Rinaldo Bellomo is here to cause some trouble! He says that critical care physiology in resuscitation has problems! Whilst the rest of the medical field has advanced and evolved over time (we no longer routinely prescribe oxygen for an acute myocardial infarction), critical care resuscitation still relies on malfunctioning physiological paradigms. Critical care clinicians can change physiology with a number of tools. They can repeatedly, often, and mercilessly change physiological variables. Blood pressure, cardiac output, cardiac filling pressures, glucose levels, positive fluid balance and countless other physiological parameters can be increased and decreased at will. This kind of “numerology” is attractive because the outcomes can be immediate, and clinicians feel powerful and effective. However, outside the obvious situations where physiology is so dangerously abnormal as to threaten life, such physiological manipulations have an unproven relationship with outcome. Importantly, patients do not care whether their cardiac output has been increased from 5L/min to 6 L/min. They only care whether they live or die, get out of hospital intact and return to their previous life. Thus, physiological gain is not patient centred. Moreover, all research focusing of the physiology of a specific intervention inevitably deals with the effect on a specific set of variables. For example, a fluid bolus may or may not increase cardiac output in the short term. However this effect is not sustained much past 20 minutes. Similarly, no studies examine the effect of such fluid bolus on anything other than haemodynamics. No one measures what the effect is on the immune system, cerebral oedema, the glycocalyx, interstitial oxygen gradient, pulmonary congestion, body temperature, haemoglobin, or white cell function. Thus, all physiological studies are “blind” to the broader effects of their intervention. Rinaldo claims that in critical care resuscitation physiology, the measurable is made important but the important may not be measured. Clinicians need to reflect on this before they become seduced by physiological manipulation. Rinaldo’s challenge to you? Look at the literature, consider biological plausibility, follow evaluated evidence, balanced, accept doubt with a smile and practice known medicine of the time whilst understanding that today’s medicine will be the source of derision in the future.

1. The Trouble with Physiology
Rinaldo Bellomo
ANZIC RC
Monash University
Melbourne

2. Human illusions
• We believe in free will (a philosophical, relativity
theory, quantum physics, neuro-cognitive, EEG,
and blood flow MR-demonstrated impossibility)
• We believe that we do is important (a historical,
biological, paleontological, sociological and cosmic
impossibility)
• We believe there are “proven” physiological facts
which, if applied in the ICU, will improve survival
• Is this another illusion?

3. Harrison’s textbook of internal medicine 1978
Management of myocardial infarction
• Physiology: Rest is good for the heart.
Associated therapy: Rest in bed for 6 weeks
• Physiology: Valsalva manoeuvre strains the heart.
Associated therapy: Toilet use only after 2 weeks
• Physiology: Beta-blockers decrease contractility.
Associated therapy: Avoid beta-blockers
• Physiology: Ectopic beats increase R on T risk
Associated therapy: Lignocaine infusion to suppress
them

4. Harrison’s textbook of internal medicine 1978
Management of myocardial infarction
• Physiology: An unstable plaque will clot if touched.
Associated therapy: No
angiography
• Physiology: Myocardial ischemia is due lack of lack of
oxygen delivery to muscle.
Associated therapy: Oxygen to all
• All based on physiological thinking. All gone !!
• We laugh at all this …but are we any better in
critical care medicine?

5. Massive physiological belief
• Sepsis = infection and organ failure
• Sepsis Physiology = microvascular shunting
• Physiological paradigm No 1 = organs must be
failing because of shunting
• Physiological paradigm No 2= Shunting must
cause tissue hypoxia. Must fix tissue hypoxia.
• Therapeutic implication = let’s increase
oxygen delivery (Early Goal Directed Therapy)

6. Small (n=263); unblinded; PI involved in patient care, PI involved in patient selection;
no information of method of randomization, de-facto interim analysis with each patient;
High mortality in control group; implausible effect
EGDT: Physiological salvation or mumbo-jumbo?

