Goal directed hemostatic therapy using the rotational thromboelastometry in patients requiring emergent cardiovascular surgery

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1 Original Article This article is accompanied by an invited commentary by Dr. Achal Dhir Goal directed hemostatic therapy using the rotational thromboelastometry in patients requiring emergent cardiovascular surgery Danièle Sartorius 1, Jean Luc Waeber 1, Gordana Pavlovic 1, Angela Frei 1, John Diaper 1, Patrick Myers 2, Tiziano Cassina 3, Marc Licker 1,4 1 Department of Anaesthesiology, Pharmacology and Intensive Care, 2 Department of Cardiovascular Surgery, University Hospital, CH 1211, Geneva, 3 Department of Anesthesia and Intensive Care, Cardiocentro Ticino, CH 6900 Lugano, Switzerland, 4 Faculty of Medicine, University of Geneva, Geneva, Switzerland ABSTRACT Received: Accepted: Aims and Objectives: We assessed the clinical impact of goal directed coagulation management based on rotational thromboelastometry (ROTEM) in patients undergoing emergent cardiovascular surgical procedures. Materials and Methods: Over a 2 year period, data from 71 patients were collected prospectively and blood samples were obtained for coagulation testing. Administration of packed red blood cells (PRBC) and hemostatic products were guided by an algorithm using ROTEM derived information and hemoglobin level. Based on the amount of PRBC, two groups were considered: High bleeders ( 5 PRBC; HB) and low bleeders (<5 PRBC; LB). Data were analyzed using Chi square test, unpaired t test and analysis of variance as appropriate. Results: Pre operatively, the HB group (n = 31) was characterized by lower blood fibrinogen and decreased clot amplitude at ROTEM compared with the LB group (n = 40). Intraoperatively, larger amounts of fibrinogen, fresh frozen plasma and platelets were required to normalize the coagulation parameters in the HB group. Post operatively, the incidence of major thromboembolic and ischemic events did not differ between the two groups (<10%) and the observed in hospital mortality was significantly less than expected by the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM score, 22% vs. 35% in HB and 5% vs. 13% in LB group). Conclusions: ROTEM derived information is helpful to detect early coagulation abnormalities and to monitor the response to hemostatic therapy. Early goal directed management of coagulopathy may improve outcome after cardiovascular surgery. Key words: Cardiovascular surgery; Postoperative bleeding; Rotational thromboelastometry Access this article online Website: PMID: *** DOI: / Quick Response Code: INTRODUCTION Massive bleeding remains a leading cause of potentially preventable death after cardiovascular surgery. [1] Surgical skills, extent of vascular injury and integrity of the hemostatic system all influence the volume of blood loss while the severity of anemia and the amount of blood transfusion are major determinants of postoperative outcome. [2 5] Impaired hemostasis may develop in surgical patients, owing to dilution of coagulation factors, hypothermia, low hematocrit and hypoperfusion associated with metabolic acidosis and low ionized calcium. [6] Although packed red blood cells (PRBC) improves tissue oxygen delivery and fresh frozen plasma (FFP) improves coagulation, homologous blood transfusion has been associated with an increased risk of mortality and a higher incidence of infection, thromboembolism, myocardial infarct, stroke and renal failure. [2,4,7] Unfortunately, conventional coagulation tests (CCTs) failed to characterize the multiple hemostatic abnormalities observed in surgical patients and they are further limited by their slow results and their poor correlation Address for correspondence: Prof. Marc Licker, Faculty of Medicine, University of Geneva, Rue Gabrielle Perret Gentil, CH 1205, Geneva, Switzerland. Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital Geneva, CH 1211, Geneva, Switzerland. E mail: marc joseph.licker@hcuge.ch 100 Annals of Cardiac Anaesthesia Vol. 17:2 Apr-Jun-2014

