Intra-operative hypotension – how low should you go?

The February issue of Anaesthesia attempts to answer the age-old question plaguing anaesthetists – what blood pressure should we be targeting and how much does it matter? We are delighted to present the first publication from the iHype study – a prospective cohort study designed and conducted by the Research and Audit Federation of Trainees (RAFT). Data from 4750 patients aged >65 y were collected over a 48 h period. They found intra-operative hypotension, and its many different definitions, to be common, with incongruence between the blood pressure anaesthetists say they will treat and their actual treatment threshold. This study is a great example of what trainee research networks can achieve and how they are a relatively untapped resource. The podcast discussion with the authors is a must for any budding trainee researcher on how to plan and perform such a large and effective study. The associated editorial highlights the discrepancy between blood pressure recordings and explores why we feel may feel the need to “fudge” the anaesthetic chart. With electronic recording becoming more prevalent in the future there may be nowhere to hide! 

Figure 1 Thresholds at which anaesthetists give vasopressor treatments and their intended treatment thresholds. Y-axis denotes the proportion of patient episodes/respondents given the defining threshold on the x-axis for (a) absolute mean arterial pressure; (b) absolute systolic blood pressure; (c) relative change in mean arterial pressure from pre-operative blood pressure; and (d) relative change in systolic blood pressure from pre-operative blood pressure.

The effect of intra-operative hypotension on acute kidney injury, postoperative mortality and length of stay following emergency hip fracture surgery is a neat single centre study investigating the incidence of intra-operative hypotension in a vulnerable group. Interestingly, they did not find an association with intra-operative hypotension and acute kidney injury. However, delay to surgery was associated with increased mortality. North Shore Hospital Anaesthetic department do use electronic intra-operative recording and the MAP was (truly) rarely below 65mmHg in their cohort. 

Why does blood pressure drop during anaesthesia and is there anything we can do to predict which patients will be most affected? The editorial by Frandsen et al. goes back to basic physiology and highlights the often forgotten about autonomic system – it is not all about intra-vascular volume. Anaesthesia causes both sympatholysis and vagolysis. If a patient already has pre-existing autonomic dysfunction, despite adequate fluid volume, anaesthesia could and does provoke hypotension and cardiac instability. By using pre-operative markers of vagal tone, such as heart rate variability, can we identify high risk patients and tailor our anaesthesia accordingly?

The pandemic has sharpened and exacerbated health and social inequalities globally. There is no doubt that patients of non-white ethnicity have poorer outcomes from SARS-CoV-2 infection. The underlying cause for this is likely to be multi-factorial but there has been anxiety that pulse oximetry is less accurate in patients with darker skin pigmentations. Wiles et al. performed a retrospective observational study to address this important concern. They compared SaO2 and SpO2 measured concurrently in patients on different ethnicities and reassuringly found no clinically significant difference. However, as mentioned in the accompanying editorial – is ethnicity the correct question to be asking, and should we actually be comparing skin pigmentation levels in order to accurately validate the use of pulse oximetry in different groups? The inclusion of different ethnic groups in both clinical research and validation studies of commercial monitoring is improving, but this topic highlights the need for both patients and medical staff to be confident that what we are both doing and using to monitor patients in different diseases is correct for all patients. 

Figure 2 Bland-Altman plot paired measurements of oxygen saturation by arterial blood gas analysis and peripheral oxygen saturation in 194 patients with COVID-19 pneumonitis who were admitted to critical care for non-invasive respiratory support. Patient ethnic origin is shown by the colour of each datum (White = yellow; Asian = purple; Black = light blue; and Other = green). The solid line represents the bias between the two measurements, the dashed line represents the limits of agreement (bias ± 1.96 SD) and the dotted line represents the 95%CI for the limits of agreement. (a) shows all paired measurements and (b) shows only those measurements when the patient was hypoxaemic (defined as SaO2 ≤94%).

