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British Journal of Anaesthesia (BJA) - Recent Medical Updates

25th Annual Meeting of Chinese Society of Anesthesiology

Zhengzhou China, September 7-10, 2017

Landmarks in UK anaesthesia

The celebrations in 2017 marking the award of a Royal Charter to the College of Anaesthetists 25 yr ago have been wide ranging and highly successful. They have acknowledged the significant contributions that the Royal College of Anaesthetists (RCoA) has since made to postgraduate education and training, to healthcare quality and patient safety, and to acute medical care both in hospital and beyond. Meetings have been held around the UK to demonstrate the commitment and accomplishments of the RCoA to all its fellows. A major part of the celebrations was the RCoA Anniversary Meeting organized under the leadership of Dr Ramana Alladi in London in March 2017. That scientific meeting entitled ‘Landmarks in UK Anaesthesia’ highlighted the major contributions that fellows of the RCoA have made to clinical and translational research, teaching and training, and healthcare quality improvement in the last 25 yr.

Intraoperative permissive oliguria – how much is too much?

Acute kidney injury (AKI) after general surgery is a serious complication. In abdominal surgery the incidence is around 13%, and it is associated with increased postoperative morbidity, length of hospital stay and a 13-fold increase in the relative risk of in-hospital or 30-day mortality.<a href="#aex387-B1" class="reflinks">1</a><a href="#aex387-B2" class="reflinks">2</a>

Cerebral blood flow and its autoregulation - when will there be some light in the black box?

When considering autoregulation, it is interesting to first consider the cerebral perfusion of a giraffe. Although their necks are about 2.5 m long, they must be able to drink water from the ground level of the oasis and then eat leaves from trees, causing large changes in cerebral perfusion pressure. Fortunately nature has provided them with several cardiovascular, anatomical and physiological adaptions to enable them to do so without fainting.<a href="#aex355-B1" class="reflinks">1</a>

Correlational studies of unconsciousness under anaesthesia: how far can preclinical studies take us?

Determining the electrophysiological correlates of loss of consciousness (LOC) and recovery of consciousness (ROC) under anaesthesia is a holy grail of biomedical science.<a href="#aex391-B1" class="reflinks">1</a> From a purely practical perspective, a non-invasive metric that tracks sensory awareness and is robust to the combination of anaesthetic drugs and patient factors would be a welcome addition to the anaesthetist’s perioperative tool kit.<a href="#aex391-B2" class="reflinks">2</a> From a theoretical perspective, such a metric would prove invaluable for endeavours to understand the neural basis of consciousness, and in particular, sensory awareness.<a href="#aex391-B2" class="reflinks">2</a> The contribution by Plourde and Arseneau<a href="#aex391-B3" class="reflinks">3</a> in this month’s British Journal of Anaesthesia provides evidence towards that end. The authors report that the α2-agonist dexmedetomidine attenuates high-frequency oscillations in the cortex and thalamus at doses that induce loss of the righting reflex. By comparing these results with their previous work on the thalamocortical effects of isoflurane and propofol,<a href="#aex391-B4" class="reflinks">4</a><a href="#aex391-B5" class="reflinks">5</a> the authors conclude that changes in thalamic γ-band signals may be electrophysiological correlates of LOC and ROC. It is interesting to note that some of the results presented here differ from previous studies, in which low γ (∼40 Hz) band power increased under anesthesia.<a href="#aex391-B6" class="reflinks">6</a> In contrast, the effects on high γ (>80 Hz) signals observed by Plourde and Arseneau<a href="#aex391-B3" class="reflinks">3</a> are likely to represent the suppression of spontaneous spiking activity under anaesthesia, which is well supported in the literature.<a href="#aex391-B7" class="reflinks">7</a>

In the December issue…

The final issue of 2017 is accompanied by a special bonus issue freely available on line: the Royal College of Anaesthetists 25th Anniversary Special Issue (see editorial by Hemmings & Hunter, pages 1073--4). This collection of narrative reviews and special articles is based on presentations from the “Landmarks in UK Anaesthesia” meeting held in London in March 2017.

Why has NHS England introduced an innovation and technology tariff to improve safer arterial systems in England?

Editor—Arterial transducer infusion sets are associated with complications such as bacterial contamination and accidental arterial injection, potentially leading to bacteraemia, tissue necrosis and limb loss.<a href="#aex361-B1" class="reflinks">1</a> In recognition of reported complications, the NHS England National Patient Safety Agency (NPSA)<a href="#aex361-B2" class="reflinks">2</a> has issued warnings on the risks associated with accidental arterial injection, and the Joint Commission and the World Health Organization (WHO) have stated that injection ports on arterial catheters should be avoided.<a href="#aex361-B3" class="reflinks">3</a> In England, after the 2008 National Awareness Alert, the NPSA required NHS hospitals to take immediate action and introduce safety systems that included training, audit, labeling of the arterial line and using red coloured transducer sets. Whilst these measures are helpful in reducing error, they do not prevent accidental arterial injection of medication intended for venous administration. Seven years after the NPSA alert we conducted a simulation study which illustrated mis-injection into the arterial line where, despite colour coding and labeling of standard arterial transducer sets, 2/3 study participants made this error in an emergency situation.<a href="#aex361-B4" class="reflinks">4</a> From January 2008 to August 2015, there have been 155 reports of this error to NHS England (Keogh B, Medical Director and Durkin M, National Director of Patient Safety, NHS England, personal communication, 2015). However, it is likely that the error is under-reported as ischaemic complications are delayed for hours in the unconscious patients by which time the incident is forgotten, denied or obscured, and national reporting is not mandatory.

