January 2001 TOP TEN SELECT PAPERS

    1   
TITLE:   Leukocytes Can Enhance Platelet-mediated Aggregation and Thromboxane
         Release via Interaction of P-selectin Glycoprotein Ligand 1 with
         P-selectin.
AUTHORS: Faraday N; Scharpf RB; Dodd-O JM; Martinez EA
      Rosenfeld BA; Dorman T
AUTHOR AFFILIATION:
      Submitted for publication May 5, 2000.
PUBLICATION TYPES:
      JOURNAL ARTICLE
LANGUAGES:
      ENG
ABSTRACT:
      BACKGROUND: Platelet-leukocyte conjugates have been observed in
      patients with unstable coronary syndromes and after cardiopulmonary
      bypass. In vitro, the binding of platelet P-selectin to leukocyte
      P-selectin glycoprotein ligand-1 (PSGL1) mediates conjugate
      formation; however, the hemostatic implications of these cell-cell
      interactions are unknown. The aims of this study were to determine
      the ability of leukocytes to modulate platelet agonist-induced
      aggregation and secretion in the blood milieu, and to investigate the
      role of P-selectin and PSGL-1 in mediating these responses. METHODS:
      Blood was drawn from healthy volunteers for in vitro analysis of
      platelet agonist-induced aggregation, secretion (adenosine
      triphosphate, beta-thromboglobulin, and thromboxane), and
      platelet-leukocyte conjugate formation. Experiments were performed on
      live cells in whole blood or plasma to simulate physiologic
      conditions. Whole-blood impedance and optical aggregometry, flow
      cytometry, and enzyme-linked immunosorbent assays were performed in
      the presence and absence of blocking antibodies to P-selectin and
      PSGL1. The platelet-specific agonists, thrombin receptor activating
      peptide and adenosine diphosphate, were used to elicit platelet
      activation responses. RESULTS: Inhibition of platelet-leukocyte
      adherence by P- selectin and PSGL1 antibodies decreased
      agonist-induced aggregation in whole blood. The presence of
      leukocytes in platelet-rich plasma increased aggregation, and this
      increase was attenuated by P-selectin blocking antibodies. Data from
      flow cytometry confirmed that platelet-leukocyte conjugate formation
      contributed to aggregation responses. Blocking antibodies reduced
      platelet agonist-induced thromboxane release but had no impact on
      adenosine triphosphate and beta-thomboglobulin secretion.
      CONCLUSIONS: Leukocytes can enhance platelet agonist- induced
      aggregation and thromboxane release in whole blood and platelet-rich
      plasma under shear conditions in vitro. Interaction of platelet
      P-selectin with leukocyte PSGL1 contributes substantially to these
      effects.

SOURCE:  Anesthesiology 2001 Jan;94(1):145-151
    2   
TITLE:   Tranexamic Acid Administration after Cardiac Surgery: A Prospective,
         Randomized, Double-blind, Placebo-controlled Study.
AUTHORS: Casati V; Bellotti F; Gerli C; Franco A; Oppizzi M
      Cossolini M; Calori G; Benussi S; Alfieri O; Torri G
AUTHOR AFFILIATION:
      Submitted for publication December 1, 1999.
PUBLICATION TYPES:
      JOURNAL ARTICLE
LANGUAGES:
      ENG
ABSTRACT:
      BACKGROUND: Many different doses and administration schemes have been
      proposed for the use of the antifibrinolytic drug tranexamic acid
      during cardiac surgery. This study evaluated the effects of the
      treatment using tranexamic acid during the intraoperative period only
      and compared the results with the effects of the treatment continued
      into the postoperative period. METHODS: Patients undergoing elective
      cardiac surgery with use of cardiopulmonary bypass (N = 510) were
      treated intraoperatively with tranexamic acid and then were
      randomized in a double-blind fashion to one of three postoperative
      treatment groups: group A: 169 patients, infusion of saline for 12 h;
      group B: 171 patients, infusion of tranexamic acid, 1 mg. kg-1. h-1
      for 12 h; group C: 170 patients, infusion of tranexamic acid, 2 mg.
