We have investigated the effect of treatment with tranexamic acid, an inhibitor of fibrinolysis, on blood loss, blood transfusion requirements and blood coagulation in a randomized, double-blind, placebo-controlled study of 42 patients after total knee arthroplasty. Tranexamic acid 15 mg kg-1 (n = 21) or an equivalent volume of normal saline (n = 21) was given 30 min before surgery and subsequently every 8 h for 3 days. Coagulation and fibrinolysis values, blood loss and blood units administered were measured before administration of tranexamic acid, 8 h after the end of surgery and at 24 and 72 h after operation. Coagulation profile was examined (bleeding time, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), plasminogen, beta-thromboglobulin and fibrinogen). Fibrinolysis was evaluated by measurement of concentrations of D-dimer and fibrinogen degradation products (FDP). Total blood loss in the tranexamic acid group was 678 (SD 352) ml compared with 1419 (607) ml in the control group (P < 0.001), and occurred primarily during the first 24 h after surgery. Thirteen patients received 1-5 u. of packed red blood cells in the control group compared with two patients in the tranexamic acid group, who received 3 u. (P < 0.001). Postoperative packed cell volume values were higher in the tranexamic acid group despite fewer blood transfusions. Postoperative concentrations of plasminogen were decreased significantly in the tranexamic acid group (P < 0.001). Platelet count, PT, aPTT, bleeding time, beta-thromboglobulin, fibrinogen and FDP concentrations did not differ between groups, but D-dimer concentrations were increased in the control group. Thromboembolic complications occurred in two patients in the control group compared with none in the tranexamic acid group.

Tranexamic acid 15 mg/kg given as a single preoperative bolus dose reduces postoperative and total blood loss, and packed cell transfusion requirements in primary total hip replacement surgery.

The influence of diclofenac, given by continuous i.v. infusion starting preoperatively, on postoperative pain and inflammation was assessed in a double-blind, randomized, placebo-controlled study in 40 patients scheduled for major orthopedic surgery. Starting 30 min before induction the patients received either diclofenac (0.35 mg.kg-1 bolus followed by a constant-rate infusion of 90 micrograms.min-1) or placebo for 24 h. The pain intensity (VAS) and the amount of rescue narcotic (piritramide on demand) were significantly lower in the diclofenac group from 4 and 6 h postsurgery, respectively, till end of infusion. Acute phase proteins used as inflammation markers (C-reactive protein, alpha 1-chymotrypsin, alpha 1-acid glycoprotein, haptoglobin and coeruloplasmin) showed similar variations in both groups for 24 h. The diclofenac treatment had no influence on hematological and coagulation profiles, nor on muscle and liver enzymes in comparison with placebo. Both patients and observer rated the diclofenac treatment as significantly superior to the placebo treatment.

This double-blind study investigated the effect of adding 1.4% bicarbonate to 0.5% bupivacaine on onset time of sensory and motor blockade after epidural administration. Forty patients were randomly divided into one of two groups. Group 1 received 20 mL of 0.5% bupivacaine (pH, 5.58 +/- 0.12) and group 2 received 20 mL of 0.5% bupivacaine + 0.6 mL of 1.4% bicarbonate (pH, 6.53 +/- 0.06). Onset of temperature sensation loss occurred at L-1 after 5 min in both groups. The first signs of motor impairment were seen after 4 min in three patients in group 1 and two patients in group 2. Maximum motor blockade was reached after 30 min in group 1 and after 36 min in group 2. No difference in motor blockade or upward spread of anesthesia was noted between the two groups. The authors conclude that alkalinization of 0.5% bupivacaine offers no improvement in the onset of epidural blockade.

Midazolam is useful as an intravenous supplement to local anaesthesia techniques in producing sedation, amnesia and anxiolysis, and has about five times the sedative potency of diazepam. Considerable interpatient variability exists in dose requirements, especially in elderly patients. The combined effects of local anaesthetics and midazolam may contribute to enhanced haemodynamic effects and changes in the respiratory pattern, impairing ventilation and oxygenation. Flumazenil can be titrated in incremental doses to reverse the residual sedative effects of midazolam, without intrinsic haemodynamic or respiratory effects, but may not fully antagonise the decrease in chemoreceptor sensitivity nor the changes in breathing pattern induced by midazolam. Patients treated with epidural or spinal anaesthesia supplemented with midazolam should be monitored to avoid hypoxaemia risks even after the administration of flumazenil.