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Ruggero De Paulis Dipartimento di Scienze Cardiovascolari Unità di Cardiochirurgia European Hospital Roma

Come ridurre i sanguinamenti del paziente rivascolarizzato: il parere del Cardiochirurgo. Ruggero De Paulis Dipartimento di Scienze Cardiovascolari Unità di Cardiochirurgia European Hospital Roma. Il “real world” in cardiochirurgia.

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Ruggero De Paulis Dipartimento di Scienze Cardiovascolari Unità di Cardiochirurgia European Hospital Roma

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  1. Come ridurre i sanguinamenti del paziente rivascolarizzato: il parere del Cardiochirurgo Ruggero De Paulis Dipartimento di Scienze Cardiovascolari Unità di Cardiochirurgia European Hospital Roma

  2. 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

  3. 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

  4. 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)

  5. 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.

  6. Tromboelastografia TEG® • Eparina • LMWH • Warfarin • rFVIIa • ATIII ridotta • Fibrinogeno/contributo piastrinico • Fibrinolisi

  7. 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

  8. TEG® non misura l’inibizione piastrinica! ticlopidina abciximab clopidogrel eptifibatide Per gentile concessione D. Colella

  9. Farmaci Abciximab Aspirina I farmaci anti-piastrinici sono somministrati a un grande numero di pazienti interni ed esterni Nella maggior parte delle cliniche non è disponibilenessun monitoraggioper questi farmaci Clopidogrel Prasugrel Tirofiban

  10. Test specifici Multiplate® TEG Platelet Mapping ®

  11. 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)

  12. Vie di attivazione della Piastrine Collagene TRAP-6 (Trombina) ADP Trombossano Cyclooxygenase pathway Acido Arachidonico TxA2 Epinefrina Ristocetina Attivazione della piastrina Esposizione di GP IIb/IIIa

  13. TEG PM (clopidogrel) Per gentile concessione D. Colella CARACT 2009

  14. TEG PM (aspirina) Per gentile concessione D. Colella CARACT 2009

  15. TEG PM (abciximab) Thrombin (max platelet activity) ADP/Reopro (decreased activity 81%) Novel activator (no thrombin platelet activity; fibrin contribution only) Per gentile concessione D. Colella CARACT 2009

  16. 2. Fattori di rischio “procedure-related” • Durata CEC • Tipo di procedura (complesse>combinati>valvolari>CABG) • Reinterventi • Interventi in urgenza • Ipotermia

  17. Strategia operatoria • Off-pump” vs “On-pump” • Ottimizzare CEC - pompe centrifughe - “low-priming” - eparina/protamina - circuiti biocompatibili

  18. Off-pump J Thorac Cardiovasc Surg. 2010 Feb 16 Off-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

  19. On-pump Eparina Protamina Piastrinopenia Inibizione recettori piastrinici Fibrinolisi Alterazioni emodinamiche • Consumo AT III • Attivazione/inibizione piastrine • Fibrinolisi • Inibizione trombina,,IXa, Xa, XIa, XIIa • Inibizione “Tissue Factor” • HIT I; HIT II Hirsh J. Heparin. N Engl J Med 1998 Harrow J. Protamine: A review of its toxicity. Anaesth Analg, 1985

  20. 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

  21. Terapie farmacologiche

  22. Antifibrinolitici (ev e/o topici) (ac. epsilon-aminocaproico/tranexamico) • Desmopressina • Fibrinogeno • Piastrine • FVIIa • Complesso protrombinico (dicumarolici)

  23. Strategie alternative

  24. Donazione autologa pre-operatoriaClasse II livello evidenza A Possibile in: Controindicata in: Pazienti acuti SCA; SA; CHF Patologie associate (IRC) • Pazienti elettivi (rigenerazione cellulare) • Patologia cardiaca stabile • Assenza di processi infettivi (endocardite) • Ematocrito adeguato (>33%) Raramente i tempi della donazione autologa preoperatoria sono compatibili con il timing chirurgico!

  25. 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)

  26. 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) Recupero sangue Haemonetics CardioPAT

  27. Recupero unwashed Classe III Livello di evidenza B 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. 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

  28. Recupero washed Classe II Livello di evidenza B 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

  29. To you, it’s a drop of blood… To your patients, it can represent peace of mind.

  30. Grazie

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