identifying modifiable risk factors for acute organ failure
TRANSCRIPT
![Page 1: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/1.jpg)
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
![Page 2: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/2.jpg)
![Page 3: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/3.jpg)
![Page 4: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/4.jpg)
![Page 5: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/5.jpg)
Source: http://www.photolib.noaa.gov/bigs/wea00816.jpg
![Page 6: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/6.jpg)
Trigger
Apoptotic mediators
Pro-inflammatory responses
Anti-inflammatory responses
Death
Acute organ failure
TIME
Disease evolution
![Page 7: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/7.jpg)
![Page 8: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/8.jpg)
Sepsis – an optical illusion?
![Page 9: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/9.jpg)
![Page 10: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/10.jpg)
What we observe is
not nature,
But nature exposed to
our method of
questioning.Werner Heisenberg
![Page 11: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/11.jpg)
Early critical
illness
Trigger
Acute organ
failure
Death
The “standard” question
![Page 12: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/12.jpg)
End result…no effective therapies
![Page 13: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/13.jpg)
![Page 14: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/14.jpg)
![Page 15: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/15.jpg)
A better question?
Early critical
illness
Trigger
Acute organ
failure
Death
![Page 16: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/16.jpg)
Alberti, et al. AJRCCM 2005
Identifying modifiable risk factors
![Page 17: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/17.jpg)
Alberti, et al. AJRCCM 2005
![Page 18: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/18.jpg)
• Mechanical ventilation
• Pneumonia
• Primary bacteremia
• Gram+ cocci
• Mechanical ventilation
• Sodium
• Systolic blood pressure
• Platelet count
19 points 18.5 points
Risk of progression –
30%
![Page 19: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/19.jpg)
Identifying risk factors that
are truly modifiable…
![Page 20: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/20.jpg)
• 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
![Page 21: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/21.jpg)
• 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
![Page 22: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/22.jpg)
Identifying risk factors
1. Mechanically ventilated ICU patients
2. Positive pressure respiratory support
3. Ward admissions with infections
![Page 23: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/23.jpg)
• Mechanically ventilated ICU patients (n=1398)
• No non-respiratory organ failure (1st 24 hours
post-admission)
• Incidence of non-respiratory AOF: 28%
![Page 24: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/24.jpg)
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
![Page 25: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/25.jpg)
Possible risk factors
Terblanche et al, Crit Care 2011
![Page 26: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/26.jpg)
• International prospective pilot cohort study
• 4 week screening (n=766)
• Any positive pressure respiratory support
• No non-respiratory organ failure on admission
![Page 27: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/27.jpg)
Terblanche et al, Crit Care 2012
Do these patients exist?
![Page 28: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/28.jpg)
Event rates
Terblanche et al, Crit Care 2012
![Page 29: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/29.jpg)
Possible risk factors
Terblanche et al, Crit Care 2012
![Page 30: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/30.jpg)
Do we have time to intervene?
Terblanche et al, Crit Care 2012
![Page 31: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/31.jpg)
Early. Late.
….But when is early or late???
Another big challenge:
TIME
![Page 32: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/32.jpg)
Iwashyna TJ, et al. AJRCCM 2012
Iwashyna TJ. AJRCCM 2012 (Editorial)
When does time start?
![Page 33: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/33.jpg)
• Prevention better than cure
• Must identify homogenous cohorts
• Modifiable risk factors…mechanisms!?
• Less phenotype, more global cellular
biology
In conclusion
![Page 34: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/34.jpg)
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
![Page 35: Identifying modifiable risk factors for acute organ failure](https://reader031.vdocument.in/reader031/viewer/2022012011/613d2c13736caf36b75a2bb9/html5/thumbnails/35.jpg)
David Hockney “Pearblossom Highway”