Prosective, Randomized Clinical Trial of the Matrix Sealant in Cardiac Surgery Giusee Nasso, MD, Felice Piancone, MD, Raffaele Bonifazi, MD, Vito Romano, MD, Giusee Visicchio, MD, Carlo Maria De Filio, MD, Barbara Imiombato, MD, Flavio Fiore, MD, Francesco Bartolomucci, MD, Francesco Alessandrini, MD, and Giusee Seziale, MD Cardiac Surgery Deartment, GVM Hositals of Care and Research, Bari, and Division of Cardiac Surgery, Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche, Catholic University of the Sacred Heart, Camobasso, Italy Background. Toical hemostatic agents comosed of a gelatin-based matrix and thrombin have been reorted to be effective, in addition to traditional means, in terminating bleeding during cardiac oerations. We comared a hemostatic matrix sealant agent (; Baxter Inc, Deerfield, IL) with alternative toical hemostatic agents in a mixed cohort of elective cardiac and thoracic aortic oerations. Methods. Following samle size calculation, in a rosective randomized study design, 209 atients were treated with matrix sealant ( grou) and 206 atients received alternative agents as toical hemostatic materials (comarison grou). is comosed of a self-exandable gelatin matrix comonent and urified bovine thrombin. Comarisons included hemostatic atches or songes comosed of either oxidized regenerated cellulose or urified orcine skin gelatin. Study endoints were the following: rate of successful intraoerative hemostasis (identified by cessation of bleeding) and time required for hemostasis; overall ostoerative bleeding; rate of transfusion of blood roducts; rate of surgical revision for bleeding; ostoerative morbidity; and intensive care unit stay. Results. Statistically higher rates of successful hemostasis and shorter time-to-hemostasis were observed in the grou ( < 0.001 both). Time-to-event analysis confirmed this finding ( 0.0025). Postoerative bleeding and rate of transfusion of blood roducts were statistically decreased in the grou ( < 0.001 both). Rates of revision for bleeding and of minor comlications were not statistically different among grous in the overall cohort, but were significantly lesser in the grou if only atients with overt intraoerative bleeding are considered ( 0.04 both). The advantages observed in the grou were not offset in atients undergoing systemic hyothermia. Conclusions. The toical hemostatic agent used in the grou is effective in terminating intraoerative bleeding as an adjunct to traditional surgical methods for stoing bleeding. Its judicious use is associated with lesser need for transfusion of blood roducts and rate of revision for bleeding. Its cost-utility rofile should be addressed in dedicated trials. (Ann Thorac Surg 2009;88:1520 6) 2009 by The Society of Thoracic Surgeons Acceted for ublication July 10, 2009. Address corresondence to Dr Nasso, Division of Cardiac Surgery, Anthea Hosital, Via Camillo Rosalba, 35-37, Bari, 70124, Italy; e-mail: gnasso@libero.it. Hemostasis, a key tenet of any surgical rocedure, is even more crucial in the cardiac surgery ractice. High-ressure anastomoses and (or) suture lines within the cardiac chambers or the great vessels are created during virtually all cardiac surgical rocedures. This renders the use of toical hemostatic agents, together with a meticulous oerative technique, one major contributor to the safety of routine oerations. In addition, hearinization for cardioulmonary byass, contact of blood with extracororeal circulation tubing-oxygenator and systemic hyothermia in selected cases, contribute to a various degree of coaguloathy in most cardiac surgical atients [1]. Postoerative bleeding is a feared comlication associated with transfusion of blood roducts, rolonged intensive care unit stay, need for surgical revision of hemostasis, and even increased mortality. It has already been suggested in controlled trials that a toical hemostatic matrix surgical sealant (; Baxter Biosurgery, Deerfield, IL), comosed by a self-exandable gelatin-based matrix and urified bovine thrombin solution obtained from bovine lasma (roduct currently available in the Euroean Union), is effective in stoing bleeding in atients subjected to cardiac oerations [2].It is versatile and can be adated to various surfaces, including actively bleeding vascular anastomoses. is reortedly useful even in other surgical secialties, including sinal surgery (98% of bleeding sites controlled within 10 minutes [3]), control of sontaneous suratentorial and intracerebral hemorrhages [4], control of Dr Nasso discloses that he has a financial relationshi with Baxter Biosurgery, Inc. 2009 by The Society of Thoracic Surgeons 0003-4975/09/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2009.07.014