2 with transfusion requirements. [8] Given the lack of a consensus in transfusion decision making, there is a wide variability in transfusion practices among different countries, hospitals and even health care providers within the same institution. [9] Currently, several point of care (POC) devices have appeared in operating theatres, with the possibility to monitor the viscoelastic changes on whole blood, thereby evaluating all four phases of the cell based coagulation processes: Initiation, propagation, amplification and clot lysis. [10] Among these POC monitors, the rotational thromboelastometry (ROTEM; Tem International GmbH, Munich, Germany) and thromboelastometry (TEG; Baintree, MA, USA) have been increasingly adopted in European and North American countries because of easy handling by the anesthetic team and rapid results leading to timely correction of coagulation abnormalities. [11] Preliminary data suggest that management of perioperative coagulopathy based on ROTEM/TEG is associated with reduced blood products administration and may help clinicians to distinguish between surgical bleeding and severe coagulopathy. [12] Although using POC coagulation devices has been shown to improve the prediction of bleeding in various surgical settings, there is currently weak evidence on the risk and benefits of any transfusion policy guided by thromboelastometry and no report has specifically involved the emergency surgical settings. [13 15] We therefore conducted a cohort study to assess whether the implementation of an algorithm based on ROTEM parameters may effectively and safely reverse coagulation abnormalities in high risk bleeding patients undergoing emergent cardiovascular surgery. MATERIALS AND METHODS Patient selection and management From January 2011 to December 2012, we included consecutive adult patients (>18 years) undergoing emergent cardiovascular procedures at the University Hospital of Geneva. During this period, thromboelastometry was routinely performed in the operating theater by nurses and physicians of the anesthesia department who had been trained to perform the ROTEM tests according to the manufacturer s instructions. Only patients at high risk of bleeding were enrolled (ongoing post intervention bleeding, combined valve and coronary bypass surgery, clopidogrel treatment within 5 days before surgery). Pregnant patients and those with severe circulatory failure (requiring mechanical support) and severe sepsis (identified infection associated with dysfunction Annals of Cardiac Anaesthesia Vol. 17:2 Apr-Jun-2014 involving at least one organ system) were excluded. The study was approved by the institutional research ethics board and informed consent was waived given the emergency context, the routine practice of POC coagulation testing and the anonymized database. An algorithm for perioperative coagulation management was implemented in our institution the preceding year [Figure 1]. Intraoperatively, forced airflow and fluid warming devices were routinely used to maintain normothermia and the blood ionized calcium concentration was kept above 1 mm/l. A restrictive transfusion strategy (hemoglobin level above g/l) was followed in euvolemic anesthetized patients whereas a hemoglobin level above g/l was targeted in patients with ongoing bleeding, ischemic heart disease and/or organ failure. All cardiac procedures were performed under cardiopulmonary bypass (CPB) with tranexamic acid (10 mg/kg in the priming fluid and 15 mg/kg slowly infused after anesthesia induction), unfractionated heparin (to achieve an activated clotting time [ACT] above 500 s) and protamine (titrated to normalize the ACT at the end of surgery). [16] Administration of blood products and hemostatic agents was guided by the results obtained with the ROTEM device that was checked every week by running standard quality control tests. Measurements Blood samples for ROTEM and CCTs were obtained as part of the routine management of surgical patients at high risk of bleeding at three time periods: Before surgery (preoperative), at the end of surgery (end surgery) and on the morning of the first postoperative day (POD1). Additional tests were performed at the discretion of the attending anesthesiologist. The CCTs included the international normalized ratio (INR), prothrombin time (Quick), partial thromboplastin time (PTT), fibrinogen concentration and the platelet count. The ROTEM analysis were performed on 300 μl citrated whole blood containing 20 μl 0.2 M calcium chloride and specific activators/inhibitors into a plastic cup to explore the whole spectrum of cell based clot formation: The extrinsic and intrinsic coagulation pathways (EXTEM, using rabbit brain thromboplastin; INTEM using ellagic acid), fibrin based thromboelastometry (FIBTEM using cytochalasin to inhibit platelet s contribution) and fibrinolysis (APTEM, using aprotinin). The motion of the rotational pin immersed in the blood sample was progressively limited by the generation of the fibrin filaments and changes in 101

