Neurobehavioral impairments in ciprofloxacin- treated osteoarthritic adult rats.

Background and purpose:

Ciprofloxacin (CIP) is a broad-spectrum antibiotic widely used in clinical practice to treat musculoskeletal infections. Fluoroquinolone-induced neurotoxic adverse events have been reported in a few case reports, all the preclinical studies on its neuropsychiatric side effects involved only healthy animals. This study firstly investigated the behavioral effects of CIP in an osteoarthritis rat model with joint destruction and pain, which can simulate inflammation-associated musculoskeletal pain. Furthermore, effects of CIP on regional brain-derived neurotrophic factor (BDNF) expression were examined given its major contributions to the neuromodulation and plasticity underlying behavior and cognition. 

Fourteen days after induction of chronic osteoarthritis, animals were administered vehicle, 33 mg/kg or 100 mg/kg CIP for five days intraperitoneally. Motor activity, behavioral motivation, and psychomotor learning were examined in a reward-based behavioral test (Ambitus) on Day 4 and sensorimotor gating by the prepulse inhibition test on Day 5. Thereafter, the prolonged BDNF mRNA and protein expression levels were measured in the hippocampus and the prefrontal cortex. 

CIP dose-dependently reduced both locomotion and reward-motivated exploratory activity, accompanied with impaired learning ability. In contrast, there were no significant differences in startle reflex and sensory gating among treatment groups; however, CIP treatment reduced motor activity of the animals in this test, too. These alterations were associated with reduced BDNF mRNA and protein expression levels in the hippocampus but not the prefrontal cortex. 

This study revealed the detrimental effects of CIP treatment on locomotor activity and motivation/learning ability during osteoarthritic condition, which might be due to, at least partially, deficient hippocampal BDNF expression and ensuing impairments in neural and synaptic plasticity.

[Effect of tranexamic acid on blood loss and soft-tissue swelling following cemented total hip replacement]. / A tranexámsav vérvesztést és kis vérzéses szövodményeket befolyásoló hatása cementes csípoprotézis beültetése után.

INTRODUCTION: Tranexamic acid (TXA) is widely used during elective joint replacement to reduce blood loss and decrease the transfusion requirement. AIM: This study assessed the efficacy of tranexamic acid in reducing minor bleeding complications following primary cemented total hip replacement, when rivaroxaban is used as thromboprophylaxis, the complicated wound healing effect of which has been published recently. METHOD: Consecutive patients undergoing hip replacement were studied. Patients receiving tranexamic acid perioperatively between January 2014 and November 2014 were designated as the TXA-group. We compared these data with those of a group of patients who underwent the same procedure between February 2012 and December 2012 (control group), before the introduction of tranexamic acid. The authors investigated the effect of tranexamic acid on surgical wound bleeding and discharge, area of hematoma on the skin surface, thigh volume changes, calculated perioperative blood loss and transfusion requirement. RESULTS: 168 patients, 81 in the TXA-group and 87 in the control group were included. The extent of postoperative thigh swelling was significantly less in the TXA-group, 270.3 mL (129.1-449.0) as compared with the control group, 539.8 mL (350.0-864.8, p<0.001). Tranexamic acid significantly reduced wound bleeding during the first 24 hours postoperatively (p<0.001). The amount of calculated blood loss was significantly less in the TXA-group (1150 mL [780-1496] versus 1579 mL [1313-2074] in the control group, p<0.001). Transfusion requirement was remarkably lower in the TXA-group than in the control group (15% versus 39%). CONCLUSIONS: Tranexamic acid reduces postoperative thigh volume, wound bleeding and area of hematoma on the skin surface when rivaroxaban is used as the anticoagulant. Further large scale studies could help establish the clinical relevance and long-term outcome of minor bleeding complications. Orv Hetil. 2019; 160(12): 456-463.

The effect of the timing of antibiotics and surgical treatment on infection rates in open long-bone fractures: a 6-year prospective study after a change in policy.

