manoj saxena - temperature and tbi: time for parity?
TRANSCRIPT
Dr Manoj SaxenaSt. George Hospital, University of New South
Temperature and TBI: time for PARITY?
UNSW
Temperature and TBI: time for PARITY?
D o e s s t r i c t n o r m o t h e r m i a ( 3 6 - 3 7 ° C ) r e d u c e d i s a b i l i t y a n d d e a t h a f t e r t r a u m a t i c b r a i n i n j u r y , c o m p a r e d t o s t a n d a r d c a r e ?
1. How reliable is current evidence?
2. What is normothermia?
5. Is a clinical trial feasible?
4. Surrogate effect/risk of the interventions?
3. What actually happens in clinical practice?
1. How reliable is the evidence for
normothermia?
Laboratory Models
Observational Clinical Studies
We have evidence ... But the data are not reliable enough
Bramlett (1995) Journal of Neurotrauma 12;3:289Dietrich WD (1996) Neurosurgery 38;3: 533
Laboratory Models
Observational Clinical Studies
No Clinical Trials
We have evidence ... But the data are not reliable enough
Laboratory Models
Observational Clinical Studies
No Clinical Trials
We have evidence ... But the data are not reliable enough
Allan SM (2003) Phil Trans R Soc 358: 1669
2. What is normothermia?
Clinical trials of induced hypothermia vs. control (n=23)
Control arm protocol Number of studiesNot reported 5“Normal body temperature” 1“No active management” 536-37°C 336.5-37.5°C 437°C 237-38°C 137-38.5°C 1Brain temperature 37.5-38.5°C
1
What is normothermia?
Sydenham E 2009 Cochrane Database of Systematic Reviews
What is normothermia?
36-37°C
1. Brain temperature2. PAIS clinical trial3. Cardiac arrest: historical control groups4. Observational cohort studies
Adjusted OR 1.43 95% CI 1.02-1.97)
The PAIS Study
36-37°C
Den Hertog HM (2009) Lancet Neurology;8:434
Nielsen 2013HACA 2002
Bernard 2002
0 10 20 30 40 50
Cardiac arrest RCTs: difference in control group outcome
Normothermia good outcome
36-37°C
Nielsen N (2013) NEJM 369;23: 2197Bernard SA (2002) NEJM 346:557HACA (2002) NEJM 346:549
What is normothermia?
36-37°C1. Brain temperature
2. PAIS clinical trial3. Cardiac arrest: historical control groups
4. Observational studies (stroke, cardiac arrest):For every 1°C rise in temperature above 37°C, there is a doubling in the risk of adverse outcome
Reith 1996 Lancet 347:422Zeiner A 2001 Arch Intern Med 161;16:2007
3. What do we actually achieve in clinical
practice?
Observational studies
The CLARITY Study: manuscript in preparationSaxena MK, SMACC 2015
Temperature and interventions
Hours/dayTime above 37°C
14-18
Time above 38°C
3-7 >90% of patients received
paracetamol > 1/3 of patients received physical
cooling The CLARITY Study: manuscript in preparationSaxena MK, SMACC 2015
Temperature and interventions
A “reactive” approach to fever management
Physical Cooling Use Median temperature C (IQR)
At initiation 38.1 (37.7 to 38.9) During 38 (37.3 to 38.5) At cessation 37.7 (37.0 to 38.2)
The CLARITY Study: manuscript in preparationSaxena MK, SMACC 2015
How could we maintain 36-37°C?
1. Paracetamol
2. NSAID
3. Physical Cooling
4. How effective are these interventions?
4. Does paracetamol reduce body temperature
after TBI?
Clinical trial
The PARITY Study: manuscript in preparationSaxena MK, SMACC 2015
TBI
1g IV Paracetamol (100mls)Every 4 hoursFor 72 hours
100 mls 0.9% SalineEvery 4 hoursFor 72 hours
Mean Bladder temperature
Physical cooling useMAPICP
Safety• Hypotension• Hepatic
1°
2°
Sample size: 38-42 patients, based on detecting 0.5°C difference
The PARITY Study: manuscript in preparationSaxena MK, SMACC 2015
1° Outcome
ParacetamolHours/day
SalineHours/day
Relative risk (95%CI)
P value
Physical cooling
2 ± 1 4 ± 1 0.57 (0.25 to 1.28)
0.17
Paracetamol°C
Saline °C Mean difference °C (95%CI)
P value
Mean Temperature
37.4± 0.1 37.7± 0.1 -0.3 (-0.6 to 0.0)
0.09
The PARITY Study: manuscript in preparationSaxena MK, SMACC 2015
How effective are the interventions?
6g/ day of Paracetamol does not significantly reduce temperature after TBINSAIDs
Physical cooling devices
Simple, safe, inexpensive
Nephrotoxicity, platelet dysfunction, GI bleeding
Shivering management Sedation Length of Stay
Loss of clinical monitoring
D o e s s t r i c t n o r m o t h e r m i a ( 3 6 -3 7 ° C ) r e d u c e d i s a b i l i t y a n d d e a t h a f t e r t r a u m a t i c b r a i n i n j u r y , c o m p a r e d t o s t a n d a r d c a r e ?
1. How reliable is current evidence? 2. What is normothermia?
5. Is a clinical trial feasible?
4. Surrogate effect /risk of the interventions?
3. What actually happens in clinical practice?
36-37°C
Two Clinical Trials
Well ResourcedHigh Acuity
StrictNormothermi
aStandard
Care
Low ResourceLow Acuity
PlaceboVs.
Drug
Physical cooling
Where to next?
Does str ict normothermia (36-37°C) reduce disabi l i ty and death after
traumatic brain injury, compared to standard care?
[email protected] @juicymango1