Population Pharmacokinetics of Intra-articular and Intravenous Administration of Tranexamic Acid in Patients Undergoing Total Knee Replacement.

BACKGROUND: Tranexamic acid (TXA), an antifibrinolytic drug, is usually administered intravenously; however, intra-articular administration has recently been proven to be as effective as intravenous administration. Limited information regarding the pharmacokinetics (PK) of TXA after intra-articular administration has been reported. AIMS: The aim of this study was to develop a population PK model of TXA administered as a single intra-articular dose and as two intravenous doses, and to study the sources of interindividual variability (IIV) in the PK processes of TXA. The developed model was used to simulate PK profiles of TXA at different dosage regimens and in patients with renal impairment. METHODS: Patients who underwent primary unilateral total knee replacement (TKR) received 1 g/10 mL (concentration of 100 mg/mL) of TXA applied directly to the surgical field before wound closure, or 2 g (two doses of 1 g) of intravenous TXA. A population PK model was developed using a nonlinear mixed-effects approach and sources of IIV, such as sex, age, body weight, height, body mass index (BMI), preoperative haemoglobin, preoperative haematocrit, and creatinine clearance. RESULTS: Twenty-four patients were included, 12 in each group. Twenty patients were female, mean age (standard deviation) was 73.7 years (5.6). The disposition of TXA was best described as a two-compartment model with clearance dependent on creatinine clearance. Bootstrap results indicated that the model was stable and robust. The estimated bioavailability for intra-articular administration was 81%. Simulations indicated that 100% of patients would have plasma concentrations associated with partial fibrinolysis at 8 h post-administration with the dosages and routes of administration used in the present study. Intra-articular administration would produce complete inhibition of fibrinolysis in only 12% of patients compared with 72.5% with intravenous administration. No adverse events were reported. CONCLUSIONS: This population PK model demonstrated that a single dose of high-concentration, low-volume intra-articular TXA can achieve antifibrinolytic plasma concentrations of the drug for 8 h, providing both local and systemic effects in patients undergoing TKR. TXA administration to the surgical field could be an alternative to the intravenous; route for patients undergoing TKR; however, clinical studies are needed to assess the toxic local effects of TXA. TRIAL REGISTRATION: Spanish Clinical Studies Registry Number: 2017-004059-22. Date of registration: 12 April 2018.

Evaluation of grip strength in hook of hamate fractures treated with osteosynthesis. Is this surgical treatment necessary?

OBJECTIVE: The aim of this study was to evaluate the outcomes of open reduction and internal fixation (ORIF) in hamate hook fractures and review the literature on this surgical procedure. METHODS: We report the outcomes of ORIF of hamate hook fractures in 13 consecutive patients (12 men and 1 woman; mean age: 32 years (range, 22-48 years)). In eight patients (61%) the fracture was associated with ulnar nerve neuritis in Guyon's canal. We assessed the following clinical data: age, sex, mechanism of injury, side of the injured hand and associated lesions, fracture classification, average time from injury to correct diagnosis, surgical technique, complications, and length of follow-up. All patients underwent radiological imaging, including standard radiographs in two planes (anteroposterior and lateral projections), and a CT study. Functional outcomes evaluated were pain, range of motion, grip strength, Disabilities of the arm, shoulder and hand (DASH) and Mayo wrist score. RESULTS: The mean follow-up was 36 months (range, 12-144 months). All 13 cases were treated with ORIF of the hook of the hamate. Mean VAS pain score was 5 preoperatively (4-9) and 1 (0-2) postoperatively. All patients returned to pre-injury level and only one patient felt pain on activity. Preoperative modified Mayo wrist score was 51 and the postoperative value was 94. All outcomes scores improved significantly from preoperative values. The patients who participated in sports postoperatively were able to do so at or near pre-injury levels. Postoperative average range of wrist motion was 76° in extension, 71° in flexion, 14° in ulnar deviation, and 21° in radial deviation. Mean grip strength in the hand with the hook fracture was 58 kg compared with 53 Kg in the unaffected hand. All patients returned to their pre-injury level of functioning after 10-12 weeks and there were no complications. Analysis of grip strength revealed values comparable with the unaffected hand. CONCLUSION: ORIF of hamate hook fractures is a safe and effective technique to restore normal grip strength and return to pre-injury level. In cases of ulnar nerve neuritis, neurolysis of the deep palmar branch is mandatory. LEVEL OF EVIDENCE: Level IV, Therapeutic study.