Formulation of a National Surgical Plan in Rwanda: a model for integration of physician and non-physician anaesthetists

Editor—Many low-income countries that have relied upon non-physician anaesthetists are now developing their own anaesthesia training programs for physician anaesthetists. Rwanda’s experience of integrating and educating NPAs and PAs might serve as a model to other countries.

The role of propofol for remote ischaemic preconditioning in the setting of cardiac surgery – a Cochrane systematic review†

Editor—The concept of remote ischaemic preconditioning (RIPC) is an easy, readily available and inexpensive strategy to increase resistance to myocardial ischaemia/reperfusion injury. Within the past decade, RIPC has been translated from experimental studies with promising results to proof-of-principle randomized controlled trials (RCTs) in the setting of cardiac surgery. Despite some beneficial effects in terms of reduced myocardial injury as expressed by blood markers,<a href="#aex357-B1" class="reflinks">1</a> most RCTs failed to show a benefit of RIPC on short or long-term clinical outcome in patients undergoing cardiac surgery.<a href="#aex357-B2" class="reflinks">2</a><a href="#aex357-B3" class="reflinks">3</a> In this context, use of the i.v. anaesthetic propofol has been repeatedly discussed as potential confounding factor that significantly interferes and inhibits RIPC’s cardioprotective effects.<a href="#aex357-B4" class="reflinks">4</a><a href="#aex357-B5" class="reflinks">5</a> We recently performed a Cochrane Systematic Review<a href="#aex357-B1" class="reflinks">1</a> to evaluate the benefits and harms of RIPC in patients undergoing coronary artery bypass grafting, with or without valve surgery. However, the potential influence of volatile anaesthetics compared with propofol anaesthesia was only part of a subgroup analysis and has not been fully evaluated yet. There is still a need to either confirm or exclude propofol as a confounding factor.

Does intraoperative magnesium lessen pain after knee replacement surgery?

Editor—I write in response to the paper by Shin and colleagues<a href="#aex406-B1" class="reflinks">1</a> regarding the use of magnesium sulphate as an analgesic in staged knee arthroplasty. Whilst the study appears well-planned and presents some convincing results, my colleagues and I were left with a few questions.

Reply to: Does intraoperative magnesium lessen pain after knee replacement surgery?

Editor—We greatly thank. Buswell & Fregene<a href="#aex407-B1" class="reflinks">1</a> for their interest in our article.<a href="#aex407-B2" class="reflinks">2</a> We are pleased to respond to their comments below.

Limitations of clinical studies evaluating tertiary hyperalgesia

Editor—Shin and colleagues<a href="#aex412-B1" class="reflinks">1</a> suggested that magnesium sulphate attenuates increased pain intensity at sites remote from the surgical site (tertiary hyperalgesia), based on the observation of reduced pain in a magnesium-administered group vs controls after a second total knee arthroplasty (TKA) during staged bilateral total knee arthroplasty. This may serve as a basis for further studies of tertiary hyperalgesia, a topic that has not been studied extensively to date. Potential confounding factors or possible misinterpretations associated with this study should be discussed to enhance its influence on future studies.

Pulse oximeter perfusion index for assessment of brachial plexus block: a holy grail or a design fail?

Editor—I read with interest the recently published article by Abdelnasser and colleagues<a href="#aex408-B1" class="reflinks">1</a> regarding prediction of successful supraclavicular brachial plexus block using the pulse oximeter perfusion index (PI). The article represents an addition to other articles evaluating the usefulness of the pulse oximeter perfusion index in objective assessment of brachial plexus blocks.<a href="#aex408-B2" class="reflinks">2–4</a>

Reply to: Pulse oximeter perfusion index for assessment of brachial plexus block: a holy grail or a design fail?

Editor—We thank Daoud for his interest in our study<a href="#aex401-B1" class="reflinks">1</a> and are pleased to address the two concerns raised in his letter.<a href="#aex401-B2" class="reflinks">2</a>

Sensitivity is not enough. Response to: Postoperative delirium portends descent to dementia

Editor—I welcome the thoughtful discussion by Aranake-Chrisinger & Avidan about testing for postoperative cognitive decline.<a href="#aex402-B1" class="reflinks">1</a> However, the penultimate paragraph is potentially misleading because it makes two common statistical errors. Firstly, there is confusion about the meaning and importance of test sensitivity. In addition to sensitivity, a test’s utility needs to be evaluated in the context of its specificity and the disease prevalence. A test with 99% sensitivity can be clinically useless if it has poor specificity, or is used in a low prevalence population.<a href="#aex402-B2" class="reflinks">2</a><a href="#aex402-B3" class="reflinks">3</a> Their equating of a 50% sensitivity with a 50% positive predictive value is another commonly made mistake. The SNOUT (negative result in a sensitive test rules out the disease) acronym is unhelpful for the same reasons. Secondly, the article states that repetition of a test can help its sensitivity. This is only true if repeated testing produces results with some degree of conditional independence.<a href="#aex402-B4" class="reflinks">4</a> There is no benefit from repeated testing if keeps giving the same result.

