Should we de-stress the distressed?

Mervyn Singer

Bloomsbury Inst of Intensive Care Medicine University College London, UK

MULTI-ORGAN FAILURE INSULT

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

FUNCTIONAL FAILURE NOT STRUCTURAL DAMAGE

WHY?????COULD IT BE THAT SUCH PATIENTS ARE ??STRESSED OUT

WE HAVEN’T EVOLVED TO DEAL WITH

ONGOING SEVERE STRESS …

.. 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 ..

We’re now living much longer …

.. far beyond what evolution ever intended

Life expectancy at birth in England (1540-2011)

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

sick, stressed patient

stressful drugs

stressful machinesstressful

environment

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

“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)

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

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

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

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

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

abnormal in critical illness; many also early prognosticators

metabolism

energy

Chicken, egg .. or both?CRITICAL ILLNESS

Type I allostatic overload??

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

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

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?

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

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 !

• 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 R Y