Identifying modifiable risk factors for acute organ failure

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”

marius.terblanche@kcl.ac.uk

Thank you for listening!