Ann Thorac Surg NASSO ET AL 2009;88:1520 6 FLOSEAL IN CARDIAC SURGERY bleeding in renal trauma and nehrectomy (enhanced renal arenchymal hemostasis [5, 6] and management of major collecting-system injury [7]), 100% hemostasis rate and excellent clot integration into the surrounding tissues in a swine model of liver and sleen ruture [8], 98% rate of successful hemostasis in a series of liver resection oerations even in the setting of cirrhotic liver [9], and successful laaroscoic alication after striing of ovarian cyst [10]. Other studies have noticed no significant differences in the clinical results of gelatin matrix sealants with or without thrombin in the setting of artial nehrectomy [11]. Nonetheless, the revious investigations focused on cardiac surgery could not associate the use of toical surgical sealant with a significant decrease in the rate of ostoerative bleeding-related comlications, ossibly due to insufficient samle size. The resent rosective, controlled study was conducted with the aim to clarify the following: (1) whether surgical sealant is effective in obtaining hemostasis in a cohort of mixed cardiac-thoracic aortic rocedures versus control toical hemostatic agents; and (2) whether the routine use of surgical sealant is associated with a decreased rate of ostoerative bleeding-related comlications within a samle size-controlled trial. One randomized controlled trial has reviously addressed the intraoerative efficacy of the matrix sealant in stoing bleeding [2]. The resent manuscrit takes into analysis the erioerative and ostoerative clinical outcome of atients treated with toical hemostatic agents. Patients and Methods The local Ethical Committee aroved the study rotocol and the atients enrolled in the study received full information, were willing to enter the trial, and rovided written informed consent. Study outcome measures included the following: rate of successful intraoerative hemostasis and time required for hemostasis; overall ostoerative bleeding (as measured by chest tube outut and indexed for body surface area); rate of transfusion of blood roducts both intraoeratively and in the ostoerative; rate of surgical revision for bleeding after initial transferal to the intensive care unit (ICU); and rate of ostoerative morbidity and total length of ICU stay. Patients Selection and Study Design The clinical trial resented herein was designed in December 2005. On the basis of historic institutional data, samle size calculation indicated that a total of 356 study cases were required to detect with a 0.80 ower a statistically significant difference between the treatment and the control grou with resect to endoint: overall ostoerative bleeding; 381 study cases with resect to endoint: rate of transfusion of blood roducts; and 363 cases with resect to endoint: rate of surgical revision for bleeding (alha level: 0.05). Therefore, starting in January 2005 all atients undergoing cardiac surgery were screened at the time of 1521 hosital admission and enrolled according to the following inclusion criteria. (1) Scheduled for elective rimary cardiac (coronary, valvular, or combined) and (or) thoracic aortic surgery. Patients undergoing cardiac reoeration were excluded. (2) Patients with known or susected hyersensitivity reaction to any comonent of study roducts or to bovine-derived material, and atients undergoing reair of acute thoracic aortic dissection were excluded. Patients with known or susected reoerative coagulation disorder