Ruggero De PaulisRuggero De PaulisDipartimento di Scienze Cardiovascolari Dipartimento di Scienze Cardiovascolari

Unità di CardiochirurgiaUnità di Cardiochirurgia

European Hospital RomaEuropean Hospital Roma

Come ridurre i sanguinamenti del

paziente rivascolarizzato: il parere del

Cardiochirurgo

Il “real world” in cardiochirurgia

15-20% dei pazienti consuma più dell’80% degli emoderivati

Ferraris V, Ferraris S. Limiting excessive postoperative blood transfusion after cardiac procedures: a review. Tex Heart Inst J 1995:22:216-30.

Oltre il 50% dei pazienti non riceve alcuna trasfusione Speiss B et al Ann. Thorac Surg:2002;74:986-7

La maggiorparte delle trasfusioni in CABG avviene entro 8 ore dall’intervento

Cosgrove DM Ann Thorac Surg 1985;40(5):519-20

Emotrasfusioni ed outcomes

Mortalità post-op. ed a lungo termine Stroke, delirium IRA Sepsi Infezione del sito chirurgico Prolungata ventilazione e

permanenza in TI Ospedalizzazione Costi

Hebert PC, Wells G et al. A multicenter randomized, controlled clinical trial of transfusion requirement in critical care. N Engl J Med 1999:340:409-17

1. Fattori di rischio “patient-related”

Età avanzata (> 70 anni)

Ridotto volume ematico (anemia pre-op. o piccola BSA)

Comorbilità non cardiache (coagulopatie; insufficienza renale; diabete mellito)

Terapia pre-op. con farmaci antiaggreganti (abciximab/clopidogrel>>>ASA)

Terapia pre-operatoria

Sospendere ASA (2-3 gg prima) tranne nei pazienti con SCA

Sospendere tienopiridine (ticlopidina/clopidogrel) 5-7 gg prima. Nei DES: valutare shift con inibitori IIb/IIIa inibitori (tirofiban/abciximab)

Sospendere LMWH 12 ore prima dell’ intervento. Negli altri casi meglio eparina non frazionata ev

Ferraris VA, Ferraris SP, Moliterno DJ, et al. The Society of Thoracic Surgeons practice guideline series: aspirin and other antiplatelet agents during operative coronary revascularization (executive

summary). Ann Thorac Surg 2005;79:1454–61.

Tromboelastografia TEG®

Eparina LMWH Warfarin rFVIIa ATIII ridotta Fibrinogeno/

contributo piastrinico

Fibrinolisi

TEG® monitored patients Reduction (%)

Post-operative haemorrhage

27

Fresh Frozen Plasma 62

Platelets 28

Cryoprcipitate 94

Overall (FFP,Platelets,Cryo) 49

Incidence of re-exploration 3,9 to 0,66

Relationship between conventional tests and post-operative bleeding

827 Patients. 451 in TEG group, 376 in routine coagulation tests group

Per gentile concessione D. Colella CARACT 2009

TEG® non misura l’inibizione piastrinica!

Per gentile concessione D. Colella

ticlopidina abciximab

clopidogrel eptifibatide

Farmaci

Aspirina

Clopidogrel

I farmaci anti-piastrinici sono somministrati a un grande numero di pazienti interni ed esterni

Nella maggior parte delle cliniche non è disponibile nessun monitoraggio per questi farmaci

Prasugrel

Abciximab

Tirofiban

Test specifici

Multiplate®

TEG Platelet Mapping ®

Multiplate ® - Test ASPItest: Determinazione dell‘aspirina con utilizzo di Acido arachidonico

ADPtest: determinazione del Clopidogrel usando l‘attivatore ADP

COLtest: Analisi globale delle piastrine utilizzando come attivatore il collagene

RISTOtest: aggregazione dipendente da GpIIb e vWF utilizza la ristocetina come attivatore

