Journal watch

Journal Watch

See which journal articles on perioperative care have caught our attention. 

Below you'll find overviews of some recent articles related to perioperative care, along with links to the open-access articles themselves.

CPOC is grateful to Trainees with an Interest in Perioperative Medicine (TrIPOM) and the Perioperative medicine for Older People undergoing Surgery (POPS) Special Interest Group at the British Geriatrics Society for their contributions to Journal Watch.

Journal Articles

McIsaac DI,Taljard M, Bryson GL et al, BJA 2020, 125 (5):704-711                 

DOI: https://doi.org/10.1016/j.bja.2020.07.003

This Canadian study is one of the first to look at postoperative trajectories in the context of frailty, and followed up 687 patients aged >65 years for the first year following major elective noncardiac surgery.

Patients’ frailty was assessed using the Fried Phenotype (FP) and the Clinical Frailty Scale (CFS). The primary outcome was patient reported disability score (using the WHO Disability Assessment) at baseline, 30, 90 and 365 days after surgery.

 Frail patients experienced a decrease in disability score at 365 days while those without frailty had no significant change in their disability score from baseline. (P<0.0001) However, patients with frailty were more likely to experience an initial postoperative worsening in disability and the authors conclude that frail patients may stand to benefit from their procedures to a greater extent, provided the initial postoperative course can be weathered.

Dr Charlotte Crossland, ST4 Anaesthetics, KSS School of Anaesthesia 

Dushianthan A, Knight M, Russell P et al,  Perioper Med 2020, 9, 30 

DOI: https://doi.org/10.1186/s13741-020-00161-5

This systematic review looked at the specific effect of GDHT on postoperative pulmonary complications (PPCs).  66 RCTs and 9548 patients were included. PPCs were defined as pneumonia, atelectasis, acute lung injury, aspiration pneumonitis, pulmonary embolism, and pulmonary oedema.

The use of GDHT reduced overall pulmonary complications significantly (OR 0.74, 95% CI 0.59 to 0.92). The incidence of pulmonary infections was lower with GDHT use (OR 0.72, CI 0.60 to 0.86) as was pulmonary oedema (OR 0.47, CI 0.30 to 0.73). There were no differences in rates of pulmonary embolism or acute respiratory distress syndrome.

Sub-group analyses demonstrated the benefit was seen in general and cardiothoracic surgery and when the GDHT protocol used fluids and inotropes/vasopressors in combination, rather than fluid alone.

Dr Charlotte Crossland, ST4 Anaesthetics, KSS School of Anaesthesia 

Buse G., Puelacher C., Gualandro D. et al. British Journal of Anaesthesia 2020 bja.2020.08.041

Link to article

A third of all surgical interventions, worldwide per year, are performed on patients with high cardiovascular risk, therefore accurate risk stratification is important to inform shared decision making, and to identify which patients should be seen in a pre-operative clinic for optimisation. Functional capacity has been identified as being a useful predictor of peri-operative risk and is measured in a manner of different ways: using cardiopulmonary exercise testing, the validated Duke Activity status index (often lengthy, patients may not be able to answer all questions) or using semi quantitative self reported functional activity with cut off reference activities. Authors hypothesised that self-reported functional capacity, estimated by the ability of climbing less than two flights of stairs (4 metabolic equivalents), was independently associated with adverse cardiac events, and the addition of functional capacity to existing risk scores improved risk classification.

They performed a preplanned secondary analysis from a prospective diagnostic cohort study on patients identified as having a high risk of perioperative cardiovascular complications undergoing noncardiac surgery. In pre-op clinic patients were asked about their ability to walk up two flights of stairs and this was recorded. 4560 patents met inclusion criteria and follow up was completed in 99.3%. After statistical analysis authors found self-reported functional capacity of less than two flights of stairs was associated with cardiac death and cardiac events at 30 days, and all-cause mortality at 30 days and 1 year. They also found that the addition of self-reported functional capacity to surgical and clinical risk (revised cardiac risk index) stratification tools resulted in significant reclassification improvement (risk of major adverse cardiac events). This will guide shared decision making and optimisation.

COVIDSurg Collaborative.(2020), Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet Published online May 29 2020

Link to open access article.

