ICS State of the Art Meeting 2015

1. Intensive Care
Intensive Care
“Learning from the iceman”
Peter Pickkers
Nijmegen, The Netherlands
State of Art, London, 2015

2. Intensive Care
Autonomic Nerve System –
Immune System
Sympathic system
Acute activation  anti-inflammatory
Jan et al., Ann Surg 2009
Experimental human endotoxemia

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ANS  autonomic!

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Let me introduce you Wim Hof, aka ‘The iceman’

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Iceman Wim Hof claims:
“I can do these things through
modulation of my autonomic nerve system.”
“By the way, I can also modulate my immune system”

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Iceman Wim Hof claims:
• “I can do these things by modulation of my autonomic nerve system.”
• “By the way, I can also modulate my immune system”

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Does this also happen in vivo?

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Previous study Wim Hof
Kox et al., Psychosom. Med. 2012
Iceman
112 subjects
TNF-α
0 2 4 6 8
0
150
300
450
600 IL-6
0 2 4 6 8
0
250
500
750
1000
Hrs post-LPS Hrs post-LPS
pg/mL
pg/mL
Cold exposure
Meditation
Breathing techniques

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Previous study Wim Hof
adrenaline
-1 0 1 2 3 4 5 6 7 8
0
0.2
0.4
0.6
0.8
1
Hrs post-LPS
nmol/L
Kox et al., Psychosom. Med. 2012
Breathing techniques
Meditation

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Previous study Wim Hof

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I can teach
this to
everybody!

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Next study
Dutch Reumatic Association
‘Serendipity grant’
Question:
Is voluntary modulation of the autonomic nerve system and
innate immune response possible with the methods of
iceman Wim Hof?

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Design
Screening visit
Friday
Travel to Poland
trained group
(n=9)
Wednesday
Return to
Netherlands
trained group
Training sessions in Poland for the trained group (4 day training, 2 days travel)
Saturday
Selection day:
Final group training.
6 subjects of the
training group (TR1-
TR6) are randomly
selected for
endotoxemia
experiments
Subjects in the trained group practice the taught techniques at home by themselves until endotoxemia experiment day
Sunday
Last training day of
subjects TR1 and
TR2 by iceman
Monday
Endotoxemia
experiment day
TR1+TR2
Tuesday
Endotoxemia
experiment day
CT1+CT2+CT3.
Last training day
of subjects
TR3 and TR4 by
iceman
Wednesday
Endotoxemia
experiment day
TR3+TR4
Thursday
Endotoxemia
experiment day
CT4+CT5+CT6
Last training day
of subjects
TR5 and TR6 by
iceman
Friday
Endotoxemia
experiment day
TR5+TR6
Study population: 30 healthy male volunteers
Study conducted in 2 blocks of 15

15. Intensive Care
Vertrek

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Training Poland

17. Intensive Care
Training in Poland

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Training in Poland

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Training Polen

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Endotoxin experiments
-1.5 -1 -0.5 0 0.5 1 1.5 2 2.5 3 4 6 8
Time (hours post-LPS)
LPS administration
(2 ng/kg i.v.)
Admittance to ICU End of
hospitalization
trained group: breathing
techniques
blood sampling:

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Example trained subject

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Time (post-LPS)
nmol/L
Results: Effect on ANS?
control
trained
adrenaline
0
1
2
3
-1 0 1 2 3 4 5 6 7 8
p<0.0001

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Kinetics of cytokines
0
100
200
300
400
500
600
700
800
900
0 1 1.5 2 3 4
0
20
40
60
80
100
120
140
TNF -α (pg /ml) IL -10 ( pg /ml)
TNF -α
IL -10
Time after LPS administration (hrs)

25. Intensive Care
Results
0
200
400
600
800
1000
Anti-inflammatory cytokine IL-10
control
trained
pg/mL
-1 0 1 2 3 4 5 6 7 8
time (post-LPS)
+194%
p=0.01
AUC

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Results
Pro-inflammatory cytokines
control
IL-8
0
100
200
300
400
500
600
IL-6
0
100
200
300
400
500
TNF-α
0
100
200
300
400
500
trained
-1 0 1 2 3 4 5 6 7 8
time (post-LPS)
-1 0 1 2 3 4 5 6 7 8 -1 0 1 2 3 4 5 6 7 8
time (post-LPS) time (post-LPS)
-53%
p=0.02
-57%
p=0.01
-51%
p=0.004
pg/mL pg/mL pg/mL
AUCAUC AUC

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Autonomic Nerve System –
Immune System
Sympathic system
Acute activation  anti-inflammatory
Jan et al., Ann Surg 2009