were excluded. After inclusion in the study, atients were randomized with the aid of a comuterized algorithm to either the grou (use of ) or to the comarator grou (control grou, other toical hemostatic agents emloyed according to the surgeon s reference, among the following: Surgicel Nu-Knit absorbable hemostat [Ethicon Inc, Somerville, NJ] and Gelfoam 12 (Ujohn and Pharmacia, Kalamazoo, MI). The above were used as control toical hemostatic agents because they were already available in hosital formulary. Additionally, both Surgicel Nu-Knit and Gelfoam reresent hemostatic atches-songes that rovide a mesh to suort the atient s activated coagulation factors. Conversely, last-generation contains human thrombin derived from ooled human lasma, and combines its biologic activity (activation of fibrinogen) with the mechanical suort of a self-exanding granule matrix. Thus, this investigation essentially addresses the usefulness of combined biologic and mechanical activity versus mechanical activity alone of toical hemostatic agents. The study was erformed under an intentionto-treat rotocol. The investigation was conducted within the Cardiac Surgery Division, Catholic University, Sede di Camobasso, Italy (University, multiseciality hosital setting) until December 2006 and afterward within the Cardiac Surgery Division, Anthea Hosital, Bari, Italy (Territorial, multiseciality hosital). One-way analysis of variance (ANOVA) was emloyed to disclose significant differences among baseline variables (as listed in Table 1) with resect to subgrous of atients obtained from each Institution. Clustering of data by site did not occur. Enrollment into the study was terminated in Setember 2008. The local Ethical Committees gave aroval to the study rotocol. Surgical Technique All oerations were erformed through full median sternotomy. Hearinization for cardioulmonary byass was accomlished by administration of 300 UI/kg hearin, and was reversed by titrated rotamine sulfate after weaning from extracororeal circulation. was reared immediately after decannulation. Purified thrombin was disersed within the gelatin matrix granules and the agent was delivered by a syringe to the target site. Among the grou atients, was alied in all instances of active bleeding (ulsatile flow, continuous flow, or oozing) after alication of ADULT CARDIAC
1522 NASSO ET AL Ann Thorac Surg FLOSEAL IN CARDIAC SURGERY 2009;88:1520 6 Table 1. Baseline s of the Study Poulation (n 209) (n 206) Sex, male 127 (60.8%) 132 (64.1%) 0.55 Age (years) 68.5 4.3 69.1 4.1 0.74 Additive EuroSCORE 3.1 0.9 3.2 0.9 0.86 Isolated coronary 76 (36.4%) 74 (35.9%) 0.99 surgery Isolated valvular surgery 59 (28.2%) 63 (30.6%) 0.67 Combined 38 (18.2%) 36 (17.5%) 0.95 coronary/valvular surgery Aortic surgery (either 36 (17.2%) 33 (16%) 0.84 alone or combined; n, %) Cardioulmonary byass 96.5 12.8 98.7 13 0.49 time (minutes) Systemic hyothermia 44 (21%) 43 (20.9%) 0.93 EuroSCORE Euroean system for cardiac oerative risk evaluation. conventional means including direct ressure, electrocautery, and suture ligation. Intraoerative bleeding sites were formally identified only after comlete administration of rotamine. No antifibrinolytic agents were used in the resent series. The study roduct was alied as follows: (1) To any bleeding site (graft anastomosis edge, suture lines at the sites of atriotomy-aortotomy, thoracic aortic-vascular rosthesis anastomosis, muscular diffuse bleeding, undersurface of the sternum during the final hemostasis hase) regardless that bleeding was stoed or not by conventional means (electrocautery, direct ressure, suture ligation, stitch lacement). (2) To any of the above sites (graft anastomosis edge, suture lines at the sites of atriotomy-aortotomy, thoracic aortic-vascular rosthesis anastomosis, muscular diffuse bleeding) even in the absence of active bleeding. grou atients were managed according to the same rotocol with the use of alternative toical hemostatic agents (Surgicel Nu-Knit absorbable hemostat; Gelfoam 12). Hemostatic agents were alied only after full reversal of hearinization by rotamine