      kg-1. h-1 for 12 h. Bleeding was considered to be a primary outcome
      variable. Hematologic data, allogeneic transfusions, thrombotic
      complications, intubation time, and intensive care unit and hospital
      stay duration also were evaluated. RESULTS: No differences were found
      among groups regarding postoperative bleeding and outcomes; however,
      the group treated with 1 mg.kg-1.h-1 tranexamic acid required more
      units of packed red blood cells because of a significantly lower
      basal value of hematocrit, as shown by multivariate analysis.
      CONCLUSIONS: Prolongation of treatment with tranexamic acid after
      cardiac surgery is not advantageous with respect to intraoperative
      administration alone in reducing bleeding and number of allogeneic
      transfusions. Although the prevalence of postoperative complications
      was similar among groups, there is an increased risk of procoagulant
      response because of antifibrinolytic treatment. Therefore, the use of
      tranexamic acid during the postoperative period should be limited to
      patients with excessive bleeding as a result of primary fibrinolysis.

SOURCE:  Anesthesiology 2001 Jan;94(1):8-14
    3   
TITLE:   Similar neurobehavioral outcome after valve or coronary artery
         operations despite differing carotid embolic counts.
AUTHORS: Neville MJ; Butterworth J; James RL; Hammon JW
      Stump DA
AUTHOR AFFILIATION:
      Departments of Anesthesiology and Cardiothoracic Surgery, Wake Forest
      University School of Medicine, Winston-Salem, NC.
PUBLICATION TYPES:
      JOURNAL ARTICLE
LANGUAGES:
      ENG
ABSTRACT:
      OBJECTIVES: The interrelationships among coronary and valvular
      operations, microemboli, and neurobehavioral outcome are unclear. We
      hypothesized that adult patients undergoing cardiac valve operations
      would have more total emboli delivered to the brain than patients
      undergoing coronary artery bypass grafting and that this would
      associate with worse neurobehavioral outcomes. METHODS: One hundred
      ninety-three patients undergoing coronary artery bypass grafting and
      73 patients undergoing cardiac valve operations were compared.
      Patients received neurologic, neuro-ophthalmologic, and 11
      standardized neurobehavioral tests preoperatively and 5 to 7 days, 1
      month, and 6 months postoperatively. Left common carotid Doppler
      ultrasonographic embolus detection was performed intraoperatively.
      Repeated measures and logistic regression analyses of outcome were
      performed. RESULTS: Patients undergoing either coronary or valve
      operations were well matched by age (61 +/- 10 and 59 +/- 12 years,
      respectively), but a significantly greater fraction of patients
      undergoing valve operations were female, diabetic, or had undergone
      previous cardiac operations. Neurobehavioral scores of patients
      undergoing either coronary artery bypass grafting or cardiac valve
      operations did not differ significantly at any time. Total embolus
      counts differed significantly: the median was 105 during coronary
      artery bypass grafting and 479 during cardiac valve operations
      (geometric means of 104 and 412, respectively; P =.0001).
      Significantly more emboli were detected in the patients undergoing
      cardiac valve operations after removal of the left ventricular vent
      and after separation from cardiopulmonary bypass, but comparable
      numbers of emboli were seen in the 2 groups before cardiopulmonary
      bypass. In both groups decreased neurobehavioral performance was
      apparent at 5 to 7 days, with improvement at 1 and 6 months.
      Increasing numbers of carotid emboli significantly associated with
      worse performance on the letter cancellation test. There were no
      significant differences between patients undergoing valve and
      coronary operations in neurobehavioral outcomes, strokes, transient
      ischemic attacks, or deaths. CONCLUSIONS: The significantly greater
      number of emboli in the group of patients undergoing cardiac valve
      operations is likely the result of the entrainment of intracardiac
      air. The greater numbers of emboli during cardiac valve operations do
      not appear associated with a commensurately greater risk of adverse
      neurologic or neurobehavioral outcome.
