Carlo Marcucci

Comparison of porcine and human coagulation by thrombelastometry

INTRODUCTION Although the pig is a standard model for the evaluation of various diseases in humans, including coagulopathy, it is not clear whether results in animals can be extrapolated to man. MATERIALS AND METHODS In 75 anesthetized pigs, we assessed reagent-supported thrombelastometry (ExTEM®), platelet-blocked thrombelastometry (FibTEM®), and aprotinin thrombelastometry (ApTEM®). Results were compared to values from 13 anesthetized humans. RESULTS (MEDIAN, 95% CI): ExTEM®: While clot strength was comparable in pigs (66 mm, 65-67 mm) and in humans (64 mm, 60-68 mm; NS), clotting time in animals was longer (pigs 64 s, 62-66 s; humans 55 s, 49-71 s; P<0.05) and clot formation time shorter (pigs 52 s, 49-54 s; humans 83 s, 67-98 s, P<0.001). The clot lysis index at 30 minutes was lower in animals (96.9%, 95.1-97.3%) than in humans (99.5%, 98.6-99.9%; P<0.001). ApTEM® showed no hyperfibrinolysis in animals. Modification of the anesthesia protocol in animals resulted in significant ExTEM® changes. FibTEM®: Complete platelet inhibition yielded significantly higher platelet contribution to clot strength in pigs (79%, 76-81%) than in humans (73%, 71-77%; P<0.05), whereas fibrinogen contribution to clot strength was higher in humans (27%, 24-29%) than in animals (21%, 19-24%; P<0.05). CONCLUSIONS Maximum clot firmness is comparable in human and porcine blood. However, clot lysis, platelet and fibrinogen contribution to clot strength, as well as initiation and propagation of clotting, are considerably different between pigs and humans. In addition, anesthesic drugs seem to influence thrombelastometry in animals. Accordingly, coagulation abnormalities in pigs subjected to diseases may not necessarily represent the coagulation profile in sick patients.

Validation of rotational thromboelastometry during cardiopulmonary bypass A prospective, observational in-vivo study

BACKGROUND Rotational thromboelastometry (ROTEM) is a whole blood point-of-test used to assess the patients coagulation status. Three of the available ROTEM tests are EXTEM, INTEM and HEPTEM. In the latter, heparinase added to the INTEM reagent inactivates heparin to reveal residual heparin effect. Performing ROTEM analysis during cardiopulmonary bypass (CPB) might allow the anaesthesiologist to anticipate the need for blood products. OBJECTIVE The goal of this study was to validate ROTEM analysis in the presence of very high heparin concentrations during CPB. DESIGN Prospective, observational trial. SETTING Single University Hospital. PARTICIPANTS Twenty patients undergoing coronary artery bypass grafting. MAIN OUTCOME MEASURE ROTEM analysis was performed before heparin administration (T0), 10 min after heparin (T1), at the end of CPB (T2) and 10 min after protamine (T3). The following tests were performed: EXTEM, INTEM, and HEPTEM. Heparin concentrations were measured at T1 and at the end of bypass (T2). RESULTS At T1, EXTEM differed from baseline for coagulation time: +26.7 s (18.4 to 34.9, P < 0.0001), &agr;: −3° (1.0 to 5.4, P = 0.006) and A10: −4.4 mm (2.3 to 6.5, P = 0.0004). INTEM at T0 was different from HEPTEM at T1 for coagulation time: + 47 s (34.3 to 59.6, P >0.0001), A10: −2.3 mm (0.5 to 4.0, P = 0.01) and &agr; −2° (1.0 to 3.0; P = 0.0007). At T2, all parameters in EXTEM and HEPTEM related to fibrin-platelet interaction deteriorated significantly compared to T1. At T3, EXTEM and INTEM were comparable to EXTEM and HEPTEM at T2. CONCLUSION HEPTEM and EXTEM measurements are valid in the presence of very high heparin concentrations and can be performed before protamine administration in patients undergoing cardiac surgery with CPB. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01455454.

Urgent reoperative transapical valve-in-valve shortly after a transapical aortic valve implantation

Urgent reoperative transapical aortic valve-in-valve has never been proposed as a treatment option in case of a failed transcatheter aortic valve implantation (TAVI) or in case of worsening of an existing paravalvular leak, if this complication occurs right after, or a few days after, the primary transapical aortic valve implantation. Experienced surgeons should argue that after a transapical TAVI, the apex is damaged and fragile, with a high risk of irreparable ventricular tears and life-threatening bleeding if a second transapical procedure is scheduled during the acute phase. Nevertheless, if the patient is inoperable and the vascular status, including the ascending aorta, limits alternative accesses, the urgent reoperative transapical valve-in-valve becomes an alternative. We illustrate, for the first time ever, our experience with an 81-year old female patient who underwent a transapical (TA) TAVI with a Sapien XT 23 mm. The day after the procedure, the patient haemodynamically worsened in combination with a worsening of a known (grade 1-2) paravalvular leak. Thus, on postoperative day two, an urgent transapical valve-in-valve was performed, and a second Sapien XT 23 mm was placed, with an excellent haemodynamic result and absence of leak. The redo apical access did not appear very complicated and the postoperative recovery was uneventful.

The influence of drugs used in cardiac anaesthesia and critical care on multiple electrode aggregometry: an in-vitro volunteer study.

