Intravenous tranexamic acid and lower limb arthroplasty-a randomised controlled feasibility study.

Tranexamic acid (TA) is widely reported to reduce bleeding and the risk of blood transfusion in patients undergoing lower limb arthroplasty. No study in this setting has had adequate power to examine for the effect of TA on either uncommon, but clinically important, adverse events or patient-centric endpoints. A large randomised controlled trial (RCT) is required to address these questions. As a preliminary feasibility study, we conducted an investigator-initiated, prospective, randomised, double blind placebo-controlled trial in 140 patients, aged 45 years or older, undergoing elective primary or revision hip or knee joint replacement. Subjects were randomised to receive intravenous (IV) TA or a placebo. The primary endpoints were the proportion of patients receiving allogenic blood transfusion and the feasibility of extending our trial methodology to a large trial of TA in this population. Secondary endpoints included a range of adverse clinical and surgical events as well as several patient-centric questionnaires. Red blood cell transfusion occurred in 15% of all patients prior to discharge from hospital. Transfusion rates were significantly different between the TA and placebo groups (8.5% versus 21.7%, P=0.03). Three out of four feasibility endpoints were met, with recruitment being slower than expected. No significant differences were seen between groups in the secondary endpoints. Despite a lower rate of transfusion than that widely reported, IV TA reduced transfusion in patients undergoing lower limb arthroplasty. Our trial methodology would be feasible in the setting of a large multicentre study to investigate whether TA is safe and reduces bleeding in lower limb arthroplasty.

Biocompatibility and immunogenicity of elastin-like recombinamer biomaterials in mouse models.

Novel thermo-sensitive elastin-like recombinamers (ELRs) containing bioactive molecules were created for use as a biomimetic biomaterial for tissue regeneration. For effective use for in vivo applications, it is essential to ensure that they do not induce adverse inflammatory, immune, or allergic responses that inhibit tissue repair. Therefore, we sought to establish a pre-clinical approach to evaluate biocompatibility in experimental mice using ELRs as a prototype biomaterial. First, we measured in vitro proliferation and cytokine production from BALB/c and C57BL/6 mouse splenocytes incubated with ELRs. Second, we used a rapid, high throughput in vivo approach in which inflammatory cells and cytokines were measured following an intraperitoneal implantation. Lastly, a subchronic in vivo approach was used in which ELRs or positive controls were subcutaneously implanted and the implantation sites were assessed for inflammation and gene expression. We found that ELRs induced mild inflammation and minimal fibrosis compared to the intense response to Vitoss. Additionally, implantation increased antigen-specific antibody titers for both groups and gene expression profiling of the implantation sites revealed the upregulation of inflammation, fibrosis, and wound healing-related genes in ELR and positive control-implanted mice compared to sham controls. These data demonstrate that ELRs appear safe for use in tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 924-934, 2018.

Comparison of preoperative and intraoperative assessment of aortic stenosis severity by echocardiography.

BACKGROUND: General anaesthesia and surgically induced changes in cardiac loading conditions may alter flow across the aortic valve. This study examined how echocardiographic assessment of the severity of aortic stenosis (AS) changes during surgery. METHODS: Patients who underwent aortic valve replacement for any severity of AS between July 2007 and June 2015 were identified. Peak velocities, mean gradients, and dimensionless indices (DI) measured with preoperative transthoracic echocardiography (TTE) were compared with those measured with intraoperative transoesophageal echocardiography (TOE). Additionally, agreement of preoperative and intraoperative grading of AS based on these measurements was assessed. RESULTS: Data from 319 patients were analysed. On average, intraoperative TOE peak velocity and mean gradient were lower by 0.59 m s -1 and 12.5 mm Hg, respectively ( P <0.0001), compared with preoperative TTE measurements, whereas the difference in mean DI was minimal at 0.008. Preoperative and intraoperative grades of AS severity (mild, moderate, and severe) by peak velocity, mean gradient, and DI agreed in 53.3, 53.7, and 83.3% of patients, respectively. The TOE grade of AS severity by peak velocity and mean gradient was at least one lower than the TTE grade in 45.1 and 42.7% of patients, respectively. Significantly fewer patients had their severity of AS reclassified based on DI ( P <0.0001). CONCLUSIONS: Intraoperative TOE peak velocities and mean gradients are often significantly lower than preoperative TTE measurements, leading to underestimation of AS severity in nearly half of our study patients. The DI is a more reliable measurement of AS severity in the intraoperative setting.

