Management of Massive Bleeding in the ICU

Ibrahim Al-Sanouri, MD, FCCP, FAAAAI

Definition Complications of massive transfusion:

coagulopathy. Therapy goals Haemostatic resuscitation Introduction of Massive Transfusion

(MMT) protocol and RBC:FFP:Plts ratio.

Key Discussion Points

Bleeding in the ICU Bleeding in the ICU: massive or not massive. Mucosal or several. Immediate or delayed. GI bleed, Trauma or post surgical intervention Massive blood transfusion: control the source

Definition of Massive Transfusion

Importance of Massive Transfusion

39% of trauma related deaths – uncontrollable bleeding

(Leading cause of preventable death)

2% of trauma patients – need massive transfusion Bleeding 2 main causes1. Vascular injury (surgical)2. Coagulopathy (non-surgical)

Massive Blood Transfusion complications

Fluid overload Thrombocytopnea Hypocalcemia Decreased oxygen release by transfused

red cells due to 2,3-bisphosphoglycerate (2,3-BPG) levels (left shift in Hg-O2 curve).

Hypothermia

Coagulopathy in massive bleeding:

Haemorrhage

Hypotension

Resuscitation

Haemodilution

CoagulopathyHypothermia

Complications of massive transfusion

Massive Blood Transfusion Management

Haemostatic Resuscitation Fluid management Metabolic acid base correction Normal temperature Calcium management

Therapeutic goals:

Maintenance of tissue perfusion and oxygenation by restoration of blood volume and haemoglobin.

Arrest of bleeding by treating any traumatic, surgical or obstetric source

Judicious use of blood component therapy to correct coagulopathy

Massive bleeding management

1-Restore circulating volume:

Insert wide bore peripheral or central cannulae Give pre-warmed crystalloid or colloid as

needed, keep patient warm. Avoid hypotension or urine output <0.5 ml/kg/h Concealed blood loss is often underestimated

2- Contact key personnel

A named senior person must take responsibility for communication and documentation.

Consultant anaesthetist Blood transfusion Biomedical Scientist Haematologist Arrange Intensive Care Unit bed

3- Stop the bleeding:

Early surgical or obstetric intervention Interventional radiology

4-Labs investigation: CBC, PT, APTT, Thrombin time, Fibrinogen, DIC

profile. Blood gases and pulse oximetry Ensure correct sample identification Repeat tests after blood component infusion Results may be affected by colloid infusion May need to give components before results

available

5-Maintain Hb> 8 g.dl Assess degree of urgency Employ blood salvage to minimize allogeneic

blood use Give red cells Group O Rh D negative In extreme emergency

Until ABO and Rh D groups known Use blood warmer and/or rapid infusion device if

flow rate >50 ml/kg/h in adult

6- Maintain adequate coagualtion

Anticipate platelet count <50 after 2 blood volume replacement.

Maintain PT & APTT < 1.5 · mean control Give FFP 12–15 ml/kg guided by tests Anticipate need for FFP after 1–1.5 blood

volume replacement Allow for 30 min thawing time

6-Maintain adequate coagulation

Maintain Fibrinogen > 1.0 g/l If not corrected by FFP give

cryoprecipitate (Two packs of pooled cryoprecipitate for an adult)

Allow for 30 min thawing time Keep ionised Ca2+ > 1Æ13 mmol/l

7-Hospital protocol: Multidisplinary services: Hospital Transfusion

Committee. Improve awareness and confidence and

ensure that the blood transfusion chain works efficiently.

Rapid communication cascade. Safe and jusdicious use of blood components.

What is Haemostatic Resuscitation?

Prevents post massive transfusion coagulopathy.

Aims to reduce use of blood products in the intensive care phase.

With 5-7 unitis PRBC’s Plt count decreases to less than 50 %

With 5 units PRBC PT is increased to more than 1.5 control.

Haemostatic Resuscitation: RBC Erythrocytes promote marginalization of

platelets so the platelet concentrates along the endothelium and remains almost seven times that of the average blood concentration

Erythrocytes support thrombin generation by activating platelets by liberating ADP.

Oxygenation delivery.

Haemostatic Resuscitation: FFP It remains controversial when and in what

dose plasma should be transfused to massively bleeding trauma patients.

The optimal ratio of FFP to RBCs remains to be established: FFP:RBC ratio greater than 1:2 is associated with improved survival compared to one lower than 1:2.

