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.

Peak power output testing: novel method for preoperative assessment of exercise capacity.

BACKGROUND: Assessment of exercise capacity is an important component of risk assessment before major surgery. Cardiopulmonary exercise testing (CPET) provides comprehensive assessment but is resource-intensive, limiting widespread adoption. Measurement of a patient's peak power output (PPO) using a simplified test on a cycle ergometer has the potential to identify patients likely to have abnormal CPET findings and to be at increased perioperative risk. The aim of this study was to investigate the potential for PPO to identify those with abnormal CPET and to determine whether PPO predicted the risk of adverse postoperative outcomes. METHODS: In a retrospective analysis of a single-centre cohort, the ability of PPO to predict a high-risk CPET result in patients undergoing major cancer surgery was analysed. The assessment was validated in patients undergoing major abdominal surgery from a UK national multicentre cohort. The association between PPO and adverse postoperative outcomes to traditional CPET-derived variables were compared. RESULTS: In 2262 patients from a single centre, PPO was an excellent discriminator of high-risk CPET, with an area under the receiver operating characteristic curve (AUROC) of 0.901 (95 per cent c.i. 0.888 to 0.913). In the national cohort of 2742 patients, there was excellent discrimination, with an AUROC of 0.856 (0.842 to 0.871). A PPO cut-off of 1.5 W/kg may be appropriate for use in screening, with a sensitivity of 90 per cent in both cohorts. PPO and traditional CPET-derived predictors demonstrated similar discrimination of major postoperative complications and death. The association between PPO and major postoperative complications persisted on multivariable analysis. CONCLUSION: These results suggest a role for the PPO test in preoperative screening and risk stratification for major surgery. Prospective evaluation is recommended.

Validation of the days alive and out of hospital outcome measure after emergency laparotomy: a retrospective cohort study.

BACKGROUND: Days alive and out of hospital (DAOH) is a composite, patient-centred outcome measure describing a patient's postoperative recovery, encompassing hospitalisation and mortality. DAOH is the number of days not in hospital over a defined postoperative period; patients who die have DAOH of zero. The Standardising Endpoints in Perioperative Medicine (StEP) group recommended DAOH as a perioperative outcome. However, DAOH has never been validated in patients undergoing emergency laparotomy. Here, we validate DAOH after emergency laparotomy and establish the optimal duration of observation. METHODS: Prospectively collected data of patients having emergency laparotomy in England (December 1, 2013-November 30, 2017) were linked to national hospital admission and mortality records for the year after surgery. We evaluated construct validity by assessing DAOH variation with known perioperative risk factors and predictive validity for 1 yr mortality using a multivariate Bayesian mixed-effects logistic regression. The optimal postoperative DAOH period (30 or 90 days) was judged on distributional and pragmatic properties. RESULTS: We analysed 78 921 records. The median 30-day DAOH (DAOH30) was 16 (inter-quartile range [IQR], 0-22) days and the median DAOH90 was 75 (46-82) days. DAOH was shorter in the presence of known perioperative risk factors. For patients surviving the first 30 postoperative days, shorter DAOH30 was associated with higher 1-yr mortality (odds ratio=0.94; 95% credible interval, 0.94-0.94). CONCLUSION: DAOH is a valid, patient-centred outcome after emergency laparotomy. We recommend its use in clinical trials, quality assurance, and quality improvement, measured at 30 days as mortality heavily skews DAOH measured at 90 days and beyond.

Seasonality in surgical outcome data: a systematic review and narrative synthesis.

BACKGROUND: Seasonal trends in patient outcomes are an under-researched area in perioperative care. This systematic review evaluates the published literature on seasonal variation in surgical outcomes worldwide. METHODS: MEDLINE, Embase, Cochrane, CINHAL, and Web of Science were searched for studies on major surgical procedures, examining mortality or other patient-relevant outcomes, across seasonal periods up to February 2019. Major surgery was defined as a procedure requiring an overnight stay in an inpatient medical facility. We included studies exploring variation according to calendar and meteorological seasons and recurring annual events including staff turnover. Quality was assessed using an adapted Downs and Black scoring system. RESULTS: The literature search identified 82 studies, including 22 210 299 patients from four continents. Because of the heterogeneity of reported outcomes and literature scope, a narrative synthesis was undertaken. Mass staff changeover was investigated in 37 studies; the majority (22) of these did not show strong evidence of worse outcomes. Of the 47 studies that examined outcomes across meteorological or calendar seasons, 33 found evidence of seasonal variation. Outcomes were often worse in winter (16 studies). This trend was particularly prominent amongst surgical procedures classed as an 'emergency' (five of nine studies). There was evidence for increased postoperative surgical site infections during summer (seven of 12 studies examining this concept). CONCLUSION: This systematic review provides tentative evidence for an increased risk of postoperative surgical site infections in summer, and an increased risk of worse outcomes after emergency surgery in winter and during staff changeover times. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42019137214.