Minimally invasive cardiac output monitoring: agreement of oesophageal Doppler, LiDCOrapid™ and Vigileo FloTrac™ monitors in non-cardiac surgery.

There is lack of data about the agreement of minimally invasive cardiac output monitors, which make it impossible to determine if they are interchangeable or differ objectively in tracking physiological trends. We studied three commonly used devices: the oesophageal Doppler and two arterial pressure-based devices, the Vigileo FloTrac™ and LiDCOrapid™. The aim of this study was to compare the agreement of these three monitors in adult patients undergoing elective non-cardiac surgery. Measurements were taken at baseline and after predefined clinical interventions of fluid, metaraminol or ephedrine bolus. From 24 patients, 131 events, averaging 5.2 events per patient, were analysed. The cardiac index of LiDCOrapid versus FloTrac had a mean bias of -6.0% (limits of agreement from -51% to 39%) and concordance of over 80% to the three clinical interventions. The cardiac index of Doppler versus LiDCOrapid and Doppler versus FloTrac, had an increasing negative bias at higher mean cardiac outputs and there was significantly poorer concordance to all interventions. Of the preload-responsive parameters, Doppler stroke volume index, Doppler systolic flow time and FloTrac stroke volume variation were fair at predicting fluid responsiveness while other parameters were poor. While there is reasonable agreement between the two arterial pressure-derived cardiac output devices (LiDCOrapid and Vigileo FloTrac), these two devices differ significantly to the oesophageal Doppler technology in response to common clinical intraoperative interventions, representing a limitation to how interchangeable these technologies are in measuring cardiac output.

Measurement of peak aortic jet velocity in the perioperative period-machine variability: implications for assessment of aortic stenosis severity.

Variation in echocardiography machines and probes are not well described in the perioperative period. We aimed to compare the estimation of severity of aortic stenosis with transthoracic echocardiography (TTE) using two semi-portable ultrasound machines. Experienced cardiac anaesthetists performed a limited transthoracic echocardiogram with two different semi-portable ultrasound machines in patients with known aortic stenosis. The peak aortic jet velocity with continuous-wave Doppler and the time taken to obtain an acceptable envelope were recorded. The Sonosite M Turbo often underestimated the peak jet velocities (median jet velocity [IQR] 2.25 m/s [1.95 to 3.4] versus 3.85 m/s (3 to 4.2); P <0.001) and required more time to get a satisfactory envelope than the GE Vivid I. There was no statistically or clinically significant difference between the velocities obtained from the Vivid I and those measured on the patient's formal cardiology preoperative transthoracic echocardiogram (median [IQR]: 3.95 m/s [3.0 to 4.7]; P=0.3). However, the velocities obtained by the M Turbo were significantly lower than those obtained by the formal preoperative transthoracic echocardiogram (P <0.001). With the expansion of transthoracic echocardiography amongst anaesthetists, underestimation of the peak aortic jet velocity can significantly underestimate the severity of aortic stenosis with potentially lethal clinical consequences. Semi-portable ultrasound machines with echocardiographic capability are not necessarily equivalent and can result in underestimation of severity of aortic stenosis.

A randomised controlled trial comparing three analgesia regimens following total knee joint replacement: continuous femoral nerve block, intrathecal morphine or both.