Haemostatic Resuscitation: FFP Meta-analysis from 2010-2012: Patients

undergoing massive transfusion, high FFP to RBC ratios was associated with a significant reduction in the risk of death (odds ratio (OR) 0.38 (95%CI 0.24-0.60) and multiorgan failure (OR 0.40 (95%CI 0.26-0.60).

Murad MH, Stubbs JR, Gandhi MJ, Wang AT, Paul A, Erwin PJ, Montori VM, Roback JD: The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion 2010, 50:1370-1383

Haemostatic Resuscitation: FFP Meta-analysis from 2012 reports of

reduced mortality in trauma patients treated with the highest FFP or PLT to RBC ratios.

Johansson PI, Oliveri R, Ostrowski SR: Hemostatic resuscitation with plasma and platelets in trauma. A meta-analysis. J Emerg Trauma Shock 2012, 5:120-125.

Coagulopathy of Massive Transfusion

Mortality Vs FFP/RBC ratio Retrospective review of 246 patients

receiving a massive transfusion (> 10 units of blood)

Borgman MA. et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital J trauma, 2007. 66:805-813

Haemostatic Resuscitation: Plts Platelets are also pivotal for hemostasis: low

Plts increases mortality. The highest survival was established in

patients who received both a high PLT:RBC and a high FFP:RBC ratio.

Holcomb JB, Wade CE, Michalek JE, Chisholm GB, Zarzabal LA, Schreiber MA, Gonzalez EA, Pomper GJ, Perkins JG, Spinella PC, Williams KL, Park MS: Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg 2008, 248:447-458.

Haemostatic Resuscitation: plt Retrospective study of massively transfused

patients: As apharesis platelet to RBC ratio increased, a stepwise improvement in survival was seen and a high apheresis PLT:RBC ratio was independently associated with improved survival.

Zink KA, Sambasivan CN, et al: A high ratio of plasma and platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large multicenter study. Am J Surg 2009, 197:565-570.

Massive transfusion protocols and ratios: 10 RBC, 4 FFP and 2 apheresis PLT for trauma patients. 211 trauma patients of who 94 received TEP and 117 were historic controls. The TEP patients received more RBC (16 vs. 11), FFP (8 vs. 4), and PLT (2

vs. 1) intraoperatively than the controls. The protocol group displayed lower 30-day mortality (51% vs. 66%). After controlling for age, sex, mechanism of injury, Trauma and Injury

Severity Score (TRISS), and 24-hour blood product usage, a 74% reduction in the odds ratio of mortality was found among patients in the TEP group.

Cotton BA, Gunter OL, Isbell J, Au BK, Robertson AM, Morris JA: St Jacques P, Young PP: Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization. J Trauma 2008, 64:1177-1182.

Pre-defined Massive Transfusion Protocols are associated with REDUCTION

of organ failure and post injury complication J Trauma 2009 Jan ; 66(1) 41-48

Ratio 10-4-2: RBC-FFP-PLts

Pre-MMT (n-141) MMT (n=129) P-values

24hr survival (%) 61 69 0.185

30d survival (%) 37.637.6 56.856.8 0.0010.001

Hospital length of stay d (+/-SD)

16.4(+/-12.1) 12 (+/-12.1) 0.049

ICU stay, (days) 6.6(+/-9.4) 5.0 (+/- 8.3) 0.239

Ventilator (days) 8.2 (+/-9.7) 5.7 (+/-7.2) 0.017

IO crystalloid, Litres 7L 4.8L <0.001

IO blood products units 11U 14.7U 0.001

24hr blood products 38.7U 31.2U 0.05

Complications comparisonPre-MMT (n-

141)MMT (n=129) P-values

Systemic inflammatory response syndromeSIRS (%)

55.3 52.8 0.682

Severe sepsis/septic shock (%)

19.8 10 0.019

Ventilator-dependent respiratory failure(%)

62.4 60.8 0.787

VAP(%) 39 27.2 0.041Abdominal compartment syndrome(%)

9.9 0 <0.001

Open abdomen(%) 30.5 6.4 <0.001Need of Renal replacement therapy(%)

2.8 3.2 0.826

Pre-defined Massive Transfusion Protocols are associated with REDUCTION of organ failure and post injury complication J Trauma 2009 Jan ; 66(1) 41-48

Ratio 10-4-2: RBC-FFP-PLts

Fresh Whole Blood: Routine use of fresh whole blood (FWB) for resuscitation

of bleeding patients was abandoned in the civilian setting. In the combat setting, however, FWB has been used. In a report of US military patients in Iraq and Afghanistan

from January 2004 to October 2007, those with hemorrhagic shock, a resuscitation strategy that included FWB was associated with improved 30-day survival (95% vs. 82%, p=0.002).