sulfate. One single realication of hemostatic agent was allowed. Systemic hyothermia was indicated as the following: (1) in the aortic cases involving oen distal aortic anastomosis or an arch rocedure requiring circulatory arrest (moderate hyothermia: 22 C to 25 C rectal temerature); and (2) as an institutional rotocol, in atients with known hemodynamically significant internal carotid artery disease and (or) ast history of cerebrovascular accidents (mild hyothermia: 30 C to 32 C rectal temerature). Collection of Data and Statistical Methods Details of oeration erformed, duration of cardioulmonary byass, and intraoerative comlications were recorded rosectively by the oerative room nurses. Patients were followed-u by 96 hours ostoeratively to track the following outcome comlications: overall bleeding from chest tubes (as indexed er body surface area); need for surgical revision of hemostasis and for transfusion of blood roducts; amount of blood roducts transfused; onset of ostoerative morbidity (including stroke, shock, sesis, myocardial infarction, renal failure, resiratory insufficiency, rolonged inotroic suort); and length of ICU stay. Data were entered into the database by surgical assistants at the time of discharge of atients from the hosital. Data were rosectively entered in a comuterized database and analyzed through SPSS software version 11.0.1 for Windows (SPSS Inc, Chicago, IL). Samle size For the urose of this study, we alied the following definitions. Time to hemostasis is the time required to obtain successful hemostasis for a single bleeding site; hemostasis time is the oerative time comrised between the removal of cardioulmonary byass cannulae and the closure of the sternum. Time to hemostasis at any bleeding oint was measured and recorded by oerative room nurses starting from alication of. Success or failure of hemostasis at any bleeding oint was noticed by the oerating surgeon and recorded by oerative room nurses. According to the ublished literature, successful hemostasis was defined as hemostasis occurring by 10 minutes after alication of the toical hemostatic agent. The oerative time comrised between decannulation and the closure of the sternum was noticed also and recorded (defined as hemostasis time). Fig 1. Study design.
Ann Thorac Surg NASSO ET AL 2009;88:1520 6 FLOSEAL IN CARDIAC SURGERY calculation was erformed through the PS software version 2.1.31 for Windows [13]. Continuous data are resented as mean standard deviation and comared through the Student t test. Categoric data are given as ercentages and comared through the 2 test. Tests were two-tailed and Yates correction was alied. Timeto-event analysis was erformed by calculation of Kalan-Meier estimates. For the uroses of the resent investigation, bleeding from a secific site (as the resonse event) and the time to successful intraoerative hemostasis for the same site were included in the Kalan-Meier calculations. Actuarial curves were comared with the log-rank test. 1523 ADULT CARDIAC Table 2. Study Endoints: Results and Intergrou Comarison (n 209) (n 206) Intraoerative bleeding 110 (52.6%) 104 (50.5%) 0.73 Bleeding sites a Coronary byass 26 32 0.38 anastomosis Atriotomy-Aortotomy 72 65 0.71 Thoracic 13 14 0.91 aortic/rosthesis anastomosis Muscular diffuse 56 52 0.91 Other 19 16 0.81 Successful hemostasis b 101 (91.8%) 64 (61%) 0.001 Time to successful 3.8 2.4 6.8 3.1 0.001 hemostasis c (min.) Hemostasis time 28.5 5.2 46.1 9.1 0.001 (minutes) d Overall ostoerative 375.2 24 528.8 36 0.001 bleeding (ml/m 2 ) Transfusion of blood 61 (29.2%) 97 (47.1%) 0.001 roducts Revision for bleeding 9 (4.3%) 16 (7.8%) 0.20 ICU stay (days) 3.1 1 3.4 1.1 0.36 Major comlications 28 (13.4%) 29 (14.1%) 0.95 Minor comlications 48 (23%) 57 (27.7%) 0.32 Oerative mortality 11 (5.3%) 12 (5.8%) 0.97 a Total of bleeding sites within the study grou; b Percentage of atients having successful hemostasis for all bleeding sites at 10 minutes from alication of toical hemostatic agent; c Time to successful hemostasis for first-bleeding site; d Oerative time comrised between decannulation and