     
SOURCE:  J Thorac Cardiovasc Surg 2001 Jan;121(1):125-136
    4   
TITLE:   Low preoperative antithrombin activity causes reduced response to
         heparin in adult but not in infant cardiac-surgical patients 
AUTHORS: Dietrich W; Braun S; Spannagl M; Richter JA
AUTHOR AFFILIATION:
      Department of Anesthesiology and Institute of Clinical Chemistry,
      German Heart Center, Munich, Germany, and the Department of
      Hematology, University Clinic, Munich, Germany.
LANGUAGES:
      Eng
ABSTRACT:
      We evaluated the interaction of preoperative antithrombin (AT)
      activity and intraoperative response to heparin in cardiac surgery.
      Heparin anticoagulation is essential during cardiopulmonary bypass
      (CPB). Heparin itself has no anticoagulant properties, however it
      causes a conformational change of the physiologic plasma inhibitor AT
      that converts this slow-acting serine protease inhibitor into a fast
      acting one. Thus, adequate AT activity is a prerequisite for
      sufficient heparin anticoagulation. AT activity is reduced by
      long-term heparin therapy. This prospective, observational study
      investigated 1516 consecutive cardiac-surgical patients (1304
      patients >1 yr (Group A) and 212 patients </=1 yr (Group I)).
      AT activity was measured the day before surgery by a chromogenic
      substrate assay. The celite-activated activated clotting time (ACT)
      was used to guide intraoperative heparin administration. Heparin
      sensitivity was calculated and the postoperative blood loss and
      perioperative blood requirement was recorded. Infant patients had
      significantly less preoperative AT activity compared with older
      patients: 84 (33)% vs 97 (17)%, median (interquartile range) (P: <
      0. 05). The subgroup of patients aged <1 mo (n = 64) demonstrated
      a preoperative AT activity of 56 (27)% as compared with 90 (23)% in
      infant patients between one month and one year (n = 148). In adult
      patients, preoperative AT activity depended predominantly on
      preoperative heparin treatment: 62% of the patients with an AT
      activity <80% were pretreated with heparin. Five minutes after
      heparin but before CPB the ACT was 587 (334) s in Group A patients
      with AT activity >/=80%, and 516 (232) in patients with AT
      activity </=80% (P: < 0.05). The target ACT of 480 s was
      achieved in 70% of patients with normal AT activity in Group A
      compared with only 54% of patients with AT activity <80% (P: <
      0.05). In Group A patients with decreased AT activity, 18%
      demonstrated an inadequate ACT response-defined as ACT <400 s-to
      the first bolus injection of heparin. In Group I, preoperative AT
      activity did not influence the ACT response (ACT 5 min after heparin:
      846 [447] s in patients with AT activity >/= 80% vs 1000 [364] s
      in patients with decreased AT activity). The heparin sensitivity was
      2.4 (1.1) s/unit heparin/kg compared with 1.5 (0.8) s/unit heparin/KG
      in group A (P: < 0.05). These results suggest that preoperative
      diminished AT activity causes reduced response to heparin in adult
      but not in infant patients. Infant patients demonstrate a higher
      heparin sensitivity despite lower preoperative AT activity.
      Measurement of preoperative AT activity identifies adult patients at
      risk of reduced sensitivity to heparin. Implications: In patients
      less than one year of age, low antithrombin (AT) activity is caused
      by the immature coagulation system. Despite low AT activity, these
      young patients demonstrate a normal or increased response to heparin
      anticoagulation before cardiopulmonary bypass (CPB). In contrast, in
      patients older than one year of age and adult patients decreased
      preoperative AT activity is mainly caused by preoperative heparin
      therapy and causes insufficient response to heparin anticoagulation
      with a standard heparin dosage. Measurement of preoperative AT
      activity identifies patients at risk of inadequate anticoagulation
      during CPB.