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Results
adrenaline
0
1
2
3
-1 0 1 2 3 4 5 6 7 8
Time (post-LPS)
nmol/L
0
200
400
600
800
1000
pg/mL
-1 0 1 2 3 4 5 6 7 8
Time (post-LPS)
IL-10
control
trained

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Results
0 1 2 3 4 5 6
0
200
400
600
800
1000
Adrenaline
IL-10
r=0.82
p=0.001

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Results
0
200
400
600
800
1000
pg/mL
-1 0 1 2 3 4 5 6 7 8
time (post-LPS)
IL-10
Resultaten
Kox et al., PNAS 2014
Ontstekingsbevorderende cytokines
IL-6
0
100
200
300
400
500
TNF-α
0
100
200
300
400
500
-1 0 1 2 3 4 5 6 7 8
tijd (uren na LPS)
-1 0 1 2 3 4
tijd (uren na
-53%
p=0.02
-57%
p=0.0
pg/mL pg/mL
Intensive Care
Resultaten
Kox et al., PNAS 2014
Ontstekingsbevorderende cytokines
IL-8
0
100
200
300
400
500
600
IL-6
0
100
200
300
400
500
TNF-α
0
100
200
300
400
500
-1 0 1 2 3 4 5 6 7 8
tijd (uren na LPS)
-1 0 1 2 3 4 5 6 7 8 -1 0 1 2 3 4
tijd (uren na LPS) tijd (uren na
-53%
p=0.02
-57%
p=0.01
-51%
p=0.00
pg/mL pg/mL pg/mL
Resultaten
Ontstekingsbevorderende cytokines
controle
IL-8
0
100
200
300
400
500
600
IL-6
0
100
200
300
400
500
TNF-α
0
100
200
300
400
500
training
-1 0 1 2 3 4 5 6 7 8
tijd (uren na LPS)
-1 0 1 2 3 4 5 6 7 8 -1 0 1 2 3 4 5 6 7 8
tijd (uren na LPS) tijd (uren na LPS)
-53%
p=0.02
-57%
p=0.01
-51%
p=0.004
pg/mL pg/mL pg/mL
control
trained

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Results
0
200
400
600
800
1000
IL-8 T=2 hours (pg/mL)
0
200
400
600
800
1000
TNF-α T=1.5 hours (pg/mL)
0 200 400 600 800 1000
IL-10 T=1 hours (pg/mL)
0 200 400 600 800 1000
r=-0.71
p=0.01
r=-0.71
p=0.01
0
200
400
600
800
1000
IL-8 T=2 hours (pg/mL)
0
200
400
600
800
1000
TNF-α T=1.5 hours (pg/mL)
0 1 2 3 4 5 6
0
200
400
600
800
1000
epinephrine T=0 hours (nmol/L)
IL-10 T=1 hours (pg/mL)
0
200
400
600
800
1000
IL-6 T=2 hours (pg/mL)
0 200 400 600 800 1000
IL-10 T=1 hours (pg/mL)
0 200 400 600 800 1000
IL-10 T=1 hours (pg/mL)
0 200 400 600 800 1000
IL-10 T=1 hours (pg/mL)
r=0.82
p=0.001
r=-0.71
p=0.01
r=-0.71
p=0.01
r=-0.59
p=0.045
A B
DC
0
200
400
600
800
1000
IL-8 T=2 hours (pg/mL)
0
200
400
600
800
1000
TNF-α T=1.5 hours (pg/mL)
0 1 2 3 4 5 6
0
200
400
600
800
1000
epinephrine T=0 hours (nmol/L)
IL-10 T=1 hours (pg/mL)
0
200
400
600
800
1000
IL-6 T=2 hours (pg/mL)
0 200 400 600 800 1000
IL-10 T=1 hours (pg/mL)
0 200 400 600 800 1000
IL-10 T=1 hours (pg/mL)
0 200 400 600 800 1000
IL-10 T=1 hours (pg/mL)
r=0.82
p=0.001
r=-0.71
p=0.01
r=-0.71
p=0.01
r=-0.59
p=0.045
A B
DC

32. Intensive Care
Conclusion
• It is possible to voluntarily influence the autonomic nerve
system and innate immune reponse
• This could represent a novel
non-pharmacological, non-invasive treatment
for diseases associated with a too pronounced or persistent
immune response

33. Intensive Care
We need to publish this!

34. Intensive Care
Tttrrrriiiinnnnggggg!!!!!

35. Intensive Care
The original
text
message:
**

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37. Intensive Care
One more thing:
Which one is out of place?

38. Intensive Care
2 31
Jenna Matthijs & PeterPamela

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June2014

40. Intensive Care
Carney S, Playboy 2014; 6: 137-145 (not available on PubMed)

41. Intensive Care
12 y/o son Marc
Really interested
in the scientific
work of dad…

42. Intensive Care
Thanks
for your
kind attention!!!