The pandemic has also made us aware of the vital importance of oxygen and how hypoxic patients do not always look the same! However, aside from being able to sketch out the oxygen dissociation curve, our actual understanding of oxygen physiology is limited. Slingo and Pandit present a narrative review aiming to introduce hypoxia-inducible factor and oxygen sensing pathways to the wider clinical community. The ability of cells to detect and respond to varying oxygen concentrations relies on a complex cascade. Manipulation of this pathway may have many clinical implications, including targeted oxygen therapy. This fascinating review also highlights the requirement for more basic science research in anaesthesia.

Figure 3 Several hundred genes are direct transcriptional targets of HIF, and are involved in diverse cellular and physiological processes in order to optimise oxygen supply and demand. A few examples are given here that will be of direct interest to clinicians in anaesthesia and critical care. VEGF, vascular endothelial growth factor; TF, transferrin; EPO, erythropoietin; Hb, haemoglobin; Hct, haematocrit; EDN1, endothelin 1; NOS, nitric oxide synthase; GLUT 1, glucose transporter 1; LDH, lactate dehydrogenase; PDK1, pyruvate dehydrogenase kinase 1.

The expanding field of peri-operative medicine is changing the focus of anaesthesia research. Along with clinical shared decision-making, patient involvement in study design is improving and with that the need for outcomes that are important for patients. Days alive and at home (DAH) is one such outcome that neatly encompasses the many factors of the post-operative journey for a patient. Ferguson et al. surveyed patients and found the minimal clinically important difference to be 3 days, with an early discharge and being discharged to home rated as important. This is important work that will guide study design in future trials. Indeed Moore et al. used a similar patient-centred outcome measure (days alive and out of hospital) to audit the implementation of the WHO Surgical Safety Checklist.

None of the above research into patient outcomes however is important if we do not have a world in which to practice anaesthesia! In light of COP26 in Glasgow in November the World Federation of Societies of Anaesthesiologists has produced a consensus statement on the principles of environmentally-sustainable anaesthesia. The main points are that patient safety should not be compromised and healthcare systems should be mandated to reduce their contributions to global heating in order to limit global heating to 1.5℃ by 2050. There is a lack of scientific evidence to underpin these guidelines and further work and investment is needed to ensure that we protect our world and current and future generations.

Elsewhere we also have a feasibility study on the use of cryoprecipitate in post-partum haemorrhage. Finally, we are recruiting! We have adverts for a Trainee FellowEditor-in-Chief and three Editors posts at Anaesthesia Reports! Join us!

Cara Hughes and Andrew Klein

Current evidence for peri-operative and critical care management of the brain

What better way to see in any new year than with a brand-new Anaesthesia Special Supplement! This year, it is all about the peri-operative and critical care management of the brain, which has been guest edited by Dr Jugdeep Dhesi and Professor Alana Flexman. Flexman and Tung begin by appraising outcomes used in neuroanaesthesia and neurocritical care. They call for a shift towards PROMS as well as perspectives from LMICs, and the tools are available now – we just have to use them. Dhesi and Moppett discuss the implications of the older brain in peri-operative care and ask – what should we do? As we most things, there is no one right answer and no ‘magic bullet’, but one of the key themes appearing throughout the issue is of multidisciplinary thinking and working. The first review seems to have caught the imagination of our followers already, which looks at the implications of nocebo. This is a key paper that could potentially change practice, but not everyone will agree, as many of the nocebos in use are enshrined in practice already (Fig. 1). Time now for phrases such as ‘bee sting’ and ‘sharp scratch’ to be thought of as clumsy verbal relics of the past? We think so!

Figure 1 Overview of the neurobiology of the nocebo effect. PONV, postoperative nausea and vomiting; ACTH, adrenocorticotrophic hormone; CCK, cholecystokinin; PFC, prefrontal cortex; ACC, anterior cingulate cortex; HPA, hypothalamic–pituitary–adrenal axis; PAG, peri-aqueductal gray.

