The ESA guidelines on management

of severe perioperative bleeding

Daniela Filipescu, MD, PhD, DEAA

Associate Professor of Associate Professor of AnaesthesiaAnaesthesia & Intensive Care Medicine& Intensive Care Medicine

Department of Cardiac Department of Cardiac AnaesthesiaAnaesthesia & Intensive Care Medicine& Intensive Care Medicine

Emergency Institute for Cardiovascular DiseasesEmergency Institute for Cardiovascular Diseases

Bucharest, RomaniaBucharest, Romania

Conflicts of interest

Honoraria for lecturing and travel reimbursement from:

Abbott, Bayer, B. Braun, Edwards, GlaxoSmithKline, Medtronic,

Fresenius Kabi, MSD, Novo Nordisk, Pfizer, Sanofi-Aventis,

Schering AG, Servier and Vifor Pharma.

Co-author of the trauma bleeding management guidelines which

were supported by unrestricted grants from CSL Behring

(Germany) and LFB Biomedicaments (France).

PlateletPlatelet

dysfunctiondysfunction

ThrombocytopeniaThrombocytopeniaBasic Basic conditioncondition

• Pharmacologically induced• Mechanical defragmentation• Renal insufficiency• Hepatic insufficiency • Dilution

• Sepsis• Consumption• HIT

Perioperative coagulopathy

Modified from: Meybohm P et al. JL Vincent ICU YearBook 2013;397

ThrombocytopeniaThrombocytopenia

Plasma Plasma coagulation coagulation

systemsystemHyperfibrinolysisHyperfibrinolysis

conditioncondition• Acidosis• Hypothermia• Hypocalcaemia

• Dilution, activation and consumption of factors

• DIC• Massive transfusion• Vitamin K deficiency• Anticoagulatory therapy

• Meta-analysis of observational studies

• 45 studies - 272,596 patients

• Included surgical (trauma, general, ortho, neuro, and cardiac) and general ICU patientscardiac) and general ICU patients

• Multivariate analysis correcting for age and illness severity

• 42 of 45 studies: risks outweighed benefits of transfusion; risk neutral in 2 studies

• Transfusion is an independent risk factor for increased:

– Mortality

– Infection

– Multi-organ dysfunction

– ARDS Crit Care Med 2008;36(9):2667-74

mortality

Risk of transfusion in

general surgery

Bernard AC et al. J Am Coll Surg 2009;208:931-937

morbidity

To assess the mounting evidence in support of restrictive transfusion strategies as being not only safe but also potentially beneficial in terms of mortality, morbidity, postoperative outcomes and long term survival in both cardiac and non-cardiac surgery patients.

Urgent need

Primum non nocere

Guidelines

Aim of these guidelines

“To provide an up-to-date review and synthesis of the evidence, with recommendations which may guide anaesthesiologists throughout Europe towards safe and cost effective strategies for throughout Europe towards safe and cost effective strategies for minimising severe non-traumatic perioperative bleeding and maximising blood conservation’’

ESA ENDORSEMENTESA ENDORSEMENT

Methodology

The Guidelines Committee of the European Society of Anaesthesiology formed a task force with members of scientific subcommittees and individual expert members of scientific subcommittees and individual expert members of the ESA.

Subcommittee Transfusion and HaemostasisSubcommittee Intensive care medicineSubcommittee CirculationSubcommittee Resuscitation and Emergency MedicineSubcommittee Evidence based practiceCopenhagen Trial Unit and Cochrane Anaesthesia Review Group

Task-force members

Austria

Belgium

DenmarkDenmark

France

Germany

Italy

Romania

Spain

UK

The process

Defining the key clinical questions: October 2010

Electronic databases searched: 2000 until 2012

Relevant systematic reviews with meta-analyses, randomized controlled trials, cohort studies, case-control studies and cross-sectional surveyssectional surveys

20.644 abstracts 1.466 references

Initial manuscript of 98 000 words in length reduced by 46% in May 2012

354 manuscript pages + 248 key messages

Grading system

The Scottish Intercollegiate Guidelines Network (SIGN)

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system

GRADEChest 2012;141;53S-70S

Decide on the direction (for/against) and grade strength (strong/weak)of the recommendation considering:

Quality of the evidenceQuality of the evidenceBalance of desirable/undesirable outcomes

Values and preferencesDecide if any revision of direction or strength is necessary considering: Resource use

The process

The final draft guideline was posted on the ESA website for four

weeks and the link was sent to all ESA members.

Comments were collated and the guidelines amended as appropriate. Comments were collated and the guidelines amended as appropriate.

Consensus meeting of the task-force on 23.11.2012

When the final draft was complete, the Guidelines Committee and

ESA Board ratified the guidelines.

Evidence-based guidance written by clinicians for clinicians!

