The lifetime risk of surgery in England: a nationwide observational cohort study.

BACKGROUND: The average number of times a person will have surgery in their lifetime, and the amount of surgical healthcare resources they use, is unknown. Lifetime risk is a measure of the risk of an average person having a specific event within their lifetime. We report the lifetime risk of surgery and the change observed during the first year of the COVID-19 pandemic. METHODS: We conducted a population cohort study using hospital episode statistics to identify all patients undergoing surgery between January 1, 2016, and December 31, 2020, in England. We calculated age- and sex-specific incidence rates of surgery and combined these with routinely available population and mortality data from the Office for National Statistics. We computed the probability of requiring surgery stratified by 5-yr epochs (age 0-4 to ≥90 yr). Our primary analysis calculated lifetime risk for all surgery using the life table method. We assessed the impact of the COVID-19 pandemic, comparing a pre-pandemic and a pandemic period. RESULTS: Between 2016 and 2020, 23 427 531 patients underwent surgery, of which 11 937 062 were first surgeries. The average denominator population for England was 55.9 million. The lifetime risk of first surgery was 60.2% (95% confidence interval 55.1-65.4%) for women and 59.1% (95% confidence interval 54.2-64.1%) for men. The COVID-19 pandemic decreased the lifetime risk of first surgery by 32.3% for women and by 31.7% for men. This estimated lifetime risk should only be applied to the English population. CONCLUSIONS: This population epidemiological analysis suggests that approximately 60% of people in England will undergo surgery in their lifetime.

Family supplemented patient monitoring after surgery (SMARTER): a pilot stepped-wedge cluster-randomised trial.

BACKGROUND: Mortality after surgery in Africa is twice that in high-income countries. Most deaths occur on wards after patients develop postoperative complications. Family members might contribute meaningfully and safely to early recognition of deteriorating patients. METHODS: This was a stepped-wedge cluster-randomised trial of an intervention training family members to support nursing staff to take and record patient vital signs every 4 h after surgery. Adult inpatients across four surgical wards (clusters) in a Ugandan hospital were included. Clusters crossed once from routine care to the SMARTER intervention at monthly intervals. The primary outcome was frequency of vital sign measurements from arrival on the postoperative ward to the end of the third postoperative day (3 days). RESULTS: We enrolled 1395 patients between April and October 2021. Mean age was 28.2 (range 5-89) yr; 85.7% were female. The most common surgical procedure was Caesarean delivery (74.8%). Median (interquartile range) number of sets of vital signs increased from 0 (0-1) in control wards to 3 (1-8) in intervention wards (incident rate ratio 12.4, 95% confidence interval [CI] 8.8-17.5, P<0.001). Mortality was 6/718 (0.84%) patients in the usual care group vs 12/677 (1.77%) in the intervention group (odds ratio 1.32, 95% CI 0.1-14.7, P=0.821). There was no difference in length of hospital stay between groups (usual care: 2 [2-3] days vs intervention: 2 [2-4] days; hazard ratio 1.11, 95% CI 0.84-1.47, P=0.44). CONCLUSIONS: Family member supplemented vital signs monitoring substantially increased the frequency of vital signs after surgery. Care interventions involving family members have the potential to positively impact patient care. CLINICAL TRIAL REGISTRATION: NCT04341558.

Clinical context and communication in shared decision-making about major surgery: Findings from a qualitative study with colorectal, orthopaedic and cardiac patients.

Increasing numbers of older people undergo major surgery in the United Kingdom (UK), with many at high risk of complications due to age, co-morbidities or frailty. This article reports on a study of such patients and their clinicians engaged in shared decision-making. Shared decision-making is a collaborative approach that seeks to value and centre patients' preferences, potentially addressing asymmetries of knowledge and power between clinicians and patients by countering medical authority with greater patient empowerment. We studied shared decision-making practices in the context of major surgery by recruiting 16 patients contemplating either colorectal, cardiac or joint replacement surgery in the UK National Health Service (NHS). Over 18 months 2019-2020, we observed and video-recorded decision-making consultations, studied the organisational and clinical context for consultations, and interviewed patients and clinicians about their experiences of making decisions. Linguistic ethnography, the study of communication and interaction in context, guided us to analyse the interplay between interactions (during consultations between clinicians, patients and family members) and clinical and organisational features of the contexts for those interactions. We found that the framing of consultations as being about life-saving or life-enhancing procedures was important in producing three different genres of consultations focused variously on: resolving problems, deliberation of options and evaluation of benefits of surgery. We conclude that medical authority persists, but can be used to create more deliberative opportunities for decision-making through amending the context for consultations in addition to adopting appropriate communication practices during surgical consultations.

