The document discusses fluid resuscitation strategies for trauma patients experiencing hemorrhagic shock. It summarizes several key studies that have compared immediate versus delayed fluid resuscitation and larger versus smaller volume resuscitation. However, the studies have shown mixed results and limitations. There remains uncertainty around the optimal timing and volume of fluid administration due to lack of large, high-quality randomized controlled trials in this area.

1. Trauma&c Hemorrhagic Shock –
An Update
KS Chew
School of Medical Sciences
Universi& Sains Malaysia

2. According to ATLS, shock in trauma to
be treated with fluid replacement pre‐
opera&vely
Is this consensus driven rather than
randomized controlled trials?
Concept of Low Volume Resuscita&on/
Permission Hypotension?
Early versus delayed?
Larger versus smaller volume?

3. 598 adults with
penetra&ng torso
injuries
A pre‐hospital systolic
blood pressure < or =
90 mm Hg
Assigned to either
prehospital fluid
resus or no fluid
resus (only IV
cannula) un&l reach
OR
Bickell, W. H., Wall, M. J., Jr., Pepe, P. E., Mar&n, R. R., Ginger, V. F., Allen, M. K. &
MaUox, K. L. (1994). Immediate versus delayed fluid resuscita&on for hypotensive
pa&ents with penetra&ng torso injuries. N Engl J Med, 331 (17), 1105‐9.

4. Bickell, W. H., Wall, M. J., Jr., Pepe, P. E., Mar&n, R. R., Ginger, V. F., Allen, M. K. &
MaUox, K. L. (1994). Immediate versus delayed fluid resuscita&on for hypotensive
pa&ents with penetra&ng torso injuries. N Engl J Med, 331 (17), 1105‐9.

5. Bickell, W. H., Wall, M. J., Jr., Pepe, P. E., Mar&n, R. R., Ginger, V. F., Allen, M. K. &
MaUox, K. L. (1994). Immediate versus delayed fluid resuscita&on for hypotensive
pa&ents with penetra&ng torso injuries. N Engl J Med, 331 (17), 1105‐9.

6. Permissive Hypotension?
• The study by Bickell et al, 1994 seems to
suggest that resuscita&on should be less
aggressive
• Allowing for permissive hypotension
• Decrease &me to defini&ve treatment in OR
• Decrease risk of dislodging clot forma&on
• RR death reduced by 1.26
Bickell, W. H., Wall, M. J., Jr., Pepe, P. E., Mar&n, R. R., Ginger, V. F., Allen, M. K. &
MaUox, K. L. (1994). Immediate versus delayed fluid resuscita&on for hypotensive
pa&ents with penetra&ng torso injuries. N Engl J Med, 331 (17), 1105‐9.

7. Problems
• The study by Bickell et al is only on
penetra&ng torso injuries
– Extrapola&on to include all types of trauma??
• Single ter&ary care center
• Short prehospital transport &me
• Poor randomiza&on, bias poten&al, lack of
blinding

8. • In a larger study by Turner et al in
2000 to assess early versus no/
delayed fluid resuscita&on in pre‐
hospital sejng showed
– no significant mortality difference (RR
of death = 1.07) with
– adequate randomiza&on, and
assessed both blunt and penetra&ng
trauma collec&vely
Turner, J., Nicholl, J., Webber, L., Cox, H., Dixon, S. & Yates, D. (2000). A randomised controlled
trial of prehospital intravenous fluid replacement therapy in serious trauma. Health Technol
Assess, 4 (31), 1‐57.

10. Randomized paramedics
rather than pa1ents

12. Cochrane Review
• Not able to conduct meta‐analysis or data‐
pooling because of considerable clinical and
sta&s&cal heterogeneity of available trials
• Un&l higher quality studies examining more
homogenous popula&ons and resuscita&on
strategies are produced, a clear set of
evidence‐based physiological goals for
trauma&c shock remain elusive

13. No evidence from trials to support or not to support
the use of early or larger volume intravenous fluid in
uncontrolled bleeding
“About one third of injury deaths are due to shock from blood loss.
Preven&ng shock in people with uncontrolled bleeding is, therefore,
very important and is generally done by giving fluids intravenously.
The aim is to maintain blood pressure and reduce &ssue damage.
The review of trials found that there is uncertainty about the best
&me to give fluid and what volume of fluid should be given. While
increasing fluids will maintain blood pressure, it may also worsen
bleeding by dilu&ng clojng factors in the blood. More research is
needed.”
Kwan, I., Bunn, F. & Roberts, I. (2003). Timing and
volume of fluid administra&on for pa&ents with
bleeding. Cochrane Database Syst Rev, (3),
CD002245.