This randomised controlled trial compared three analgesia regimens following primary unilateral total knee joint replacement: continuous femoral nerve block (CFNB), intrathecal morphine (ITM), and both. The primary outcome was pain ratings over the first 24 hours. Secondary outcomes included morphine consumption, nausea, pruritus and sedation ratings, oxygen saturation (SpO2) ratings, and ability to mobilise postoperatively. All patients received a spinal anaesthetic and a postoperative patient-controlled morphine pump. Patients were randomised to receive CFNB, ITM, or both. In patients with no CFNB, the use of ITM was blinded. Eighty-one patients were randomised and there were no withdrawals. At 24 hours, the ITM-only group had higher pain ratings than either of the other groups (P=0.04 versus CFNB, P=0.01 versus combination). In the 18 to 24 hour period, the ITM group used more morphine than either of the other groups. There were no statistically significant differences in pain ratings or morphine consumption at earlier time intervals. The ITM group were less likely to be able to sit out of bed on day one. Patients who received ITM were more likely to have pruritus. There were no statistically significant differences in nausea, SpO2or sedation ratings. This study showed that a CFNB resulted in reduced pain and was also associated with less morphine consumption and improved mobilisation at 24 hours compared to ITM. This study did not show any statistically significant differences between CFNB alone and CFNB+ITM.

The relationship between superior vena cava diameter and collapsibility and central venous pressure.

The aim of this study was to assess the relationship between superior vena cava (SVC) diameter, collapsibility and central venous pressure (CVP) in cardiac surgical patients. SVC maximum and minimum diameters, plus collapsibility with ventilation, were measured with transoesophageal echocardiography in the mid-oesophageal bicaval view with M-mode. Simultaneously, CVP was measured via the right atrial port of a pulmonary artery catheter. Measurements were possible in 91 out of 92 patients. The median CVP was 10 mmHg with a range of 2 to 19 mmHg. There was a weak, but statistically significant, correlation between CVP and SVC collapsibility index (r=-0.21, P=0.049). There was no statistically significant correlation between maximum SVC diameter and CVP. Maximum SVC diameter was statistically significantly correlated with weight (Pearson's r=0.28, P=0.008). There was no statistically significant correlation between CVP and age or body dimensions. Our findings indicate that SVC diameter and collapsibility are easily measured with transoesophageal echocardiography but do not reliably reflect CVP in anaesthetised cardiac surgical patients.

The utility of transoesophageal echocardiography for estimating right ventricular systolic pressure.

With the reduction in use of the pulmonary artery catheter, alternative methods of pulmonary pressure estimation are required. The use of echocardiographically-derived right ventricular systolic pressure has recently been questioned, but this technique has not been validated in anaesthetised surgical patients with transoesophageal echocardiography. One hundred measurements of right ventricular systolic pressure with transoesophageal echocardiography were compared with the pulmonary artery systolic pressure obtained simultaneously from a pulmonary artery catheter in patients undergoing cardiac surgery. Simultaneous right ventricular systolic pressure and pulmonary artery systolic pressure measurements were possible in all patients, and these measurements were strongly correlated (r = 0.98, p < 0.001), with minimal bias and narrow limits of agreement (approximately -5 to +5 mmHg), across a broad range of pulmonary pressures. Measurement of right ventricular systolic pressure using tranoesophageal echocardiography is readily achievable and closely correlates with pulmonary artery systolic pressure, with minimal bias, in cardiac surgical patients undergoing general anaesthesia and positive pressure mechanical ventilation of the lungs.

Psychometric evaluation of a direct observation of procedural skills assessment tool for ultrasound-guided regional anaesthesia.

Assessment tools must be investigated for reliability, validity and feasibility before being implemented. In 2013, the Australian and New Zealand College of Anaesthetists introduced workplace-based assessments, including a direct observation of a procedural skills assessment tool. The objective of this study was to evaluate the psychometric properties of this assessment tool for ultrasound-guided regional anaesthesia. Six experts assessed 30 video-recorded trainee performances of ultrasound-guided regional anaesthesia. Inter-rater reliability, assessed using absolute agreement intraclass correlation coefficients, varied from 0.10 to 0.49 for the nine individual nine-point scale items, and was 0.25 for a 'total score' of all items. Internal consistency was measured by correlation between 'total score' and 'overall performance' scale item (r = 0.68, p < 0.001). Construct validity was demonstrated by the 'total score' correlating with trainee experience (r = 0.51, p = 0.004). The mean time taken to complete assessments was 6 min 35 s.