3 Figure 1: Algorithm for perioperative goal-directed coagulation management. Physiological targets: Central temperature >35.5 C; ph >7.25; lactate <2.5 mm/l; Ca++ >1.0 mm/l; Hb >70 g/l; fibrinogen >1.5 g/l; platelets >50,000/ml. Persistent hypocoagulation: Consider FXIII and/or recombinant activated FVII the viscoelastic properties of blood were graphically displayed over time. To characterize the initiation of fibrin strand formation, thrombin generation and lysis, several parameters were recorded: Clotting time (CT), alpha angle (α, rate of clot formation), clot amplitude after 15 min (CA15), maximum clot firmness (MCF) and clot formation time (CFT). As previously reported, ROTEM yields consistent values and reference ranges for the tests parameters have been determined in a multi center investigation. [17] Demographic and clinical data, incidence of pre operative anticoagulant/antiplatelet medications, type of surgery, intraoperative administration of fluids (crystalloids, colloids), blood transfusion products (PRBC, FFP, platelets concentrates (PC)) as well as other hemostatic agents (fibrinogen, tranexamic acid and activated recombinant factor VII [rfviia]) were all prospectively recorded on a dedicated case report form. In addition, the electronic medical files were examined to report hospital and intensive care unit length of stay as well as major post operative complications (in hospital mortality, acute respiratory failure, infections, renal failure, thromboembolic events, myocardial infarct, and heart failure). Mortality was estimated from variables included in the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (P POSSUM). [18,19] Study design In this prospective cohort study, we divided the population sample in two groups depending on the number of PRBC being : At least 5 units of PRBC (high bleeding, HB group) and <5 (low bleeding, LB group). Given the inability to accurately measure blood loss, the number of PRBC units was used as a surrogate of excessive bleeding and the 5 unit threshold has been previously shown to be an inflection point where mortality increased significantly. [20] Statistical analysis Data are presented as means (± standard deviation), numbers and percentage as appropriate. Statistical calculations were performed with SPSS version 13.0 for Windows. Normally distributed data (Kolmogorov Smirnov test) were analyzed by the Student two tailed t test for unpaired samples and repeated measures analysis of variance. Data which were not normally distributed were analyzed by the Mann Whitney U test. For analysis of frequency, the X 2 test was used. In all tests, an a priori α error P < 0.05 was considered to be statistically significant. RESULTS During the study period, a total of 102 patients at high risk of bleeding underwent emergent cardiovascular 102 Annals of Cardiac Anaesthesia Vol. 17:2 Apr-Jun-2014

4 a b c d Figure 2: Perioperative time course of rotational thromboelastometry-derived parameters: Clotting time, clotting formation time and maximal clot firmness; specific assays for extrinsic activated test (EXTEM; a), intrinsic activated test (INTEM; b), fibrin clot obtained by platelet inhibition with cytochalasin (FIBTEM; c) and fibrinolysis (APTEM; d); POD1: Postoperative day 1 surgery. The ROTEM tests were not available in 31 of these patients, because the POC device was not available, or data were missing or the anesthesia personnel were too busy to perform these tests. Thus, complete data were obtained in 71 patients of whom 31 received >5 units of PRBC (HB group, 43.7%) and 40 received <5 units of PRBC (LB group, 54.3%). In the operating theater, ROTEM analyses were repeated several times from the time of anesthesia induction until the end of surgery (median values of 2 with interquartile range of 2 3 per patient in both groups). Patient s pre operative clinical and surgical characteristics as well as baseline laboratory tests were similar in the two groups; except for a longer duration of surgery and a lower blood fibrinogen in the HB group compared with the LB group [Tables 1 and 2]. Pre operatively, CCTs (including fibrinogen) results were within the normal reference range, except a prolonged PTT in the