This is the first paper published by COVIDSurg – an international, observational cohort study assessing the outcomes of surgical patients with COVID-19 infection.

1128 patients with perioperative SARS-CoV-2 infection between January and March 2020 were included. 235 hospitals in 24 countries contributed data.

Perioperative infection: SARS-CoV-2 infection diagnosed within 7 days before or 30 days after surgery.

Surgery: any indication and with any type of anaesthesia.

Diagnosis of SARS-CoV-2 infection: RT-PCR testing (86% of patients), clinical or radiological findings.

The majority (74%) of patients were undergoing emergency surgery. A minority (26%) had the infection confirmed preoperatively, with the rest postoperatively.

Very high rates of mortality and postoperative pulmonary complications were found.

30-day mortality was 24% - a higher mortality than the highest risk groups in the 2019 NELA report.

Mortality was higher in males, those over 70, ASA3-5 and those undergoing emergency surgery, major surgery or surgery for malignancy. The greatest increased risk was for age >70 (OR 2.3) and ASA 3-5 compared with ASA1-2 (OR 2.35)

Postoperative pulmonary complications occurred in half (51%) of patients with perioperative COVID-19 and 30-day mortality in these patients was 38%.

There are clear drawbacks to a retrospective study without a control arm – it may be that SARS-CoV-2 infected patients who did well postoperatively were less likely to be tested or diagnosed, making the complication and death rate in the positive group appear falsely higher. However, the mortality rates found are exceptionally high and plausible, given the combination of the inflammatory and prothrombotic state that results from COVID-19 and that that results from surgery.

The difficult next step is how health care systems and individual doctors use this information to inform the risk/benefit conversation around restarting elective surgery both on a population and on an individual level. The authors of the paper suggest that thresholds for surgery should be higher than normal, particularly in the higher risk groups, and non-operative treatment should be considered where possible.

The future CovidSurg-Cancer study will be looking at the safety of surgery for cancers during the pandemic and the impact the pandemic has had on cancer treatment pathways and will hopefully add to the information we need for this discussion. 

Published comment from Paul Myles and Salome Maswime can be read here.

Boyd‐Carson, H., Shah, A., Sugavanam, A., Reid, J., Stanworth, S.J. and Oliver, C.M. (2020), The association of pre‐operative anaemia with morbidity and mortality after emergency laparotomy. Anaesthesia 75: 904-912. doi:10.1111/anae.15021

Link to open access article.

This study adds to the growing body of evidence that pre-operative anaemia is associated with poorer outcomes, with previous studies mostly concentrating on elective surgery. It remains unclear whether this relationship is causal although current thinking is that it should be investigated and treated prior to elective surgery.

The NELA group looked at outcomes for patients undergoing laparotomy (excluding laparotomy for haemorrhage) between December 2013 - November 2017.

52% of patients were anaemic (WHO definitions). All levels of anaemia were associated with increased 30 and 90-day mortality and prolonged hospital stay. Moderate and severe anaemia were also associated with an increased risk of return to theatre.

It remains unclear how this information should be used. The timescale available in emergency surgery to address anaemia is small and red cell transfusions are known to be associated with harm. It is not known whether targeted treatment with v iron, B12 or folic acid would improve outcomes in this group.

Odor P M, Bampoe S, Gilhooly D, Creagh-Brown B, Moonesinghe S R (2020), Perioperative interventions for prevention of postoperative pulmonary complications: systematic review and meta-analysis BMJ 2020;368:m540

Postoperative pulmonary complications (PPCs) are a common cause of perioperative morbidity and mortality and are particularly topical with recent data indicating a very high rate among patients infected with SARS-CoV2.  Diverse, pre-, intra- and post-operative interventions have been considered to try and reduce PPCs.

This group looked at RCTs of protocolised interventions aimed at reducing PPCs in non-cardiac surgery.

95 trials were studied but no high-quality evidence was found for any intervention.

Moderate quality evidence supported a reduction in PPCs with lung protective intraoperative ventilation and goal directed haemodynamic therapy.  Further (trial sequential) analysis showed evidence of benefit for goal directed haemodynamic therapy, enhanced recovery pathways, prophylactic respiratory physiotherapy and epidural analgesia.

Moderate quality evidence showed no benefit for incentive spirometry.