the closure of the sternum. Major ostoerative comlications: stroke, shock, sesis, myocardial infarction. Minor ostoerative comlications: renal failure, resiratory insufficiency, inotroic suort lasting more than 24 hours. Oerative mortality: death within 30 days from the oeration. ICU intensive care unit. Fig 2. Kalan-Meier lot: time to successful hemostasis for first bleeding site (entire study cohort). (Control grou : e control, control-censored; grou : e, censored; log-rank test.) Results Study design is summarized in Figure 1. The two study grous were comarable with resect to baseline characteristics as outlined in Table 1. Isolated coronary surgery was the most frequent category of oeration erformed, but more comlex oerations (combined coronary and valvular surgery) associated with rolonged cardioulmonary byass time, and aortic oerations requiring systemic hyothermia were erformed in a substantial amount of cases. Systemic hyothermia was indeed emloyed in 21% of grou 1 atients and in 20% of grou 2 atients. Both hyothermia and rolonged cardioulmonary byass time have been associated with a variable degree of alteration of the coagulation cascade [14 16]. Study fallout was 5 atients (3 from the Table 3. Transfusion of Blood Products in the Entire Study Cohort (n 209) (n 206) Any transfusion 56% 72% 0.001 Average units transfused a 1.6 3.1 0.001 (acked RBC) Fresh frozen lasma-latelets 9% 15% 0.045 transfusion Average units transfused a (fresh frozen lasmalatelets) 4.5 7.1 0.01 a Average number of units transfused er atient who received transfusion. RBC red blood cells.
1524 NASSO ET AL Ann Thorac Surg FLOSEAL IN CARDIAC SURGERY 2009;88:1520 6 Table 4. Study Endoints and Results Among Patients Having Intraoerative Bleeding (n 110) (n 104) Hemostasis time (minutes) a 32.1 5.4 56.3 8 0.001 Transfusion of blood 31 (28.2%) 63 (60.6%) 0.001 roducts Revision for bleeding 5 (4.5%) 14 (13.5%) 0.04 ICU stay (days) 3.12 1 3.6 1.2 0.10 Major comlications 13 (11.8%) 18 (17.3%) 0.34 Minor comlications 23 (20.9%) 35 (33.6%) 0.04 a Oerative time comrised between decannulation and closure of the sternum. Major ostoerative comlications: stroke, shock, sesis, myocardial infarction. Minor ostoerative comlications: renal failure, resiratory insufficiency, inotroic suort lasting more than 24 hours. ICU intensive care unit. grou and 2 from the comarator grou) who deceased within the 96th ostoerative hour and hence did not comlete the study follow-u. Endoints The rate of intraoerative bleeding was comarable among grous (Table 2), involving 214 atients from both grous and a total of 186 bleeding sites in the grou and 179 sites in the comarator grou. Distribution of bleeding sites was not statistically different among grous. Use of was statistically associated with a higher ercentage of successful hemostasis at 10 minutes versus control (92% vs 61%) and a shorter mean time required to obtain the hemostasis (3.8 vs 6.8 minutes, resectively). Such finding was confirmed by the timeto-event analysis (Fig 2), which suggested that the matrix sealant is raid and effective in obtaining hemostasis. Additionally, atients who were treated with showed a less total ostoerative bleeding from the chest tubes and a significantly lower rate of transfusion of blood roducts. Blood roducts were administered during the stay in the ICU in the majority of cases (56% of cases in grou and 72% of cases in comarator grou) (Table 3). Among individuals who received transfusion, an average of 3.1 acked red blood cells units er Table 5. Study Endoints and Results Among Patients Undergoing Systemic Hyothermia During Cardiac Surgery (n 44) (n 43) Hemostasis time (minutes) a 33 5.4 51.1 6.7 0.001 Transfusion of blood 24 (54%) 31 (72.1%) 0.14 roducts Revision for bleeding 2 (4.5%) 8 (18.6%) 0.049 a Oerative time comrised between decannulation and closure of the sternum. atient were transfused in the comarator grou versus 1.6 units er atient in the grou ( 0.001). Fresh frozen lasma and latelets were transfused less frequently (9% of atients in the grou and 15% of atients in the comarator grou). The