Haemostatic resuscitation

Reviewed and revised 5 August 2015

OVERVIEW

• Haemostatic resuscitation is a key component of damage control resuscitation and forms the basis of most massive transfusion protocols
• involves resuscitation with blood components resembling whole blood
• aims to avoid or ameliorate acute coagulopathy of trauma and the complications of aggressive crystalloid fluid resuscitation while maintaining circulating volume
• damage control resuscitation is an approach to major trauma that integrates permissive hypotension, haemostatic resuscitation and damage control surgery

TRADITIONAL APPROACH

Past management practices for haemorrhagic shock involved:

• aggressive fluid resuscitation with crystalloid solutions
• aiming to achieve and maintain a near normal blood pressure

Unfortunately this lead to following complications occurring:

• Oedema, compartment syndrome and acute lung injury
• Exacerbation of anaemia, thrombocytopenia and coagulopathy due to haemodilution (‘dilutional coagulopathy’)
• Exacerbation of bleeding due to possible clot disruption

HAEMOSTATIC RESUSCITATION APPROACH

Provides resuscitation with blood components resembling whole blood with the aims of

• maintain circulating volume
• limit ongoing bleeding, and
• prevent the lethal trial of hypothermia, acidosis and acute coagulopathy of trauma

Typical triggers are:

• expected or actual haemorrhagic shock
• 4 PRBCs administered and instability persists

Involves blood component ratios of 1 or 2 RBCs : 1 FFP : 1 platelets

• Rick Dutton freely admits that he made up the ratio of 1:1:1 (!)  based in the rationale that it mimics the composition of whole blood
• Australian National Guidelines advocates this strategy:
  — 2:1:1 ratio
  — consider tranexamic acid 1g IV over 10 minutes then 1g IV over 8 hours
  — consider cryoprecipitate
  — achieve this ratio within 6 hours
• Frequent patient reassessment and coagulation tests are used to guide ongoing therapy

Other agents may be given based on blood tests:

• INR >1.5 -> FFP
• Hb <100 in an actively bleeding -> PRBCs
• Calcium <0.8 -> calcium gluconate
• Platelets <80 -> platelets
• platelet dysfunction (e.g. drugs, urea) -> DDAVP +/- platelets

Some centers use viscoelastic haemostatic assays (TEG/ROTEM) to guide the administration if additional blood products and therapies such as tranexamic acid.

RATIONALE

Correct hypothermia

• Decreases platelet responsiveness
• Increases platelet sequestration in liver and spleen
• Reduces Factor function eg Factors XI and XII
• Alters fibrinolysis

Correct acidosis

• pH strongly effects activity of Factors V, VIIa and X
• Acidosis inhibits thrombin generation
• Cardiovascular effects of acidosis (pH <7.2) – decreased contractility and CO, vasodilatation and hypotension, bradycardia and increased dysrhythmias

Treat coagulopathy early and aggressively

• Many coagulopathic changes occur early after trauma, therefore need to correct early
• Use much higher FFP to PRBC ratios (1:1/2:3) than previously used. Is associated with improved survival
• Higher platelet to PRBC transfusion ratios also becoming more popular but evidence is less clear
• Cryoprecipitate provides an additional option for Factor replacement for a lower volume of fluid, supported by MATTERS2 study
• rFVIIa has been used in trauma, but off label and anecdotally

The use of blood products instead of isotonic crystalloid fluid aiming for limited volume replacement

• Large volume crystalloids can lead to dilutional coagulopathy and exacerbate bleeding.
• Crystalloids have no O2 carrying capacity and do little to correct the anaerobic metabolism and O2 debt associated with shock.
• Need less volume of blood product therefore likely to be less tissue and organ (e.g. lung, small intestine mucosa) oedema and failure (eg pulmonary oedema, abdominal compartment syndrome)
• Hypertonic saline is another option (proven restored microvascular flow, decreased tissue oedema, attenuated inflammatory response)