Don’t crush the sensitive snout. Reply to: Sensitivity is not enough

Editor—We entirely agree with Wilson’s comments on our paper<a href="#aex403-B1" class="reflinks">1</a> that sensitivity and positive predictive value (PPV) cannot be equated,<a href="#aex403-B2" class="reflinks">2</a> and appreciate the opportunity to clarify this point. Indeed, it is important to highlight that a sensitive test often has a low PPV (<a href="#aex403-T1" class="reflinks">Table 1</a>).<a href="#aex403-B3" class="reflinks">3</a> In the editorial, we did not in fact liken sensitivity to PPV, but rather related sensitivity to negative predictive value (NPV), using the acronym SNOUT (a negative result in a sensitive test rules out the disease). Table 1NPV, negative predictive value. PPV, positive predictive value. This table illustrates that a sensitive test (e.g.≥90%) has a high NPV (e.g.≥80%), except when the prevalence of a disorder is high and the specificity of the test is lowPrevalence %Sensitivity %Specificity %PPV %NPV %190908.399.9190501.899.8190201.199.520909069.297.320905031.095.220902022.088.950909090.090.050905064.383.350902052.966.7

Perioperative cognitive disorders. Response to: Postoperative delirium portends descent to dementia

Editor—We read with great interest the recent editorial by Aranake-Chrisinger & Avidan.<a href="#aex404-B1" class="reflinks">1</a> We were pleased to see that this editorial contains terminology developed over several yr by the multi-disciplinary International Perioperative Cognition Nomenclature Working Group. At the same time, we were surprised and disappointed that the terminology is presented before the official release (in the British Journal of Anaesthesia as well as Anesthesia & Analgesia, Canadian Journal of Anesthesiology, Acta Anaesthesiologica Scandinavica, Journal of Alzheimers Disease and Anesthesiology),<a href="#aex404-B2" class="reflinks">2</a> without the necessary definitions or attributions. This was particularly surprising given the senior author of the editorial was privy to the work of this group and reviewed final drafts of the manuscript. We presume this oversight simply reflects enthusiasm for adopting this new nomenclature.

New nomenclature: Clarion call or siren song. Reply to: perioperative cognitive disorders

Editor—We thank Evered and Eckenhoff<a href="#aex405-B1" class="reflinks">1</a> for their great interest in our editorial.<a href="#aex405-B2" class="reflinks">2</a> We agree entirely with their perspective that much previous research into postoperative cognitive decline (POCD) is tainted, and that methodological weaknesses have led to incorrect conclusions. For example, the most reliable evidence (e.g. from randomized controlled trials) suggests that persistent POCD (both mild and major neurocognitive disorders [postoperative]) is likely to be a post hoc ergo propter hoc (after this therefore because of this) misattribution fallacy.<a href="#aex405-B3" class="reflinks">3</a> We hope, as they do, that future research into this topic will be more rigorous.

Response to: ‘Failed supraglottic airway’: an algorithm for suboptimally placed supraglottic airway devices based on videolaryngoscopy

Editor—We read with interest the editorial by van Zundert and colleagues<a href="#aex409-B1" class="reflinks">1</a> in the recent issue of British Journal of Anaesthesia. We strongly commend the authors for highlighting the problem of suboptimal laryngeal mask airway (LMA) placement. As a single specialty ear, nose, and throat hospital, we are perhaps in a unique position in that the majority of our caseload is shared airway using first-generation flexible LMAs. Since the flexible LMA was introduced at our hospital in 1990, we estimate that we have performed >135 000 ENT operations, with 80–85% performed with flexible LMAs. This includes a large number of shared airway procedures, such as tonsillectomy. These procedures, in themselves, are a good test of LMA function, requiring the maintenance of optimal ventilation whilst also protecting the larynx from blood and debris.

Author's reply to Thomas et al.

Editor—We are pleased that Thomas and colleagues<a href="#aex410-B1" class="reflinks">1</a> agree with many of the conclusions in our Editorial and audit<a href="#aex410-B2" class="reflinks">2</a><a href="#aex410-B3" class="reflinks">3</a> of suboptimal laryngeal mask airway (LMA) placement. We agree with several points they make in their letter. If initial attempts fail, Magill forceps can be used to guide the flexible LMA beyond the epiglottis, or the cuff can be deflated even further, or more jaw thrust can be applied. All of these are included in our proposals. It is self-evident that there should be adequate levels of anaesthesia, but it would have been unnecessary to repeat such a fundamental point, as that necessity has been emphasized elsewhere.<a href="#aex410-B4" class="reflinks">4</a>

Predicting delirium: are we there yet?

British Journal of Anaesthesia, 2017; 119(2): 281–3, DOI <a href="article.aspx?volume=&page=">10.1093/bja/aex082</a>

Effectiveness of enhanced pulse oximetry sonifications for conveying oxygen saturation ranges: a laboratory comparison of five auditory displays

British Journal of Anaesthesia, 2017; 1–7, DOI <a href="article.aspx?volume=&page=">10.1093/bja/aex343</a>

Attenuation of high-frequency (30–200 Hz) thalamocortical EEG rhythms as correlate of anaesthetic action: evidence from dexmedetomidine

