Systematic elucidation of effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass surgery.

The aim of this study was to systematically elucidate the effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass (CPB) surgery. Twenty-two patients undergoing CPB surgery were randomized to receive 100 mg/kg tranexamic acid or an equal volume of saline after anesthesia induction and prior to skin incision. Plasma levels of tissue plasminogen activator (t-PA) antigen and activity, crosslinked fibrin degradation products (D-dimer), alpha2-antiplasmin-plasmin complex, and plasminogen activator inhibitor-1 (PAI-1) antigen were measured. Blood samples were obtained after induction of anesthesia, before, during, and after CPB, at the end of surgery, and the next morning after surgery. Intraoperative and postoperative blood loss during 24 h after surgery was recorded. Patients' demographics were similar between the two groups. No patients suffered from thrombotic complications after surgery. In the tranexamic acid group, fibrinolytic activity and secondary fibrinolysis as measured by t-PA activity and D-dimer were markedly suppressed during CPB surgery (P=.042 and P=.015, respectively). Decreased fibrinolytic activity and fibrinolysis were accompanied by reduction of perioperative bleeding in the tranexamic acid group. We could also find a good positive correlation between the peak levels of t-PA activity and D-dimer (r(2)=.4203, P=.0011). No differences in the t-PA antigen, PAI-1 antigen release, and plasmin inhibition by alpha2-antiplasmin were apparent between the two groups. In a randomized, prospective trial of patients undergoing CPB surgery, we demonstrated that the synthetic antifibrinolytic drug tranexamic acid effectively suppresses fibrinolysis by inhibiting t-PA and plasmin activity with clear reduction of perioperative blood loss. While tranexamic acid had no effects on the other important fibrinolytic inhibitors like PAI-1 and alpha2-antiplasmin.

Another point of view on the mechanism of thrombin generation during cardiopulmonary bypass: role of tissue factor pathway inhibitor.

OBJECTIVE: To determine the role of tissue factor and tissue factor pathway inhibitor (TFPI) in coagulation activation during cardiopulmonary bypass (CPB). DESIGN: Prospective, observational study. SETTING: Operating room in a city hospital. PARTICIPANTS: Thirty-one patients undergoing cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The plasma levels of tissue factor antigen (tissue factor), total and free TFPI, several markers of thrombin generation (prothrombin fragment F1+2, thrombin antithrombin complex, and fibrinopeptide A), and heparin concentration were measured. Blood samples were obtained after induction of anesthesia (baseline level), before and after CPB, and at the end of the surgery. Despite an average heparin concentration of 2.9 +/- 0.2 IU/ mL, markers of thrombin generation, fibrin formation and its degradation (D-dimer) were observed during CPB. Significant increases of total and free TFPI levels (p < 0.0001) were found during CPB associated with lower tissue factor concentration (p < 0.0001) compared with the baseline values. Heparin concentration correlated with levels of total TFPI (r2 = 0.613, p < 0.0001) and free TFPI (r2 = 0.689, p < 0.0001). Tissue factor concentration showed significant negative correlations with levels of total TFPI (r2 = 0.128, p = 0.0003) and free TFPI (r2 = 0.070, p = 0.0078). CONCLUSION: These data indicate that TFPI release by heparin probably has an important role in the suppression of the tissue factor-dependent coagulation pathway during CPB. These changes occur along with ongoing thrombin generation and its activation. Either insufficient prevention of thrombin generation by TFPI or indirect activation of the intrinsic coagulation pathway occurs during CPB.

[Anesthetic management of a patient with amyotrophic lateral sclerosis].

A 49-year-old male with amyotrophic lateral sclerosis (ALS) was scheduled for gastrectomy. Anesthetic management was performed under general anesthesia with sevoflurane and epidural anesthesia with lidocaine. He showed increased response to vecuronium under monitoring of neuromuscular block. But he responded favorably to anticholineesterase. He had little pain and showed no progress in neurological symptoms in the postoperative period. Neuromuscular monitoring is essential in administrating non-depolarizing neuromuscular blocking agents to patients with ALS, and epidural anesthesia may be useful for perioperative management of patients with ALS.

[Intubation of a patient with rheumatoid arthritis with a 7.5-mm-ID armored endotracheal tube using a laryngeal mask airway].

