1. Critical illness is a highly stressful state driven by the underlying disease, treatments, and ICU environment. 2. Prolonged stress can lead to "allostatic overload" and decompensation of organ systems even if no structural damage is present. 3. There is a need to reduce stress in critically ill patients through minimizing stressful interventions, providing psychological support, optimizing the environment, and exploring pharmacological de-stressing therapies.

1. Should we de-stress the distressed?
Mervyn Singer
Bloomsbury Inst of Intensive Care Medicine
University College London, UK

2. MULTI-ORGAN FAILURE
INSULT

3. ORGANS LOOK NORMAL IN PATIENTS
DYING OF MULTI-ORGAN FAILURE ...
“.. no evidence of injury to cardiac myocytes in patients with sepsis
who had myocardial depression.”
“.. in patients with sepsis and acute renal failure only focal injury
with preservation of normal glomeruli and tubules.”
HOTCHKISS + KARL, NEJM 2003

4. FUNCTIONAL FAILURE NOT STRUCTURAL DAMAGE
WHY?????
COULD IT BE THAT SUCH PATIENTS ARE ??STRESSED OUT

5. WE HAVEN’T EVOLVED TO DEAL WITH
ONGOING SEVERE STRESS …

6. .. ability to cope with blood loss
and tissue trauma
.. ability to heal quickly
.. endogenous food reserves
- “auto-cannabilization”
.. a functioning immune system
SURVIVAL DEPENDED ON ..

7. We’re now living much longer …
.. far beyond what evolution ever intended
Life expectancy at birth in England (1540-2011)

8. W E H AV E N ’ T E V O LV E D T O C O P E W I T H …
old age
multiple co-morbidities
prolonged critical illness
modern life-saving drugs
and organ supports

9. sick, stressed
patient
stressful drugs
stressful machines
stressful
environment

10. S T R E S S
crucial coping mechanism
to deal with stressors
changes in behaviour
autonomic & hormonal modulation of:
inflammatory & immune systems
cardiovascular, respiratory systems
metabolic activity ….
too much of a good thing becomes bad

11. “acute stress response” (1915)
World War 1 - studied physiological effect of emotions
threat -> sympathetic discharge -> primes for fight/flight
generally adaptive & protective..
.. though noted nervous exhaustion
-> ± manifest as physical illness
Walter Cannon (1871-1945)

12. Hans Seyle (1936)
- “General Adaptation Syndrome”
Physiological systems protect & restore the body against stress ..
but can also cause harm
Stress
—> ‘distress’ when body can no longer withstand insult
—> functional compromise
Various insults (cold, trauma, spinal cord transection, xs exercise,
drugs) -> similar pathological findings

13. TA K O T S U B O C A R D I O M Y O PAT H Y
• heart failure
• first recognized in Japan in early 90s
• follows emotional stress, e.g. argument, bereavement, public speaking ..
• normal coronaries
• related to excess catecholamine levels

14. physiological and behavioural changes
generally adaptive in the short term
allostatic load = physiological costs of chronic stress exposure
allostatic overload - when serious pathophysiology may occur
type 1 overload - when energy demand exceeds supply:
• animal goes into survival mode that decreases allostatic load and
regains positive energy balance
• normal life cycle resumes when insult passes
(Sterling & Eyer 1988)
A L L O S TA S I S

15. Hibernation (extreme cold)
• bears, mice…
Estivation (extreme heat / drought)
• reptiles, mammals, snails,
• fish, trees
Deep-sea diving (anoxia)
• turtles
Dormancy
• bacteria (e.g. TB
A L L O S TAT I C A D A P TAT I O N

16. .. protects against persisting hypoperfusion
M Y O C A R D I A L H I B E R N AT I O N

17. abnormal in critical illness;
many also early prognosticators

20. metabolism
energy
Chicken, egg .. or both?
CRITICAL ILLNESS
Type I allostatic overload??

22. physiological
pharmacological
psychological
delirium
& PTSD
pro-thromboticmuscle loss/wasting
arrhythmias,
heart failure
immunosuppressive
CHRONIC CRITICAL ILLNESS
B E I N G A N I C U PAT I E N T I S S T R E S S F U L

23. Singer M. Lancet 2007; 370: 636-7
obvious e.g. tachyarrhythmias, digital ischaemia
stimulation of bacterial growth + virulence
immunosuppression
metabolic modulation, insulin resistance
catabolism
thrombogenic
decreased bioenergetic efficiency
increased cardiac work
ventricular remodelling
myocardial damage

24. failed organs .. yet usually structurally normal
tissue PO2 high, i.e. O2 available but not utilized
if patient survives, organs usually recover - even those that are
poorly regenerative
Is MOF an allostatic response to severe, prolonged inflammation??
However, does too extreme a phenotype become maladaptive?

25. good analgesia
other drug approaches
prevent hypoxia
reduce/remove anxiety
wake-sleep cycles
quality sleep
access to daylight & views
communication aids
mobilisation
privacy
music
alleviate boredom
noise reduction
alternative therapies
D E - S T R E S S I N G
P R O C E D U R E S

29. C O M E T O T H I S A F T E R N O O N ’ S TA L K
F O R S O M E L I F E - S AV I N G D E - S T R E S S I N G
T H E R A P I E S
… AT L E A S T I N R O D E N T S !

30. • Critical illness is a stressful event
• Stress driven by underlying disease process, our treatments
and the ICU environment
• Excess stress -> decompensation (‘allostatic overload’)
• Need to destress patients …
• minimise stressful interventions
• psychological supports
• optimize environment
• pharmacological de-stressing
S U M M A RY