Preoperative N-terminal pro-B-type natriuretic peptide and myocardial injury after stopping or continuing renin-angiotensin system inhibitors in noncardiac surgery: a prespecified analysis of a phase 2 randomised controlled multicentre trial.

BACKGROUND: Patients with elevated preoperative plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP >100 pg ml-1) experience more complications after noncardiac surgery. Individuals prescribed renin-angiotensin system (RAS) inhibitors for cardiometabolic disease are at particular risk of perioperative myocardial injury and complications. We hypothesised that stopping RAS inhibitors before surgery increases the risk of perioperative myocardial injury, depending on preoperative risk stratified by plasma NT-proBNP concentrations. METHODS: In a preplanned analysis of a phase 2a trial in six UK centres, patients ≥60 yr old undergoing elective noncardiac surgery were randomly assigned either to stop or continue RAS inhibitors before surgery. The pharmacokinetic profile of individual RAS inhibitors determined for how long they were stopped before surgery. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury (plasma high-sensitivity troponin-T ≥15 ng L-1 or a ≥5 ng L-1 increase, when preoperative high-sensitivity troponin-T ≥15 ng L-1) within 48 h after surgery. The co-exposures of interest were preoperative plasma NT-proBNP (< or >100 pg ml -1) and stopping or continuing RAS inhibitors. RESULTS: Of 241 participants, 101 (41.9%; mean age 71 [7] yr; 48% females) had preoperative NT-proBNP >100 pg ml -1 (median 339 [160-833] pg ml-1), of whom 9/101 (8.9%) had a formal diagnosis of cardiac failure. Myocardial injury occurred in 63/101 (62.4%) subjects with NT-proBNP >100 pg ml-1, compared with 45/140 (32.1%) subjects with NT-proBNP <100 pg ml -1 {odds ratio (OR) 3.50 (95% confidence interval [CI] 2.05-5.99); P<0.0001}. For subjects with preoperative NT-proBNP <100 pg ml-1, 30/75 (40%) who stopped RAS inhibitors had myocardial injury, compared with 15/65 (23.1%) who continued RAS inhibitors (OR for stopping 2.22 [95% CI 1.06-4.65]; P=0.03). For preoperative NT-proBNP >100 pg ml-1, myocardial injury rates were similar regardless of stopping (62.2%) or continuing (62.5%) RAS inhibitors (OR for stopping 0.98 [95% CI 0.44-2.22]). CONCLUSIONS: Stopping renin-angiotensin system inhibitors in lower-risk patients (preoperative NT-proBNP <100 pg ml -1) increased the likelihood of myocardial injury before noncardiac surgery.

Creatine supplementation for optimization of physical function in the patient at risk of functional disability: A systematic review and meta-analysis.

BACKGROUND: The efficacy of creatine replacement through supplementation for the optimization of physical function in the population at risk of functional disability is unclear. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane Library, and CINAHL from inception to November 2022. Studies included were randomized controlled trials (RCTs) comparing creatine supplementation with placebos in older adults and adults with chronic disease. The primary outcome was physical function measured by the sit-to-stand test after pooling data using random-effects modeling. We also performed a Bayesian meta-analysis to describe the treatment effect in probability terms. Secondary outcomes included other measures of physical function, muscle function, and body composition. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: We identified 33 RCTs, comprising 1076 participants. From six trials reporting the primary outcome, the pooled standardized mean difference (SMD) was 0.51 (95% confidence interval [CI]: 0.01-1.00; I2 = 62%; P = 0.04); using weakly informative priors, the posterior probability that creatine supplementation improves physical function was 66.7%. Upper-body muscle strength (SMD: 0.25; 95% CI: 0.06-0.44; I2 = 0%; P = 0.01), handgrip strength (SMD 0.23; 95% CI: 0.01-0.45; I2 = 0%; P = 0.04), and lean tissue mass (MD 1.08 kg; 95% CI: 0.77-1.38; I2 = 26%; P < 0.01) improved with creatine supplementation. The quality of evidence for all outcomes was low or very low because of a high risk of bias. CONCLUSION: Creatine supplementation improves sit-to-stand performance, muscle function, and lean tissue mass. It is crucial to conduct high-quality prospective RCTs to confirm these hypotheses (PROSPERO number, CRD42023354929).