Left ventricular volume and ejection fraction assessment with transoesophageal echocardiography: 2D vs 3D imaging.

BACKGROUND: Developments in transducer technology have enabled the use of three-dimensional transoesophageal echocardiography (3D TOE) in the operating theatre. Transthoracic echocardiography (TTE) 3D left ventricular (LV) volumes and ejection fraction (EF) agree better with magnetic resonance imaging (MRI) measurements, with less intra- and inter-observer variability compared with 2D. This has not been validated with 3D TOE. The aim of this study was to assess the bias, limits of agreement, and reproducibility of 3D TOE and 2D TOE LV volumes and EF in cardiac surgical patients. METHODS: Sixty-three patients having cardiac surgery with TOE were evaluated. LV volumes and EF were calculated using modified Simpson's method on 2D mid-oesophageal four- and two-chamber views, xPlane, and from a 3D full-volume data set. Intra- and inter-observer variability were assessed in a subset of 17 patients. RESULTS: Real-time 3D TOE volume and EF assessment was possible in 59 of the 63 patients. Median end-diastolic volumes (EDVs) as measured by 2D, xPlane, and 3D techniques were 98.5, 94, and 97 ml. Median ESVs were 38.5, 40 and 35.6 ml. Median EFs were 58, 54 and 62.2%. There were no significant pairwise differences between these measurements. The limits of agreement for all comparisons were wide, and there were no statistically significant differences between the three methods in intra- or inter-observer variability. CONCLUSION: The intraoperative use of 3D TOE to estimate LV volumes and EF has small bias compared with 2D assessments, wide limits of agreement, and no clear advantages compared with standard 2D TOE imaging in terms of LV volume and EF assessment.

A comparison of three minimally invasive cardiac output devices with thermodilution in elective cardiac surgery.

This study compared the cardiac output responses to haemodynamic interventions as measured by three minimally invasive monitors (Oesophageal Doppler Monitor the VigileoFlotrac and the LiDCOrapid) to the responses measured concurrently using thermodilution, in cardiac surgical patients. The study also assessed the precision and bias of these monitors in relation to thermodilution measurements. After a fluid bolus of at least 250 ml, the measured change in cardiac output was different among the devices, showing an increase with thermodilution in 82% of measurements, Oesophageal Doppler Monitor 68%, VigileoFlotrac 57% and LiDCOrapid 41%. When comparing the test devices to thermodilution, the kappa statistic showed at best only fair agreement, Oesophageal Doppler Monitor 0.34, LiDCOrapid 0.28 and VigileoFlotrac -0.03. After vasopressor administration, there was also significant variation in the change in cardiac output measured by the devices. Using Bland-Altman analysis, the precision of the devices in comparison to thermodilution showed minimal bias, but wide limits of agreement with percentage errors of Oesophageal Doppler Monitor 64.5%, VigileoFlotrac 47.6% and LiDCOrapid 54.2%. These findings indicate that these three devices differ in their responses, do not always provide the same information as thermodilution and should not be used interchangeably to track cardiac output changes.

Evaluation of systolic murmurs using transthoracic echocardiography by anaesthetic trainees.