7. Fundamental truth
“The amount of energy
necessary to refute
bullshit is an order of
magnitude bigger than to
produce it”

8. Millions of dollars and pounds!
15 times the number of patients
as in River’s study to
“refute belief”
No salvation – Just illusion

9. CCM Paradigms promoted by physiological
thinking
• Physiology: Glucose levels are high in ICU patients
• Associated therapy: Normalize glucose to avoid risks of
hyperglycemia
• Physiology: Protein C is low in sepsis and is being consumed
• Associated therapy: Give protein C in severe sepsis
• Physiology: Resuscitation with albumin decreases tissue edema
• Associated therapy: Give albumin to brain trauma patients to
decrease cerebral edema
• Physiology: Very high Intracranial pressure can kill. So high
intracranial pressure must be treated aggressively.
• Associated therapy: Decompress the brain by craniectomy

10. Fix physiology
Normalize glycaemia . All will be ok
Really???

11. Give protein C in sepsis – its levels are low! – really?

12. For $ 15,000/patient
…..not much value

13. Albumin resuscitation in TBI patients: it helps decrease tissue edema – really?

14. The effect of commercial
4% albumin on ICP
in health sheep

15. Decompress the brain. Increased ICP is bad post TBI –really?

16. Awesome – we have reduced ICP big time!!

17. ICP physiology looks awesome !! Pity about the brain

18. More mad physiology….
• Physiology: Critically ill patients have
increased caloric expenditure
• Associated therapy: Feed early and
aggressively
• Physiology: Critically ill patients have low
glutamine levels
• Associated Therapy: Give lots of glutamine

19. Feed early – nutrition is essential – really?
We can do it!!

20. The problem is…it’s a stupid thing to do

21. Caloric expenditure
during critical illness is high
Feeding early is a
physiological priority.
We can do it.

22. Oops!
Another waste
of time

23. Let’s give glutamine – they are all deficient – really?

24. More mad physiology
• Physiology: Fluids can increase blood
pressure. Children with sepsis have a
low blood pressure.
• Associated therapy: Resuscitate
septic children with lots of fluids

25. Fluids for children – It’s self evident they need it !!
It is recommended by SCCM guidelines!
Oops….physiology just
killed quite a few African kids!
Mortality

26. More mad physiology
• Physiology: Large artificial colloids can
expand intravascular volume more than
crystalloids and have longer intravascular
dwell time
• Associated therapy: Let’s use starch to
resuscitate

27. Oops…. physiology just killed
a few Scandinavians!

28. RRT: 21% higher with starch
P=0.04
Adverse events: 90% higher!
P<0.001
Ooops…
Physiology just lost us a few Aussie and Kiwi kidneys
(and they will be scratching themselves for years)

29. Why does all this happen?
Are doctors particularly stupid?
• Well…actually…yes
• However…to be fair…doctors have to make
decisions
• The poor fools can’t tolerate the thought they
actually do not know what they are doing
• Physiological gain is seductive in ICU (but pretty
much regularly misleading)
• Physiological seduction is pretty much regularly
associated with attribution bias

30. Attribution bias
• Anecdotal and selective observations of
favourable effects attributed to the
intervention which lead to undue confidence
in its effectiveness (sounds familiar?)
• Physiology is particularly diabolical because it
also carries a high chance of immediacy bias

31. Immediacy bias
• The selective immediate observations of
favourable effect attributed to the
intervention which lead to undue weight
being placed on such changes rather than
others that are either invisible (because
unmeasured or unmeasurable) or delayed
• Sounds familiar?

32. IV fluid bolus: attribution and immediacy bias
• IV fluids are given to patients during and after surgery to
replace estimated losses. Such approach seems innocent
enough (maybe)
• But IV fluids are also given as “boluses” to deal with
perceived physiological states based on clinical
observations
• Such boluses are common and perceived to have
clinical value (they are given incessantly) …but…do they?
• Are we dealing with attribution and immediacy bias?

