B. Shelley

Interoperator and Intraoperator Variability of Whole Blood Coagulation Assays: A Comparison of Thromboelastography and Rotational Thromboelastometry

OBJECTIVES Near-patient viscoelastic tests have proved useful in decreasing blood and blood product use in cardiac surgery. Two different analyzers are available, TEG and ROTEM. Many different individuals operate these devices, which raises concern that this factor may significantly affect results. The present study sought to objectively assess variability in results between operators. DESIGN Prospective study. SETTING Regional cardiac center. PARTICIPANTS Adult patients undergoing elective cardiac surgery. INTERVENTIONS Thirty-six mL of blood were taken from each of 21 patients. TEG kaolin and functional fibrinogen (FF) analyses and the equivalent ROTEM INTEM S and FIBTEM S analyses were performed. Six operators performed one of each test per patient to assess interoperator variability. One further operator performed 6 of each test per patient to assess intraoperator variability. MEASUREMENTS AND MAIN RESULTS All routine measurement parameters were noted and the coefficient of variation (CV) calculated, analyzing comparable parameters. All inter-operator CVs were significantly lower for ROTEM analyses compared with TEG. CV for INTEM S CT/ kaolin r time was 4.7 versus 16.3 and MCF/MA was 2.6 versus 4.3 (p < 0.01). Similarly, FIBTEM S MCF/ FF MA was 8.3 versus 12.2. All intraoperator CVs were significantly lower for ROTEM analyses compared with TEG (p<0.01). CV for INTEM S CT/kaolin r time was 3.1 versus 9.8 and MCF/ MA was 1.6 versus 4. Similarly, FIBTEM S MCF/ MA was 6.9 versus 12.1. CONCLUSIONS This series of results suggested ROTEM analyses are more reproducible than TEG and, consequently, that ROTEM may be better suited for use in a multiuser environment.

Where now for thoracic paravertebral blockade

In this issue of Anaesthesia, Luyet et al. report an elegant study examining the reliability of the classical landmark approach to paravertebral blockade (PVB) [1]. While this report will no doubt be of interest to thoracic anaesthetists, we urge all general anaesthetists not to be too hasty in turning the page, as this work has broader application. In 2006, Exadaktylos et al. published a retrospective study analysing the medical records of 129 consecutive patients undergoing surgery for breast cancer. The findings suggested that paravertebral anaesthesia and analgesia for breast cancer surgery may reduce the risk of tumour recurrence or metastasis [2]. While confirmation from prospective randomised controlled trials is awaited, the volume of in vitro data to support such a hypothesis is growing [3]. Should such an approach be convincingly demonstrated to confer survival benefits, the delivery of effective regional anaesthesia and analgesia will become an established standard of care in cancer surgery. This increases the drive to develop a safe, effective and reliable technique for unilateral regional blockade. In thoracic surgery, debate surrounding the ideal analgesic technique for thoracotomy has intensified in recent years with the suggestion that PVB has a better side-effect profile and has been associated with a reduction in complications compared with thoracic epidural analgesia (TEA) [4, 5]. The current practice of thoracic anaesthesia in the UK is represented by an approximately 2:1 split in favour of TEA over PVB [6], a split that has remained consistent over several years, perhaps suggesting that to many, either the reliability or the benefits of PVB over TEA are yet to be sufficiently proven to change practice. Luyet et al. report an observational study aiming to explore the association between the location of paravertebral catheters placed using the classical landmark technique, the distribution of contrast dye delivered through the catheter, and the extent of subsequent somatic block [1]. In doing so, the authors encounter one of the many methodological difficulties that challenges studies of this sort: what constitutes failure of regional anaesthetic blockade? In one recent, high-profile, meta-analysis comparing the analgesic efficacy and side effects of PVB versus TEA for thoracotomy, the included studies defined failed technique as anything from failure to catheterise the epidural space and inadequate analgesia (technique failure) to unavailability of an infusion pump (system failure) [4]. When appraising the regional anaesthetic literature, clinicians must pay careful attention to definitions of failure and decide what constitutes a clinically meaningful failure in their practice. It has been said that regional anaesthesia always works provided you put the right dose, of the right drug, in the right place [7]. The pertinent question is: how do you deliver local anaesthetic to the right place within the paravertebral space? It has been demonstrated that the analgesic effect of single-shot PVB lasts approximately six hours, and that as such, in order to provide prolonged postoperative analgesia via PVB, a catheter technique is required [8]. In Luyet et al.s study, the authors attempted to place PVB catheters by a percutaneous landmark technique in 31 patients. In one patient, difficulties were encountered during paravertebral catheter placement, leading the investigators to switch to an ultrasound-guided approach (undoubtedly a case of technique failure). The authors define the spread of contrast dye within the paravertebral space either close to the intervertebral neural foramen, extrapleural laterally at the level of the ribs, extrapleurally at the level of the vertebral bodies or anterior to the vertebral bodies, as a successful radiological endpoint; the right place. In nine out of 30 catheters, dye was not seen in these locations. Including the failed catheterisation,

