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.

A cis-acting regulatory element that affects the alternative splicing of a muscle-specific exon in the mouse NCAM gene.

The pre-mRNA encoding the neural cell adhesion molecule (NCAM) is spliced to generate NCAM isoforms containing the muscle-specific domain (MSD) during myogenesis. Utilizing chimeric NCAM minigenes, we searched for cis-acting elements that contribute to the alternative selection of exon MSDb, one of the four exons encoding MSD, and identified an intronic cis-element located downstream of exon MSDb. The cis-element acted as a negative regulator for the selection of exon MSDb in nonmuscle fibroblasts but not in myoblasts, that are already destined to differentiate into muscle cells. The suppressive effect of this cis-element on the selection of exon MSDb was released in the process of myogenesis. When MyoD was co-expressed with a minigene containing this element in fibroblasts, the suppressive effect of the cis-element was released as the cells underwent differentiation. We propose that this cis-element contributes at least as one of the regulatory elements in the differentiation state-dependent selection of MSD exons in vivo.

[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.

[Increased fibrinolytic activity during cardiopulmonary bypass is caused by activated protein C system].

To examine the hypothesis that activated protein C system during cardiopulmonary bypass surgery may increase fibrinolytic activity during cardiopulmonary bypass, protein C activity, protein C antigen and thrombomodulin of sixteen patients undergoing elective cardiopulmonary bypass surgery were investigated after induction of anesthesia, before and after cardiopulmonary bypass, and at the end of operation. Protein C activity decreased and thrombomodulin increased significantly after the cardiopulmonary bypass. There were no significant correlations of thrombomodulin with protein C activity and protein C antigen. In conclusion, we have demonstrated that protein C system is activated and circulating thrombomodulin appears in the systemic circulation during cardiopulmonary bypass surgery and this enhanced activation of protein C system is possibly related to the reported increase of fibrinolytic activity during cardiopulmonary bypass.

[Pharmacodynamics of vecuronium in the kidney transplant recipient and the patient with normal renal function].

Pharmacodynamics of vecuronium were evaluated in seven kidney transplant recipients and compared with seven patients with normal renal function. Vecuronium 0.12 mg.kg-1 was used for the initial dose and 0.03 mg.kg-1 for the second dose for each patient under general anesthesia with either isoflurane, sevoflurane or halothane plus nitrous oxide after induction by thiamylal. The effect of vecuronium was evaluated by a muscle relaxation monitor. The time to the maximum blockade (onset time) and the time of 25% recovery of the first twitch height (duration time) were measured after each administration of vecuronium in patients of both groups. The onset times after the initial and second doses were similar in both groups (180.0 +/- 15.5 sec for recipients versus 185.7 +/- 14.9 sec for patients of normal renal function). However, duration was significantly longer in recipients than in patients of normal renal function. Durations after the initial and second doses were 130 +/- 19 min for the initial dose and 86 +/- 12 min for the second dose in recipients, whereas they were 51 +/- 5 min and 37 +/- 5 min in patients of normal renal function. The prolonged durations of vecuronium in the kidney transplant recipient were speculated to be mainly due to delayed elimination of the drug and effect of cyclosporin, an immunosuppressive agent in the recipients. These results suggest that the titrated administration of vecuronium by keen monitoring of muscle relaxation is needed in the kidney transplant recipient to avoid unnecessary prolongation in duration of action.

[Perioperative management for patients with hypertrophic cardiomyopathy undergoing noncardiac surgery].

We had two patients with hypertrophic cardiomyopathy for noncardiac surgeries. Case 1: A 74-year-old man for right nephrectomy received epidural lidocaine and nitrous oxide combined with 0.2-0.6% isoflurane. During the operation, heart rate and blood pressure were relatively unstable, but he woke up promptly after the operation. Early on the morning of the 2nd post-operative day, he was found dead on his bed. Case 2: A 52-year-old man for gastrectomy was anesthetized with nitrous oxide and halothane with continuous propranolol infusion. Through the operative period, heart rate and blood pressure were stable and postoperative course was uneventful. In these two patients, preoperative Holter ECG showed ventricular tachycardia, which may increase the risk of a sudden death. These cases demonstrate that general anesthesia with nitrous oxide combined with halothane, can be administered with a low risk in patients with HCM for noncardiac surgery and that postoperative intensive care unit monitoring is necessary for these patients for several days to prevent a sudden death.