Core Outcome Measures for Perioperative and Anaesthetic Care (COMPAC): a modified Delphi process to develop a core outcome set for trials in perioperative care and anaesthesia.

BACKGROUND: Outcome selection underpins clinical trial interpretation. Inconsistency in outcome selection and reporting hinders comparison of different trials' results, reducing the utility of research findings. METHODS: We conducted an iterative consensus process to develop a set of Core Outcome Measures for Perioperative and Anaesthetic Care (COMPAC), following the established Core Outcome Measures for Effectiveness Trials (COMET) methodology. First, we undertook a systematic review of RCTs in high-impact journals to describe current outcome reporting trends. We then surveyed patients, carers, researchers, and perioperative clinicians about important outcomes after surgery. Finally, a purposive stakeholder sample participated in a modified Delphi process to develop a core outcome set for perioperative and anaesthesia trials. RESULTS: Our systematic review revealed widespread inconsistency in outcome reporting, with variable or absent definitions, levels of detail, and temporal criteria. In the survey, almost all patients, carers, and clinicians rated clinical outcome measures critically important, but clinicians rated patient-centred outcomes less highly than patients and carers. The final core outcome set was: (i) mortality/survival (postoperative mortality, long-term survival); (ii) perioperative complications (major postoperative complications/adverse events; complications/adverse events causing permanent harm); (iii) resource use (length of hospital stay, unplanned readmission within 30 days); (iv) short-term recovery (discharge destination, level of dependence, or both); and (v) longer-term recovery (overall health-related quality of life). CONCLUSIONS: This core set, incorporating important outcomes for both clinicians and patients, should guide outcome selection in future perioperative medicine or anaesthesia trials. Mapping these alongside standardised endpoint definitions will yield a comprehensive perioperative outcome framework.

Quality metrics for emergency abdominal surgery in children: a systematic review.

BACKGROUND: There is variation in care quality and outcomes for children undergoing emergency abdominal surgery, such as appedectomy. Addressing this requires paediatric-specific quality metrics. The aim of this study was to identify perioperative structure and process measures that are associated with improved outcomes for these children. METHODS: We performed a systematic review searching MEDLINE, Embase, CINAHL, Cochrane Library, and Google Scholar for articles published between January 1, 1980 and September 29, 2020 about the perioperative care of children undergoing emergency abdominal surgery. We also conducted secondary searching of references and citations, and we included international professional publications. RESULTS: We identified and analysed 383 peer-reviewed articles and 18 grey literature publications. High-grade evidence pertaining to the perioperative care of this patient group is limited. Most of the evidence available relates to improving diagnostic accuracy using preoperative blood testing, imaging, and clinical decision tools. Processes associated with clinical outcomes include time lapse between time of presentation or initial assessment and surgery, and the use of particular analgesia and antibiotic protocols. Structural factors identified include hospital and surgeon caseload and the use of perioperative care pathways. CONCLUSIONS: This review summarises the structural and process measures associated with outcome in paediatric emergency abdominal surgery. Such measures provide a means of evaluating care and identifying areas of practice that require quality improvement, especially in children with appendicitis. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42017055285.

Perioperative care for older people.

Increasing numbers of older people are undergoing surgery with benefits including symptom relief and extended longevity. Despite these benefits, older people are more likely than younger patients to experience postoperative complications, which are predominantly medical as opposed to surgical. Comprehensive Geriatric Assessment and optimisation offers a systematic approach to risk assessment and risk modification in the perioperative period. Clinical evidence shows that Comprehensive Geriatric Assessment and optimisation reduces postoperative medical complications and is cost effective in the perioperative setting. These benefits have been observed in patients undergoing elective and emergency surgery. Challenges in the implementation of perioperative Comprehensive Geriatric Assessment and optimisation services are acknowledged. These include the necessary involvement of a wide stakeholder group, limited available geriatric medicine workforce and ensuring fidelity to Comprehensive Geriatric Assessment methodology with adaptation to the local context. Addressing these challenges needs a cross-specialty, interdisciplinary approach underpinned by evidence-based medicine and implementation science with upskilling to facilitate innovative use of the extended workforce. Future delivery of quality patient-centred perioperative care requires proactive engagement with national audit, collaborative guidelines and establishment of networks to share best practice.