two groups. At the end of surgery, hemoglobin concentration, platelet count, fibrinogen Annals of Cardiac Anaesthesia Vol. 17:2 Apr-Jun-2014 level and Quick test were all similarly decreased in both groups compared with pre operative values; in contrast, blood lactate was increased in the HB group whereas it remained unchanged in the LB group. At the start of surgery, the values of CT (EXTEM) and MCF (FIBTEM) were outside the normal range and several ROTEM parameters differed between the two groups: MCF (with EXTEM, FIBTEM and APTEM), CA15 (with EXTEM, INTEM, FIBTEM and APTEM) and CFT (with APTEM), were all significantly decreased in the HB group compared with the LB group [Table 3]. As shown in Figure 2, all these ROTEM derived data tended to shift toward normal values at the end of surgery and on POD1, with no difference between the two groups [Figure 2 and Table 2]. Intraoperatively, larger amounts of crystalloids, PRBCs, FFP, PC, protamine sulfate and fibrinogen were administered in the HB group compared with the LB group [Table 4]. In hospital mortality was higher in the HB group (22% vs. 5% in the LB group) although it was significantly lower than the predicted 103

5 Table 1: Clinical and surgical data of patients at high risk of bleeding undergoing emergent cardiovascular surgery mortality based on the POSSUM score (35% in the HB group and 13% in the LB group). The incidence of major complications was comparable in the two groups [Table 5]. Of note, the incidence of thromboembolic and ischemic events was <10% in both groups. DISCUSSION with >5 n = 31 P value with <5 n = 40 Age (year) 68 (14) 63 (14) BMI, kg/(m 2 ) (4.5) 26.2 (4.6) Gender (M/F) (%) 21 (68) / 10 (32) 32 (80) / 8 (20) ASA score 3 4 (n, %) 25 (81) 36 (90) Comorbidities (n, %) Renal failure 6 (19) 10 (26) Coronary artery disease 12 (39) 15 (38) Arterial hypertension 18 (58) 23 (59) Diabetes mellitus 4 (13) 6 (15) Arrhythmia 7 (23) 10 (25) Hypercholesterolemia 13 (42) 12 (31) Preoperative medications (n, %) Aspirin 15 (48) 23 (59) Clopidogrel 8 (26) 10 (26) Vitamin K antagonists 2 (6.5) 6 (15) Low molecular weight heparin 3 (10) 3 (8) Unfractionated heparin 7 (23) 17 (44) Type of surgery (n, %) Combined cardiac surgery 2 (6) 1 (3) CABGS 9 (29) 13 (33) Valve surgery 11 (35) 8 (20) Major vascular surgery 4 (13) 15 (38) Re operation for bleeding 9 (29) 7 (18) Surgical time (min) 294 (193) 182 (96) ASA: American society of anesthesiology physical status classification, BMI: Body mass index, CABGS: Coronary artery bypass graft surgery, PRBC: Packed red blood cell Early and aggressive management of coagulopathy is of vital importance in emergency surgical procedures. The main findings of this prospective clinical trial are summarized as following: (1) Information derived from a ROTEM POC monitor was more helpful for anesthesiologists than CCTs to detect preoperative abnormalities in clot formation in surgical patients at high risk of bleeding, (2) implementation of a goal directed hemostatic protocol led to normalization of the ROTEM parameters at the end of surgery, (3) although patients with increased need of allogenic blood transfusion received larger amounts of hemostatic agents, the observed in hospital mortality was lower Table 2: Conventional laboratory tests in patients at high risk of bleeding undergoing emergent cardiovascular surgery Hemoglobin (N: g/dl) with >5 n = 31 with <5 n = 40 P value Pre operative 10.9 (2.3) 11.9 (2.8) End of surgery 9.2 (1.5) 9.0 (1.7) POD1 9.8 (1.0) 9.9 (1.5) Lactate (N: <2 mmol/l) Pre operative 2.0 (2.5) 1.7 (2.3) End of surgery 3.7 (2.9) 1.8 (1.6) POD1 2.1 (1.1) 2.0 (1.6) Creatinine (N: µmol/l) Preoperative 103 (37) 124 (75) End of surgery NA NA NA POD1 135 (98) 135 (88) INR (N: ) Pre operative 1.2 (0.5) 1.3 (0.7) End of surgery 1.4 (0.2) 1.5 (0.6) POD1 1.5 (0.6) 1.6 (0.8) PTT (N: s) Pre operative 46 (22) 59 (61) End of surgery 65 (36) 63 (41) POD1 43 (29) 57 (37) Quick (N: %) Pre operative 79 (20) 79 (22) End of surgery 59 (17) 61 (19) POD1 84 (13) 79 (17) Fibrinogen (N: 2 4 g/l) Pre operative 3.4 (1.4) 4.5 (2.0) End of surgery 1.9 (0.5) 2.1 (1.5) POD1 4.8 (1.5) 4.5 (1.6) Platelet count (N: G/L) Preoperative 196 (98) 193 (79) End of surgery 70 (35) 98 (59) POD1 128 (74) 152 (76) PRBC: Packed red blood cell, INR: International normalized ratio, NA: Not applicable, POD1: Postoperative day 1, PTT: Prothrombin time. P < 0.05, compared with preoperative period than expected