SOURCE:  Anesth Analg 2001 Jan;92(1):66-71
    5   
TITLE:   Jejunal mucosal perfusion is well maintained during mild hypothermic
         cardiopulmonary bypass in humans 
AUTHORS: Thoren A; Elam M; Ricksten SE
AUTHOR AFFILIATION:
      Departments of Cardiothoracic Anesthesia and Intensive Care and
      Clinical Neurophysiology, Sahlgrenska University Hospital, Goteborg,
      Sweden.
LANGUAGES:
      Eng
ABSTRACT:
      In the present study, the effects of mild hypothermic (34 degrees C)
      cardiopulmonary bypass (CPB) on jejunal mucosal perfusion (JMP),
      gastric tonometry, splanchnic lactate, and oxygen extraction were
      studied in low-risk cardiac surgical patients (n = 10), anesthetized
      and managed according to clinical routine. JMP was assessed by
      endoluminal laser Doppler flowmetry. Patients were studied during
      seven 10-min measurement periods before, during, and 1 h after the
      end of CPB. Splanchnic oxygen extraction increased during hypothermia
      and particularly during rewarming and warm CPB. JMP increased during
      hypothermia (26%), rewarming (31%), and warm CPB (38%) and was higher
      1 h after CPB (42%), compared with pre-CPB control. The
      gastric-arterial PCO(2) difference was slightly increased (range
      0.04-2.26 kPa) during rewarming and warm CPB as well as 1 h after
      CPB, indicating a mismatch between gastric mucosal oxygen delivery
      and demand. None of the patients produced lactate during CPB. We
      conclude that jejunal mucosal perfusion appears well preserved during
      CPB and moderate (34 degrees C) hypothermia; this finding is in
      contrast to previous studies showing gastric mucosal hypoperfusion
      during CPB. Implications: Jejunal mucosal perfusion increases during
      mild hypothermic cardiopulmonary bypass (CPB). Intestinal laser
      Doppler flowmetry, gastric tonometry, and measurements of splanchnic
      lactate extraction could not reveal a local or global splanchnic
      ischemia during or after CPB. A mismatch between splanchnic oxygen
      delivery and demand was seen, particularly during rewarming and warm
      CPB.
SOURCE:  Anesth Analg 2001 Jan;92(1):5-11
        
    6   
TITLE:   Gene therapy with vascular endothelial growth factor for inoperable
         coronary artery disease: anesthetic management and results 
AUTHORS: Lathi KG; Vale PR; Losordo DW; Cespedes RM; Symes JF
      Esakof DD; Maysky M; Isner JM
AUTHOR AFFILIATION:
      Departments of Anesthesiology, Surgery, and Medicine, St. Elizabeth's
      Medical Center and Tufts University School of Medicine, Boston,
      Massachusetts.
LANGUAGES:
      Eng
ABSTRACT:
      Gene transfer for therapeutic angiogenesis represents a novel
      treatment for medically intractable angina in patients judged not
      amenable to further conventional revascularization. We describe the
      anesthetic management of 30 patients with class 3 or 4 angina,
      enrolled in a Phase 1 clinical trial to assess the safety and
      bioactivity of direct myocardial gene transfer of naked DNA-encoding
      vascular endothelial growth factor (phVEGF(165)), as sole therapy for
      refractory angina. The phVEGF(165) was injected directly into the
      myocardium through a mini-thoracotomy. All patients had major
      clinical predictors for adverse perioperative cardiac complications.
      Fast-track anesthetic management with remifentanil and desflurane,
      multimodal analgesia, and aggressive hemodynamic control with
      nitroglycerin and esmolol were used. All patients tolerated
      anesthesia and surgery without problems. No perioperative myocardial
      infarction, hemodynamic instability, or ventricular failure occurred.
      VEGF injections caused no clinically significant changes in
      cardiovascular function. Mean hospital stay was 3.8 days. There was
      one late death (5 months postoperative). Twenty-nine of 30 patients
      experienced reduced angina (56.2 +/- 4.1 episodes/week preoperatively
      versus 3.8 +/- 1.6 postoperatively, P: < 0.0001) and reduced
      sublingual nitroglycerin consumption (60.1 +/- 4.4 tablets/week
      preoperatively versus 2.9 +/- 1.1 postoperatively, P: < 0.0001).