Socioeconomic deprivation and long-term outcomes after elective surgery: analysis of prospective data from two observational studies.

BACKGROUND: Socioeconomic deprivation is associated with health inequalities. We explored relationships between socioeconomic group and outcomes after elective surgery in the UK National Health Service (NHS). METHODS: We combined data from two observational studies in 115 NHS hospitals and determined socioeconomic group using the Index of Multiple Deprivation (IMD) quintiles based on place of residence. Postoperative complications and 3-yr survival were assessed using logistic and Cox regression. Univariate analyses were adjusted for age differences between IMD quintiles. Multivariable analyses were used to account for other baseline risk factors including sex and comorbid disease. Results are reported as n (%), hazard ratios (HR) or odds ratios (OR) with 95% confidence intervals. RESULTS: Postoperative complications developed in 971/9051 patients (10.7%) and 1597/9043 patients (17.7%) died within 3 yr. Complication rates increased with deprivation (reference group least-deprived IMD5): IMD1 (OR=1.44 [1.17-1.78]; P<0.001), IMD2 (OR=1.38 [1.12-1.70]; P<0.01), IMD3 (OR=1.09 [0.88-1.35]: P=0.44), IMD4 (OR=0.89 [0.71-1.11]; P=0.30). More patients from the most deprived quintile died (IMD1) (n=349, 18.8%) compared with the least deprived (IMD5) (n=297, 15.9%) with a trend across the socioeconomic spectrum (P=0.01). After age adjustment, patients in the most deprived areas experienced reduced 3-yr survival: IMD1 (HR=1.43 [1.23-1.67]; P<0.0001), IMD2 (HR=1.35 [1.15-1.57]; P<0.001), IMD3 (HR=1.04 [0.89-1.23]; P=0.60), and IMD4 (HR=1.11 [0.95-1.30]; P=0.19). This finding persisted in risk-adjusted analyses. Increased complication rates only partially explained this reduced survival. CONCLUSIONS: Socioeconomic deprivation is associated with worse long-term outcomes after elective surgery. This risk factor should be considered when planning perioperative care for patients from deprived areas.

Developing and validating subjective and objective risk-assessment measures for predicting mortality after major surgery: An international prospective cohort study.

BACKGROUND: Preoperative risk prediction is important for guiding clinical decision-making and resource allocation. Clinicians frequently rely solely on their own clinical judgement for risk prediction rather than objective measures. We aimed to compare the accuracy of freely available objective surgical risk tools with subjective clinical assessment in predicting 30-day mortality. METHODS AND FINDINGS: We conducted a prospective observational study in 274 hospitals in the United Kingdom (UK), Australia, and New Zealand. For 1 week in 2017, prospective risk, surgical, and outcome data were collected on all adults aged 18 years and over undergoing surgery requiring at least a 1-night stay in hospital. Recruitment bias was avoided through an ethical waiver to patient consent; a mixture of rural, urban, district, and university hospitals participated. We compared subjective assessment with 3 previously published, open-access objective risk tools for predicting 30-day mortality: the Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality (P-POSSUM), Surgical Risk Scale (SRS), and Surgical Outcome Risk Tool (SORT). We then developed a logistic regression model combining subjective assessment and the best objective tool and compared its performance to each constituent method alone. We included 22,631 patients in the study: 52.8% were female, median age was 62 years (interquartile range [IQR] 46 to 73 years), median postoperative length of stay was 3 days (IQR 1 to 6), and inpatient 30-day mortality was 1.4%. Clinicians used subjective assessment alone in 88.7% of cases. All methods overpredicted risk, but visual inspection of plots showed the SORT to have the best calibration. The SORT demonstrated the best discrimination of the objective tools (SORT Area Under Receiver Operating Characteristic curve [AUROC] = 0.90, 95% confidence interval [CI]: 0.88-0.92; P-POSSUM = 0.89, 95% CI 0.88-0.91; SRS = 0.85, 95% CI 0.82-0.87). Subjective assessment demonstrated good discrimination (AUROC = 0.89, 95% CI: 0.86-0.91) that was not different from the SORT (p = 0.309). Combining subjective assessment and the SORT improved discrimination (bootstrap optimism-corrected AUROC = 0.92, 95% CI: 0.90-0.94) and demonstrated continuous Net Reclassification Improvement (NRI = 0.13, 95% CI: 0.06-0.20, p < 0.001) compared with subjective assessment alone. Decision-curve analysis (DCA) confirmed the superiority of the SORT over other previously published models, and the SORT-clinical judgement model again performed best overall. Our study is limited by the low mortality rate, by the lack of blinding in the 'subjective' risk assessments, and because we only compared the performance of clinical risk scores as opposed to other prediction tools such as exercise testing or frailty assessment. CONCLUSIONS: In this study, we observed that the combination of subjective assessment with a parsimonious risk model improved perioperative risk estimation. This may be of value in helping clinicians allocate finite resources such as critical care and to support patient involvement in clinical decision-making.