TRAPtest: attivazione diretta recettori della trombina tramite peptide TRAP (thrombin receptor activating peptide)

Cyclooxygenase pathway

TxA2

Attivazione della piastrinaEsposizione di GP IIb/IIIa

Collagene TRAP-6 (Trombina)

ADP

Ristocetina

Acido Arachidonico

Vie di attivazione della Piastrine

Trombossano

Epinefrina

TEG PM (clopidogrel)

Per gentile concessione D. Colella CARACT 2009

TEG PM (aspirina)

Per gentile concessione D. Colella CARACT 2009

TEG PM (abciximab)

Per gentile concessione D. Colella CARACT 2009

Novel activator (no thrombin platelet activity; fibrin contribution only)

Thrombin (max platelet activity)

ADP/Reopro (decreased activity 81%)

2. Fattori di rischio “procedure-related”

Durata CEC Tipo di procedura

(complesse>combinati>valvolari>CABG)

Reinterventi Interventi in urgenza Ipotermia

Strategia operatoria

Off-pump” vs “On-pump”

Ottimizzare CEC- pompe centrifughe- “low-priming”- eparina/protamina- circuiti biocompatibili

Off-pumpJ Thorac Cardiovasc Surg. 2010 Feb 16Off-pump versus on-pump coronary artery bypass grafting: A systematic review and meta-analysis of propensity score analyses.

OBJECTIVE: Despite numerous randomized and nonrandomized trials on off- and on-pump coronary artery bypass grafting, it remains open which method is superior. Patient selection and small sample sizes limit the evidence from randomized trials; lack of randomization limits the evidence from nonrandomized trials. Propensity score analyses are expected to improve on at least some of these problems. We aimed to systematically review all propensity score analyses comparing off- and on-pump coronary artery bypass grafting. METHODS: Propensity score analyses comparing off- and on-pump surgery were identified from 8 bibliographic databases, citation tracking, and a free web search. Two independent reviewers abstracted data on 11 binary short-term outcomes. RESULTS: A total of 35 of 58 initially retrieved propensity score analyses were included, accounting for a total of 123,137 patients. The estimated overall odds ratio was less than 1 for all outcomes, favoring off-pump surgery. This benefit was statistically significant for mortality (odds ratio, 0.69; 95% confidence interval, 0.60-0.75), stroke, renal failure, red blood cell transfusion (P < .0001), wound infection (P < .001), prolonged ventilation (P < .01), inotropic support (P = .02), and intraaortic balloon pump support (P = .05). The odds ratios for myocardial infarction, atrial fibrillation, and reoperation for bleeding were not significant. CONCLUSION: Our systematic review and meta-analysis of propensity score analyses finds off-pump surgery superior to on-pump surgery in all of the assessed short-term outcomes. This advantage was statistically significant and clinically relevant for most outcomes, especially for mortality, the most valid criterion. These results agree with previous systematic reviews of randomized and nonrandomized trials

On-pump

Eparina Consumo AT III Attivazione/inibizione

piastrine Fibrinolisi Inibizione

trombina,,IXa, Xa, XIa, XIIa

Inibizione “Tissue Factor”

HIT I; HIT II

Protamina Piastrinopenia

Inibizione recettori piastrinici

Fibrinolisi

Alterazioni emodinamiche

Hirsh J. Heparin. N Engl J Med 1998Harrow J. Protamine: A review of its toxicity. Anaesth Analg, 1985

Dose-risposta eparina/protamina

Hemocron® HMS®

L’utilizzo delle nuove tecnologie nei dosaggi di eparina e protamina in CEC garantisce una

protezione del sistema coagulativo ed una riduzione del sanguinamento post-operatorio e delle

emotrasfusioni

Terapie farmacologiche

Antifibrinolitici (ev e/o topici)(ac. epsilon-aminocaproico/tranexamico)

Desmopressina Fibrinogeno Piastrine FVIIa Complesso protrombinico

(dicumarolici)

