identifying modifiable risk factors for acute organ failure
TRANSCRIPT
Dr. Marius Terblanche
Director, Critical Illness Dynamic Systems Collaboration
Co-Chair, Critical Care & Peri-operative Research Group
King’s Health Partners AHSC, London, UK
Identifying modifiable risk
factors for acute organ failure
Source: http://www.photolib.noaa.gov/bigs/wea00816.jpg
Trigger
Apoptotic mediators
Pro-inflammatory responses
Anti-inflammatory responses
Death
Acute organ failure
TIME
Disease evolution
Sepsis – an optical illusion?
What we observe is
not nature,
But nature exposed to
our method of
questioning.Werner Heisenberg
Early critical
illness
Trigger
Acute organ
failure
Death
The “standard” question
End result…no effective therapies
A better question?
Early critical
illness
Trigger
Acute organ
failure
Death
Alberti, et al. AJRCCM 2005
Identifying modifiable risk factors
Alberti, et al. AJRCCM 2005
• Mechanical ventilation
• Pneumonia
• Primary bacteremia
• Gram+ cocci
• Mechanical ventilation
• Sodium
• Systolic blood pressure
• Platelet count
19 points 18.5 points
Risk of progression –
30%
Identifying risk factors that
are truly modifiable…
• What population?
• What is the disease burden?
• What are the event rates?
• Is there enough time to intervene?
• Do these patients exist?
Plus…
• Understand biological processes
• Appropriate outcomes
Methodological challenges
• Anecdotal…something’s up!
• Ventilation = high risk
• International community agreement
Alberti, et al. AJRCCM 2005
Shankar-Hari, et al. BMC Pharm 2012
A potential target population…
positive pressure resp support
Identifying risk factors
1. Mechanically ventilated ICU patients
2. Positive pressure respiratory support
3. Ward admissions with infections
• Mechanically ventilated ICU patients (n=1398)
• No non-respiratory organ failure (1st 24 hours
post-admission)
• Incidence of non-respiratory AOF: 28%
Terblanche et al, Crit Care 2011
OUTCOMES FOR PATIENTS IF ANY ONE ORGAN DETERIORATED FROM A LOWER LEVEL OF SEVERITY
DURING FOLLOW-UP PERIOD
Overall No acute organ failure or
dysfunction
Acute organ dysfunction, but
not failure
Acute organ failure
Mortality:
ICU, % (95%CI) Hosp, % (95%CI)
12.7 (11 – 15) 19.4 (17 – 22)
7.6 (6 – 10)
12.8 (11 – 15)
16.0 (13 – 20) 23.8 (20 – 28)
26.6 (22 – 31) 36.3 (31 – 41)
ICU LOS:
Mean (SD), days Median (IQR), days
9.3 (15.8)
5 (7)
4.9 (5) 3 (3)
13.5 (14)
9 (13)
18.10 (26.8)
11 (15)
Hospital LOS:
Mean (SD), days Median (IQR), days
28.0 (37.8)
15 (25)
20.7 (29) 29 (29)
36.6 (44) 21 (34)
40.3 (46.0)
24 (34)
Disease burden
Possible risk factors
Terblanche et al, Crit Care 2011
• International prospective pilot cohort study
• 4 week screening (n=766)
• Any positive pressure respiratory support
• No non-respiratory organ failure on admission
Terblanche et al, Crit Care 2012
Do these patients exist?
Event rates
Terblanche et al, Crit Care 2012
Possible risk factors
Terblanche et al, Crit Care 2012
Do we have time to intervene?
Terblanche et al, Crit Care 2012
Early. Late.
….But when is early or late???
Another big challenge:
TIME
Iwashyna TJ, et al. AJRCCM 2012
Iwashyna TJ. AJRCCM 2012 (Editorial)
When does time start?
• Prevention better than cure
• Must identify homogenous cohorts
• Modifiable risk factors…mechanisms!?
• Less phenotype, more global cellular
biology
In conclusion
Demographic & socioeconomic
factors
Past medical history
Chronic medications
Initiating acute conditions
Concurrent acute
treatments
Complex biological processes
Short term morbidity
• Short term cumulative burden
Long term morbidity
• Functional status
• Psychological status
• Quality of life
Resource use
• Shot term costs
• Long term economic impact
Mortality
• Short term
• Long term
David Hockney “Pearblossom Highway”