A 71-year-old male patient with rheumatoid arthritis was scheduled for posterior fusion of the cervical spine. He showed limited cervical movement and atrophic mandible. Tracheal intubation was difficult in his last anesthetic management for the same surgery. This time, we planned a special procedure for predicted difficult tracheal intubation. After induction of general anesthesia, a size-4 laryngeal mask airway was inserted. Next, a flexible fiberscope sheathed with a 6.0-mm-ID cuffed endotracheal tube was inserted through a laryngeal mask airway into the trachea, and the fiberscope was withdrawn. Then, an endotracheal tube changer was inserted through the endotracheal tube. The laryngeal mask airway and the endotracheal tube were withdrawn simultaneously leaving the tube changer. Finally, a 7.5-mm-ID armored endotracheal tube was inserted through the tube changer. The procedure applied in this case is a safe and reliable intubating method in patients with difficult tracheal intubation.

[The duration of action of vecuronium in five patients after kidney transplantation--comparison with that during kidney transplantation].

We compared the duration of vecuronium action in five patients after the kidney transplantation with that during kidney transplantation. After the transplantation, three patients required no hemodialysis therapy but two patients underwent hemodialysis therapy again. In all these five patients, including patients who were back to hemodialysis therapy, the durations of vecuronium action after receiving transplanted kidney were shorter than those during kidney transplantation. These shortened durations are speculated to be mainly due to excretion of vecuronium by the transplanted kidney and the effect of long term steroid therapy. However in this study the durations of vecuronium action in patients who required further hemodialysis therapy were also shorter than those during kidney transplantation. To determine whether this is a common or exceptional phenomenon, further evaluation should be needed.

Secondary hyperparathyroidism shortens the action of vecuronium in patients with chronic renal failure.

The authors studied the duration of action of vecuronium in 15 patients with normal renal function and 40 patients with chronic renal failure to evaluate the effect of secondary hyperparathyroidism on the action of vecuronium. The patients were divided into four groups: 15 patients with normal renal function (Group A); nine patients with chronic renal failure who did not need haemodialysis (Group B); 15 anephric patients who did not require parathyroidectomy (Group C); and 16 anephric patients who underwent parathyroidectomy because of severe secondary hyperparathyroidism (Group D). The ratio of the height of the first twitch (T1) to the baseline value before vecuronium administration was measured by an electromyogram. Baseline T1 was obtained after anaesthesia induction with thiamylal iv. The time to 10% recovery of the first twitch (REC 10) after administration of vecuronium 0.12 mg.kg-1 iv was measured in each group. Anaesthesia was maintained with isoflurane and nitrous oxide in oxygen, and supplemented with fentanyl iv. Patients in Group D showed shorter REC 10 (51 +/- 4 min) than those in Groups B (71 +/- 6 min) and C (80 +/- 10 min) (P < 0.05), but similar REC 10 to patients in Group A (37 +/- 4 min). These results suggest that the duration of action of vecuronium in anephric patients with secondary hyperparathyroidism is shorter than in those without secondary hyperparathyroidism.

[Postoperative pain relief by preanesthetic administration of buprenorphine suppository in elective mastectomy].

Seventy female patients scheduled for elective mastectomy were divided into three groups: Buprenorphine suppository (BPS) 0.4 mg group (n = 29); BPS 0.2 mg (n = 23) group; and control (scopolia extract and tannic acid suppository) group (n = 18). Suppositories were administered rectally to patients of each group one hour before induction of anesthesia. Plasma buprenorphine concentrations, sedation scores at entering the operating room, postoperative pain scores and side effects were evaluated. There were no significant differences in sedation effects of suppository among the three groups. Although there were significant differences in pain scores except at the time when patients left the operating room between BPS 0.2 mg group and the control group, postoperative pain relief in BPS 0.2 mg group was judged not enough. However, postoperative pain relief was more satisfactory in the BPS 0.4 mg group. Plasma concentrations of the BPS 0.4 mg group were higher than those of the BPS 0.2 mg group. Although nausea and vomiting were observed in 5 patients (17.2%) of the BPS 0.4 mg group and 4 patients (17.4%) of the BPS 0.2 mg group, respiratory depression and changes in blood pressure and heart rate were not observed in all groups. In conclusion, preanesthetic administration of the BPS 0.4 mg seemed to be useful for postoperative pain relief after elective mastectomy.