Women empowerment in anaesthesia research and clinical practice: meeting report from the British Journal of Anaesthesia Women in Anaesthesia Research symposium.

The Women in Anaesthesia Research Symposium (Prato, Italy; 4 June, 2019), supported by the British Journal of Anaesthesia in collaboration with Monash University, was organised to discuss challenges facing women in anaesthesia clinical practice and research. We provide an overview of institutional or departmental measures that were proposed during the symposium that may empower women in anaesthesia today.

Causal inference in perioperative medicine observational research: part 1, a graphical introduction.

Graphical models have emerged as a tool to map out the interplay between multiple measured and unmeasured variables, and can help strengthen the case for a causal association between exposures and outcomes in observational studies. In Part 1 of this methods series, we will introduce the reader to graphical models for causal inference in perioperative medicine, and set the framework for Part 2 of the series involving advanced methods for causal inference.

Pediatric perioperative outcomes: Protocol for a systematic literature review and identification of a core outcome set for infants, children, and young people requiring anesthesia and surgery.

Clinical outcomes are measurable changes in health, function, or quality of life that are important for evaluating the quality of care and comparing the efficacy of interventions. However, clinical outcomes and related measurement tools need to be well-defined, relevant, and valid. In adults, Core Outcome Measures in Effectiveness Trials (COMET) methodology has been used to develop core outcome sets for perioperative care. Systematic literature reviews identified standardized endpoints (StEP) and valid measurement tools, and consensus across a broader range of relevant stakeholders was achieved via a Delphi process to establish Core Outcome Measures in Perioperative and Anaesthetic Care (COMPAC). Core outcome sets for pediatric perioperative care cannot be directly extrapolated from adult data. The type and weighting of endpoints within particular domains can be influenced by age-dependent differences in the indications for and/or nature of surgery and medical comorbidities, and the validity and utility of many measurement tools vary significantly with developmental stage and age. The involvement of parents/carers is essential as they frequently act as surrogate responders for preverbal and developmentally delayed children, parental response may influence child outcome, and parental and/or child ranking of outcomes may differ from those of health professionals. Here, we describe the formation of the international Pediatric Perioperative Outcomes Group, which aims to identify and create validated, broadly applicable, patient-centered outcome measures for infants, children, and young people. Methodologies parallel that of the StEP and COMPAC projects, and systematic literature searches have been performed within agreed age-dependent subpopulations to identify reported outcomes and measurement tools. This represents the first steps for developing core outcome sets for pediatric perioperative care.

Patient-reported outcomes for ambulatory surgery.

PURPOSE OF REVIEW: To discuss the importance of validated tools that measure patient-reported outcomes and their use in ambulatory surgery. RECENT FINDINGS: Sustained increases in ambulatory surgical care reflect advances in surgical techniques and perioperative anaesthetic care. Use of patient-reported outcomes allows identification of minor adverse events that are more common in this population compared with traditional endpoints such as mortality. Variability in reported outcomes restricts research potential and limits the ability to benchmark providers. The standardized endpoints in perioperative medicine initiative's recommendations on patient-reported outcomes and patient comfort measures are relevant to evaluating ambulatory care. Combining validated generic and disease-specific patient-reported outcome measures (PROMs) examines the widest spectrum of outcomes. Technological advances can be used to facilitate outcome measurement in ambulatory surgery with digital integration optimizing accurate real-time data collection. Telephone or web-based applications for reviewing ambulatory patients were found to be acceptable in multiple international settings and should be harnessed to allow remote follow-up. SUMMARY: Use of validated tools to measure patient-reported outcomes allows internal and external quality comparison. Tools can be combined to measure objective outcomes and patient satisfaction. These are both key factors in driving forward improvements in perioperative ambulatory surgical care.

Preoperative chronic beta-blocker prescription in elderly patients as a risk factor for postoperative mortality stratified by preoperative blood pressure: a cohort study.