Focused transthoracic echocardiography by anaesthetists in the peri-operative period has recently been described; the data suggest that the specific skills required can be obtained by non cardiology physicians with limited training. Aortic stenosis is known to increase significantly the peri-operative risk in non-cardiac surgery. This study aimed to assess the ability of echocardiography naive trainee anaesthetists to recognise and assess the severity of aortic stenosis after a set amount of training. Five trainees underwent 2 h of didactic and hands-on teaching in evaluation of the aortic valve, after which they scanned 20 patients each. Their results were compared with those obtained by an experienced cardiac anaesthetist with echocardiography training and qualifications. There was 100% concordance between trainees and the consultant for assessment of clinically significant aortic stenosis, with no cases of misdiagnosis. There was also 90-100% agreement (kappa statistic 0.8-1) between the consultant and each trainee's assessment of clinically significant aortic stenosis based on a peak aortic velocity > 3 m.sec(-1). Anaesthesia trainees can be successfully and rapidly trained to recognise and estimate the severity of aortic stenosis.

Defining intra-operative hypotension--a pilot comparison of blood pressure during sleep and general anaesthesia.

The scientific justification for particular values of intra-operative hypotension is poorly substantiated. To provide a rationale for appropriate values we recorded blood pressure measurements at home for 24 h using an automated non-invasive ambulatory blood pressure measurement device. These blood pressures were compared with blood pressure measured before and during general anaesthesia in 18 subjects undergoing elective day surgery. We confirmed that a pre-operative reading taken upon admission to hospital is significantly elevated compared to a usual daytime blood pressure in the same patient. The median (IQR [range]) increases in systolic and mean arterial pressures were 10 (2-15 [-5 to 59]) mmHg, p = 0.003 and 10 (5-14 [-5 to 35]) mmHg, p = 0.002, respectively. When using this admission blood pressure measurement as a 'baseline', systolic and mean arterial pressures decreased during sleep by 41 (30-46 [6-83]) mmHg and 34 (26-36 [6-58]) mmHg, respectively (p = 0.001). This decreased even further intra-operatively: systolic blood pressure by 49 (36-64 [15-96]) mmHg and mean arterial pressure by 36 (26-46 [8-66]) mmHg (p = 0.001).

Investigation of a new echogenic needle for use with ultrasound peripheral nerve blocks.

A new 'texturing method' has been developed for nerve block needles in an attempt to improve the ultrasonic image of the needles. Using a synthetic phantom, these textured needles were compared to currently available needles. The textured needle had improved visibility under ultrasound. This type of needle may assist the anaesthetist perform ultrasound-guided regional anaesthesia.

Influence of high tibial osteotomy on bone marrow edema in the knee.

To determine the influence of high tibial osteotomy on subchondral bone marrow edema in medial osteoarthritis of the varus knee, full leg-length radiographs and magnetic resonance imaging were performed in 20 patients (20 knees) before surgery, 1 year postoperatively, and at a mean of 7 years postoperatively. The extent of bone marrow edema in the medial compartment was quantified with magnetic resonance imaging in two planes using the formula for a prolate ellipsoid as follows: length x width x depth x pi/6. We used the Japanese Orthopaedic Association knee score for clinical evaluation. At the last followup, all knees with valgus alignment (10/10) showed reduced edema. In contrast, bone marrow edema increased or remained unchanged in four of 10 knees with neutral or varus alignment. The percentage of satisfactory results was 100% (10/10) in valgus knees and only 30% (3/10) in neutral or varus knees. Extent of bone marrow edema at the followup correlated with the mechanical axis and knee score. Because of the prognostic value of bone marrow abnormalities in the medial compartment observed on magnetic resonance imaging, early lateral closing wedge osteotomy should be considered in patients with varus malalignment and bone marrow edema even in mild cases of medial osteoarthritis.

10,000 reasons to step out--exercise patterns and pedometer evaluation of consultant anaesthetists.