time required by the surgeon to obtain adequate hemostasis in the entire oerative field and to close the sternum was also statistically lower in the grou. Subanalyses If only the atients who suffered from intraoerative bleeding are taken into analysis, it emerges that the use of is associated not only with decreased hemostasis time and rate of transfusion of blood roducts, but also with lower rate of surgical revision for bleeding in the immediate ostoerative eriod (Table 4). Revision for bleeding was erformed in the oerating room with full ersonnel. Even the rate of minor ostoerative comlications resulted to be lower in the grou. This finding can be cautiously interreted as a corollary of the lesser incidence of revision for bleeding and transfusion of blood roducts, both of which have been recognized as markers of oorer immediate ostoerative course [14, 17]. Patients undergoing systemic hyothermia are more comlex under the rofile of intraoerative hemostasis. In a further subanalysis, only atients from both grous undergoing hyothermic CPB were taken into account and comared (Table 5). The favorable effects observed in the grou versus the comarator grou (shorter hemostasis time, lower rate of revision for bleeding) were not influenced by the emloyment of systemic hyothermia. Conversely, there was no statistically significant intergrou difference in the rate of transfusion of blood roducts. In addition, time-to-event analysis revealed an advantage in terms of rate of successful hemostasis and time required to obtain hemostasis for atients belonging to the grou (Fig 3). The above findings suggest that the erformance of the matrix sealant are adequate even in the context of variable degrees of imairment in the coagulation cascade, although dedicated investigations are required to address this issue. Comment The rimary objective of this study was to evaluate the intraoerative erformance of the hemostatic matrix as a toical hemostatic agent in a cohort of various rimary cardiac oerations. A key element of novelty with resect to the reviously ublished studies is reresented by the assessment of the immediate clinical course of the atients with resect to bleeding and bleeding-related comlications. A wide variety of toical hemostatic agents have been develoed so far, including fibrin and thrombin sealants, oxidized cellulose, gauze songes, and absorbable gelatin songes. Such adjuvant materials, not intended as a substitute for a meticulous surgical technique and for a judicious use of traditional surgical means for stoing bleeding (direct ressure, suture ligation, and electrocautery), have been anyway
Ann Thorac Surg NASSO ET AL 2009;88:1520 6 FLOSEAL IN CARDIAC SURGERY Fig 3. Kalan-Meier lot: time to successful hemostasis for first bleeding site (atients who underwent systemic hyothermia). (Control grou : e control, control-censored; grou : e, -censored; log-rank test.) associated with facilitated termination of bleeding. However, toical hemostatic agents are of limited efficacy in the setting of high-ressure bleeding if traditional surgical means to control bleeding are not used and coaguloathy is not corrected. The resent study brought into comarison the efficacy of the matrix sealant with other commercially available toical hemostatic agents. An additional control grou comosed of atients with rohibition to the use of toical hemostatic agents was not included because it was considered to be ethically objectionable. The resent investigation indicates that the routine use of is associated with a significantly higher rate of successful hemostasis and shorter time for achievement of hemostasis in comarison with control materials (gelatin songes and oxidized cellulose). Such result is obtained in a global cohort of atients, including those not resenting major sites of intraoerative bleeding during the hemostasis hase. In the latter cases, toical hemostatic agents were alied to all otential sources of bleeding including coronary graft anastomoses and sites of cardiotomy. This olicy may be questioned as an overtreatment and economically unjustified. Nonetheless, in