Prospective

Terence Luk

4/F, Department of Anaesthesia & Intensive Care,
Prince of Wales Hospital,
Ngan Shing Street,
Hong Kong

26322735

luktinghin@gmail.com

Department of Anaesthesia & Intensive Care, Prince of Wales Hospital

Hong Kong

Terence Luk

4/F, Department of Anaesthesia & Intensive Care,
Prince of Wales Hospital,
Ngan Shing Street,
Hong Kong

98797133

luktinghin@gmail.com

Department of Anaesthesia & Intensive Care, Prince of Wales Hospital, Prince of Wales Hospital

Hong Kong

利用血栓彈力圖來引導輸注血液製品對心臟手術後的出血量及血液製品使用量之影響

Yes

2015-08-30

Joint CUHK-NTEC Clinical Research Ethics Committee

CRE-2014.406

Device

Thromboelastography is a viscoelastic hemostatic test of whole blood that evaluates all phases of the coagulation process, including clot formation and lysis [1,2]. Compared to standard laboratory tests (platelet count, prothrombin time, activated partial thromboplastintime) which are limited by a poor correlation with bleeding tendency and slow response times [2], thromboelastography provides rapid point-of-care assessment that allows prompt identification of specific hemostatic abnormalities to guide treatment [3]. The principles and tracing of TEG are illustrated in Figure 1, and the normal values and clinical implications of TEG parameters are listed in Table 1.
Patients undergoing cardiac surgical procedures are at risk of massive blood loss. Cardiopulmonary bypass in cardiac surgery causes severe disturbances in the hemostatic system, due to the actions of heparin, inadequate protamine administration, hypothermia, hemodilution, excessive fibrinolysis, and depletion of clotting factors and platelets [4,5], and this in turn leads to microvascular bleeding [6]. As a result, hemostatic blood components are transfused and often contribute significantly to the transfusion burden of patients undergoing cardiac surgery. Empirically administering multiple components can lead to deleterious effects, including multi-organ failure, adult respiratory distress syndrome (ARDS) and nosocomial infection [7]. To improve outcomes, efforts have been made to improve transfusion strategies by developing structured transfusion algorithm based on point-of-care tests such as TEG that rapidly measure and report hemostatic function.
An early prospective study showed that abnormal TEG results correlated with post-operative blood loss and transfusion requirements [8], although TEG parameters have low sensitivity and specificity in predicting ‘bleeders’ [9]. Emerging evidence from randomized, controlled trials suggest that the use of TEG to guide transfusion management can reduce blood product transfusion requirements, without increasing blood loss as measured by mediastinal tube drainage [3,4,6,10]. Shore-Lesserson et al suggested that TEG-guided algorithm reduced the proportion of patients receiving blood product transfusion from 33% to 13% [3], an effect which was verified by subsequent research [4,10]. More significantly, Royston et al demonstrated as much as a fourfold reduction in the volume of fresh frozen plasma and platelets transfused [10]. However, these studies were limited by the use of a less potent celite activator in TEG analysis [3,10], a delay to wait till microvascular bleeding has occurred before testing and treatment [3], inclusion of patients undergoing coronary artery bypass grafting (CABG) alone [6], and incorporation of other point-of-care test other than TEG in the algorithm [6].
The use of TEG to guide transfusion has been studied outside the field of cardiac surgery. A recent systematic review [2] showed that in patients at risk of massive transfusion, thromboelastography-guided transfusion algorithms significantly reduced blood loss, but more studies are required to support the use of TEG as a tool to guide transfusion.
It is believed that TEG allows earlier and specific identification of hemostatic disorders so that appropriate blood products can be given, although the exact mechanism through which TEG-guided hemostatic management can reduce blood product usage remains unclear. Also, the impact of TEG-guided transfusion algorithm on blood component use has not been extensively studied in the subgroup of patients undergoing single or dual valve replacement surgery with moderate to high risk of bleeding. Therefore, we hypothesize that TEG-guided transfusion management reduces blood product transfusion without increasing post-operative bleeding, in patients undergoing single or multiple valve replacement with or without CABG.
A randomized, controlled trial is conducted to compare the effects of TEG-guided transfusion algorithm versus clinician-determined transfusion on post-operative mediastinal chest tube drainage, transfusion of packed red cells, platelets, fresh frozen plasma and cryoprecipitate in patients undergoing complex cardiac surgery. Secondary outcomes include post-operative respiratory complications, renal dysfunction, length of ICU stay, surgical re-exploration and early mortality within 48 hours. Baseline clinical characteristics including age, sex, body mass index, past medical history including history of diabetes mellitus, hypertension, chronic obstructive pulmonary disease, renal impairment, ischemic heart disease and valvular heart disease as well as medications; clinical data including type of operation, total bypass time, total ischemic time, minimal temperature on bypass, total heparin use, total protamine use, use of transamine, use of blood products and recombinant factor VII; intra-operative activated clotting time after protamine; laboratory results of hemoglobin, platelets, prothrombin time, activated partial thromboplastin time, fibrinogen level are collected.