      Implications: Previously revascularized patients now judged
      "inoperable," continue to present with chronic, recurrent
      angina. Our study describes the anesthetic considerations and
      management of such patients treated with a novel approach by using
      gene therapy to stimulate angiogenesis and improve perfusion to
      ischemic myocardium.

SOURCE:  Anesth Analg 2001 Jan;92(1):19-25
    7   
TITLE:   Coronary artery bypass grafting in patients with mild renal
         insufficiency.
AUTHORS: Hayashida N; Chihara S; Tayama E; Takaseya T
      Yokose S; Hiratsuka R; Enomoto N; Kawara T; Aoyagi S
AUTHOR AFFILIATION:
      Department of Surgery, Kurume University, Fukuoka, Japan.
      nobuhiko@med.kurume-u.ac.jp
PUBLICATION TYPES:
      Journal Article
LANGUAGES:
      eng
ABSTRACT:
      It is well known that dialysis-dependent renal failure increases the
      likelihood of a poor outcome following cardiac surgery. However, it
      is not known whether non-dialysis-dependent mild renal insufficiency
      also influences clinical outcome. Fifty-five patients with
      non-dialysis-dependent renal insufficiency undergoing coronary artery
      bypass grafting (CABG) (Renal group: serum creatinine level >1.5
      mg/dl) were enrolled. These patients were then matched on prognostic
      variables to 148 patients with normal renal function (Control group:
      serum creatinine level <1.5 mg/dl). The early postoperative
      clinical results showed that patients in the Renal group were more
      likely to develop postoperative renal failure (18% vs 1%: p=0.0002)
      and hemorrhage requiring re-exploration (11% vs 2%; p=0.01). Total
      morbidity was significantly higher in the Renal group (40% vs 22%;
      p=0.01). Multivariate analysis revealed that the Renal group was the
      second most important predictor of morbidity (odds ratio (OR) =2.2)
      behind left ventricular dysfunction (OR=2.9). The Renal group was
      also the second most important predictor of postoperative renal
      failure (OR=12.5). Therefore, non-dialysis-dependent mild renal
      insufficiency also increases the risk of morbidity following CABG.
SOURCE:  Jpn Circ J 2001 Jan;65(1):28-32
    
    8   
TITLE:   Interaction between paracrine tumor necrosis factor-alpha and
         paracrine angiotensin II during myocardial ischemia.
AUTHORS: Frolkis I; Gurevitch J; Yuhas Y; Iaina A; Wollman Y
      Chernichovski T; Paz Y; Matsa M; Pevni D; Kramer A; Shapira I; Mohr R
AUTHOR AFFILIATION:
      Department of Thoracic and Cardiovascular Surgery, Tel Aviv Medical
      Center, Israel.
PUBLICATION TYPES:
      Journal Article
LANGUAGES:
      eng
ABSTRACT:
      OBJECTIVES: The purpose of this study was to explore interactions
      between paracrine angiotensin II (Ang-II) and tumor necrosis
      factor-alpha (TNF-alpha) during myocardial ischemia. BACKGROUND:
      Ischemic myocardium releases significant amounts of TNF-alpha. This
      paracrine release correlated with postischemic myocardial injury.
