1. mm
Hypotensive resuscitation FROm animal study to clinical practice Dr YW Wong United Christian Hospital

4. Outline History of fluid resuscitation Clinical trial Guideline
Animal studies
Human studies
Guideline
Controversies
Conclusion

5. Trauma
Trauma had long been a major cause of preventable deaths worldwide.
One-third of trauma deaths because the victims bleed to death within the first several hours

6. Lethal triad
In the past, high volume resuscitation strategies was used to reverse haemorrhagic shock
However, still a number of patient develop lethal triad and leads to mortality
Acidosis, hypothermia, coagulopathy
Can be due to the injury, or due to resuscitation

7. History of Fluid resuscitation
Controlled hemorrhage animal models in 1950s.
Wiggers insert a IV catheter, allow the animal to bleed and maintain a predetermined level of hypotension
Fluid deficit was corrected with crystalloid 3 times the blood loss
Lead to traditional fluid replacement regimen of 3:1 crystalloid: blood

8. Wiggers’ model may not be accurate
Blood pressure is controlled by investigator by controlling the blood loss through the iv catheter

9. Aggressive fluid resuscitation
Early aggressive fluid resuscitation was used routinely in Vietnam War in 1970s
Coincidentally, ARDS was commonly described

10. 1980s
Uncontrolled haemorrhagic models were developed to simulate blunt trauma
maximal vasoconstriction
thrombus formation
Animal study : Aggressive resuscitation with isotonic crystalloid
Increase blood pressure and increase blood loss
Did not reduce mortality

11. Hypotensive Resuscitation

12. Hypotensive Resuscitation
In haemorrhagic shock patient, hypotension and vasoconstriction help to stalilized the clot
Increasing the blood pressure places additional stress on formed clot
Blood pressure greater than 90mmHg associated with higher risk of re-bleeding
Hypotensive resuscitation aim at keeping the blood pressure low enough while maintaining perfusion of end organ.

13. Hypotensive Resuscitation
Walter Cannon proposed it in 1918
“If the pressure is raised before the surgeon is ready to check any bleeding that may take place, blood that is sorely needed may be lost”
The preventive treatment of wound shock
JAMA 70:
George Higginson Professor of Physiology
Who invented the word ‘homeostasis’

14. MAP 40
MAP 80
MAP 0
By Aortotomy
MAP 40mmHg group had better survival than MAP 80mmHg group
Map 40mmHg group also had less blood loss

15. 2003
Hypotensive resuscitation improved mortality compared to traditional resuscitation

16. How about Human Studies?

17. Prospective controlled trial Single centre
Penetrating torso injury with SBP < 90mmHg
Exclude: pregnant, age <16, revised trauma score 0, fatal gunshot to head, not requiring operation
Immediate Resuscitation (309)
traditional resuscitation with crystalloid
Delayed Resuscitation (289)
Withhold IV Fluid until arrival to operative theatre VS

18. Delayed resuscitation:
Less fluid and packed cell given
Delayed resuscitation: pre op
Lower SBP
Better Hb, plt, clotting profile

19. Delayed resuscitation:
Improved survival
(62% vs 70%)
Shorter length of stay
Delayed resuscitation:
Trend of less ARDS

20. Randomized controlled trial Single centre
Trauma patient with SBP <90mmHg
Exclude: pregnant, CNS injury/ impaired consciousness, age >55, history of DM/ IHD
Target SBP > 100mmHg (55) VS Target SBP 70mmHg (55)
Titrating Crystalloid or blood product
Fluid restriction to lower BP
Until active bleeding was stopped

21. SBP VS SBP
Similar survival: 92.7%

22. Cochrane Review
Timing and volume of fluid administration for patients with bleeding (2003)
We found no evidence from randomized controlled trials for or against early or larger volume of intravenous fluid administration in uncontrolled haemorrhage.
While increasing fluids will maintain blood pressure, it may also worsen bleeding by diluting clotting factors.

23. That was 10 years ago
Few more studies published recently

24. Retrospective cohort study Single centre
Including patient with emergent damage control laparotomy
Exclude: age <18, pregnant, die on scene or during OT
Normotenive group (282) VS
Hypotensive group (108)

25. Hypotensive group: Better: Fluid: Survival:
temp, heart rate, plt, INR, fibrinogen, pH, base value, lactate
Fluid:
Less fluid given (13.9L vs 5L)
Less RBC, plasma, platelet transfusion
Survival:
24hr survival ( 97% vs 88%)
30day survival ( 86% vs 76%)

26. Ongoing study

27. Target Intra-op MAP 50mmHg Target Intra-op MAP 65mmHg Ongoing RCT
Single centre
Trauma patients with SBP <90mmHg need laparotomy or thoracotomy
Exclude: age >45, <14, pregnant, history of IHD/CVA, head injury
Minimum blood pressure to trigger further resuscitation
If spontaneously MAP higher than target, no further action
A randomized trial is under way ay Baylor University looking at permissive hypotension
Preliminary findings, published earlier this year in the Journal of Trauma, shows that targeting resuscitation to a mean arterial pressure of 50mmHg results in
reduced intraoperative red blood cell and plasma transfusion
less post operative coagulopathy
higher 24Hr survival.
Target Intra-op
MAP 50mmHg
Target Intra-op
MAP 65mmHg VS

28. Survival MAP 50mmHg had better 24hr survival
reduced transfuion requirement
Less coagulopathy

29. So Which way is correct
Consequences of aggressive fluid resuscitation and bursting the clot
Consequences of hypotension and decreased organ prefusion

30. Different Parties have different practice

31. ATLS Everyone gets 2 liters of crystalloid initially Responders
Transient responders
 rebolus or blood for ongoing bleeding
Non-responders
blood for serious ongoing bleeding

32. NICE guideline Recommendation on trauma Adults and older children
IV fluid should not be administered if radial pulse is present
250ml IV fluid should be given if pulse cannot be felt
Burns, Blast injuries, Head injuries exception to permissive hypotension

33. US Army Stop bleeding 500ml fluid if If positive response, stop fluids
No radial pulse or
Decrease mental status
If positive response, stop fluids

34. Something is still missing

35. Unsolved problems Concept of hypotensive resuscitation is clear
But the definition is not!
Different studies use different definition
SBP? MAP? Limit crystaloid? Complete withhold or titrate against target BP?

36. Unsolved problems Application in concomitant head injury patient?
Need to maintain CPP

37. Unsolved problems Application in concomitant head injury patient?
Lack of human study on this area
Animal study: Stern 2000
Swine model on uncontrolled haemorrhage and brain injury
MAP 60 vs 80
Survival: MAP 60 better and MAP 80
Similar ICP and cerebral blood flow
Draw back: no long term neurological outcome

38. Unsolved problems
Duration of hypotensive resuscitation before irreversible damage
Lack of consensus
In Dutton’s studies
Mean duration is 2.57 hour
Similar survival between 2 group

39. Difficult area for research
Heterogeneous definition of hypotensive resuscitation
Heterogeneous group of trauma patients
US: both penetrating and blunt trauma
UK: most blunt trauma and head injury
Ethical issue, difficult to recruit trauma patient
Limited paper focus on this topic

40. Conclusion
Aggressive fluid resuscitation in trauma case may not be totally beneficial
Multiple animal studies demonstrate benefits of hypotensive resuscitation
Equivocal result from human studies. Yet more recent studies demonstrate beneficial effect of hypotensive resuscitation
Different parties had different practice worldwide
Ongoing RCT may help to provide more evidence in near future

41. Thank You