Method of Anesthesia and Perioperative Risk Factors, Maternal Anesthesia Complications, and Neonatal Mortality Following Cesarean Delivery in Africa: A Substudy of a 7-Day Prospective Observational Cohort Study.

BACKGROUND: The African Surgical Outcomes Study (ASOS) found that maternal mortality following cesarean delivery in Africa is 50 times higher than in high-income countries, and associated with obstetric hemorrhage and anesthesia complications. Mothers who died were more likely to receive general anesthesia (GA). The associations between GA versus spinal anesthesia (SA) and preoperative risk factors, maternal anesthesia complications, and neonatal outcomes following cesarean delivery in Africa are unknown. METHODS: This is a secondary explanatory analysis of 3792 patients undergoing cesarean delivery in ASOS, a prospective observational cohort study, across 22 African countries. The primary aim was to estimate the association between preoperative risk factors and the outcome of the method of anesthesia delivered. Secondary aims were to estimate the association between the method of anesthesia and the outcomes (1) maternal intraoperative hypotension, (2) severe maternal anesthesia complications, and (3) neonatal mortality. Generalized linear mixed models adjusting for obstetric gravidity and gestation, American Society of Anesthesiologists (ASA) category, urgency of surgery, maternal comorbidities, fetal distress, and level of anesthesia provider were used. RESULTS: Of 3709 patients, SA was performed in 2968 (80%) and GA in 741 (20%). Preoperative factors independently associated with GA for cesarean delivery were gestational age (adjusted odds ratio [aOR], 1.093; 95% confidence interval [CI], 1.052-1.135), ASA categories III (aOR, 11.84; 95% CI, 2.93-46.31) and IV (aOR, 11.48; 95% CI, 2.93-44.93), eclampsia (aOR, 3.92; 95% CI, 2.18-7.06), placental abruption (aOR, 6.23; 95% CI, 3.36-11.54), and ruptured uterus (aOR, 3.61; 95% CI, 1.36-9.63). SA was administered to 48 of 94 (51.1%) patients with eclampsia, 12 of 28 (42.9%) with cardiac disease, 14 of 19 (73.7%) with preoperative sepsis, 48 of 76 (63.2%) with antepartum hemorrhage, 30 of 55 (54.5%) with placenta previa, 33 of 78 (42.3%) with placental abruption, and 12 of 29 (41.4%) with a ruptured uterus. The composite maternal outcome "all anesthesia complications" was more frequent in GA than SA (9/741 [1.2%] vs 3/2968 [0.1%], P < .001). The unadjusted neonatal mortality was higher with GA than SA (65/662 [9.8%] vs 73/2669 [2.7%], P < .001). The adjusted analyses demonstrated no association between method of anesthesia and (1) intraoperative maternal hypotension and (2) neonatal mortality. CONCLUSIONS: Analysis of patients undergoing anesthesia for cesarean delivery in Africa indicated patients more likely to receive GA. Anesthesia complications and neonatal mortality were more frequent following GA. SA was often administered to high-risk patients, including those with eclampsia or obstetric hemorrhage. Training in the principles of selection of method of anesthesia, and the skills of safe GA and neonatal resuscitation, is recommended.

A Transcriptomic Approach to Understand Patient Susceptibility to Pneumonia After Abdominal Surgery.

OBJECTIVE: To describe immune pathways and gene networks altered following major abdominal surgery and to identify transcriptomic patterns associated with postoperative pneumonia. BACKGROUND: Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major abdominal surgery, with postoperative pneumonia associated with an almost 5-fold increase in 30-day mortality. METHODS: From a prospective consecutive cohort (n=150) undergoing major abdominal surgery, whole-blood RNA was collected preoperatively and at 3 time-points postoperatively (2-6, 24, and 48 h). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing. RESULTS: Compared to preoperative sampling, 3639 genes were upregulated and 5043 downregulated at 2 to 6 hours. Pathway analysis demonstrated innate-immune activation with neutrophil degranulation and Toll-like-receptor signaling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil degranulation was associated with postoperative pneumonia acquisition ( P =0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil dysfunction and a more dysregulated host response, at 48 hours postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free ( P =0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection. CONCLUSIONS: Major abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.

Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial.

BACKGROUND AND AIMS: Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear. METHODS: From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy. RESULTS: Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)]. CONCLUSIONS: Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.

Prediction, prognosis, and professionalism in perioperative medicine.

Guidelines provide a framework to take better care of our patients. They are published by different professional groups and are based on all the research done for us by hardworking colleagues. Compiling a guideline is an enormous amount of work and is generally done with the utmost care. However, recommendations often require a subjective interpretation of published research, where personal and academic interests can influence the outcome. We discuss two recently published guidelines on perioperative cardiovascular assessment that led to different conclusions on some important areas of patient care.

One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

Long-term healthcare use after postoperative complications: an analysis of linked primary and secondary care routine data.

Background: Postoperative complications are associated with reduced long-term survival. We characterise healthcare use changes after sentinel postoperative complications. Methods: We linked primary and secondary care records of patients undergoing elective surgery at four East London hospitals (2012-7) with at least 90 days follow-up. Complication codes (wound infection, urinary tract infection, pneumonia, new stroke, and new myocardial infarction) recorded within 90 days of surgery were identified from primary or secondary care. Outcomes were change in healthcare contact days in the 2 yr before and after surgery, and 2 yr mortality. We report rate ratios (RaR) with 95% confidence intervals and adjusted for baseline healthcare use and confounders using negative binomial regression. Results: We included 49 913 patients (median age 49 yr [inter-quartile range {IQR}: 34-64]), 27 958 (56.0%) were female. Amongst 3883 (7.8%) patients with complications (median age 58 [IQR: 43-72]), there were 18.4 days per year in contact with healthcare before surgery and 25.3 days after surgery (RaR: 1.38 [1.37-1.39]). Patients without complications (median age 48 [IQR: 33-63]) had 12.3 days per year in contact with healthcare before surgery and 14.0 days after surgery (RaR: 1.14 [1.14-1.15]). The adjusted incidence rate ratio of days in contact with healthcare associated with complications was 1.67 (1.49-1.87). More patients (391; 10.1%) with complications died within 2 yr than those without (1428; 3.1%). Conclusions: Patients with postoperative complications are older with greater healthcare use before surgery. However, their absolute and relative increases in healthcare use after surgery are greater than patients without complications.

Long-term disease interactions amongst surgical patients: a population cohort study.

BACKGROUND: The average age of the surgical population continues to increase, as does prevalence of long-term diseases. However, outcomes amongst multi-morbid surgical patients are not well described. METHODS: We included adults undergoing non-obstetric surgical procedures in the English National Health Service between January 2010 and December 2015. Patients could be included multiple times in sequential 90-day procedure spells. Multi-morbidity was defined as presence of two or more long-term diseases identified using a modified Charlson comorbidity index. The primary outcome was 90-day postoperative death. Secondary outcomes included emergency hospital readmission within 90 days. We calculated age- and sex-adjusted odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. We compared the outcomes associated with different disease combinations. RESULTS: We identified 20 193 659 procedure spells among 13 062 715 individuals aged 57 (standard deviation 19) yr. Multi-morbidity was present among 2 577 049 (12.8%) spells with 195 965 deaths (7.6%), compared with 17 616 610 (88.2%) spells without multi-morbidity with 163 529 deaths (0.9%). Multi-morbidity was present in 1 902 859/16 946 808 (11.2%) elective spells, with 57 663 deaths (2.7%, OR 4.9 [95% CI: 4.9-4.9]), and 674 190/3 246 851 (20.7%) non-elective spells, with 138 302 deaths (20.5%, OR 3.0 [95% CI: 3.0-3.1]). Emergency readmission followed 547 399 (22.0%) spells with multi-morbidity compared with 1 255 526 (7.2%) without. Multi-morbid patients accounted for 57 663/114 783 (50.2%) deaths after elective spells, and 138 302/244 711 (56.5%) after non-elective spells. The rate of death varied five-fold from lowest to highest risk disease pairs. CONCLUSION: One in eight patients undergoing surgery have multi-morbidity, accounting for more than half of all postoperative deaths. Disease interactions amongst multi-morbid patients is an important determinant of patient outcome.