14. Conclusion:
While it is clear that resuscita&on to supraphysiological
values is not necessary, resuscita&on allowing permissive
hypotension in penetra&ng trauma pa&ents cannot be
recommended with confidence

15. Colloids vs Crystalloids in
Trauma Fluid
Resuscita&on?

16. Favorable Unfavorable
Physiological
Crystalloids Familiar, experience in Poor plasma expander (e.g.
usage 40 ml plasma expansion per
500 ml NS)
Minimal side effects or drug Inters&&al expansion,
interac&ons worsen lung oxygena&on
Large volume of NS cause
hyperchloremic NAGMA
Colloids Onco&c pressure >30 Coagulopathy
mOsm/l
Good plasma expander Reduced renal excre&on in
renal impaired pa&ents
Low risk of inters&&al Anaphylaxis/allergic
edema reac&on
Administra1on/cost
Crystalloid Cheap; usually no max dose
Colloids Up to 50 &mes cost; dose
depends on types & BW

17. Use of Hypertonic Saline?
• HS 7.5% has been used in trauma&c brain injury but
with equivocal results from different studies
• Cooper, D. J., Myles, P. S., McDermoU, F. T., Murray, L. J., Laidlaw, J.,
Cooper, G., Tremayne, A. B., Bernard, S. S. & Ponsford, J. (2004).
Prehospital hypertonic saline resuscita&on of pa&ents with
hypotension and severe trauma&c brain injury: a randomized
controlled trial. JAMA, 291 (11), 1350‐7.
• Bajson, C., Andrews, P. J., Graham, C. & PeUy, T. (2005).
Randomized, controlled trial on the effect of a 20% mannitol
solu&on and a 7.5% saline/6% dextran solu&on on increased
intracranial pressure ater brain injury. Crit Care Med, 33 (1),
196‐202; discussion 257‐8.

18. Hypertonic (7.5%) Saline
Theore&cal benefits Reduced need to carry large fluid volumes (in disaster, developing
na&on, war, etc)
Reduced need for blood donors
Reduced need for refrigera&on (e.g. in disasters)
Reduced &me required to infuse volume (e.g. in war, disasters,
etc)
Clinical Data Decreased inters&&al edema and intracranial pressure
Increases plasma volume up to 10 &mes the equivalent volume of
NS
Trends towards improved survival in hemorrhagic shock
Poten&al side effects Hyperosmolarity, hypernatremia, central pon&ne myelinolysis
Vassar, M. J., Fischer, R. P., O'Brien, P. E., Bachulis, B. L., Chambers, J. A., Hoyt, D. B. & Holcrot, J.
W. (1993). A mul&center trial for resuscita&on of injured pa&ents with 7.5% sodium chloride.
The effect of added dextran 70. The Mul&center Group for the Study of Hypertonic Saline in
Trauma Pa&ents. Arch Surg, 128 (9), 1003‐11; discussion 1011‐3.

19. Use of Hypertonic Saline?
• A meta‐analysis compared HS vs NS in 230
pa&ents with hemorrhagic shock following
penetra&ng torso trauma
• Found a non‐significant trends towards
improved survival in HS (HS = 82.5%, NS =
75.5%, p=0.19)
• Among those requiring surgery, improved
survival in HS group (HS = 84.5% vs NS = 0.01)
Wade, C. E., Grady, J. J. & Kramer, G. C. (2003). Efficacy of hypertonic saline dextran fluid
resuscita&on for pa&ents with hypotension from penetra&ng trauma. J Trauma, 54 (5 Suppl),
S144‐8.

20. Conclusion
• While evidence seems to
suggest that HS is not
harmful, and may have
large applica&on in a
variety of clinical
situa&ons, there is s&ll
lack of larger clinical
studies

21. The Use of Recombinant Ac&vated
Factor VII in Trauma&c Hemorrhagic
Shock

22. When the vessel wall is disrupted, subendothelial &ssue factor becomes exposed to circula&ng blood and
may bind factor VIIa (Panel A). This binding ac&vates factor X, and ac&vated factor X (factor Xa) generates
small amounts of thrombin. The thrombin (factor IIa) in turn ac&vates platelets and factors V and VIII.
Ac&vated platelets bind circula&ng factor VIIa (Panel B), resul&ng in further factor Xa genera&on as well as
ac&va&on of factor IX. Ac&vated factor IX (factor IXa) (with its cofactor VIIIa) yields addi&onal factor Xa. The
complex of factor Xa and its cofactor Va then converts prothrombin (factor II) into thrombin (factor IIa) in
amounts that are sufficient to induce the conversion of fibrinogen to fibrin.

23. Recombinant ac&vated Factor VII
• Binds to exposed &ssue factor to create a
thrombin burst
• Risk of thomboembolic events – myocardial
infarc&on, cerebral infarc&on, etc due to &ssue
factor exposure at sites other than &ssue
injury (e.g. unstable coronary plaques)
• Not for first line treatment – only as an
adjunct

24. Recombinant ac&vated Factor VII
Target for:
• Hematocrit >24%
• Platelets >50,000 * 109/L
• Fibrinogen >0.5 – 1.0 g/l
• Not to forget – address the lethal triad of
trauma: coagulopathy, acidosis and
hypothermia

25. Recombinant ac&vated Factor VII
• The focus of recombinant ac&vated factor VII
is to reduce the need for blood products
rather than &me to bleeding cessa&on
• No consistent mortality benefit has yet been
shown
• Its volume of distribu&on and clearance is
variable; therefore op&mal dosing unclear
(range 40 mcg/kg – 200 mcg/kg)
Spahn, D. R., Cerny, V., Coats, T. J., Duranteau, J., Fernandez‐Mondejar, E., Gordini, G., Stahel, P.
F., Hunt, B. J., Komadina, R., Neugebauer, E., Ozier, Y., Riddez, L., Schultz, A., Vincent, J. L. &
Rossaint, R. (2007). Management of bleeding following major trauma: a European guideline. Crit
Care, 11 (1), R17.

26. Ques&ons and Answers