PPCs are a diverse group of complications, their measurement can be subjective and blinding to (often visible, physical) interventions can be problematic making studies in this area difficult. Hopefully future trials will provide greater clarity.

Campbell AM, Axon DR, Martin JR, Slack MK, Mollon L, Lee JK. Melatonin for the prevention of postoperative delirium in older adults: a systematic review and meta-analysis. BMC Geriatr. 2019;19(1):272. Published 2019 Oct 16. doi:10.1186/s12877-019-1297-6

Link to open access article

Postoperative delirium is a common complication of surgery, particularly in the elderly, and is associated with poor outcomes such as prolonged reduction in cognition, institutionalisation and mortality. Many non-pharmacological strategies are already recommended for reducing delirium but pharmacological interventions are limited.

Six studies were considered (4 using melatonin, 2 using ramelteon – a melatonin receptor agonist).

Patients taking melatonin had 37% lower odds of experiencing delirium.

There were only a small number of studies that met inclusion criteria, dosing was heterogenous and delirium assessment and diagnosis was variable. However, melatonin is a relatively low-cost drug with few side effects and this paper highlights a promising line of future research into the prevention of delirium - a complication we have, thus far, had limited success in reducing.

McIlveen, E.C., Wright, E., Shaw, Edwards, J., Vella, M., Quasim, T. and Moug, S.J. (2020), A prospective cohort study characterising patients declined emergency laparotomy: survival in the ‘NoLap’ population. Anaesthesia, 75: 54-62. doi:10.1111/anae.14

Link to open access article.

This single centre UK-based study considered the often-overlooked group where laparotomy is indicated but not performed (the ‘NoLap group’). Of 314 patients 68.2% had surgery, 31.8% did not (cf Australian audit – 94% had surgery)1 The main reason for lack of surgery was futility (80%).

NoLap group patients unsurprisingly had higher predicted mortality (P-POSSUM and a general survival model), worse renal function, higher lactate, a higher ASA and were older, more dependant and co-morbid and more likely to have bowel ischaemia.

Two variables were associated with survival (after multivariate analysis) – background mortality and acute pre-op lactate.

Post op mortality rates over the follow up period (median 1.3 years) in those undergoing surgery were similar to those predicted (24%). A third of the NoLap patients survived to 30 days and mortality rates were higher than would have been predicted had they had surgery, indicating that surgery might prolong in some of these patients. However, there may be unmeasured confounding factors in the discrepancy between expected and observed mortality rates in this group and an increase in survival duration may not be in accordance with the patient’s wishes or best interests -the decision not to operate is complex and must be individualised.

  1. Broughton KJ, Aldridge O, Pradhan S, JR A, The Perth Emergency Laparotomy Audit. Australia and New Zealand Journal of Surgery 2017;87.

The HIP ATTACK investigators. Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial. Lancet Published Online Feb 9, 2020 

Link to open access article. 

This international RCT looked at patients >45 yrs requiring hip fracture surgery. 770 fulfilled eligibility criteria, 2970 were enrolled - lack of operating space being the main limiting factor.

Patients were allocated to a goal of surgery <6hrs from diagnosis or to standard care (median time to surgery from diagnosis 24 hours). Accelerated surgery was only performed during normal working hours.

No significant different difference was found between the groups in 90-day mortality or a composite of major complications. Accelerated surgery was associated with a lower risk of delirium and infection, faster mobilisation, fewer strokes, moderate to severe pain and a shorter length of stay. No harm was seen from the accelerated pathway.

Post-hoc analysis demonstrated a mortality benefit from earlier surgery in those with pre-operative elevated troponins.

Sessler, D , Pei L, Huang Y, Fleischmann E, Marhofer P, Kurz A et al  Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial. Lancet 2019 394(10211); 1807-1815 doi: 10.1016/S0140-6736(19)32313-X.

 

The ongoing concern that use of volatile anaesthetics and opiates worsen breast cancer recurrence rates was examined in this international RCT. Women undergoing surgery for breast cancer were randomised to anaesthesia with paravertebral blocks and propofol or sevoflurane (volatile) and opiates. Effects on incisional pain was also considered.