the entire study cohort a significantly lower overall ostoerative bleeding was observed. More imortantly, a significantly lower rate of need for transfusion of blood roducts was noticed too, even though atients treated with sealant in the absence of overt bleeding were included. Bleeding from any target site may indeed develo later during the earliest ostoerative hours even though it was not aarent during the surgical hemostasis hase in the oerative room. 1525 If the only atients who were recorded to have intraoerative bleeding from any site are taken into analysis, the above intergrou differences become more striking. Additionally, atients in the grou dislay a statistically lower incidence of need for surgical revision of hemostasis and, interestingly, a slightly decreased incidence of minor ostoerative morbidity. Such finding may be reasonably linked with the following: (1) the lower incidence of surgical reexloration and the decreased need for transfusion, both factors strongly associated with oorer ostoerative course and occurrence of morbidity after cardiac surgery [14, 17]; and (2) better end-organ erfusion in the absence of significant early ostoerative blood loss. These concets may be corroborated by the finding that the duration of ICU stay was shorter among the grou atients who had intraoerative bleeding versus equivalent comarator grou atients; although not statistically significant, this finding may have a clinical significance to be further addressed within larger atient series. While our samle size calculation was not tailored on the incidence of ostoerative morbidity, the rosective, randomized design of the study renders a selection bias to this oint unlikely. To suort this idea the calculated Euroean System for Cardiac Oerative Risk Evaluation, the most widely adoted cardiac surgery risk stratification system [18], was comarable among the study grous. Taking into analysis the atients who underwent mildto-moderate systemic hyothermia for brain rotection during cardiac surgery, still the advantages associated with the use of are aarent (shorter hemostasis time and lower rate of surgical revision for bleeding). Nonetheless, the rate of transfusion of blood roducts was not statistically different among grous. Such discreancy in comarison with the general cohort is robably linked with the different kind of transfusion erformed. Packed red blood cells were more frequently transfused in the general cohort and among atients having intraoerative bleeding, on the basis of reduced hemoglobin level due to hemorrhage. Conversely, a substantial number of atients in the hyothermia subgrou received fresh frozen lasma and latelet transfusion on the basis of overt coaguloathy. Although the resent study did not include a formal cost-utility and cost-efficacy analysis, it is acceted that an efficient control of bleeding both intraoeratively and ostoeratively contributes to the reduction of hosital costs by decreasing the need for blood transfusion, the requirements for additional treatments, and even the duration of ICU stay. Postoerative morbidity, which was found to be increased among comarator grou atients, is associated with the need for additional harmacologic treatments, emloyment of nurse time, and rolonged hosital stay. Similarly, revision for bleeding is an extra treatment with additional hosital costs (emloyment of ersonnel and oerative room time) as far as clinical shortcomings (increased risk of wound infection). Dedicated cost-analysis aers can be devoted to this issue. Additionally, does not contain bovine thrombin. This comonent may elicit immune resonse with anti- ADULT CARDIAC