BACKGROUND: Recent data suggest that beta blockers are associated with increased perioperative risk in hypertensive patients. We investigated whether beta blockers were associated with an increased risk in elderly patients with raised preoperative arterial blood pressure. METHODS: We conducted a propensity-score-matched cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13), including 84 633 patients aged 65 yr or over. Conditional logistic regression models, including factors that were significantly associated with the outcome, were constructed for 30-day mortality after elective noncardiac surgery. The effects of beta blockers (primary outcome), renin-angiotensin system (RAS) inhibitors, calcium-channel blockers, thiazides, loop diuretics, and statins were investigated at systolic and diastolic arterial pressure thresholds. RESULTS: Beta blockers were associated with increased odds of postoperative 30-day mortality in patients with systolic hypertension (defined as systolic BP >140 mm Hg; adjusted odds ratio [aOR]: 1.92; 95% confidence interval [CI]: 1.05-3.51). After excluding patients for whom prior data suggest benefit from perioperative beta blockade (patients with prior myocardial infarction or heart failure), rather than adjusting for them, the point estimate shifted slightly (aOR: 2.06; 95% CI: 1.09-3.89). Compared with no use, statins (aOR: 0.35; 95% CI: 0.17-0.75) and thiazides (aOR: 0.28; 95% CI: 0.10-0.78) were associated with lower mortality in patients with systolic hypertension. CONCLUSIONS: These data suggest that the safety of perioperative beta blockers may be influenced by preoperative blood pressure thresholds. A randomised controlled trial of beta-blocker withdrawal, in select populations, is required to identify a causal relationship.

Comprehensive Geriatric Assessment in the perioperative setting; where next?

Comprehensive Geriatric Assessment (CGA) is being employed in the perioperative setting to improve outcomes for older surgical patients. Traditionally CGA is delivered by a geriatrician led multidisciplinary team but with the acknowledged workforce challenges in geriatric medicine, it has been suggested that non-geriatricians may be able to deliver CGA. HOW-CGA developed a toolkit to facilitate the delivery of CGA by non-geriatricians in the perioperative setting. Across two hospital sites uptake and implementation of this toolkit was limited by a potential lack of face validity, behavioural and cultural barriers and an acknowledgement that geriatric medicine expertise is key to CGA and optimisation. In-keeping with this finding there has been an observed expansion in geriatrician led CGA services for older surgical patients in the UK. In order to demonstrate the effectiveness of perioperative CGA services, implementation science should be combined with health services research methodology and the use of big data through linked national audit.

Metabolic dysfunction in lymphocytes promotes postoperative morbidity.

Perioperative lymphopenia has been linked with an increased risk of postoperative infectious complications, but the mechanisms remain unclear. We tested the hypothesis that bioenergetic dysfunction is an important mechanism underlying lymphopenia, impaired functionality and infectious complications. In two cohorts of patients (61-82 years old) undergoing orthopaedic joint replacement (n=417 and 328, respectively), we confirmed prospectively that preoperative lymphopenia (≤1.3 x 10(9)·l(-1); <20% white cell count; prevalence 15-18%) was associated with infectious complications (relative risk 1.5 (95% confidence interval 1.1-2.0); P=0.008) and prolonged hospital stay. Lymphocyte respirometry, mitochondrial bioenergetics and function were assessed (n=93 patients). Postoperative lymphocytes showed a median 43% fall (range: 26-65%; P=0.029; n=13 patients) in spare respiratory capacity, the extra capacity available to produce energy in response to stress. This was accompanied by reduced glycolytic capacity. A similar hypometabolic phenotype was observed in lymphocytes sampled preoperatively from chronically lymphopenic patients (n=21). This hypometabolic phenotype was associated with functional lymphocyte impairment including reduced T-cell proliferation, lower intracellular cytokine production and excess apoptosis induced by a range of common stressors. Glucocorticoids, which are ubiquitously elevated for a prolonged period postoperatively, generated increased levels of mitochondrial reactive oxygen species, activated caspase-1 and mature interleukin (IL)-1ß in human lymphocytes, suggesting inflammasome activation. mRNA transcription of the NLRP1 inflammasome was increased in lymphocytes postoperatively. Genetic ablation of the murine NLRP3 inflammasome failed to prevent glucocorticoid-induced lymphocyte apoptosis and caspase-1 activity, but increased NLRP1 protein expression. Our findings suggest that the hypometabolic phenotype observed in chronically lymphopenic patients and/or acquired postoperatively increases the risk of postoperative infection through glucocorticoid activation of caspase-1 via the NLRP1 inflammasome.