In the TEG group, hemostatic transfusion is based on heparinase-modified TEG during cardiopulmonary bypass. The specific hemostatic abnormality is corrected according to an algorithm outlined in Table 2. TEG will be checked again after all the blood products and protamine given in theatre. In the control group, intraoperative transfusion management will be empirically guided by responsible cardiac anesthetist, according to standard clinical practice at our institution and by using the criteria obtained from abnormal conventional laboratory tests, absence of visible clots and presence of generalized oozing-type bleeding in the surgical field.
Initially, fifty patients will be recruited in a pilot study to determine the sample size. In the pilot study, the transfusion management is the same as current clinical practice, i.e. guided clinically in the theatre and by conventional laboratory results. TEG results will be obtained during cardiopulmonary bypass and after protamine and blood products are given; but these results are blinded to the clinician. The TEG results will be used to estimate hypothetically the transfusion requirement if a TEG-guided transfusion algorithm (Table 2) is applied. The actual component use is then compared with that estimated from a TEG-guided transfusion algorithm. As we hypothesize that a TEG-guided algorithm will decrease the transfusion requirement as compared to clinician-determined approach, the reduction in transfusions in terms of difference in total packs of blood component transfused is a surrogate for effect size for sample size calculation. Power analysis is performed in order to detect the risk reduction (obtained from the pilot series) in total packs of blood component transfusion, with an 80% power & significance level of 0.05.
References
1. Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfusion medicine reviews. Jan 2012;26(1):1-13.
2. Wikkelsoe AJ, Afshari A, Wetterslev J, Brok J, Moeller AM. Monitoring patients at risk of massive transfusion with Thrombelastography or Thromboelastometry: a systematic review. Acta anaesthesiologica Scandinavica. Nov 2011;55(10):1174-1189.
1. Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfusion medicine reviews. Jan 2012;26(1):1-13.
2. Wikkelsoe AJ, Afshari A, Wetterslev J, Brok J, Moeller AM. Monitoring patients at risk of massive transfusion with Thrombelastography or Thromboelastometry: a systematic review. Acta anaesthesiologica Scandinavica. Nov 2011;55(10):1174-1189.
3. Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, Vela-Cantos F, Ergin MA. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesthesia and analgesia. Feb 1999;88(2):312-319.
4. Avidan MS, Alcock EL, Da Fonseca J, et al. Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery. British journal of anaesthesia. Feb 2004;92(2):178-186.
5. Paparella D, Brister SJ, Buchanan MR. Coagulation disorders of cardiopulmonary bypass: a review. Intensive care medicine. Oct 2004;30(10):1873-1881.
6. Ak K, Isbir CS, Tetik S, et al. Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: a prospective randomized study. Journal of cardiac surgery. Jul-Aug 2009;24(4):404-410.
7. Watson GA, Sperry JL, Rosengart MR, et al. Fresh frozen plasma is independently associated with a higher risk of multiple organ failure and acute respiratory distress syndrome. The Journal of trauma. Aug 2009;67(2):221-227; discussion 228-230.
8. Essell JH, Martin TJ, Salinas J, Thompson JM, Smith VC. Comparison of thromboelastography to bleeding time and standard coagulation tests in patients after cardiopulmonary bypass. Journal of cardiothoracic and vascular anesthesia. Aug 1993;7(4):410-415.
9. Ronald A, Dunning J. Can the use of thromboelastography predict and decrease bleeding and blood and blood product requirements in adult patients undergoing cardiac surgery? Interactive cardiovascular and thoracic surgery. Oct 2005;4(5):456-463.
10. Royston D, von Kier S. Reduced haemostatic factor transfusion using heparinase-modified thrombelastography during cardiopulmonary bypass. British journal of anaesthesia. Apr 2001;86(4):575-578.

N/A

N/A

Intra-operative use

Intra-operative use

Standard clinical practice, as above.

N/A

N/A

N/A

N/A

Patients undergoing single or multiple valve replacement with or without CABG; all subjects required cardiopulmonary bypass. All study subjects should be capable to provide informed consent.

Haemodynamically unstable requiring inotropes and intra-aortic balloon pump, Active malignancy, Bleeding diathesis, preexsisiting platelet count <100 x10^9/L or INR <1.5, Use of low molecular weight heparin within 4 hours, Use of warfarin within 72 hours, Use of aspirin >325mg per day, Use of clopidogrel within 5 days, Recent treatment with glycoprotein IIbIIIa antagonist within 5days, Liver disease with raised liver enzyme, Renal dysfunction Cr >2mg/dL or>177 mmol/L, Resternotomy case

18

N/A

Both Male and Female

Randomized

Computer-generated, sealed-envelop

Placebo

Open label

Parallel

Other

Clinical

No