NO

Funding

NO honoraria, company sponsoring, medical writing support

Systematic evidence search 2000-2012 by co-author from Cochrane Anaesthesia Review Group, funded by the ESA Editorial assistance funded by ŐGARI

���� Coagulation monitoring

���� Anemia managementanemia correction, optimization of macro and micro circulation, blood

product transfusion

Main chapters

���� Coagulation management

���� Multimodal approach in specific clinical fieldscardiovascular surgery, gynecology & obstetrics, orthopedic

surgery & neurosurgery, visceral & transplant surgery, pediatric surgery

���� Anticoagulant & anti-platelet therapy

���� Management in congenital bleeding disorders

1) pre-operative identification of bleeding risksanamnesis & laboratory testing

2) peri-operative optimization and tolerance of bleeding

Key areas

2) peri-operative optimization and tolerance of bleedingpre-operative anemia correction, stabilization of macro-& microcirculation

3) targeted pro-coagulant intervention to reduce bleedingmulti-modal approach in various clinical settings

We recommend the use of a structured patient interview or

questionnaire before surgery or invasive procedures, which

considers clinical and family bleeding history and detailed

information on patients’ medication

Assessment of potential

bleeding risk

1C

We recommend the use of standardised questionnaires on

bleeding and drug history as preferable to the routine use of

conventional coagulation screening tests such as aPTT, PT and

platelet count in elective surgery

1C

Epistaxis Oral cavity Surgery Muscle haematoma

Cutaneous GI bleeding Menorrhagia Haemarthrosis

Example of a quantitative questionnaire

Modified from Tosetto A et al. J Thromb Haemost 2011:1143-1148

Cutaneous GI bleeding Menorrhagia Haemarthrosis

Bleeding from Tooth extraction Post-partum CNS bleeding minor wounds hemorrhage

We recommend that patients at risk for bleeding are

assessed for anaemia 4–8 weeks before surgery

1C

Pre-operative assessment of anemia

If anaemia is present, we recommend

identifying the cause (iron deficiency,

renal deficiency or inflammation)

1C

Goodnough & Shander Anaesth and Analg 2013

Proposed algorithm for the detection,

evaluation, and management of preoperative anaemia

Goodnough L T et al. Br. J. Anaesth. 2011;106:13-22

We recommend treating iron deficiency with iron

supplementation (oral or intravenous)

1B

If iron deficiency has been ruled out, we suggest treating

Pre-operative correction of anemia

If iron deficiency has been ruled out, we suggest treating

anaemic patients with erythropoietin-stimulating agents

2A

We recommend that aspirin therapy should continue perioperatively in most surgical settings, especially in cardiac surgery

1C

Clopidogrel increases perioperative bleeding. In cases of

Antiplatelet therapy

Clopidogrel increases perioperative bleeding. In cases of increased bleeding risk, we recommend that it should be withdrawn for no more than 5 days.

1C

We recommend postponement of elective surgery followingcoronary stenting (at least 6 to 12 weeks for bare metal stent and one year for drug-eluting stents).

1C

Antiplatelet therapy

We recommend that a multidisciplinary team meeting should decide on the perioperative use of antiplatelet agents in urgent and semi-urgent surgery.

1C

Intra-operative strategy

Let’s just start cutting and see what happens

We recommend against the use central venous pressure and

pulmonary artery occlusion pressure as the only variables to guide

fluid therapy and to optimise preload during severe bleeding;

dynamic assessment of fluid responsiveness and non-invasive

Optimizing macro-circulation

measurement of cardiac output should be considered instead

1B

We recommend repeated measurements of a combination of

Ht/Hb, serum lactate, and base deficit in order to monitor

tissue perfusion, tissue oxygenation and the dynamics of blood

Monitoring tissue perfusion

loss during acute bleeding. These parameters can be extended

by measurement of cardiac output, dynamic parameters of

volume status and central venous saturation

1C

We recommend a restrictive transfusion strategy which is

beneficial in reducing exposure to allogeneic blood products

1A

Transfusion

Avoiding transfusion is a skill

We recommend a target haemoglobin concentration

of 7–9 g dl–1 during active bleeding

1C

Red blood cells

1C

We recommend that RBCs up to 42 days of age be transfused

according to the first-in-first-out method in the blood services

to minimise wastage of erythrocytes

1C

We recommend against the use of FFP for pre-proceduralcorrection of mild to moderately elevated INR.

1C

Fresh frozen plasma

We suggest that FFP may be used if no other fibrinogen

source is available.

2C

We suggest that the indication for cryoprecipitate is lack of available fibrinogen concentrate for the treatment of bleeding and hypofibrinogenaemia

Cryoprecipitate

and hypofibrinogenaemia

2C

We suggest that transfusion of platelet concentrates maybe considered if platelet count is <50 000–100 000 ml–1 .

2C

Platelets

For intra- or postoperative bleeding clearly related to aspirin, we suggest that platelet transfusion be considered (dose: 0.7x1011

[i.e. two standard concentrates] per 7 kg body weight in adults).

