow can predispose individuals to thrombus formation. Long lasting effects of thrombi for astronauts, potentially affecting crew performance (i.e. risk of anticoagulation, emboli, then leading to reduced performance affecting the crew and mission).

The study design.
Primary research => prospective cohort study (follow a similar patient group over time, comparing a particular outcome). Subjects were 11 astronauts, on the ISS.
Method:
Ultrasonographic assessment of left IJV (IJV are main conduits of cerebral drainage)
                        - pre flight (3 positions, seated, supine & head down tilt)
                        - at approximately D50 and D150 of spaceflight
                        - with and without LBNP (approx the same days, Russian Chibis-M LBNP)​
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• Primary Findings
• Secondary Findings

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Images B & C copyright: Article authors / JAMA Network Open

9 crew members participated in LBNP sessions. 17 LBNP sessions, 10 of these (59%) showed improved IJV blood flow patterns. Other 7 sessions were equal or worse flow. No syncopal episodes recorded.
Potential countermeasure to blood flow stasis and thrombosis (but DIDN’T reach seated baseline in +1Gz).

Flaws? Biases? Limitations?
All papers that involve human subjects in space have a common flaw => lack of numbers (compared to terrestrial studies)
Non-invasive pressure measuring of IJV likely overestimated values. Only the left IJV was assessed (right IJV has been examined previously). No lower limb assessment either (i.e. for DVTs). Measurements over 150 days, LOTS of variables (exercise, EVAs, other activities, diet, etc).

Can these results be applied to your patient population? (i.e. other astronauts)
In my opinion => YES!
Tough with small sample size to draw definitive conclusions. However, it would almost be irresponsible to ignore and say it is a ‘one off’.
Tested in similar population in similar conditions (i.e. not in a lab or analogue in simulated conditions like 6o head down). Space medicine is often ‘best evidence we have’ based, augmented with experts and experience.

Is this clinically relevant and how could this affect future management and treatment?
There needs to be a lot more research to determine the actual level of risk of thrombus formation in microgravity, affects of countermeasures on venous blood flow, and benefits of screening pre and during flight.
Then future management -crews performing point of care ultrasound with minimal support (with time delays going to Mars), limited resources and pharmacy, prophylaxis, risk/benefit of anticoagulation, and so many more questions!​

DISCUSSION

Discussion of the paper after the critical appraisal was very interesting with a variety of topics and issues raised, such as:

• If healthy, extensively screened, astronauts are at risk of venous thrombus, how will this affect the private space sector? How do you manage that risk or assess these individuals who may not be as healthy or may have other co-morbidities?
• Discussed mechanical and chemical VTE prophylaxis, what are the risks/benefits? And this lead to discussions of using limited resources or needing to bring VAST amounts of medication to treat and manage, which raises the issue of mass/volume/power when flying anything into space.
• Paper was a small sample size, so very difficult to draw definitive conclusions. Was this a 1 in a million event that we happened to pick up, or have there be many thrombi that have been missed in 50 years of human spaceflight?
• And what about other factors, such as trauma and radiation? These can all increase risk or thrombus formation by causing endothelial damage and dysfunction.
• Would there be a role for point-of-care testing with TEG (thromboelastography) to assess coagulation profiles during spaceflight/in microgravity? And would the TEG machine work in microgravity?
• If possible, it would be interesting to image cerebral vessels in microgravity, and whether there is static flow in the cerebral sinuses, as a cerebral sinus thrombus can have significant neurological consequences.
• Trauma and EVAs, how do you manage these if someone is on blood thinners/anticoagulation? Example from the paper is the stopping of anticoagulation 4 days before re-entry to Earth - risk/benefit discussion (i.e. if the astronaut suffered a significant trauma on re-entry they may develop a life threatening haemorrhage that would be difficult to control and manage being so far away from a trauma hospital.
• This leads on to a broader discussion of the risk/benefit we experience everyday in hospital and how we could apply this to astronaut populations. 

Additional reading
Surveillance for jugular venous thrombosis in astronauts. Pavela et al 2022
https://journals.sagepub.com/doi/full/10.1177/1358863X221086619
The Vascular Frontier: Exploring the diagnosis and management of vascular conditions in spaceflight. Drudi et al 2022
https://journals.sagepub.com/stoken/default+domain/RI2YQPUZTFUKTETSURTI/full?utm_campaign=vmj_may2022&utm_content=articlepromo&utm_medium=referral&utm_source=sagepub.com
Venous Thrombosis during Spaceflight. Auñón-Chancello et al 2020
https://www.nejm.org/doi/full/10.1056/NEJMc1905875
The effect of microgravity on the human venous system and blood coagulation: a systematic review. Kim et al 2021
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/EP089409
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