1526 NASSO ET AL Ann Thorac Surg FLOSEAL IN CARDIAC SURGERY 2009;88:1520 6 body formation and cross-reaction with the host s coagulation factors, leading to rare cases of comlex ostoerative coaguloathies [12]. In conclusion, the resent controlled trial indicates that the routine use of the matrix sealant is efficient in terminating bleeding as an adjunct to basilar surgical hemostatic maneuvers in a samle size-controlled cohort of mixed cardiac rocedures. Its cautious use may be justified on high-ressure anastomoses and cardiotomy suture lines even in the absence of overt bleeding. In our overall study cohort it is associated with shorter time for hemostasis and decreased need for blood transfusion and of surgical reexloration for bleeding. Such advantages are amlified if only the atients with imortant intraoerative bleeding are analyzed, and are not offset by the coexistence of factors facilitating bleeding such as the use of systemic hyothermia. No intraoerative or ostoerative adverse events were referred to the use of the matrix sealant during the resent investigation. This clinical study not only demonstrates the agent under investigation to be effective for hemostasis but translates this benefit to outcomes such as reduction in blood transfusion, revision for bleeding, ICU stay, and minor comlications. Hosital decision-makers may be able to leverage these clinical outcomes and translate these benefits to actual cost savings within the context of their own hosital institution. References 1. Levy JH, Desotis GJ. Transfusion and hemostasis in cardiac surgery. Transfusion 2008;48:1S. 2. Oz MC, Cosgrove DM III, Badduke BR, et al. Controlled clinical trial of a novel hemostatic agent in cardiac surgery. Ann Thorac Surg 2000;69:1376 82. 3. Renkens KL, Payner TD, Leizig TJ, et al. A multicenter, rosective, randomized trial evaluating a new hemostatic agent for sinal surgery. Sine (Phila Pa 1976) 2001; 26:1645 50. 4. Gazzeri R, Galarza M, Neroni M, Alfieri A, Esosito F. Minimal craniotomy and matrix hemostatic sealant for the treatment of sontaneous suratentorial intracerebral hemorrhage. J Neurosurg 2009;110:939 42. 5. Gill IS, Ramani AP, Saliviero M, et al. Imroved hemostasis during laaroscoic artial nehrectomy using gelatin matrix thrombin sealant. Urology 2005;65:463 6. 6. Björses K, Holst J. Toical haemostatics in renal trauma an evaluation of four different substances in an exerimental setting. J Trauma 2009;66:602 11. 7. L Eserance JO, Sung JC, Marguet CG, et al. Controlled survival study of the effects of Tisseel or a combination of and Tisseel on major vascular injury and major collecting-system injury during artial nehrectomy in a orcine model. J Endourol 2005;19:1114 21. 8. Leixnering M, Reichetseder J, Schultz A, et al. Gelatin thrombin granules for hemostasis in a severe traumatic liver and sleen ruture model in swine. J Trauma 2008; 64:456 61. 9. Izzo F, Di Giacomo R, Falco P, et al. Efficacy of a haemostatic matrix for the management of bleeding in atients undergoing liver resection: results from 237 cases. Curr Med Res Oin 2008;24:1011 5. 10. Angioli R, Muzii L, Montera R, et al. Feasibility of use of novel matrix hemostatic sealant () to achieve hemostasis during laaroscoic excision of endometrioma. J Minim Invasive Gynecol 2009;16:153 6. 11. Guzzo TJ, Pollock RA, Forney A, Aggarwal P, Matlaga BR, Allaf ME. Safety and efficacy of a surgeon-reared gelatin hemostatic agent comared with for hemostasis in laaroscoic artial nehrectomy. J Endourol 2009; 23:279 82. 12. Lawson JH. The clinical use and immunologic imact of thrombin in surgery. Semin Thromb Hemost 2006;32[sul 1]:98 110. 13. Duont WD, Plummer WD, Jr. Power and samle size calculation for studies involving linear regression. Controlled Clinical Trials 1998;19:589 601. 14. Levy JH. Pharmacologic methods to reduce erioerative bleeding. Transfusion 2008;48:31S 8S. 15. Liu B, Belboul A, Larsson S, Roberts D. Factors influencing haemostasis and blood transfusion in cardiac surgery. Perfusion 1996;11:131 43. 16. Desotis G, Eby C, Lublin DM. A review of transfusion risk and otimal management of erioerative bleeding with cardiac surgery. Transfusion 2008;48(1 sul):2s 30S. 17. Whitson BA, Huddleston SJ, Savik K, Shumway SJ. Bloodless cardiac surgery is associated with decreased morbidity and mortality. J Card Surg 2007;22:373 8. 18. Nashef SA, Roques F, Hammill BG, et al. Validation of Euroean System for cardiac oerative risk evaluation (EuroSCORE) in North American cardiac surgery. Eur J Cardiothorac Surg 2002;22:101 5.