and the incidence of thromboembolic and ischemic events was similar than in patients receiving fewer PRBCs. In cardiovascular surgery, transfusion of blood products is currently guided by clinical judgment and CCTs that often include activated PTT, prothrombin time (PT, Quick), platelet count and plasma fibrinogen. [8,21] However, none of these tests were developed to predict bleeding or to guide coagulation management in the surgical setting, with the major limitations being the inability to identify coagulation factor deficiencies and the lack of real time monitoring of the hemostatic response to surgical trauma, fluid infusion and specific pro and anticoagulant treatment. [22] 104 Annals of Cardiac Anaesthesia Vol. 17:2 Apr-Jun-2014

6 Table 3: Pre operative rotational thromboelastometric tests in patients at high risk of bleeding undergoing emergent cardiovascular surgery EXTEM with >5 n = 31 Based on a 2 year experience in POC supported coagulation management in elective major surgery, our team has developed and implemented a POC supported algorithm for goal directed hemostatic therapy using a transfusion trigger for PRBC and different procoagulant interventions (e.g., fibrinogen concentrates, FFPs, antifibrinolytic agents, protamine and rfviia). In the current study, we selectively focused on a group of patients scheduled for emergent cardiovascular surgical procedures and at high risk of bleeding. These patients had multiple comorbidities and acquired coagulopathic disorders owing to major tissue trauma, CPB, large volume fluid resuscitation and antiplatelet/anticoagulant drug therapies. In previous reports, [1,23 25] major bleeding and allogenic blood transfusions have been identified as strong predictors of poor clinical outcome. In the current study, fourfold higher perioperative mortality was found in patients requiring five PRBC or more compared with those requiring <5 units, although both groups Annals of Cardiac Anaesthesia Vol. 17:2 Apr-Jun-2014 with <5 n = 40 P value CT (N: s) 85 (38) 74 (24) CFT (N: s) 103 (35) 112 (51) Alpha angle (N: 63 81) 66 (12) 71 (10) MCF (N: mm) 53 (9) 61 (10) CA15 (N: mm) 47 (10) 56 (12) INTEM CT (N: s) 201 (64) 184 (68) CFT (N: s) 162 (186) 117 (69) Alpha angle (N: 71 82) 66 (11) 68 (12) MCF (N: mm) 54 (11) 59 (13) CA15 (N: mm) 50 (11) 56 (12) FIBTEM CT (N: s) 74 (28) 86 (35) CFT (N: ) 240 (160) 176 (106) Alpha angle (N: ) 69 (9) 68 (15) MCF (N: 9 25 mm) 11 (4) 15 (8) CA15 (N: 8 22 mm) 11 (5) 14 (7) APTEM CT (N: s) 97 (55) 88 (38) CFT (N: s) 165 (75) 112 (58) Alpha angle (N: ) 65 (10) 68 (15) MCF (N: mm) 53 (9) 60 (12) CA15 (N: mm) 48 (10) 55 (15) CT: Coagulation time, CFT: Clot formation time, MCF: Maximum clot firmness, CA15: Clot amplitude after 15 min, PRBC: Packed red blood cell Table 4: Intraoperative administration of fluids and hemostatic agents in patients with high risk of bleeding undergoing emergent cardiovascular surgery with >5 units PRBC n = 31 with <5 units PRBC n = 40 P value Crystalloids (ml) 3908 (1850) 3020 (1356) Colloids (ml) 245 (412) 171 (306) PRBC N patients (%) 31 (100) 29 (73) Volume (ml) 2577 (1247) 570 (376) <0.001 FFP PC N patients (%) 25 (81) 17 (43) Volume (ml) 1612 (1378) 378 (499) <0.001 N patients (%) 26 (84) 13 (33) <0.001 Volume (ml) 1.8 (1.1) 0.6 (1.0) <0.001 Protamine sulfate N patients (%) 22 (71) 15 (38) Fibrinogen N patients (%) 23 (74) 15 (38) Dose (g) 3.7 (3.0) 1.2 (1.7) <0.001 rafvii N patients (%) 2 (6) 2 (5) Aminocaproic acid N patients (%) 17 (55) 18 (45) Dose (mg) 656 (709) 760 (907) FFP: Fresh frozen plasma, PC: Platelet concentrate, PRBC: Packed red blood cell, rafvii: Recombinant activated factor VII presented similar clinical characteristics. These high bleeders underwent more stressful surgical procedures as reflected by the prolonged duration of surgery, a higher blood lactate concentrations and the need for a larger amount of fluid infusion compared with low bleeders. The lower than expected in hospital mortality (i.e., 22% vs. 35%) in these high risk surgical population could be attributed to timely perioperative medical management, particularly adherence to standardized clinical care bundles and also the application of an algorithm aimed to correct perioperative coagulation abnormalities and to minimize allogenic blood transfusion. [26] Yet, no favorable impact has been demonstrated regarding early mortality and length of stay in intensive care unit, several studies indicate that target hemostatic management using ROTEM derived information leads to reduced transfusion of coagulation products and earlier re intervention in case of persistent bleeding associated with a normal clot formation. [27,28] Since the initial reports in 1987 by Tuman and Spiess, [29 32] at least 20 studies involving viscoelastic hemostatic assays such as ROTEM or TEG have been conducted, including more than 7500 cardiac surgical 105

