The effect of pre‐operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised,double‐blind,placebo‐controlled trial

We wished to evaluate whether inhibition of the systemic inflammatory response by a single pre‐operative dose of methylprednisolone reduced markers of early endothelial damage after fast‐track total knee arthroplasty. We randomly allocated 70 patients undergoing elective unilateral total knee arthroplasty (1:1) to receive either pre‐operative intravenous methylprednisolone 125 mg (methylprednisolone group) or isotonic saline (control group). All procedures were performed under spinal anaesthesia without a tourniquet, using a standardised multimodal analgesic regime. The outcomes included changes in Syndecan‐1 concentrations, a marker of glycocalyx degradation, markers of endothelial cell damage and activation (plasma soluble thrombomodulin and sE‐Selectin), and permeability by vascular endothelial growth factor, as well as C‐reactive protein concentrations. Blood samples were collected at baseline and 2 h, 6 h and 24 h after surgery, with complete sampling from 63 patients for analyses. Methylprednisolone significantly reduced markers of endothelial damage at 24 h following surgery compared with saline (methylprednisolone group vs. control group, adjusted means (SEM)) expressed by circulating Syndecan‐1: 11.6 (1.0) ng.ml^?1 vs. 13.4 (1.1) ng.ml^?1 p = 0.046; soluble thrombomodulin: 5.1 (0.1) ng.ml^?1 vs. 5.7 (0.2) ng.ml^?1, p = 0.009; sE‐Selectin: 64.8 (1.8) ng.ml^?1 vs. 75.7 (1.9) ng.ml^?1, p = 0.001, and vascular endothelial growth factor: 35.3 (2.7) ng.ml^?1 vs. 58.5 (2.8) ng.ml^?1, p < 0.001. The effect of the intervention increased with time for soluble thrombomodulin, sE‐Selectin and vascular endothelial growth factor, and was more pronounced in patients with high baseline values. Finally, methylprednisolone reduced the C‐reactive protein response 24 h postoperatively; 31.1 (1.1) mg.l^?1 vs. 68.4 (1.1) mg.l^?1, p < 0.001. Pre‐operative administration of methylprednisolone 125 mg reduced circulating markers of endothelial activation and damage, as well as the systemic inflammatory response (C‐reactive protein) early after fast‐track total knee arthroplasty. These findings may have a positive effect on surgical outcome, but require studies in major surgery.     

Dutasteride in men receiving testosterone therapy: a randomised,double‐blind study

We investigate the impact of dutasteride on prostate specific antigen (PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty‐three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone (DHT) and responses to the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire (MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume (PV) was measured using transrectal ultrasound (TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (?0.46 ± 0.81 ng ml^?1; P = 0.04) and in PV (?6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo (P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (?0.46 versus 0.21 ng ml^?1; P = 0.11), PV (?6.65% versus 3.4%; P = 0.08) and MSHQ scores (?10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy.     

Measurement of post‐operative cognitive dysfunction after cardiac surgery: a systematic review

Post‐operative cognitive dysfunction (POCD) is a decline in cognitive function from pre‐operative levels, which has been frequently described after cardiac surgery. The purpose of this study was to examine the variability in the measurement and definitions for POCD using the framework of a 1995 Consensus Statement on measurement of POCD. Electronic medical literature databases were searched for the intersection of the search terms ‘thoracic surgery’ and ‘cognition, dementia, and neuropsychological test.’ Abstracts were reviewed independently by two reviewers. English articles with >50 participants published since 1995 that performed pre‐operative and post‐operative psychometric testing in patients undergoing cardiac surgery were reviewed. Data relevant to the measurement and definition of POCD were abstracted and compared with the recommendations of the Consensus Statement. Sixty‐two studies of POCD in patients undergoing cardiac surgery were identified. Of these studies, the recommended neuropsychological tests were carried out in less than half of the studies. The cognitive domains measured most frequently were attention (n=56; 93%) and memory (n=57; 95%); motor skills were measured less frequently (n=36; 60%). Additionally, less than half of the studies examined anxiety and depression, performed neurological exam, or accounted for learning. Four definitions of POCD emerged: per cent decline (n=15), standard deviation decline (n=14), factor analysis (n=13), and analysis of performance on individual tests (n=12). There is marked variability in the measurement and definition of POCD. This heterogeneity may impede progress by reducing the ability to compare studies on the causes and treatment of POCD.     