<div class="boxTitle">Abstract</div>Background. Gamma (30–80 Hz) and high-gamma (80–200 Hz) thalamocortical EEG rhythms are involved in conscious processes and are attenuated by isoflurane and propofol. To explore the hypothesis that this attenuation is a correlate of anaesthetic action, we characterized the effect dexmedetomidine, a selective adrenergic α-2 agonist with lesser hypnotic potency, on these rhythms.Methods. We recorded local field potentials from barrel cortex and ventroposteromedial thalamic nucleus in ten previously instrumented rats to measure spectral power (30–50 Hz, 51–75 Hz, 76–125 Hz, 126–200 Hz bands) during baseline, at four dexmedetomidine plasma concentrations obtained by i.v. target-controlled infusion (1.86, 3.75, 5.63 and 7.50 ng ml−1), and during recovery. Thalamocortical coherence over 0.3–200 Hz was also measured.Results. Loss of righting reflex (LORR) occurred with 5.63 ng ml−1. Dexmedetomidine produced a linear concentration-dependent attenuation of cortical (P<0.04) and thalamic (P ≤ 0.0051) log power in all bands. Slopes for cortex and thalamus were similar. The slope for dexmedetomidine on thalamic power in the 76–200 Hz range was less than half that of the other agents (P<0.003). LORR was associated with an increase in delta band (0.3–4.0 Hz) thalamocortical coherence (P<0.001). Increased low-frequency coherence also occurred with propofol and isoflurane.Conclusions. Dexmedetomidine attenuates high-frequency thalamocortical rhythms, but to a lesser degree than isoflurane and propofol. The main differences between dexmedetomidine and the other anaesthetics involved thalamic rhythms, further substantiating the link between impaired thalamic function and anaesthesia. Increased delta coherence likely reflects cyclic hyperpolarization of thalamocortical networks and may be a marker for loss of consciousness.

Individualized positive end-expiratory pressure in obese patients during general anaesthesia: a randomized controlled clinical trial using electrical impedance tomography

<div class="boxTitle">Abstract</div>Background. General anaesthesia leads to atelectasis, reduced end-expiratory lung volume (EELV), and diminished arterial oxygenation in obese patients. We hypothesized that a combination of a recruitment manoeuvre (RM) and individualized positive end-expiratory pressure (PEEP) can avoid these effects.Methods. Patients with a BMI ≥35 kg m−2 undergoing elective laparoscopic surgery were randomly allocated to mechanical ventilation with a tidal volume of 8 ml kg−1 predicted body weight and (i) an RM followed by individualized PEEP titrated using electrical impedance tomography (PEEPIND) or (ii) no RM and PEEP of 5 cm H2O (PEEP5). Gas exchange, regional ventilation distribution, and EELV (multiple breath nitrogen washout method) were determined before, during, and after anaesthesia. The primary end point was the ratio of arterial partial pressure of oxygen to inspiratory oxygen fraction (PaO2/FiO2).Results. For PEEPIND (n=25) and PEEP5 (n=25) arms together, PaO2/FiO2 and EELV decreased by 15 kPa [95% confidence interval (CI) 11–20 kPa, P<0.001] and 1.2 litres (95% CI 0.9–1.6 litres, P<0.001), respectively, after intubation. Mean (sd) PEEPIND was 18.5 (5.6) cm H2O. In the PEEPIND arm, PaO2/FiO2 before extubation was 23 kPa higher (95% CI 16–29 kPa; P<0.001), EELV was 1.8 litres larger (95% CI 1.5–2.2 litres; P<0.001), driving pressure was 6.7 cm H2O lower (95% CI 5.4–7.9 cm H2O; P<0.001), and regional ventilation was more equally distributed than for PEEP5. After extubation, however, these differences between the arms vanished.Conclusions. In obese patients, an RM and higher PEEPIND restored EELV, regional ventilation distribution, and oxygenation during anaesthesia, but these differences did not persist after extubation. Therefore, lung protection strategies should include the postoperative period.Clinical trial registration. German clinical trials register DRKS00004199, <a href="http://www.who.int/ictrp/network/drks2/en/">www.who.int/ictrp/network/drks2/en/</a>.

Drug safety in paediatric anaesthesia

British Journal of Anaesthesia, 2017; 118(5): 670–9, DOI <a href="article.aspx?volume=&page=">10.1093/bja/aex072</a>

Early pitfalls in establishing the British Journal of Anaesthesia

‘Those who do not remember the past are condemned to repeat it.’George Santayana (1863-1952)

Activation of cannabinoid receptor 1 is involved in protection against mitochondrial dysfunction and cerebral ischaemic tolerance induced by isoflurane preconditioning

<div class="boxTitle">Abstract</div>Background. Isoflurane preconditioning (IPC) induces cerebral ischaemic tolerance, but the mechanism remains poorly understood. The aim of this study was to determine changes in mitochondrial function in the brain after IPC, and whether the cannabinoid receptor 1 (CB1R) could be involved in the mechanism of mitochondrial protection mediated by IPC.Methods. Adult male Sprague–Dawley rats were pretreated with isoflurane 2% for 1 h day−1, for 5 days consecutively, and then subjected to 120 min right middle cerebral artery occlusion. Cannabinoid receptor 1 expression in the cellular and mitochondrial membrane was measured. The CB1R agonist HU-210 was administered alone, or the antagonists AM251 and SR141716A were given to the animals before each preconditioning. Neurological scores, infarct volume, apoptosis, and mitochondrial function were examined after middle cerebral artery occlusion.Results. Expression of CB1R on cellular and mitochondrial membranes was increased 6 h after preconditioning. Both IPC and HU-210 administration before middle cerebral artery occlusion improved neurological outcomes and reduced infarct volume. Isoflurane preconditioning increased the expression of the anti-apoptotic proteins Bcl-2 and Bcl-XL and reduced apoptosis in neurones. Isoflurane preconditioning and HU-210 also markedly preserved the activity of respiratory chain complexes, reduced mitochondrial radical generation, preserved mitochondrial membrane potential, and inhibited mitochondrial permeability transition pore opening. Cannabinoid receptor 1 antagonists abolished the improvement in mitochondrial function and the neuroprotective effects induced by IPC.Conclusions. Our results indicate that IPC elicits brain ischaemic tolerance and mitochondrial protection by activating the CB1R, which provides a new mechanism for IPC-induced neuroprotection against cerebral ischaemia.

