Traumatic Hemorrhagic Shock - An Update

Trauma&c Hemorrhagic Shock – An Update

KS Chew School of Medical Sciences

Universi& Sains Malaysia

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?

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.

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

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



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

•  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.

Randomized paramedics rather than pa1ents

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

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.

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

Colloids vs Crystalloids in Trauma Fluid Resuscita&on?

Favorable Unfavorable

Physiological

Crystalloids Familiar, experience in usage

Poor plasma expander (e.g. 40 ml plasma expansion per 500 ml NS)

Minimal side effects or drug interac&ons

Inters&&al expansion, worsen lung oxygena&on

Large volume of NS cause hyperchloremic NAGMA

Colloids Onco&c pressure >30 mOsm/l

Coagulopathy

Good plasma expander Reduced renal excre&on in renal impaired pa&ents

Low risk of inters&&al edema

Anaphylaxis/allergic reac&on

Administra1on/cost

Crystalloid Cheap; usually no max dose

Colloids Up to 50 &mes cost; dose depends on types & BW

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.

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.

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.

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

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

Shock

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.

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

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


•  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.


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Traumatic Hemorrhagic Shock - An Update

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