Spinella PC, Perkins JG, Grathwohl KW, Beekley AC, Holcomb JB: Warm fresh whole blood is independently associated with improved survival for patients with combat-related traumatic injuries. J Trauma 2009, 66:S69-S76.

Haemostatic Agents:

Antifibrinolytis: Shakur H, et al: CRASH-2 Trial collaborators: Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant hemorrhage (CRASH-2): a randomized, placebo-controlled trial. Lancet 2010, 376:23-32.

Recombinant factor VII: Hauser CJ at al: Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage. J Trauma 2010, 69:489-500.

Fibrinogen concentrate Prothrombin complex concentrate

Hospital Alert: Active Hemorrhage SBP < 90 HR > 100 Ph < 7.35 BE < - 2 Uncontrollable active bleeding Poor responder to fluid

Activation of MMT by team leader only- Registrar or above.

Once administered check:FBC, Clotting, fibrinogen and ABG

RE-ASSESSMENTABCDE

If haemorrhage continue

Activate MMT PACK 2Please, specify location of

patient

MMT PACK 2

HAEMOSTASIS

HAEMORRHAGE CONTROL:SurgeryStabilize fracturesPelvic brace

PREVENT HYPOTHERMIA

HAEMOSTATIC DRUGS:Consider the following if bleeding persist despite surgical interventions:Activated factor VII Beriplex (consider when patient who is on anti-coagulant) Antifibrinolitic agentsPlease discuss any of these therapeutic measures with Haematologist on call)

INTRA-OPERATIVE CELL SALVAGE:Transfuse 1 x FFP every 250 ml of bloodTransfuse 1 x ATD platelets every 1000 ml of blood

2 x packs of Cryoprecipitate if Fibrinogen is < 1.0 g/l

Fail to reach targets

MANAGEMENT of MASSIVE TRANSFUSION (MMT) for TRAUMA

4 X RBC4 X FFP

1 pharased Platelets

MMT ACTIVATION For Trauma

PATIENT ARRIVALTake bloods (FBC, U&E, Clotting, fibrinogen and X-match and ABG)Send pink bottle with X-match form to blood bank urgently ( please obtain 2 samples for x-match at different time if possible)

MMT PACK 1 4 x O –ve RBC ( female) or O+ve(Male) 2 FFP

(or Group specific if possible)

THERAPY TARGET end point:

Hb: 8-10 g/dlPlatelets > 100PT&APTT (INR)< 1.5Fibrinogen > 1.0 g/lCa² > 1 mmol/l⁺pH: 7.35-7.45BE: ± 2Tª > 36 °C

Pre-hospital MMT alert:

•Systolic BP < 90•Poor response to initial fluid resuscitation•Suspected active haemorrhageIf so activate MMT (match 3 of the ocriteria)

Hospital MMT alert confirmation(patient requiring urgent transfusion)

- SBP < 90, - HR > 100- Ph < 7.35- BE < - 2- Obvious signs of uncontrollable active bleeding- Poor responder to fluid resuscitation(Trauma Team leader must declare MMT Activation to blood bank ,Co-ordinate Porter urgently to standby for Collection of MMT pack one

When MMT stopsNotify blood bank Return any unused products Resume standard ordering practices

PREVENT

HYPOTHERMI A

AC I DOS I S

COAGULOPATHY

Summery:

Immediate labs service is important to identify coagulopathy, and guide ongoing transfusion therapy.

Massive hemorrhage could results in serious life threatening complications

Massive bleeding and massive transfusion could lead to severe coagulaopthy which tight a viscous cycle that could cause mortality

Summery:

While resuscitation your patient keep patient warm with normal calcium level

Identify and correct source of bleeding. Implementation of a homeostatic control

resuscitation strategy to massively bleeding patients seems both reasonable and lifesaving.

Thank You!Questions?

Ibrahim Al-Sanouri, MD.