Over 2000 women were included and followed up for a median of 36 months. Despite a putative mechanism in favour of regional anaesthesia reducing recurrence rates (reduction in the immune suppressive stress response to surgery) and evidence from animal models, no effect was found overall nor in the subpopulations considered (age, oestrogen receptor status, tumour stage). There was also no impact on persistent incisional pain levels.

 

Webb, A.R., Coward, L., Soh, L., Waugh, L., Parsons, L., Lynch, M., Stokan, L.‐A. and Borland, R. (2020), Smoking cessation in elective surgical patients offered free nicotine patches at listing: a pilot study. Anaesthesia, 75: 171-178. doi:10.1111/anae.14863

Link to open access article. 

The risks of smoking in general as well as perioperatively are well known, as are the benefits of quitting. Surgery is being increasingly seen as a ’teachable moment’ – an opportunity to help people make lifestyle changes to benefit their health both for surgery and thereafter.

This group randomly assigned 600 smokers awaiting non-urgent surgery to a written offer of 5 weeks’ worth of free nicotine patches or usual care (which included written information about stopping smoking). 39% of those offered the patches accepted them and 12.5% used them for >3 weeks. Of those offered patches, 9% quit smoking for >4 weeks before surgery compared with 6% of controls (non-significant difference). Significantly more of those offered nicotine replacement had i) attempted quitting during the study period, ii) reduced their smoking by the time of surgery. Of those who had given up smoking on the day of surgery, 59% had relapsed at 6 months.

The study suggests a high number needed to treat (31) but at low cost. The authors comment that adding fast-acting oral nicotine to patches increases cessation rates and might increase the effectiveness of the intervention.

Richards T, Baikady R R, Clevenger B, Butcher A et al. Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial. The Lancet (2020) 

Link to open article.

This free to access trial has produced results that were unexpected by most and caused some debate as to what to do next. 


30-60% of patients undergoing elective surgery are anaemic, the commonest cause being iron deficiency. This is associated with an increased risk of blood transfusion, complications and delayed discharge. Inflammation (as often seen due to the disease process in surgical patients) limits oral absorption of iron and hence intravenous (IV) iron has been recommended in recent years in the UK (NICE, NHSE)


A double-blind RCT was conducted to look at whether IV iron given to anaemic patients before major open elective abdominal surgery would correct anaemia, reduce the need for blood transfusion and improve patent outcomes. Anaemia was defined as <130g/L for men and <120 g/L for women. 487 participants were allocated to IV iron (1000mg ferric carboxymaltose) or placebo 10-42 days before surgery between 2014 and 2018. There was no significant difference in transfusion rates or death. There were no differences in safety endpoints measured.


The IV iron group had significantly higher Hb concentrations at 8 weeks but levels were similar between the two groups in the immediate postoperative period. Postoperative complications were similar in the two groups and there was no difference in hospital length of stay. Readmissions following discharge were significantly lower in the IV iron group in the first 8 weeks following surgery with the most common reason for readmission being a post-operative complication or wound infection. 


There was no comment on any adverse outcomes resulting from IV iron. 


Further considerations – anaemia is associated with poorer outcomes but this may due to it being a marker of underlying disease rather than it being the direct cause. The effect on Hb came later than the surgical event and may be related to the reduction in readmission rates.

Aucoin SD, Hao M, Sohi R, Shaw J, et al . Accuracy and Feasibility of Clinically Applied Frailty Instruments before Surgery: A Systematic Review and Meta-analysis. Anesthesiology. 2020;133(1):78-95. doi:10.1097/ALN.0000000000003257

Link to open access article.

Preoperative assessment of frailty is strongly recommended but implementation is not routine – a barrier may be confusion around which of the many tools to use. This free to access work considered which frailty score is the best predictor of adverse perioperative outcomes. 


A systematic review and meta-analysis of 45 studies looking at 35 frailty assessment tools found that different tools were better predictors for different outcomes: 
•    The Clinical Frailty Scale (CFS) was found to be most strongly associated with mortality and discharge not to home. 
•    The Edmonton Frail Scare (EFS) was a better predictor of complications. 
•    The Frailty (Fried) Phenotype was most strongly associated with postoperative delirium. 


Looking at overall feasibility (ease of use, logistical and environmental barriers and time to administrate) and accuracy, the authors concluded that the evidence best supported the use of the CFS for preoperative use. The Fried Phenotype was also felt to be accurate but took considerably longer to complete than the CFS.