Pre‐operative brachial plexus block compared with an identical block performed at the end of surgery: a prospective,double‐blind,randomised clinical trial

We evaluated whether pre‐emptive analgesia with a pre‐operative ultrasound‐guided infraclavicular brachial plexus block resulted in better postoperative analgesia than an identical block performed postoperatively. Fifty‐two patients undergoing fixation of a fractured radius were included. All patients received general anaesthesia with remifentanil and propofol. Patients were randomly allocated into two groups: a pre‐operative block or a postoperative block with 0.5 ml.kg^?1 ropivacaine 0.75%. After surgery, all patients received regular paracetamol plus opioids for breakthrough pain. Mean (SD) time to first rescue analgesic after emergence from general anaesthesia was 544 (217) min in the pre‐operative block group compared with 343 (316) min in the postoperative block group (p = 0.015). Postoperative pain scores were higher and more patients required rescue analgesia during the first 4 h after surgery in the postoperative block group. There were no significant differences in plasma stress mediators between the groups. Analgesic consumption was lower at day seven in the pre‐operative block group. Pain was described as very strong at block resolution in 27 (63%) patients and 26 (76%) had episodes of mild pain after 6 months. We conclude that a pre‐operative ultrasound‐guided infraclavicular brachial plexus block provides longer and better analgesia in the acute postoperative period compared with an identical postoperative block in patients undergoing surgery for fractured radius.     

Analgesic efficacy of subcutaneous local anaesthetic wound infiltration in bilateral knee arthroplasty: a randomised,placebo‐controlled,double‐blind trial

Background: High‐volume wound local infiltration analgesia is effective in knee arthroplasty, but the analgesic efficacy of subcutaneous wound infiltration has not been evaluated. Methods: In a randomised, double‐blind, placebo‐controlled trial in 16 patients undergoing bilateral knee arthroplasty with high‐volume local infiltration analgesia in the deeper layers, saline or ropivacaine 2 mg/ml was infiltrated into the subcutaneous part of the wound in each knee along with the placement of multi‐fenestrated catheters in the subcutaneous wound layers in both knees. Pain was assessed for 6 h post‐operatively and for 3 h after a bolus injection given through the catheter 24 h post‐operatively. Results: Visual analogue scale (VAS) pain scores were significantly lower from the knee infiltrated with ropivacaine compared with the knee infiltrated with saline in the subcutaneous layer of the wound, at rest (P<0.02), with flexion of the knee (P<0.04) and when the leg was straight and elevated (P<0.04). Twenty‐four hours post‐operatively, a decline in the VAS pain scores was observed in both groups, with no statistically significant difference between injection of ropivacaine or saline in the subcutaneously placed catheters (P>0.05). Conclusion: As part of a total wound infiltration analgesia intraoperative subcutaneous infiltration with ropivacaine in bilateral total knee arthroplasty is effective in early post‐operative pain management, while a post‐operative subcutaneous bolus administration through a multiholed catheter 24 h post‐operatively did not show improved analgesia compared with the administration of saline.     

Fetal effects of combined spinal‐epidural vs epidural labour analgesia: a prospective,randomised double‐blind study

We have compared fetal heart rate patterns, Apgar scores and umbilical cord gas values following initiation of labour analgesia using either combined spinal‐epidural or epidural. One hundred and fifteen healthy women requesting neuraxial analgesia in the first stage of labour were randomly assigned to receive either combined spinal‐epidural (n = 62) or epidural analgesia (n = 53). Fetal heart rate traces, recorded for 30 min before and 60 min after neuraxial block, were categorised as normal, suspicious or pathological according to national guidelines. Sixty‐one fetal heart rate tracings were analysed in the combined spinal‐epidural group and 52 in the epidural group. No significant differences were found in fetal heart rate patterns, Apgar scores or umbilical artery and vein acid‐base status between groups. However, in both combined spinal‐epidural and epidural groups, there was a significant increase in the incidence of abnormal fetal heart rate patterns following neuraxial analgesia (p < 0.0001); two before compared with eight after analgesia in the combined spinal‐epidural group and zero before compared with 11 after in the epidural group. These changes comprised increased decelerations (p = 0.0045) (combined spinal‐epidural group nine before and 14 after analgesia, epidural group four before and 16 after), increased late decelerations (p < 0.0001) (combined spinal‐epidural group zero before and seven after analgesia, epidural group zero before and eight after), and a reduction in acceleration rate (p = 0.034) (combined spinal‐epidural group mean (SD) 12.2 (6.7) h^?1 before and 9.9 (6.1) h^?1 after analgesia, epidural group 11.0 (7.3)  h^?1 before and 8.4 (5.9) h^?1 after). These fetal heart rate changes did not affect neonatal outcome in this healthy population.     