Major international bodies recommend that adults should accumulate at least 30 minutes of moderate intensity physical activity every day. Ten thousand steps a day has been found to approximate 30 minutes of exercise. A questionnaire regarding exercise patterns was sent to all (584) Victorian consultant anaesthetists, and 30 consultants wore a pedometer for one week, during working hours only. The questionnaire response rate was 59.4% (347). Of these respondents, 58% indicated that they had a formal exercise program. There were no significant differences between people with a set exercise program and those without, with respect to age, gender, working hours or smoking. Those with a set exercise program exercised a median of four times per week and the commonest exercise listed was gymnasium attendance (40%). The main reasons cited for having a regular exercise program were maintenance of physical health (77%), mental health (71%) and weight control (35%). The main reasons for not having an exercise program were fatigue (40%), too busy (70%), family commitments (67%) or just not interested (18%). The overall median steps per day for the pedometer group was 4770 with a range of 1667 to 9630, fitting into the classification of 'sedentary'. In summary this study has shown that a significant number of anaesthetists do not achieve adequate physical activity in or out of working hours and has identified some reasons for this behaviour. This will hopefully provide motivation and information for the implementation of useful strategies to increase the level of physical activity performed by anaesthetists.

Removal of the surface layers of human cortical bone allografts restores in vitro osteoclast function reduced by processing and frozen storage.

A major complication of cortical bone grafting is nonunion at the host-graft junction. Many factors are thought to be involved in successful engraftment including the quality of the graft and the host response to it. In particular, the recipient osteoclasts (OCs) play a critical role by resorbing the engrafted bone. Thus, effective engraftment may depend on the inherent biological properties of the bone graft, which subsequently correlates with early and effective OC resorption. Normally, bone grafts are stored and processed by freezing, freeze-drying, irradiation, and lipid extraction. We sought to determine whether processing and storage affected bone quality, as evaluated by OC bone resorption. Cortical bone specimens from six human donors were either fresh, frozen at -75 degrees C, or had undergone combinations of freezing at -75 degrees C, freeze-drying, lipid extraction, irradiation, and treatment with hydrogen peroxide. Bone slices of 0.5-mm thickness taken from the surface, beneath the surface, and at a depth of 7.5 mm were incubated with isolated rabbit OCs and resorption lacunae were measured. We observed highest OC activity with fresh bone followed by frozen, partially processed, and fully processed bone. When allografts were stored at -75 degrees C for 12 months, there was up to a 4.2-fold reduction in OC activity on the surface layer. Additionally, we found reduced OC activity upon the outer surface bone compared to the inner layers. Removal of more than 0.5 mm of frozen and processed bone significantly improved OC activity. These results imply that inner bone layers of stored and processed bone allografts are protected against degradation of bone matrix components, except when frozen for extended periods of time. Taken together, these data suggest that bone allografts should be stored for less than 1 year and require the removal of at least 0.5 mm from their surface prior to transplantation.

Elevated levels of lipoprotein(a) in familial bone marrow edema syndrome of the hip.

There is controversy whether bone marrow edema syndrome represents a distinct transient disease or reflects an early reversible phase of spontaneous osteonecrosis of the hip. Hypofibrinolysis on the basis of elevated plasma levels of plasminogen activator inhibitor or lipoprotein(a) or both has been reported to favor the development of bone marrow edema syndrome and nontraumatic avascular necrosis. The current authors report on the familial occurrence of transient bone marrow edema syndrome of the hip in three female family members. Plasma concentrations of lipoprotein(a) were elevated in all three patients, whereas serum levels of plasminogen activator inhibitor were within normal ranges. This first familial description of transient bone marrow edema syndrome of the hip strongly suggests that a genetically determined elevation of lipoprotein(a) may be an important predisposing factor in these patients.

Decomposition of 2-(1-hydroxybenzyl)thiamin. Ruling out stepwise cationic fragmentation.

[reaction: see text] The rapid fragmentation of 2-(1-hydroxybenzyl)thiamin (1) is initiated by transfer of a proton from C2alpha to give an enamine. The subsequent irreversible process can be written as a concerted (or stepwise) rearrangement involving migration of the hydroxyl hydrogen to the methylene bridge. An attractive alternative is internal addition of C2alpha to the pyrimidine, generating a carbocation. However, addition of azide to the reaction solution, which could trap the carbocation, has no effect on the rate or products of reaction.