      Other studies showed myocardial protection obtained by the use of
      angiotensin-converting enzyme inhibitors (i.e., captopril) and the
      Ang-II type 1 receptor antagonist losartan after ischemia. The
      possibility that these agents decrease TNF-alpha synthesis has not
      yet been investigated. METHODS: Using the modified Langendorff model,
      isolated rat hearts underwent either 90 min of nonischemic perfusion
      (control group) or 1 h of global cardioplegic ischemia. In both
      groups, either captopril (360 micromol/liter) or losartan (182.2
      micromol/liter) was added before ischemia. The hearts were assayed
      for messenger ribonucleic acid (mRNA) expression and effluent
      TNF-alpha levels. In addition, cardiac myocytes were incubated in
      cell culture with Ang-II. RESULTS: After ischemia, TNF-alpha mRNA
      expression intensified from 0.63 +/- 0.06 (control group) to 0.92 +/-
      0.12 (p < 0.03), and effluent TNF-alpha levels were 711 +/- 154
      pg/ml. The TNF-alpha mRNA expression declined to 0.46 +/- 0.07 (p
      < 0.01) and 0.65 +/- 0.08 (p < 0.02) in captopril- and
      losartan-treated hearts, respectively. Effluent TNF-alpha was below
      detectable levels. Concentrations of TNF-alpha in supernatants of
      incubated cardiac myocytes treated with 10 and 50 nmol/liter of
      Ang-II were 206.0 +/- 47.0 pg/ml and 810 +/- 130 pg/ml, respectively
      (p < 0.004). When pretreated with 700 micromol/liter of losartan,
      TNF-alpha was below detectable levels. CONCLUSIONS: This study
      presents an original explanation for previously reported myocardial
      protection after ischemia, obtained by the use of captopril and
      losartan. These drugs reduce TNF-alpha synthesis, providing strong
      evidence of active interactions between paracrine TNF-alpha and
      Ang-II in the evolution of the ischemic cascade.

SOURCE:  J Am Coll Cardiol 2001 Jan;37(1):316-22
    9   
TITLE:   Protein kinase C isoform-dependent myocardial protection by ischemic
         preconditioning and potassium cardioplegia.
AUTHORS: Lu K; Otani H; Yamamura T; Nakao Y; Hattori R
      Ninomiya H; Osako M; Imamura H
AUTHOR AFFILIATION:
      Department of Thoracic and Cardiovascular Surgery, Kansai Medical
      University, Moriguchi City, Osaka, Japan.
PUBLICATION TYPES:
      JOURNAL ARTICLE
LANGUAGES:
      ENG
ABSTRACT:
      OBJECTIVE: Ischemic preconditioning combined with potassium
      cardioplegia does not always confer additive myocardial protection.
      This study tested the hypothesis that the efficacy of ischemic
      preconditioning under potassium cardioplegia is dependent on protein
      kinase C isoform. METHODS: Isolated and crystalloid-perfused rat
      hearts underwent 5 cycles of 1 minute of ischemia and 5 minutes of
      reperfusion (low-grade ischemic preconditioning) or 3 cycles of 5
      minutes of ischemia and 5 minutes of reperfusion (high-grade ischemic
      preconditioning) or time-matched continuous perfusion. These hearts
      received a further 5 minutes of infusion of normal buffer or
      oxygenated potassium cardioplegic solution. The isoform nonselective
      protein kinase C inhibitor chelerythrine (5 mumol/L) was administered
      throughout the preischemic period. All hearts underwent 35 minutes of
      normothermic global ischemia followed by 30 minutes of reperfusion.