7 Table 5: Clinical outcome of patients at high risk of bleeding undergoing emergent cardiovascular surgery with >5 units PRBC n = 31 with <5 units PRBC n = 40 LOS in ICU (days) 9 (9) 8 (10) LOS in hospital (days) 28 (21) 21 (19) Mortality (%) 7 (22.6)* 2 (5.1) Blood loss (>800 ml) (%) 6 (19) 5 (13) Thrombo embolic event #, (%) 2 (6) 2 (5) Stroke (%) 3 (10) 0 (0) Myocardial infarct (%) 3 (10) 0 (0) Heart failure (%) 7 (23) 8 (21) Arrhythmia (%) 13 (42) 13 (33) ARDS (%) 0 (0) 3 (8) Acute renal dysfunction* (%) 3 (10) 0 (0) Infections # (%) 7 (23) 3 (8) PRBC: Packed red blood cell, LOS: Length of stay, ICU: Intensive care unit, ARDS: Acute respiratory distress syndrome. Peripheral arterial and pulmonary embolism, venous thrombosis, *Post operative decrease in glomerular filtration rate >75%, # Pneumonia and wound infections patients. [10,33 35] Compared with CCTs, the viscoelastic hemostatic assays offer several advantages. Firstly, the POC tests are usually performed by trained anesthesia personnel in the operating theater and the turn around time is reduced to min instead of min with CCTs. [12] Secondly, both ROTEM and TEG provide accurate assessment of the initiation, propagation and amplification of the clotting processes followed by fibrinolysis; both the intrinsic and extrinsic plasmatic pathways as well as the contribution of platelets corresponding to the cell based coagulation model are explored. [36] Thirdly, in all clinical studies, viscoelastic hemostatic assays have been found superior to the CCTs in predicting subsequent bleeding and the need for reoperation. [15,37 40] Importantly, a Cochrane meta analysis of 9 randomized controlled trials found that ROTEM guided therapy resulted in lesser bleeding and reduced need for transfusing platelets and FFPs in patients undergoing liver transplantation or cardiac surgery. [27] Finally, substituting or combining CCTs with TEG/ROTEM is a cost effective approach resulting in up to 50% cost savings in blood transfusion products in addition to sparing medical resources implicated in the treatment of transfusion related complications. [41] The current study confirms that fibrinogen is a key coagulation factor whose activity needs to be monitored and corrected during fluid resuscitation and surgery. [42] Pre operatively, the HB patients differed from the LB patients by their lower fibrinogen levels and weaker clot amplitude (MCF in EXTEM, FIBTEM and APTEM). In agreement with our data, clot firmness and clot P amplitude (with EXTEM, INTEM and FIBTEM) have been found to best correlate with platelet function and fibrinogen levels. [10,35,43] In one study involving liver transplantation, clot amplitude at 10 min exceeding 35 mm with EXTEM or exceeding 8 mm with FIBTEM was associated with efficient clot formation and a low probability of non surgical bleeding. [44] All preoperative abnormalities in ROTEM parameters reverted to normal at the end of surgery by adopting a goal directed hemostatic protocol. Consequently, larger amounts of fibrinogen, FFPs and platelets were needed in the HB group. Importantly, such hemostatic treatment was associated with lower than expected mortality (in both groups) and the three fold higher dose of fibrinogen in the HB group was not associated with an increased incidence of thromboembolic events. Interestingly, a decreased rate of thrombotic/thromboembolic events has even been reported by Gorlinger et al. after the implementation of a POC ROTEM algorithm using various coagulation factor concentrates in a large cohort of 3865 patients undergoing elective or emergent cardiovascular surgery (1.8% vs. 3.2%). [45] Several limitations of the study have to be acknowledged. First, this study was performed at a single tertiary center and we analyzed a small sample of patients undergoing various procedures, with or without CPB; thus our results are not generalizable and they need to be replicated in other institutions and other surgical settings. Second, in its current version, the