Effectiveness of enhanced pulse oximetry sonifications for conveying oxygen saturation ranges: a laboratory comparison of five auditory displays

<div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Anaesthetists monitor auditory information about a patient’s vital signs in an environment that can be noisy and while performing other cognitively demanding tasks. It can be difficult to identify oxygen saturation (SpO2) values using existing pulse oximeter auditory displays (sonifications).<div class="boxTitle">Methods</div>In a laboratory setting, we compared the ability of non-clinician participants to detect transitions into and out of an SpO2 target range using five different sonifications while they performed a secondary distractor arithmetic task in the presence of background noise. The control sonification was based on the auditory display of current pulse oximeters and comprised a variable pitch with an alarm. The four experimental conditions included an Alarm Only condition, a Variable pitch only condition, and two conditions using sonifications enhanced with additional sound dimensions. Accuracy to detect SpO2 target transitions was the primary outcome.<div class="boxTitle">Results</div>We found that participants using the two sonifications enhanced with the additional sound dimensions of tremolo and brightness were significantly more accurate (83 and 96%, respectively) at detecting transitions to and from a target SpO2 range than participants using a pitch only sonification plus alarms (57%) as implemented in current pulse oximeters.<div class="boxTitle">Conclusions</div>Enhanced sonifications are more informative than conventional sonification. The implication is that they might allow anaesthetists to judge better when desaturation decreases below, or returns to, a target range.

Influence of deep neuromuscular block on the surgeonś assessment of surgical conditions during laparotomy: a randomized controlled double blinded trial with rocuronium and sugammadex

British Journal of Anaesthesia, 2017; 119(3): 435–42, DOI <a href="article.aspx?volume=&page=">10.1093/bja/aex241</a>

Changes in platelet Bax levels contribute to impaired platelet response to thrombin after cardiopulmonary bypass: prospective observational clinical and laboratory investigations

<div class="boxTitle">Abstract</div>Background. Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery.Methods. We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery (n=20 each). We also evaluated the in vitro effects of platelet Bax increase in eight healthy volunteers.Results. Thrombin-induced platelet calcium mobilisation and platelet-surface glycoprotein Ib (GPIb) expression were lowest at weaning from CPB and did not recover on postoperative day one. On-pump surgery increased platelet expression of Bax, especially the oligomerised form, along with translocation of Bax from the cytosol to mitochondria and platelet-surface tumour necrosis factor-alpha (TNF-α)–converting enzyme (TACE) expression. In contrast, mitochondrial cytochrome c expression was reduced. While similar in direction, the magnitude of the observed changes was smaller in patients having off-pump surgery. In vitro, a cell-permeable Bax peptide increased platelet Bax expression to the same extent seen during bypass and produced similar platelet changes. These apoptotic-like changes were largely reversed by Bcl-xL pre-administration, and were completely reversed by combined application of inhibitors that stabilise outer mitochondrial membrane permeability and TACE.Conclusions. CPB increases platelet Bax expression, which contributes to reduced platelet-surface GPIb expression and thrombin-induced platelet calcium changes. These changes in platelet apoptotic signalling might contribute to platelet dysfunction after CPB.Clinical trial registration. UMIN Clinical Trials Registry (number UMIN000006033).

Is postspinal hypotension a sign of impaired cardiac performance in the elderly? An observational mechanistic study

<div class="boxTitle">Abstract</div>Background. We have previously reported that stroke volume is reduced in a majority of elderly patients undergoing surgical repair of hip fracture before and after intrathecal injection of anaesthetic. We aimed to investigate these observations further in a prospective study of elderly patients undergoing elective hip or knee arthroplasty under spinal anaesthesia.Methods. Patients ≥65 yr undergoing elective arthroplasty were monitored with LiDCOplus™ preoperatively (baseline), before and continuously for 45 min after spinal anaesthesia. Postspinal hypotension was defined as systolic blood pressure (bp) < 100 mm Hg or > 30% decrease from baseline. Associations between post-spinal hypotension and haemodynamic changes before (i.e. between baseline and before injection) spinal anaesthesia were analysed by logistic regression analysis.Results. Twenty patients with a mean age of 74 (range 66–89) yr were included. Stroke volume index decreased by 14% (95% CI 9.3%–19%) before spinal anaesthesia. When patients were categorised according to post-spinal hypotension (Y/N) the patterns of haemodynamic changes differed. In the hypotensive patients, cardiac index progressively decreased whereas it increased initially in the non-hypotensive patients. Reduction of cardiac index from baseline before spinal anaesthesia was associated with increased risk of hypotension: OR 0.79 (95% CI 0.60, 0.91). The predictive value of reduced cardiac index was good (AUC under ROC curve 0.91).Conclusions. A decrease in cardiac output from baseline before spinal anaesthesia and an inability to increase it after induction may be important features of postspinal hypotension in elderly patients.