2C

We recommend that all countries implement national

haemovigilance quality systems

1C

We recommend that blood services implement standard

Optimal blood use

We recommend that blood services implement standard operating procedures for patient identification and that staff be trained in early recognition of, and prompt response to, transfusion reactions

1C

We recommend that multiparous women be excluded from donating blood for the preparation of FFP and for the suspension of platelets in order to reduce the incidence of TRALI

1C

Optimal blood use

Immunological complications

1C

We recommend that labile blood components used for transfusion

are leuko-depleted

1B

We recommend the application of transfusion algorithms

incorporating predefined intervention triggers to guide haemostatic

intervention during intra-operative bleeding

1B

Algorithms & triggers

1B

We recommend the application of transfusion algorithms

incorporating predefined intervention triggers based on POC

coagulation monitoring assays (thrombelastography or thromboelastometry)

to guide haemostatic intervention

during cardiovascular surgery

1C

Coagulation management

We recommend maintaining perioperative normothermia as it reduces blood loss and transfusion requirements

1BWhile pH correction alone cannot immediately correct acidosis-induced coagulopathy, we recommend that pH correction be

Correction of confounding factors

induced coagulopathy, we recommend that pH correction be pursued during treatment of acidotic coagulopathy

1CWe suggest that calcium be administered during massive transfusion if Ca2+ levels are low, in order to preserve normocalcaemia (≥0.9 mmol/L)

2B

We recommend the consideration of tranexamic acid (20–25 mg kg–1)

1A

Tranexamic acid

We suggest administering tranexamic acid in total hip arthroplasty, total knee arthroplasty, and major spine surgery.

2A

• 252 RCTs

• Over 25,000 participantsparticipants

• Type of surgery

Cardiac 173

Orthopedic 53

Liver 14

Vascular 5

Thoracic 4

Henry DA, et al. Cochrane Database of Systematic Reviews 2011

Vascular and death event in hip

fracture

• 110 pts. operated in less than 48 hours after injury

• TXA 15 mg/kg x 2• TXA 15 mg/kg x 2

• 6 weeks follow up

• No symptomatic venous thrombosis or pulmonary embolism

• A non-significant but three fold increased risk of vascular events with the use of TXA when compared with placebo

1 asymptomatic proximal DVT, 4 asymptomatic distal DVTs,

3 acute coronary syndromes , 1 stroke, 1 death.

We recommend treatment with fibrinogen concentrate if significant bleeding is accompanied by at least suspected low fibrinogen levels or function

1C

Fibrinogen concentrate

1C

We recommend plasma fibrinogen level <1.5–2.0 g l–1 or ROTEM/TEG signs of functional fibrinogen deficit as triggers for fibrinogen substitution

1C

We suggest an initial fibrinogen concentrate dose of 25-50 mg kg–1

2C

We recommend that patients on oral anti-coagulant therapy be given PCC and vitamin K before any other coagulation management steps for severe perioperative bleeding

1B

Prothrombin complex

concentrate (PCC)

1B

We suggest that PCC (20–30 IU kgBW–1) can also be administered to patients not on oral anti-coagulant therapy, in case of elevated bleeding tendency and prolonged clotting time. Prolonged INR/PT alone is not an indication for PCC, especially in critically ill patients

2C

We suggest that off-label administration of rFVIIa can be considered for bleeding that cannot be stopped by conventional, surgical or interventional radiological means and/or when comprehensive coagulation therapy fails

2C

Recombinant activated FVII

2C

35 RCTs, mixt surgical and medical

Multimodal approach in

specific clinical fields

���� Systematically developed statements���� May be adopted, modified or rejected���� Cannot guarantee prevention of adverse outcome���� May improve risk stratification and quality of care

Summary

���� May improve risk stratification and quality of care���� Subject to revision���� Require dissemination & implementation

Stand back and lookat the Big Picture !

Traditional way of replacement

therapy in severe bleeding

Paradigm shift: goal-directed therapy?

3,865 pts.

High risk of

bleeding or bleeding or

clinically

relevant

diffuse

bleeding

after

protamine

Haemostatic therapy algorithms with POC testing reduced:

1. the number transfused units of RBC, FFP, PC

2. complications

3. costs of therapy

A Prospective, Randomized Clinical Trial of Efficacy in Coagulopathic Cardiac Surgery Patients

Weber C et al. Anesthesiology 2012

First study showingimproved survival !

But under powered !!

Triple bundle

• the use of point-of-care methods

• algorithms

Paradigm shift: bundle therapy?

• algorithms

• using single factor compounds

Individualized, goal-directed coagulation

management

Meybohm P et al. JL Vincent ICU YearBook 2013;397

Spahn DR. J Cariothorac Vasc Anesth. 2013:S16

Risk versus benefitRisk versus benefit

ThrombosisThrombosisThrombosisThrombosis

BleedingBleeding

TransfusionTransfusion

• Smart phone application

• Translations

• Collaboration

• Update in 2015…

Never ending educational effortNever ending educational effort

Creation and implementation of

institutional algorithms

Regular assessment of adherence to

them

Follow up of the patients for long

term outcomes

We welcome you to

ESA Autumn meeting ESA Autumn meeting

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