Characterising biological mechanisms underlying ethnicity-associated outcomes in COVID-19 through biomarker trajectories: a multicentre registry analysis.

BACKGROUND: Differences in routinely collected biomarkers between ethnic groups could reflect dysregulated host responses to disease and to treatments, and be associated with excess morbidity and mortality in COVID-19. METHODS: A multicentre registry analysis from patients aged ≥16 yr with SARS-CoV-2 infection and emergency admission to Barts Health NHS Trust hospitals during January 1, 2020 to May 13, 2020 (wave 1) and September 1, 2020 to February 17, 2021 (wave 2) was subjected to unsupervised longitudinal clustering techniques to identify distinct phenotypic patient clusters based on trajectories of routine blood results over the first 15 days of hospital admission. Distribution of trajectory clusters across ethnic categories was determined, and associations between ethnicity, trajectory clusters, and 30-day survival were assessed using multivariable Cox proportional hazards modelling. Secondary outcomes were ICU admission, survival to hospital discharge, and long-term survival to 640 days. RESULTS: We included 3237 patients with hospital length of stay ≥7 days. In patients who died, there was greater representation of Black and Asian ethnicity in trajectory clusters for C-reactive protein and urea-to-creatinine ratio associated with increased risk of death. Inclusion of trajectory clusters in survival analyses attenuated or abrogated the higher risk of death in Asian and Black patients. Inclusion of C-reactive protein went from hazard ratio (HR) 1.36 [0.95-1.94] to HR 0.97 [0.59-1.59] (wave 1), and from HR 1.42 [1.15-1.75]) to HR 1.04 [0.78-1.39] (wave 2) in Asian patients. Trajectory clusters associated with reduced 30-day survival were similarly associated with worse secondary outcomes. CONCLUSIONS: Clinical biochemical monitoring of COVID-19 and progression and treatment response in SARS-CoV-2 infection should be interpreted in the context of ethnic background.

Fluid Optimisation in Emergency Laparotomy (FLO-ELA) Trial: study protocol for a multi-centre randomised trial of cardiac output-guided fluid therapy compared to usual care in patients undergoing major emergency gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in patients undergoing major emergency gastrointestinal surgery are a major burden on healthcare systems. Optimal management of perioperative intravenous fluids may reduce mortality rates and improve outcomes from surgery. Previous small trials of cardiac-output guided haemodynamic therapy algorithms in patients undergoing gastrointestinal surgery have suggested this intervention results in reduced complications and a modest reduction in mortality. However, this existing evidence is based mainly on elective (planned) surgery, with little evaluation in the emergency setting. There are fundamental clinical and pathophysiological differences between the planned and emergency surgical setting which may influence the effects of this intervention. A large definitive trial in emergency surgery is needed to confirm or refute the potential benefits observed in elective surgery and to inform widespread clinical practice. METHODS: The FLO-ELA trial is a multi-centre, parallel-group, open, randomised controlled trial. 3138 patients aged 50 and over undergoing major emergency gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intra-venous fluid, or usual care without cardiac output monitoring. The trial intervention will be carried out during surgery and for up to 6 h postoperatively. The trial is funded through an efficient design call by the National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) programme and uses existing routinely collected datasets for the majority of data collection. The primary outcome is the number of days alive and out of hospital within 90 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation. Participant recruitment started in September 2017 with a 1-year internal pilot phase and is ongoing at the time of publication. DISCUSSION: This will be the largest contemporary randomised trial examining the effectiveness of perioperative cardiac output-guided haemodynamic therapy in patients undergoing major emergency gastrointestinal surgery. The multi-centre design and broad inclusion criteria support the external validity of the trial. Although the clinical teams delivering the trial interventions will not be blinded, significant trial outcome measures are objective and not subject to detection bias. TRIAL REGISTRATION: ISRCTN 14729158. Registered on 02 May 2017.

Comparison of Cystatin C and Creatinine in the Assessment of Measured Kidney Function during Critical Illness.