Intraoperative oliguria predicts acute kidney injury after major abdominal surgery

<div class="boxTitle">Abstract</div>Background. The threshold of intraoperative urine output below which the risk of acute kidney injury (AKI) increases is unclear. The aim of this retrospective cohort study was to investigate the relationship between intraoperative urine output during major abdominal surgery and the development of postoperative AKI and to identify an optimal threshold for predicting the differential risk of AKI.Methods. Perioperative data were collected retrospectively on 3560 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or oesophageal resection) at Kyoto University Hospital. We evaluated the relationship between intraoperative urine output and the development of postoperative AKI as defined by recent guidelines. Logistic regression analysis was performed to adjust for patient and operative variables, and the minimum P-value approach was used to determine the threshold of intraoperative urine output that independently altered the risk of AKI.Results. The overall incidence of AKI in the study population was 6.3%. Using the minimum P-value approach, a threshold of 0.3 ml kg−1 h−1 was identified, below which there was an increased risk of AKI (adjusted odds ratio, 2.65; 95% confidence interval, 1.77–3.97; P<0.001). The addition of oliguria <0.3 ml kg−1 h−1 to a model with conventional risk factors significantly improved risk stratification for AKI (net reclassification improvement, 0.159; 95% confidence interval, 0.049–0.270; P=0.005).Conclusions. Among patients undergoing major abdominal surgery, intraoperative oliguria <0.3 ml kg−1 h−1 was significantly associated with increased risk of postoperative AKI.

Overuse of preoperative laboratory coagulation testing and ABO blood typing: a French national study

<div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Following publication of guidelines on routine preoperative tests, the French Society of Anaesthesiology and Intensive Care (SFAR), in association with French national public health insurance, conducted a survey to evaluate adherence to guidelines and the economic consequences.<div class="boxTitle">Methods</div>Using the French Hospital Discharge Database and National Health Insurance Information system, tests performed during the 30 days before surgery were analysed for two situations: (1) standard laboratory coagulation tests and ABO blood typing in children able to walk and scheduled for tonsillectomy/adenoidectomy; and (2) ABO blood typing in adults before laparoscopic cholecystectomy, thyroidectomy, lumbar discectomy or breast surgery. Guidelines do not recommend any preoperative tests in these settings.<div class="boxTitle">Results</div>Between 2013 and 2015, a coagulation test was performed in 49% of the 241 017 children who underwent tonsillectomy and 39% of the 133 790 children who underwent adenoidectomy. A similar pattern was observed for ABO blood typing although re-operation rates for bleeding on the first postoperative day were very low (0.12–0.31% for tonsillectomy and 0.01–0.02% for adenoidectomy). Between 2012 and 2015, ABO blood typing was performed in 32–45% of the 1 114 082 patients who underwent one of the four selected procedures. The transfusion rate was very low (0.02–0.31%). The mean cost for the four procedures over the 4 yr period was €5 310 000 (sd €325 000).<div class="boxTitle">Conclusions</div>Standard laboratory coagulation tests and ABO blood typing are still routinely prescribed before surgery and anaesthesia despite current guidelines. This over-prescription represents a high and unnecessary cost, and should therefore be addressed.

Novel method for intraoperative assessment of cerebral autoregulation by paced breathing

<div class="boxTitle">Abstract</div>Background. Cerebral autoregulation (CA) is the mechanism that maintains constancy of cerebral blood flow (CBF) despite variations in blood pressure (BP). Patients with attenuated CA have been shown to have an increased incidence of peri-operative stroke. Studies of CA in anaesthetized subjects are rare, because a simple and non-invasive method to quantify the integrity of CA is not available. In this study, we set out to improve non-invasive quantification of CA during surgery. For this purpose, we introduce a novel method to amplify spontaneous BP fluctuations during surgery by imposing mechanical positive pressure ventilation at three different frequencies and quantify CA from the resulting BP oscillations.Methods. Fourteen patients undergoing sevoflurane anaesthesia were included in the study. Continuous non-invasive BP and transcranial Doppler-derived CBF velocity (CBFV) were obtained before surgery during 3 min of paced breathing at 6, 10, and 15 bpm and during surgery from mechanical positive pressure ventilation at identical frequencies. Data were analysed using frequency domain analysis to obtain CBFV-to-BP phase lead as a continuous measure of CA efficacy. Group averages were calculated. Values are means (sd), and P<0.05 was used to indicate statistical significance.Results. Preoperative vs intraoperative CBFV-to-BP phase lead was 43 (9) vs 45 (8)°, 25 (8) vs 24 (10)°, and 4 (6) vs −2 (12)° during 6, 10, and 15 bpm, respectively (all P=NS).Conclusions. During surgery, cerebral autoregulation indices were similar to values determined before surgery. This indicates that CA can be quantified reliably and non-invasively using this novel method and confirms earlier evidence that CA is unaffected by sevoflurane anaesthesia.Clinical trial registration. NCT03071432.

Is science the answer?