Our current protocol in treating open long-bone fractures includes early administration of intravenous antibiotics and surgery on a scheduled trauma list. This represents a change from a previous protocol where treatment as soon as possible after injury was carried out. This review reports the infection rates in the period 6 years after the start of this protocol. Two hundred and twenty open long-bone fractures were reviewed. Data collected included time of administration of antibiotics, time to theatre and seniority of surgeon involved. The patients were followed up until clinical or radiological union occurred or until a secondary procedure for non-union or infection was performed. Clinical, radiological and haematological signs of infection were documented. If present, infection was classified as deep or superficial. Surgical debridement was performed within 6 h of injury in 45 % of cases and after 6 h in 55 % of cases. Overall infection rates were 11 and 15.7 %, respectively (p = 0.49). The overall deep infection rate was 4.3 %. There was also no statistically significant difference in the subgroups of deep (p = 0.46) and superficial (p = 0.78) infection. Intravenous antibiotics were administered within 3 h of injury in 80 % of cases and after 3 h in 20 % of cases. The infection rates were 14 and 12.5 %, respectively (p = 1.0). There was no statistically significant difference in the subgroups of deep (p = 0.62) and superficial (p = 0.73) infection. Further statistical analysis did not reveal a significant difference in infection rates for any combination of timing of antibiotics and surgical debridement. Infection rates where the most senior surgeon present was a consultant were 9.5 % as opposed to 16 % with the consultant not present, but this trend was not statistically significant. These results suggest that the change in policy may have contributed to an improvement of the deep infection rate to 4.3 % from the previous figure of 8.5 % although this decrease is not statistically significant. Surgeons may have had concerns that delaying theatre may lead to an increased infection rate, but these results do not substantiate this concern.

Comparison of minor bleeding complications using dabigatran or enoxaparin after cemented total hip arthroplasty.

BACKGROUND: Orally administered chemical thromboprophylactic agents for total hip replacement (THR) have become popular in recent years. Certain clinical trials suggest that the efficacy and the risk of major bleeding after administration of direct thrombin inhibitor dabigatran etexilate are equivalent to the clinical trial comparator, subcutaneous low-molecular-weight heparin enoxaparin. Our aim was to compare and evaluate the incidence of minor haemorrhagic and soft-tissue adverse effects of enoxaparin and dabigatran. MATERIALS AND METHODS: 122 patients who were treated by elective cemented primary THR were enrolled in our quasi-randomised study. Two groups were formed according to which perioperative thromboprophylactic agent was used: 61 patients in enoxaparin group versus 61 patients in dabigatran group. Thigh volume changes, calculated perioperative blood loss, area of haematoma, wound bleeding, duration of wound discharge and intensity of serous wound discharge on postoperative day 3 and day 7 were recorded. RESULTS: The duration and intensity of serous wound discharge differed significantly between the two groups. Duration of wound discharge after drain removal was 2.2 (±2.7) days in the dabigatran group and 1.2 (±1.9) days in the enoxaparin group (p < 0.05). Significant increase in serous discharge was found in the dabigatran group (p < 0.05) on third and seventh postoperative days compared to the enoxaparin group. CONCLUSION: Both thromboprophylactic agents were found to have appropriate antithrombotic effects after THR. However, dabigatran was associated with an increased incidence of prolonged serous wound discharge, which might cause longer hospitalization and might instigate the use of prolonged antibiotic prophylaxis.

Development of bronchoconstriction after administration of muscle relaxants in rabbits with normal or hyperreactive airways.

Neuromuscular blocking drugs can induce intraoperative bronchospasm. We characterized the magnitude and the temporal profile of the constriction in normal or in hyperresponsive airways after injections of neuromuscular blocking drugs. Respiratory system impedance (Zrs) was measured continuously over a 90-s apneic period in naïve and rabbits sensitized to allergens by ovalbumin. Fifteen s after the start of Zrs recordings, succinylcholine, mivacurium, or pipecuronium was administered in random order. Zrs was then also recorded during the administration of increasing doses of exogenous histamine. To monitor the changes in the airway mechanics during these maneuvers, Zrs was averaged for 2-s time windows, and the airway resistance (Raw) was determined by model fitting. The increases in Raw were significantly larger in the sensitized rabbits than in the naïve animals. The largest increases in Raw and the maximum rate of change in Raw were obtained for succinylcholine (146% +/- 29% and 0.80 +/- 0.12 cm H2O/L, respectively) and mivacurium (80% +/- 25% and 0.71 +/- 0.13 cm H2O/L) and the smallest were obtained for pipecuronium (40% +/- 12% and 0.41 +/- 0.04 cm H2O/L). Allergic sensitization leads to severe and rapidly developing bronchospasm after administrations of mivacurium or succinylcholine. These deleterious side effects should be considered when succinylcholine or mivacurium is administered in the presence of bronchial hyperreactivity.