EVIDENCE

• There is no RCT evidence for RBC:FFP:platelet ratios of 1-2:1:1 versus other ratios/ fluids
• Haemostatic resuscitation with higher ratios of FPP and platelets to RBCs is supported by numerous observational studies. Much of this evidence is primarily from the military setting, although the multi-center hospital-based observational PROMMTT study had similar findings. A criticism of many of these studies is that they may be affected by ‘survivor bias’ (i.e. patients that live long enough, have greater opportunity to receive blood products, and are thus more likely to achieve the required ratio)
• Tranexamic acid use is supported by the CRASH2 trial, a multicenter international RCT which showed a mortality benefit if given to major trauma patients within 3 hours of injury. Some question the external validity of the study in ‘first world’ centers with well developed trauma systems; the PATCH trial is underway to assess the utility of tranexamic acid in this setting.
• The MATTERS study (a retrospective observational study in a military setting) also favoured use of tranexamic acid. The MATTERS2 study (another retrospective observational study in a military setting) found that decreased mortality was independently associated with tranexamic acid and cryoprecipitate use.
• The PROPPR trial (2015) found no statistically significant mortality difference on the primary outcome of mortality between massive transfusion protocols based on 1:1:1 and 2:1:1 ratios. There was an absolute difference in mortality of about 4% favouring the 1:1:1 ratio, but the study was not powered to detect this. A post-hoc secondary outcome of death by exsanguination in the first 24 hours also favoured the 1:1:1 ratio. The trial was a pragmatic unblinded outcome and neither arm of the trial managed to achieve the intended blood product ratios, though there was clear separation between the 2 groups.

VIDEO

Hemostatic Resuscitation by Richard Dutton, MD by Richard Dutton:

References and Links

LITFL

• CCC — Permissive hypotension
• CCC — Major haemorrhage in trauma
• CCC — Damage control surgery and damage control resuscitation

Journal articles and Textbooks

• Cole E, Davenport R, Willett K, Brohi K. Tranexamic acid use in severely injured civilian patients and the effects on outcomes: a prospective cohort study. Ann Surg. 2015;261:(2)390-4. [pubmed]
• Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313:(5)471-82. [pubmed] [Free Full Text]
• Holcomb JB, del Junco DJ, Fox EE, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg. 2013;148:(2)127-36. [pubmed]
• Ker K, Roberts I, Shakur H, Coats TJ. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev. 2015;5:CD004896. [pubmed]
• Roberts I, Prieto-Merino D. Applying results from clinical trials: tranexamic acid in trauma patients. J Intensive Care. 2014;2:(1)56. [pubmed]
• Roberts I, Perel P, Prieto-Merino D, et al. Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial. BMJ. 2012;345:e5839. [pubmed]
• Roberts I, Prieto-Merino D, Manno D. Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial. Crit Care. 2014;18:(6)685. [pubmed]
• Shakur H, Roberts I, Bautista R, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376: 23-32. [pubmed]
• Spahn DR, Bouillon B, Cerny V, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013;17:(2)R76. [pubmed]

FOAM and web resources

• Broome Docs — Managing Traumatic bleeding: how can we apply the evidence in smaller hospitals? (2011)
• EMCrit Lecture: Haemostatic Resuscitation by Richard Dutton (2011)
• EMCrit Podcast 30 – Haemorrhagic Shock Resuscitation (2010)
• EMCrit Podcast 67 – Tranexamic Acid (TXA), Crash 2, & Pragmatism with Tim Coats (2011)
• EMCrit Podcast 144 – The PROPPR trial with John Holcomb (2015)
• Resus.ME — Battlefield Resuscitation (2012)
• Resus.ME — Plasma: Red cell ratios (survivor bias) (2011)
• SGEM — SGEM#80: CRASH-2 (Classic Paper) (2014)
• St Emlyns — JC: Getting the Balance Right: The PROPPR Trial (2015)
• The Bottom Line — PROPPR (2015)