Nearly ten years ago, Tobin described the irony that evidence-based medicine (EBM) lacks a sound scientific basis.<a href="#aex334-B1" class="reflinks">1</a> A sentinel paper concluded that most results of medical research were false,<a href="#aex334-B2" class="reflinks">2</a> and now the same author, a well-lauded EBM proponent, argues that even if true, most clinical research is not useful<a href="#aex334-B3" class="reflinks">3</a> and now concedes that EBM has been ‘hijacked’ by ‘vested interests’ including industry and researchers.<a href="#aex334-B4" class="reflinks">4</a> The community expends vast resources on research, yet it has been estimated that there is an 85% ‘waste in the production and reporting of research evidence’.<a href="#aex334-B5" class="reflinks">5</a>

Evidence-based medicine: the clue is in the name

Keane and Berg<a href="#aex337-B1" class="reflinks">1</a> have taken issue with the scientific basis of medicine. Their premise is built on the following three challenges: that ‘science’ (in particular, the randomized controlled trial) is fundamentally unsuited to complex health care; that the evolutionary processes described in economics are a better fit to health care; and that attempts to grade recommendations are unnecessary and unhelpful. Their editorial raises genuine concerns and merits careful reading. But this perhaps presents a Utopian fallacy; evidence-based medicine isn’t perfect so it must be replaced. The term ‘evidence-based medicine’ is frequently misused, misapplied, and misunderstood. Evidence-based medicine (if it is to live up to its name) should be open to scrutiny and challenge. It is certainly not a religious creed that cannot be questioned. Unthinking misapplication of ‘evidence’ leads both directly and indirectly to poor patient outcomes. Evidence-based medicine has many definitions, but Masic and colleagues<a href="#aex337-B2" class="reflinks">2</a> described it well: ‘Evidence based medicine is the conscientious, explicit, judicious and reasonable use of modern, best evidence in making decisions about the care of individual patients. Evidence based medicine integrates clinical experience and patient values with the best available research information.’

Guidelines on informed consent in anaesthesia: unrealistic, unethical, untenable….

‘Informed consent’ has become the primary paradigm for protecting the legal rights of patients and guiding the ethical practice of medicine.<a href="#aex347-B1" class="reflinks">1</a> The Association of Anaesthetists of Great Britain and Ireland (AAGBI) ‘informed consent’ guidelines have recently been updated in response to ‘the changing ethical and legal background against which anaesthetists, intensivists and pain specialists, currently work’.<a href="#aex347-B2" class="reflinks">2</a> This guidance aims to advise its members (and others) how to provide information about anaesthesia that respects patient autonomy and stays within the law.<a href="#aex347-B3" class="reflinks">3</a> This raises the question, are we really achieving the key principles of primum non nocere,<a href="#aex347-B4" class="reflinks">4</a> respect for patient autonomy,<a href="#aex347-B5" class="reflinks">5</a> and the need to provide adequate information?<a href="#aex347-B6" class="reflinks">6</a> Current guidance has been almost solely based on medicolegal determinations around inadequate informed consent, focusing on the failure to disclose a ‘material risk’.<a href="#aex347-B7" class="reflinks">7</a><a href="#aex347-B8" class="reflinks">8</a> This has led health authorities and many clinicians to interpret the guidelines as a directive, informing patients of an ever-increasing list of potential anaesthesia-related adverse events. Misguided attempts to include every possible ‘material risk’ are leaving patients bombarded with excessive amounts of largely irrelevant and incomprehensible information.<a href="#aex347-B9" class="reflinks">9</a><a href="#aex347-B10" class="reflinks">10</a> This practice is also leading to unnecessary alarm and confusion, not to mention exposure of patients to the adverse effects of nocebo communications (negative suggestion).<a href="#aex347-B11" class="reflinks">11</a>

An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers

<div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg.<div class="boxTitle">Methods</div>Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal PCO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake.<div class="boxTitle">Results</div>All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference −5.0 L min−1, 95% confidence interval: −7.1 to −2.9 L min−1, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05).<div class="boxTitle">Conclusions</div>In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.

Effectiveness of tip rotation in fibreoptic bronchoscopy under different experimental conditions: an in vitro crossover study

<div class="boxTitle">Abstract</div>Background. Proper manipulation of fibreoptic bronchoscopes is essential for successful tracheal intubation or diagnostic bronchoscopy. Failure of proper navigation and rotation of the fibrescope may lead to difficulties in advancing the fibrescope and might also be responsible for (unnecessary) difficulties and delays in fibreoptic tracheal intubation, with subsequent hypoxaemia. The present study, therefore, aimed to assess the effectiveness of tip rotation in flexible bronchoscopes in different experimental conditions.Methods. Five differently sized pairs of fibrescopes (outer diameters of 2.2, 2.4, 3.5, 4.2, and 5.2 mm) were inserted into paediatric airway manikins via an appropriately sized laryngeal mask and were turned clockwise or anticlockwise at the fibrescope body or cord to 45, 90, and 180°, with the cord held either straight or bent. The primary outcome measure was the ratio of rotation measured at the tip over the rotation performed with the fibrescope body or cord.Results. Overall, the ‘body’ turn was significantly less effective when a bent cord was present (mean difference ranging from 29.8% (95% confidence interval 8.8–50.9) to 117.4% (93.6–141.2). This difference was diminished when the ‘cord’ turn was performed. Smaller fibrescopes, with outer diameters of 2.2 and 2.4 mm, were inferior with respect to the transmission of ‘body’ rotation to the tip.Conclusions. ‘Cord’ turning of the fibrescope appears to be more effective in rotating the tip than a turn of the fibrescope ‘body’ only. Straightening the fibrescope cord and combined ‘body’ and ‘cord’ turning are recommended.