ROTEM device is not well suited to investigate platelet function; [10,11] other POC device such as the Platelet Function Analyser (PFA 100) and the multiple electrode platelet aggregometry (Multiplate Analyser) are now introduced in the perioperative field, enabling a quick and exhaustive assessment of platelet function and allowing individually guided therapy, particularly in the increasing number of patients taking antiplatelet drugs. [36] Third, we were unable to detect primary or secondary fibrinolysis since tranexamic acid was routinely administered in all cases requiring CPB. Finally, our ROTEM supported coagulation algorithm has not been validated previously; thus we are unable to identify the real impact of different hemostatic interventions that may contribute to improve outcome. Nevertheless, a strong body of knowledge support the benefit of a transfusion protocol in decreasing the need for transfusion. [26] Other authors have emphasized the potential beneficial impact of replacing FFP with the administration of prothrombin complex concentrate and fibrinogen; [45,46] however, there are few evidence based data and adverse events are likely underreported. [47] 106 Annals of Cardiac Anaesthesia Vol. 17:2 Apr-Jun-2014

8 CONCLUSION We have demonstrated that, in contrast with CCTs, ROTEM derived parameters enable the clinicians to detect early coagulation defects and to normalize clot formation by implementing a goal directed hemostatic protocol with no increased risk of thromboembolic event. Given these favorable preliminary results, randomized controlled trials are required to ascertain the safety and effectiveness of specific hemostatic interventions based on POC coagulation devices. REFERENCES 1. Ranucci M, Baryshnikova E, Castelvecchio S, Pelissero G, Surgical and Clinical Outcome Research (SCORE) Group. Major bleeding, transfusions, and anemia: The deadly triad of cardiac surgery. Ann Thorac Surg 2013;96: Glance LG, Dick AW, Mukamel DB, Fleming FJ, Zollo RA, Wissler R, et al. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery. Anesthesiology 2011;114: Stone GW, Clayton TC, Mehran R, Dangas G, Parise H, Fahy M, et al. 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Transfus Med Rev 2013;27: Cite this article as: Sartorius D, Waeber J, Pavlovic G, Frei A, Diaper J, Myers P, et al. Goal-directed hemostatic therapy using the rotational thromboelastometry in patients requiring emergent cardiovascular surgery. Ann Card Anaesth 2014;17: Source of Support: Nil, Conflict of Interest: None declared. Invited Commentary Point of care tests of coagulation Have they come of age? With astounding advances in the field of medicine, physicians are now able to manage patients who were considered inoperable a few years ago. Our cardiac surgical population is ever changing. Anesthesiologists are dealing with sicker and elderly patients who have multiple comorbidities and take newer antithrombotic and antiplatelet agents. When such patients are subjected to repeat, complex or emergency cardiac surgical procedures, perioperative bleeding takes the center stage. Acute blood loss leading to anemia and organ hypo perfusion is bad. Blood loss significant enough to trigger blood transfusion is even worse while a revisit to the operating room for bleeding is worst. Vivacqua et al. showed that morbidity and mortality were lowest in patients who received no blood transfusion, higher for patients receiving blood transfusion but had no reoperation, higher still for those requiring reoperation but no blood transfusion, and highest among those who received blood transfusion and also a reoperation. [1] To avoid indiscriminate use of allogeneic blood transfusion during severe perioperative bleeding, European Society of Anaesthesiology (ESA) guidelines [2] strongly recommend the application of transfusion algorithms incorporating predefined intervention triggers to guide hemostatic intervention. Perioperative bleeding is complex and multifactorial. In the majority of patients who were re explored for bleeding, the cause of bleeding was found to be surgical. Coagulopathy accounted for 23% of re explorations (coagulopathy alone in 13% while the combination of coagulopathy with surgical factors in another 10%). [1] Defects in any stage of the hemostatic process (primary hemostasis, thrombin generation, clot formation, or fibrinolysis) 108 Annals of Cardiac Anaesthesia Vol. 17:2 Apr-Jun-2014