Stubbs et al. use a stereotyped peri-operative journey to highlight the decision-making points where the expertise of professionals from across the peri-operative medicine team may play an important role for patients with chronic subdural haematoma. The key point is that most patients are managed outside neuroscience centres, and more research is needed to improve the associated care pathways. Peri-operative neurocognitive disorders are the most common complication experienced by older individuals undergoing anaesthesia and surgery. Evered et al. discuss the clinical and practical implications of peri-operative neurocognitive disorder on patients, and possible pathways for identifying at-risk individuals and assessment of modifiable factors.Possible mechanisms include: neurodegenerative disease; inflammation; neuronal damage; and frailty. No longer should we refer to patients as ‘pleasantly confused’ as arguably, there is nothing pleasant about delirium. 

There is much emerging evidence of COVID-19-associated delirium, and White and Jackson have brought it all together for us. They describe how it differs from ‘classical’ delirium, as well as potential mechanisms and practical approaches to management (Fig. 2). It turns out that it is more prevalent, longer lasting and associated with worse outcomes. The management remains the same, except for distressing end of life agitation where the need for higher-than-normal doses of sedatives may be required. One area of persistent controversy in neuroanaesthesia relates to the mode of anaesthesia and its relation with outcomes for mechanical thrombectomy. Dinsmore and Tan review the evidence, and suggest more important targets such as blood pressure management, diagnosis and timely management

Figure 2 Lived experience of delirium for patients, staff and families.

Is anyone using POCUS for acute brain injury? Dinsmore and Venkatraghavan describe the techniques and applications for and provide evidence of its utility in guiding clinical management both in the peri-operative period and on ICU. They list the commonly used acoustic windows and the structures that are visible. They argue it is an effective, non-invasive, safe and readily available technique for the rapid assessment of cerebral anatomy and cerebral haemodynamics. Will it become an alternative routine imaging technique? The results seem comparable. Most doctors will encounter status epilepticus in their carrer. Migdady et al. discuss the definitions of status epilepticus, evidence behind treatment regimens at various stages, treatment goals, outcomes and the role for newer drugs. Implementing early, evidence-based treatment modalities is important to prevent mortality and complications from prolonged status epilepticus, and this paper is arguably of important relevance for all!

Figure 3 Treatment timeline of convulsive status epilepticus. *intramuscular (IM) or buccal (depending on availability) preferred in patients without i.v. access. Diazepam can be used if lorazepam and midazolam are not available. ABC, airway, breathing and circulation; IV, intravenous; AED, anti-epileptic drug; CBC, complete blood count; CMP, complete metabolic panel; CT, computed tomography; EEG, electroencephalogram; MRI, magnetic resonance imaging; KD, ketogenic diet; rTMS, repetitive transcranial magnetic stimulation; and VNS, vagal nerve stimulator.

Have you been busy with COVID-19 over the last few years and missed the most recent CPD relevant to the management of traumatic brain injury? Fear not, Matt Wiles has reviewed the recent evidence and brought it all together. In summary, there are few clear therapeutic interventions that are associated with meaningful improvements in mortality, or more importantly, neurological outcome. The early administration of TXA appears to offer a clinically important early mortality benefit and early tracheostomy appears to be of value. Kayambankadzanja et al. review pragmatic sedation strategies to prevent secondary brain injury in low-resource settings, which is common. They emphasise the importance of analgesia, the choice of drugs, the associated risks and the monitoring required for these patients in these settings. Elsewhere we have reviews of: strategies to reduce the incidence of postoperative deliriumperi-operative neurological monitoring with electroencephalography and cerebral oximetry; and the peri-operative management of patients with Parkinson’s disease

Figure 4 Summary of recent evidence-based recommendations for the management of traumatic brain injury.

We hope you enjoyed the live broadcast to accompany the issue which was seen by over 2.5k viewers! This has now been converted into a podcast which available in all the usual places. Enjoy!

Mike Charlesworth and Andrew Klein