BACKGROUND: Incomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded by muscle loss and may improve identification of persistent kidney dysfunction. METHODS: To assess kidney function during prolonged critical illness, we enrolled 38 mechanically ventilated patients with an expected length of stay of >72 hours near admission to intensive care unit (ICU) in a single academic medical center. We assessed sequential kidney function using creatinine, cystatin C, and iohexol clearance measurements. The primary outcome was difference between eGFR creatinine and eGFR cystatin C at ICU discharge using Bayesian regression modeling. We simultaneously measured muscle mass by ultrasound of the rectus femoris to assess the confounding effect on serum creatinine generation. RESULTS: Longer length of ICU stay was associated with greater difference between eGFR creatinine and eGFR cystatin C at a predicted rate of 2 ml/min per 1.73 m 2 per day (95% confidence interval [CI], 1 to 2). By ICU discharge, the posterior mean difference between creatinine and cystatin C eGFR was 33 ml/min per 1.73 m 2 (95% credible interval [CrI], 24 to 42). In 27 patients with iohexol clearance measured close to ICU discharge, eGFR creatinine was on average two-fold greater than the iohexol gold standard, and posterior mean difference was 59 ml/min per 1.73 m 2 (95% CrI, 49 to 69). The posterior mean for eGFR cystatin C suggested a 22 ml/min per 1.73 m 2 (95% CrI, 13 to 31) overestimation of measured GFR. Each day in ICU resulted in a predicted 2% (95% CI, 1% to 3%) decrease in muscle area. Change in creatinine-to-cystatin C ratio showed good longitudinal, repeated measures correlation with muscle loss, R =0.61 (95% CI, 0.50 to 0.72). CONCLUSIONS: eGFR creatinine systematically overestimated kidney function after prolonged critical illness. Cystatin C better estimated true kidney function because it seemed unaffected by the muscle loss from prolonged critical illness. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Skeletal Muscle Wasting and Renal Dysfunction After Critical Illness Trauma - Outcomes Study (KRATOS), NCT03736005 .

Systematic reviews and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: mortality, morbidity, and organ failure.

BACKGROUND: Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials. METHODS: Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process. RESULTS: A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien-Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien-Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus. CONCLUSIONS: Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien-Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.

Liberal or restrictive antimicrobial prophylaxis for surgical site infection: systematic review and meta-analysis of randomised trials.

BACKGROUND: Antimicrobial prophylaxis is widely used to prevent surgical site infection. Amid growing concern about antimicrobial resistance, we determined the effectiveness of antimicrobial prophylaxis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and WHO-ICTRP between January 1, 1990 and January 1, 2020 for trials randomising adults undergoing surgery to liberal (more doses) or restrictive (fewer or no doses) perioperative antimicrobial prophylaxis. Pairs of researchers reviewed articles and extracted data, and a senior author resolved discrepancies. The primary outcome measure was surgical site infection or bacteriuria for urological procedures. We calculated average risk difference (RD) with 95% confidence intervals and prediction intervals (PI) using random effects models, and present risk ratios (RR). We assessed evidence certainty using GRADE methodology, and risk of bias using the Cochrane Risk of Bias tool (PROSPERO: CRD42018116946). RESULTS: From 6593 records, we identified 294 trials including 86 146 patients. Surgical site infection occurred in 2237/44 113 (5.1%) patients receiving liberal prophylaxis vs 2889/42 033 (6.9%) receiving restrictive prophylaxis (RD -0.01 [-0.02 to -0.01]; relative risk 0.72 [0.67-0.77]; I2=52%, PI -0.05-0.02). There was a small benefit of prophylaxis in 161 trials comparing no prophylaxis with ≥1 dose (RD -0.02 [-0.03 to -0.02]; RR 0.58 [0.52-0.65]; I2=62%, PI -0.06-0.02). Treatment effect varied from a strong effect in urology to no benefit in 7/19 specialities. Tests for publication bias suggest 62 unreported trials and evidence certainty was very low. Treatment harms were reported in 43/294 trials. CONCLUSIONS: A systematic review and meta-analysis of randomised trials revealed that more liberal antimicrobial prophylaxis is associated with a small reduction in the risk of surgical site infection, although antimicrobial harms are poorly reported. Further evidence about the risks of antimicrobial prophylaxis to inform current widespread use is urgently needed.