33. You say…as long as we
follow the physiology
of “fluid responsiveness”
all is just fine

34. Author Journal Year Diagnosis Patients, N Type of Fluid Volume Duration Indication
FR assessment
Variable
FR, ∆ %
Time from
end of the
bolus
Device
Feissel ICM 2007 sepsis 23 6% HES 8 mL / kg - VE CI ≥ 15%
30' TTE
Lamia ICM 2007 ACF 24 Saline 500 ml 15' ACF SVI ≥ 15%
0 TTE
Maizel ICM 2007 ACF 34 Saline 500 ml 15' ACF CO ≥ 12%
0 TTE
Wyffels Anesth Analg 2007 Post Card Surg 32 6% HES 500 ml 20' VE CI ≥ 15%
0 PAC
Auler Anesth Analg 2008 Post Card Surg 59 Lactated Ringer's 20 mL / kg 20' VE CI ≥ 15%
0 PAC
Biasis Br J Anesth 2008 Post Liver Transp 40 Albumin 4% 20ml / BMI 20' ACF CI ≥ 15%
0 TOE, PAC
Biasis CC 2009 ACF 34 Saline 500 ml 15' ACF SV-TTE ≥ 15%
0 TTE + Vigileo
Monnet CCM 2009 ACF 34 Saline 500 ml 10' ACF CI ≥ 15%
0 PiCCO
Thiel CC 2009 ACF 89
Saline,Ringer's Lactated
and HES
at least 500 ml rapid ACF SV ≥ 15%
0 TTE
Benomar ICM 2010 Post Card Surg 75 Colloid 500 ml 15' VE CO -
3' Bioreactance
Lakhal ICM 2010 ACF 102 Modified Gelatin 300 ml + 200 ml 18' + 12' ACF CO ≥ 15%
0 PAC, PiCCO
Preau CCM 2010
sepsis/acute
pancreatitis
34 6% HES 500 ml 30' VE SV ≥ 15%
0 TTE
Guinot CC 2011 ARDS + vvECMO 25 Saline 500 ml 15' VE SV ≥ 15%
0 TTE
Alas...another sad case of immediacy bias

35. The problem with immediacy bias
Fluid bolus: it’s all over 15 minutes later!!!
Change from
baseline

36. Change in stroke volume index
The problem with immediacy bias
Change in
ml/min/m2
All over in 20 minutes?

37. Do fluids actually do anything at all?
Or is it just giving some “cold stuff” into people’s veins?

38. Oh dear!!
It’s the temp, not the fluid
The cold stuff makes you pee!
Temp. associated changes in V/Q matching?

39. ANALYS UNDER HÄNDELSE 2
elapsed i sekunder sedan bolusstart
Interaction P = 0.0003
Higher MAP with cold fluids – same amount
Maria Cronjort et al
cold

40. Interaction P = 0.001
Higher cardiac output with warm fluids – same amount
warm

41. Interaction P = 0.01
Higher HR to increase CO with warm fluids – same amount
warm

42. The physiological knowledge illusion

43. Overclaiming bias! – People (doctors) overclaim to the extent that
they perceive personal expertise favourably

44. Overclaiming bias
• People overestimate their knowledge sometimes claiming
knowledge of concept, places. or people that do not exist
• They overclaim to the extent that they perceive their expertise
favourably
• Self perceived knowledge in specific domains is specifically
associated with overclaiming is such domains
• Warning that some concept were fictitious does not reduce the
relationship between self perceived knowledge and overclaiming
• Boosting self-perceived expertise in geography led to asserion of
familiarity with non-existent places (assocition b/w self-perceived
expertise and impossible knowledge)
• Does this remind you of anyone you know?

45. Is it all just Rational Astrology?
• A rational astrology is a set of beliefs which one rationally behaves
as if were true, regardless of whether they are in fact true.
• Rational astrologies need not be entirely fake or false.
• The essential characteristic is the indifference to truth or
falsehood of the factors that compel one’s behavior.
• Some rational astrologies may turn out to be largely true, and that
happy coincidence can be a great blessing.
• But they are still a rational astrologies to the degree the factors
that persuade us to behave as though the beliefs are true are not
closely related to the fact of their truth.
• Some rational astrologies: fluid boluses are helpful in oliguria;
vitamin C is good for you; breakfast is the most important meal of
the day; oxygen is good for patients with myocardial infarction

47. Don’t worry: you are safe!
• Luckily, all these concerns relate only to other doctors. They have
nothing to do with doctors at SMACC.
• Unlike other doctors, SMACC doctors read the relevant physiological
literature in detail, consider biological plausibility, follow carefully
evaluated evidence, are open-minded, balanced, carefully
sceptical, and not unduly cynical.
• They accept doubt with a smile and practice the known medicine of
their time with the understanding that today’s physiological truth
is tomorrow’s target of derision.
• More importantly they enrol patients in high quality randomized
controlled trials so that known medicine can be improved
• How lucky are you to be such a doctor in such a group !