BACKGROUND Multiple electrode aggregometry (MEA) is a point-of-care test evaluating platelet function and the efficacy of platelet inhibitors. In MEA, electrical impedance of whole blood is measured after addition of a platelet activator. Reduced impedance implies platelet dysfunction or the presence of platelet inhibitors. MEA plays an increasingly important role in the management of perioperative platelet dysfunction. In vitro, midazolam, propofol, lidocaine and magnesium have known antiplatelet effects and these may interfere with MEA interpretation. OBJECTIVE To evaluate the extent to which MEA is modified in the presence of these drugs. DESIGN An in-vitro study using blood collected from healthy volunteers. SETTING Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 2010 to 2011. PATIENTS Twenty healthy volunteers. INTERVENTION Measurement of baseline MEA was using four activators: arachidonic acid, ADP, TRAP-6 and collagen. The study drugs were then added in three increasing, clinically relevant concentrations. MAIN OUTCOME MEASURE MEA was compared with baseline for each study drug. RESULTS Midazolam, propofol and lidocaine showed no effect on MEA at any concentration. Magnesium at 2.5 mmol l−1 had a significant effect on the ADP and TRAP tests (31 ± 13 and 96 ± 39 AU, versus 73 ± 21 and 133 ± 28 AU at baseline, respectively), and a less pronounced effect at 1 mmol l−1 on the ADP test (39 ± 0 AU). CONCLUSION Midazolam, propofol and lidocaine do not interfere with MEA measurement. In patients treated with high to normal doses of magnesium, MEA results for ADP and TRAP-tests should be interpreted with caution. TRIAL REGISTRATION Clinicaltrials.gov (no. NCT01454427)

Antiplatelet Therapy and Anticoagulation

Preoperative withdrawal of antiplatelet (AP) therapy in secondary prevention multiplies the risk of myocardial infarction, stent thrombosis, stroke, or death, by five to ten times. Aspirin is a lifelong therapy and should never be interrupted. Dual AP therapy with aspirin plus clopidogrel, prasugrel, or ticagrelor is essential for at least 6 weeks after coronary revascularization using bare-metal stents, 12 months after treatment for acute coronary syndrome, and 6–12 months after implanting drug-eluting stents. These time spans might even be prolonged in high-risk cases. Elective surgery should be postponed until after these periods. Vital or urgent operations undertaken earlier must be performed under continued dual AP therapy.

Point-of-Care Platelet Function Tests

Platelets play a key role in primary hemostasis but are also important contributors to pathological thrombotic disorders. Inherited or acquired platelet dysfunction (e.g., cardiac patients on dual antiplatelet therapy) can influence bleeding during surgery. However, in the literature, evidence for the usefulness of perioperative platelet function monitoring is still sparse. Several point-of-care platelet function tests have been developed recently; these can be performed on whole blood in near-patient settings such as in operating theaters or intensive care units. The potential advantages of these tests are simplified workflows, rapid turnaround times, and targeted management of coagulation disorders. The ideal point-of-care platelet analyzer does not exist; every technique has its strengths and weaknesses. It is therefore important to understand the potential indications and limitations of the different devices available. In this chapter, we will present the five point-of-care platelet function analyzers most widely used in perioperative care today.

Experimental ex vivo lung perfusion with sevoflurane: effects on damaged donor lung grafts

OBJECTIVES Volatile anaesthetics can provide significant protection against reperfusion injury in various experimental settings. The aim of this study was to assess the potential of sevoflurane treatment, the most commonly used volatile anaesthetic in modern anaesthesia, in rat lungs donated after circulatory death and reconditioned in an ex vivo lung perfusion (EVLP) system. METHODS Fifteen rats were sacrificed and divided into 3 groups. In the control and sevoflurane groups, the heart-lung blocks were exposed to 1 h of warm ischaemia and 2 h of cold ischaemia and were mounted on an EVLP circuit for 3 h, in the absence or in the presence of 2% sevoflurane. In the baseline group, heart-lung blocks were harvested immediately after euthanasia. Physiological data, lung nitro-oxidative stress, lactate dehydrogenase (LDH), expression of cytokines, oedema and histopathological findings were assessed during or post-EVLP. RESULTS The sevoflurane group showed significantly reduced LDH (8.82 ± 3.58 arbitrary unit vs 3.80 ± 3.02 arbitrary unit, P = 0.03), protein carbonyl (1.17 ± 0.44 nmol⋅mg-1 vs 0.55 ± 0.11 nmol⋅mg-1, P = 0.006), 3-nitrotyrosine (197.44 ± 18.47 pg⋅mg-1 vs 151.05 ± 23.54 pg⋅mg-1, P = 0.004), cytokine-induced neutrophil chemoattractant factor 1 (1.17 ± 0.32 ng⋅mg-1 vs 0.66 ± 0.28 ng⋅mg-1, P = 0.03) and tumour necrosis factor alpha (1.50 ± 0.59 vs 0.59 ± 0.38 ng⋅mg-1, P = 0.02) when compared with the control group. In addition, sevoflurane lungs gained significantly less weight (0.72 ± 0.09 g vs 0.72 ± 0.09 g, P = 0.044), had less perivascular oedema (0.58 ± 0.09 vs 0.47 ± 0.07, P = 0.036), and improved static pulmonary compliance (+0.215 ml⋅cmH2O-1, P = 0.003) and peak airways pressure (-1.33 cmH2O, P = 0.04) but similar oxygenation capacity (+1.61 mmHg, P = 0.77) and pulmonary vascular resistances (+0.078 mmHg⋅min⋅ml-1, P = 0.15) when compared with the control group. CONCLUSIONS These findings suggest that the potential of sevoflurane in protecting the lungs donated after cardiac death and reconditioned using EVLP could improve the outcome of these lungs following subsequent transplantation.