Strategie alternative

Donazione autologa pre-operatoria

Classe II livello evidenza A

Possibile in:

Pazienti elettivi (rigenerazione cellulare)

Patologia cardiaca stabile

Assenza di processi infettivi (endocardite)

Ematocrito adeguato (>33%)

Controindicata in:

Pazienti acuti SCA; SA; CHF Patologie associate (IRC)

Raramente i tempi della donazione autologa preoperatoria Raramente i tempi della donazione autologa preoperatoria sono compatibili con il timing chirurgico!sono compatibili con il timing chirurgico!

Preoperative very short-term, high-dose erythropoietin administration diminishes blood transfusion rate in off-

pump coronary artery bypass: A randomized blind controlled study

Human recombinant erythropoietin has been used to obtain a rapid increase in red blood cells before surgery. Previously, the shortest preparatory interval has been 4 days, but at the European Hospital only 2.4 days on average separate hospitalization and surgery. We therefore proposed a randomized blind trial to test the efficacy of high-dose erythropoietin for very short-term administration.

All patients presenting with a diagnosis of isolated coronary vessel disease were randomized to either erythropoietin therapy or a control group. Patients with a creatinine level greater than 2 mg/dL or hemoglobin level greater than 14.5 g/dL were excluded. Hemoglobin values were collected preoperatively and on postoperative days 1 and 4. Blood loss and blood transfusion rate were recorded at the time of discharg

We enrolled 320 consecutive patients in the study. No significant difference was found in preoperative parameters, postoperative blood loss, or mean preoperative hemoglobin levels. On postoperative day 4, mean hemoglobin was 15.5% higher in the erythropoietin group (10.70 ± 0.72 g/dL vs 9.26 ± 0.71 g/dL; P < .05). This group required 0.33 units of blood per patient, whereas the controls required 0.76 units per patient (risk ratio 0.43, P = .008).

A significant reduction in transfusion rate and a significant increase in hemoglobin values were observed in the erythropoietin group. No adverse events related to erythropoietin administration were recorded. A very short preoperative erythropoietin administration seems to be a safe and easy method to reduce the need for blood transfusions.

L. Weltert et al. Volume 139, Issue 3, Pages 621-627 (March 2010)

Recupero sangue

L’utilizzo routinario intraoperatorio di sistemi di “red cell saving” in interventi on-pump è utile per il risparmio di sangue, eccetto in pazienti con infezioni in atto o neoplasie (Classe I evidenza A)

L’utilizzo di sistemi di recupero riduce le citochine infiammatorie e limita gli eventi embolici legati a particelle lipidiche contenute nel sangue (Classe II evidenza B)

Haemonetics CardioPAT

Recupero unwashed

La reinfusione di sangue mediastinico non processato può causare severe reazioni immunomediate e sequele neurologiche

Kincaid EH, Jones TJ, Stump DA, et al. Processing scavenged blood

with a cell saver reduces cerebral lipid microembolization. Ann Thorac Surg. 2000;70:1296 –1300.

Classe III Livello di evidenza B

Clinical Practice Guideline Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery. The

Society of Thoracic Surgeons Blood Conservation Guideline Task Force. Ann Thorac Surg 2007;83:27-86

Recupero washed

L’utilizzo di sistemi di recupero riduce le citochine infiammatorie e limita gli eventi

embolici legati a particelle lipidiche contenute nel sangue

Laub GW, Dharan M, Riebman JB, et al. The impact of intraoperative autotransfusion on cardiac surgery. A prospective randomized double-blind study. Chest 1993;104:

686–9.

Clinical Practice Guideline Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery. The

Society of Thoracic Surgeons Blood Conservation Guideline Task Force. Ann Thorac Surg 2007;83:27-86

Classe II Livello di evidenza B

To you, it’s a drop of blood…

To your patients, it can represent

peace of mind.

Grazie