Assessment of changes in lactate concentration with intravascular microdialysis during high-risk cardiac surgery using the trend interchangeability method

<div class="boxTitle">Abstract</div>Background. Blood lactate is a strong predictor of mortality, and repeated blood lactate assays are recommended during surgery in high-risk patients. We hypothesized that the use of intravascular microdialysis incorporated in a central venous catheter would be interchangeable with the reference blood gas technique to monitor changes in blood lactate.Methods. Microdialysis and central venous blood lactate measurements were recorded simultaneously in high-risk cardiac surgical patients. The correlation between absolute values was determined by linear regression, and the Bland–Altman test for repeated measurements was used to compare bias, precision, and limits of agreement. Changes in lactate measurements were evaluated with a four-quadrant plot and trend interchangeability method (TIM).Results. In the 23 patients analysed, the central venous catheter was used as part of standard care, with no complications. The correlation coefficient for absolute values (n=104) was 0.96 (P<0.0001). The bias, precision, and limits of agreement were −0.19, 0.51, and −1.20 to 0.82 mmol litre−1, respectively. The concordance rate for changes in blood lactate measurements (n=80) was 94% with the four-quadrant plot. In contrast, the TIM showed that 23 (29) changes in lactate measurements were not interpretable, and among the remaining 57 (71) interpretable changes, 18 (32) were interchangeable, 8 (14) were in the grey zone, and 31 (54) were not interchangeable.Conclusions. Microdialysis with a central venous catheter appears to provide reliable absolute blood lactate values. Although changes in blood lactate measurements showed an excellent concordance rate, changes between the two methods were poorly interchangeable with the TIM.Clinical trial registration. NCT02296593.

Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial

<div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone.<div class="boxTitle">Methods</div>Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml−1 remifentanil with 0.05 μg kg−1 h−1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml−1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery.<div class="boxTitle">Results</div>The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22–3.84) vs 3.84 (3.76–4.00) vs 3.80 (3.69–4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups.<div class="boxTitle">Conclusions</div>The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain.<div class="boxTitle">Clinical trial registration</div>NCT02856087.

Peripheral i.v. analysis (PIVA) of venous waveforms for volume assessment in patients undergoing haemodialysis

<div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>The assessment of intravascular volume status remains a challenge for clinicians. Peripheral i.v. analysis (PIVA) is a method for analysing the peripheral venous waveform that has been used to monitor volume status. We present a proof-of-concept study for evaluating the efficacy of PIVA in detecting changes in fluid volume.<div class="boxTitle">Methods</div>We enrolled 37 hospitalized patients undergoing haemodialysis (HD) as a controlled model for intravascular volume loss. Respiratory rate (F0) and pulse rate (F1) frequencies were measured. PIVA signal was obtained by fast Fourier analysis of the venous waveform followed by weighing the magnitude of the amplitude of the pulse rate frequency. PIVA was compared with peripheral venous pressure and standard monitoring of vital signs.<div class="boxTitle">Results</div>Regression analysis showed a linear correlation between volume loss and change in the PIVA signal (R2=0.77). Receiver operator curves demonstrated that the PIVA signal showed an area under the curve of 0.89 for detection of 20 ml kg−1 change in volume. There was no correlation between volume loss and peripheral venous pressure, blood pressure or pulse rate. PIVA-derived pulse rate and respiratory rate were consistent with similar numbers derived from the bio-impedance and electrical signals from the electrocardiogram.<div class="boxTitle">Conclusions</div>PIVA is a minimally invasive, novel modality for detecting changes in fluid volume status, respiratory rate and pulse rate in spontaneously breathing patients with peripheral i.v. cannulas.

Systematic review to determine which validated measurement tools can be used to assess risk of problematic analgesic use in patients with chronic pain

<div class="boxTitle">Abstract</div>Background. Misuse of prescription opioids, and other drugs prescribed for chronic pain, has increased, with major concerns about harm. This review was undertaken to identify validated measurement tools for risk assessment and monitoring of chronic non-cancer pain patients being considered for, or currently prescribed, analgesic drugs with abuse potential.Methods. Selected databases (Embase, Medline, Cochrane library/CENTRAL, PsycINFO, PubMed, CINAHL) were systematically searched for studies evaluating tools for risk of analgesic misuse, either before, or during, analgesic therapy for chronic pain, using predetermined inclusion/exclusion criteria. Two independent reviewers assessed abstracts, selected full texts, extracted data and assessed quality.Results. 30 studies from 1844 met inclusion criteria, including three systematic reviews, with an additional four studies from bibliography review. The studies covered 14 tools pertaining to opioid use, with none for non-opioid analgesics.Although there is no single, clear factor identifying opioid misuse, previous substance misuse appears important. Deception, including lying to clinicians, and using drugs belonging to others are common features. Smoking history may be relevant.Conclusions. For predicting prescription opioid misuse, the pain medication questionnaire (PMQ) and the screener and opioid assessment for patients with pain (SOAPP) had the best evidence; both developed and validated in five separate studies (four each of acceptable quality). The current opioid misuse measure (COMM) performed best screening for current misuse, developed and validated in three studies of acceptable quality. A small number of tools may accurately predict, or identify, opioid misuse. There are none for non-opioid analgesics, where there is a potential need.

Acute traumatic coagulopathy: pathophysiology and resuscitation

British Journal of Anaesthesia, 2016; 117(S3): iii31–iii43, DOI <a href="article.aspx?volume=&page=">10.1093/bja/aew328</a>

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