Further considerations may be how reliable frailty assessment is when done by non-geriatricians and whether the type of surgery has an effect on the outcome as predicted by frailty scores. 

Aitken R M, Partridge J S L, Oliver C M, Murray D, et al. Older patients undergoing emergency laparotomy: observations from the National Emergency Laparotomy Audit (NELA) years 1–4, Age and Ageing 2020; 49 (4) July 2020, P 656–663

Link to open article.

This free to access study looks at patients 65 years included in the National Emergency Laparotomy Audit (NELA). This group is the largest in the NELA population (57%). Perhaps unsurprisingly the authors found that patients 65 years had higher mortality rates, longer LOS and were more likely to be discharged to a care-home than younger patients. However, mortality rates did reduce over time (2013-2017) and this reduction was greater in the older population than the reduction seen in younger patients. The proportion of older NELA patients seen post-operatively by a geriatrician increased over time (although only 16.5% are seen). Preoperative geriatrician review was associated with higher mortality. These patients also had a longer median time to theatres, were more likely to be ASA 4, have a predicted mortality 5% and have been admitted from care homes, indicating that the sickest patients were referred. The patients referred post operatively to geriatricians had similar profiles (were also the sickest) but mortality reduced significantly in those reviewed by geriatricians (P<0.001). 


The authors point out that NELA does not record those who do not go onto have emergency laparotomies and that this may account for some of the decline in mortality rates in older patients as higher-risk patients may have been excluded from surgery. Additionally, patient reported outcomes are still not measured. Barriers to increasing geriatrician input into this high-risk group of patients include funding, workforce and interspeciality collaboration. 
 

Deiner S, Baxter M G, Mincer J S, Sano M, et al. Human Plasma biomarker responses to inhalational general anaesthesia without surgery. Brit J Anaes 2020; 125(3) p282-290

Link to article. 

There is increasing interest in postoperative cognitive dysfunction and this study aimed to separate out the effects of a general anaesthetic (GA) from those of surgery. Previous studies have demonstrated an increase in cytokines and other biomarkers in patients undergoing surgery under GA and there are theories that the anaesthesia causes a form of neurotoxicity in vulnerable patients. The biomarkers included (IL-6), TNF, CRP and markers of neural injury such as tau, glial fibrillary acidic protein (GFAP) and neurofilament light (NF-L). Healthy volunteers aged 40-80 years underwent a 2 hour GA without surgery and biomarker levels were recorded. 5 hours after induction of anaesthesia (sevoflurane) IL-6 was increased by a biologically insignificant degree, TNF and CRP were unchanged and the neural injury markers were significantly decreased. The authors conclude that GA with sevoflurane did not provoke an inflammatory state or neuronal injury in the hours after induction, perhaps indicating that the inflammation is provoked by the surgery itself. 


Further considerations may be in the measurement of NF-L and GFAP which were found to increase with age in this study, and might offer a mechanism for risk stratification, changes in biomarkers at later time points and in the effects of non-inhalational anaesthesia. 

Recent Guidelines

Woodcock, T., Barker, P., Daniel, S., Fletcher, S., Wass, J.A.H., Tomlinson, J.W., Misra, U., Dattani, M., Arlt, W. and Vercueil, A. (2020),

Guidelines for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency. Anaesthesia. doi:10.1111/anae.14963

Access the guidelines. 

Review

Santhirapala, R., Partridge, J. and MacEwen, C.J. (2020),

The older surgical patient – to operate or not? A state of the art review. Anaesthesia, 75: e46-e53. doi:10.1111/anae.14910

Link to open access article. 

A free to access review article looking at the need to, difficulties in and benefits of integrating shared decision making and personalised care into our perioperative care pathways. It considers the increased post-operative burden of medical complications suffered by older patients and the need for patient reported outcome measures in this group. The outcome benefits of a comprehensive geriatric assessment in surgical patients as well as preoperative investigations to guide risk assessment and therefore shared decision making are looked at. The need for appropriately trained health care professionals to have these discussions is highlighted. The benefits and unanswered questions around physiological prehab in the elderly population are considered as well as the emerging evidence for psychological preparation, including the use of surgical schools. The overriding need for excellent leadership and true teamworking between specialities is stressed.