Low-serum 25-hydroxyvitamin D reflects severity of illness in critically ill patients

To the Editor: We read with interest the article by Braun et al (1), reporting that, in a large observational study, the relationship between low circulating concentrations of 25-hydroxyvitamin D (25[OH]D) and increased mortality of patients with critical illness. The authors interpret these findings as causal and give a comprehensive discussion of the potential biological plausibility of such an interpretation, concluding that the present study together with their previous study “provide a link between vitamin D at the time of critical care initiation and outcomes”. Finally, they suggest that correction of such vitamin-D deficiency may be beneficial and that supplementation studies be carried out. It is of interest that the authors do acknowledge the possibility of “reverse causation” whereby critical illness may cause lower serum 25(OH)D concentrations. However, they state, “It is not known if critical illness is associated with decreasing 25(OH)D levels.” Therefore, we wish to bring to the attention of Braun et al and the wider critical-care community recent relevant publications. We have recently reported that, following elective knee arthroscopy, circulating concentrations of 25(OH)D decreased rapidly and significantly in response to the systemic inflammatory injury of surgery (2, 3). This year we also have reported that the circulating concentrations of a variety of micronutrients including vitamin D decrease with the increasing severity of the systemic inflammatory response (4). Taken together, these studies question whether circulating concentrations of plasma of 25(OH)D can act as a reliable measure of vitamin-D status in subjects with evidence of a significant systemic inflammatory response. Since the administration of large doses of vitamin D required to raise circulating concentrations of 25(OH)D may be toxic (5), we urge workers in the field of critical care to consider these reports carefully, and consider other approaches to the assessment of vitamin-D status in their patients. For example, when intracellular concentrations of vitamins B2, B-6, and E are compared to plasma concentrations (both in critically ill patients and in surgical models of inflammation), plasma concentrations decrease rapidly, while intracellular concentrations remain stable (2, 4). Therefore, given that in the report by Braun et al the majority of serum 25(OH) D measurements were taken on the day of, or on the days after critical-care initiation (>80% of samples), it is plausible their results were confounded by injury severity. In conclusion, while we do not dispute the observed relationship between plasma vitamin-D levels and mortality in critically ill patients reported in the present study, we suggest that these levels merely reflect injury severity. Furthermore, in this era of evidence-based medicine, we urge caution when interpreting low circulating concentrations of vitamin D and other micronutrients in patients with critical illness. In particular, it is simply not proven that low serum 25(OH)D levels are in themselves harmful, nor can the case for studying vitamin-D supplementation be reasonably advocated at this point. The authors have not disclosed any potential conflicts of interest.

Critical care after lung resection: CALoR 1, a single-centre pilot study.

Lung resection is associated with significant perioperative morbidity, and a proportion of patients will require intensive care following surgery. We set out to characterise this population, assess their burden of disease and investigate the influence of anaesthetic and surgical techniques on their admission rate. Over a two‐year period, 1169 patients underwent surgery, with 30 patients (2.6%) requiring unplanned intensive care. Patients requiring support had a higher mortality (0.2% vs 26.7%, p < 0.001). Logistic regression (following adjustment for Thoracoscore) revealed that an open surgical approach was associated with higher likelihood of admission (p = 0.025, odds ratio = 5.25). There was also a trend towards increased likelihood of admission in patients who received volatile anaesthesia (p = 0.061, odds ratio = 2.08). This topic has been selected for further investigation as part of the 2015 Association of Cardiothoracic Anaesthetists (ACTA) second national collaborative audit, with this study providing pilot data before a multi‐centre study.