      Isovolumic left ventricular function and creatine kinase release were
      measured as the end points of myocardial protection. Distribution of
      protein kinase C alpha, delta, and epsilon in the cytosol and the
      membrane fractions were analyzed by Western blotting and quantified
      by a densitometric assay. RESULTS: Low-grade ischemic preconditioning
      was almost as beneficial as potassium cardioplegia in improving
      functional recovery; left ventricular developed pressure 30 minutes
      after reperfusion was 70 +/- 15 mm Hg (P <.01) in low-grade
      ischemic preconditioning and 77 +/- 14 mm Hg (P <.001) in
      potassium cardioplegia compared with values found in unprotected
      control hearts (39 +/- 12 mm Hg). Creatine kinase release during
      reperfusion was also equally inhibited by low-grade ischemic
      preconditioning (18.2 +/- 10.6 IU/g dry weight, P <.05) and
      potassium cardioplegia (17.6 +/- 6.7 IU/g, P <.01) compared with
      control values. However, low-grade ischemic preconditioning in
      combination with potassium cardioplegia conferred no significant
      additional myocardial protection; left ventricular developed pressure
      was 80 +/- 17 mm Hg, and creatine kinase release was 14.8 +/- 11.0
      IU/g. In contrast, high-grade ischemic preconditioning with potassium
      cardioplegia conferred better myocardial protection than potassium
      cardioplegia alone; left ventricular developed pressure was 121 +/-
      16 mm Hg (P <.001), and creatine kinase release was 8.3 +/- 5.8
      IU/g (P <.05). Chelerythrine itself had no significant effect on
      functional recovery and creatine kinase release in the control
      hearts, but it did inhibit the salutary effects not only of low-grade
      and high-grade ischemic preconditioning but also those of potassium
      cardioplegia. Low-grade ischemic preconditioning and potassium
      cardioplegia enhanced translocation of protein kinase C alpha to the
      membrane, whereas high-grade ischemic preconditioning also enhanced
      translocation of protein kinase C delta and epsilon. Chelerythrine
      inhibited translocation of all 3 protein kinase C isoforms.
      CONCLUSIONS: These results suggest that myocardial protection by
      low-grade ischemic preconditioning and potassium cardioplegia are
      mediated through enhanced translocation of protein kinase C alpha to
      the membrane. It is therefore suggested that activation of the novel
      protein kinase C isoforms is necessary to potentiate myocardial
      protection under potassium cardioplegia.
SOURCE:  J Thorac Cardiovasc Surg 2001 Jan;121(1):137-148
 
    10   
TITLE:   Tranexamic Acid Administration after Cardiac Surgery: A Prospective,
         Randomized, Double-blind, Placebo-controlled Study.
AUTHORS: Casati V; Bellotti F; Gerli C; Franco A; Oppizzi M
      Cossolini M; Calori G; Benussi S; Alfieri O; Torri G
AUTHOR AFFILIATION:
      Submitted for publication December 1, 1999.
PUBLICATION TYPES:
      JOURNAL ARTICLE
LANGUAGES:
      ENG
ABSTRACT:
      BACKGROUND: Many different doses and administration schemes have been
      proposed for the use of the antifibrinolytic drug tranexamic acid
      during cardiac surgery. This study evaluated the effects of the
      treatment using tranexamic acid during the intraoperative period only
      and compared the results with the effects of the treatment continued
      into the postoperative period. METHODS: Patients undergoing elective
      cardiac surgery with use of cardiopulmonary bypass (N = 510) were
      treated intraoperatively with tranexamic acid and then were
      randomized in a double-blind fashion to one of three postoperative
      treatment groups: group A: 169 patients, infusion of saline for 12 h;
      group B: 171 patients, infusion of tranexamic acid, 1 mg. kg-1. h-1
      for 12 h; group C: 170 patients, infusion of tranexamic acid, 2 mg.
      kg-1. h-1 for 12 h. Bleeding was considered to be a primary outcome
      variable. Hematologic data, allogeneic transfusions, thrombotic
      complications, intubation time, and intensive care unit and hospital
      stay duration also were evaluated. RESULTS: No differences were found
      among groups regarding postoperative bleeding and outcomes; however,
      the group treated with 1 mg.kg-1.h-1 tranexamic acid required more
      units of packed red blood cells because of a significantly lower
      basal value of hematocrit, as shown by multivariate analysis.
      CONCLUSIONS: Prolongation of treatment with tranexamic acid after
      cardiac surgery is not advantageous with respect to intraoperative
      administration alone in reducing bleeding and number of allogeneic
      transfusions. Although the prevalence of postoperative complications
      was similar among groups, there is an increased risk of procoagulant
      response because of antifibrinolytic treatment. Therefore, the use of
      tranexamic acid during the postoperative period should be limited to
      patients with excessive bleeding as a result of primary fibrinolysis.
SOURCE:  Anesthesiology 2001 Jan;94(1):8-14
 
       

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