Effects of propofol,desflurane, and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients

BACKGROUND: The present study investigated the effects of propofol, desflurane, and sevoflurane on recovery of myocardial function in high-risk coronary surgery patients. High-risk patients were defined as those older than 70 yr with three-vessel disease and an ejection fraction less than 50% with impaired length-dependent regulation of myocardial function. METHODS: Coronary surgery patients (n = 45) were randomly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with desflurane or sevoflurane. Cardiac function was assessed perioperatively and during 24 h postoperatively using a Swan-Ganz catheter. Perioperatively, a high-fidelity pressure catheter was positioned in the left and right atrium and ventricle. Response to increased cardiac load, obtained by leg elevation, was assessed before and after cardiopulmonary bypass (CPB). Effects on contraction were evaluated by analysis of changes in dP/dt(max). Effects on relaxation were assessed by analysis of the load-dependence of myocardial relaxation. Postoperative levels of cardiac troponin I were followed for 36 h. RESULTS: After CPB, cardiac index and dP/dt(max) were significantly lower in patients under propofol anesthesia. Post-CPB, leg elevation resulted in a significantly greater decrease in dP/dt(max) in the propofol group, whereas the responses in the desflurane and sevoflurane groups were comparable with the responses before CPB. After CPB, load dependence of left ventricular pressure drop was significantly higher in the propofol group than in the desflurane and sevoflurane group. Troponin I levels were significantly higher in the propofol group. CONCLUSIONS: Sevoflurane and desflurane but not propofol preserved left ventricular function after CPB in high-risk coronary surgery patients with less evidence of myocardial damage postoperatively.     

Home readiness after day-case knee arthroscopy: spinal, desflurane, isoflurane or propofol anaesthesia?

In this study, four accepted methods of anaesthesia were compared during out-patient knee arthroscopy (KA). Immediate (<2 h) postoperative recovery was evaluated in terms of pain, sedation, nausea and time for home readiness. 173 patients undergoing elective KA were randomised to receive either spinal, propofol infusion, isoflurane or desflurane inhalation anaesthesia. Postoperative pain, sedation and nausea were recorded at 30, 60, 90 and 120 min after arrival in the recovery unit (RU). Discharge readiness was defined as fulfilment of the following criteria in all groups: alert, stable vital signs, able to ambulate, able to take oral fluids, no nausea and pain controllable by oral medication. Postoperative pain, in general, was low in all groups. The spinal patients had significantly lower VAS scores (p<0.001) than the general anaesthesia patients at 30, 60 and 90 min after arrival in RU. At 120 min the pain level was equal in all groups. No remarkable differences between the general anaesthesia groups were noted in terms of pain and nausea. The overall incidence of nausea was 3.4%. Propofol and isoflurane patients were more sedated at 30 min postoperatively than spinal and desflurane patients. At 60 min postoperatively all groups were alert. The time required for home readiness was significantly shorter in all the general anaesthesia groups (propofol 55 min, isoflurane 56 min and desflurane 46 min) than in the spinal anaesthesia group (168 min) (p<0.001). General anaesthesia is a practical alternative in elective knee arthroscopy. The immediate recovery profile is smooth with low levels of pain and nausea and home readiness is achieved significantly sooner than after spinal anaesthesia.     

A randomised,controlled, double‐blind trial of ultrasound‐guided phrenic nerve block to prevent shoulder pain after thoracic surgery

Moderate to severe ipsilateral shoulder pain is a common complaint following thoracic surgery. In this prospective, parallel‐group study at Odense University Hospital, 76 patients (aged > 18 years) scheduled for lobectomy or pneumonectomy were randomised 1:1 using a computer‐generated list to receive an ultrasound‐guided supraclavicular phrenic nerve block with 10 ml ropivacaine or 10 ml saline (placebo) immediately following surgery. A nerve catheter was subsequently inserted and treatment continued for 3 days. The study drug was pharmaceutically pre‐packed in sequentially numbered identical vials assuring that all participants, healthcare providers and data collectors were blinded. The primary outcome was the incidence of unilateral shoulder pain within the first 6 h after surgery. Pain was evaluated using a numeric rating scale. Nine of 38 patients in the ropivacaine group and 26 of 38 patients in the placebo group experienced shoulder pain during the first 6 h after surgery (absolute risk reduction 44% (95% CI 22–67%), relative risk reduction 65% (95% CI 41–80%); p = 0.00009). No major complications, including respiratory compromise or nerve injury, were observed. We conclude that ultrasound‐guided supraclavicular phrenic nerve block is an effective technique for reducing the incidence of ipsilateral shoulder pain after thoracic surgery.