The association between intraoperative driving pressure and outcome following one lung ventilation

relaxants. A link between MH susceptibility and potential impairment in oxygen metabolism suggests the possibility of chronic mitochondrial dysfunction. Here we evaluated mitochondrial function in skeletal muscle biopsies after in vitro contracture test (IVCT) from MH susceptible (MHS) and nonsusceptible (MHN) individuals, by measuring oxygen consumption rate as flux control ratios (FCR) using the Oroboros Oxograph-2k analyzer. Biopsy samples were permeabilized with saponin and subjected to a protocol adapted for high resolution respirometry. Samples taken before and after static halothane IVCT were assessed for differences in FCR for each mitochondrial complex state. Compared with MHN samples, human MHS samples showed significant activity reduction in complex II, likely the result of mitochondrial damage caused by chronically elevated resting calcium previously reported in MHS muscle. Halothane exposure during IVCT significantly increased FCR in complex II and the max electron transport system (ETS) state of MHS muscle only (Fig. 6). Based on these data we conclude that there is clear evidence of altered oxygen metabolism in MHS skeletal muscle mitochondria, which we hypothesize to be a result of chronic mutant RYR1 induced increases in cytoplasmic Ca2þ, supporting a connection between MH susceptibility and mitochondrial dysfunction.

Perioperative medicine and UK plc

GLA is supported by British Journal of Anaesthesia/Royal College of Anaesthetists basic science Career Development award, British Oxygen Company research chair grant in anaesthesia from the Royal College of Anaesthetists and British Heart Foundation Programme Grant (RG/14/4/30736). HFG: funded by the Association of Anaesthetists of Great Britain and Ireland, the British Journal of Anaesthesia/Royal College of Anaesthetists and the Melville Trust. BGS: Chief Scientific Officer/NHS Research Scotland Career Research Fellow award. DGL: BBSRC; British Journal of Anaesthesia PhD studentship.

Type III procollagen as a biomarker of susceptibility to ARDS

Dear Editor, We read with interest Forel and colleagues’ prospective study of serum and alveolar N-terminal-peptide type III procollagen (NT-PCP III) levels in the setting of ARDS. The authors provide convincing histological evidence supporting NT-PCP III as a biomarker of fibroproliferation in established ARDS [1]. This adds to previous work describing type III procollagen (PCP III) and its related peptide byproducts (NT-PCP III and C-terminal-propeptide type III procollagen) as ‘early biomarkers’ of ARDS and a previously reported association between PCP III level and increased mortality [2, 3]. Forel et al. and previous investigators have focused on the potential role of PCP III to guide diagnosis and therapy in ARDS. We write to describe our pilot study investigating the role of PCP III in a human one-lung ventilation (OLV) model of ARDS [4] and to offer the hypothesis that PCP III may also serve as a biomarker of susceptibility to lung injury. With research ethics committee approval and informed consent we collected perioperative blood samples from 22 patients undergoing lateral thoracotomy for resection of primary lung cancer. Serum PCP III was directly measured by enzyme immunoassay (USCN Life Science Inc, China) pre-, immediately postand 24 h postoperatively. A PaO2/FiO2 ratio of 300 mmHg or less at 6 h postoperatively was defined as a surrogate end point reflecting poor postoperative oxygenation as described previously in an OLV population [5]. As hypothesised, PCP III levels were negatively associated with poor postoperative oxygenation (PaO2/ FiO2 ratio) immediately (r = -0.52, p = 0.02) and 24 h postoperatively (r = -0.50, p = 0.04; Pearson correlation). Somewhat unexpectedly however, a negative association also existed between preoperative PCP III levels and oxygenation at 6 h postoperatively (r = -0.55, p = 0.01; Fig. 1). A preoperative PCP III level of greater than 73.2 ng/ml had a sensitivity of 0.56 and specificity of 0.89 for a PaO2/FiO2 ratio of 300 mmHg or less at 6 h postoperatively with a positive predictive value of 83.3 % and a negative predictive value of 66.7 %. This was signified by an area under the receiver operating characteristic curve (AUROC) of 0.80, 95 % CI 0.58–1.00 (p = 0.03). The role of PCP III as a biomarker of susceptibility to ARDS is biologically plausible. PCP III has previously been described as a biomarker of both hepatic and pulmonary fibrosis and may be elevated in major trauma i.e. groups known to be at an increased risk of developing ARDS. A possible explanation for our hypothesis is that PCP III is a preoperative marker of subclinical concurrent disease which is increasing susceptibility to ARDS. If validated, a reliable biomarker to predict susceptibility to lung injury could prove valuable in patients undergoing all types of high-risk surgery and throughout the wider hospital population. We are currently conducting a larger study investigating the predictive role of PCP III in a