A protocol for a prospective, multicentre observational study to determine if nonanaemic iron deficiency worsens postoperative outcome in patients undergoing elective surgery for resection of colorectal cancer: The NATO study.

BACKGROUND: Preoperative absolute and functional iron deficiency anaemia is associated with poor postoperative outcomes in patients undergoing surgery for colorectal cancer. It is biologically plausible that "early", or "nonanaemic" iron deficiency may also be associated with worse postoperative outcomes in similar cohorts, albeit at lesser severity than that seen for anaemia. The evidence supporting this assertion is of low quality. METHODS: We have designed a prospective, observational study to delineate associations between preoperative non-anaemic iron deficiency and postoperative outcomes after surgery for colorectal cancer. Patients without anaemia, undergoing elective surgery for colorectal cancer will be allocated to an iron replete or an iron deficient group based on preoperative transferrin saturation. The primary outcome is days alive and at home on postoperative day 90. Secondary outcomes include days alive and at home on postoperative day 30, length of hospital stay, readmission to acute care, postoperative complications, health-related quality of life scores, quality of postoperative recovery, and requirement for allogeneic blood transfusion. The planned sample size is 422 patients, which has 80% power to detect a two-day difference in the primary outcome. The study commenced in May 2019. CONCLUSION: The results of this study will provide patients and clinicians with high-quality evidence concerning associations between nonanaemic iron deficiency and patient-centred outcomes after surgery for colorectal cancer. The study will be conducted in multiple urban and rural centres across Australia and New Zealand. The results will be highly generalisable to contemporary surgical practice and should be rapidly translated.

The epidemiology of rapid response team activation amongst patients undergoing major gastrointestinal surgery.

BACKGROUND: Clinical deterioration requiring rapid response team (RRT) review is associated with increased morbidity amongst hospitalised patients. The frequency of and association with RRT calls in patients undergoing major gastrointestinal surgery is unknown. Understanding the epidemiology of RRT calls might identify areas for quality improvement in this cohort. OBJECTIVES: The objective of this study is to identify perioperative risks and outcome associations with RRT review following major gastrointestinal surgery. METHODS: We conducted a retrospective cohort study using electronic databases at a large Australian university hospital. We included adult patients admitted for major gastrointestinal surgery between 1 January 2015 and 31 March 2018. RESULTS: Of 7158 patients, 514 (7.4%) required RRT activation postoperatively. After adjustment, variables associated with RRT activation included the following: hemiplegia/paraplegia (odds ratio [OR]: 8.0, 95% confidence interval [CI]: 2.3 to 27.8, p = 0.001), heart failure (OR: 6.9, 95% CI: 3.3 to 14.6, p < 0.001), peripheral vascular disease (OR: 5.3, 95% CI: 2.7 to 10.4, p < 0.001), peptic ulcer disease (OR: 4.2, 95% CI: 2.2 to 8.0, p < 0.001), chronic obstructive pulmonary disease (OR: 4.0, 95% CI: 2.2 to 7.2, p < 0.001), and emergency admission status (OR: 2.6, 95% CI: 2.1 to 3.3, p < 0.001). Following the index operation, 46% of first RRT activations occurred within 24 h of surgery and 61% had occurred within 48 h. The most common triggers for RRT activation were tachycardia, hypotension, and tachypnoea. Postoperative RRT activation was associated with in-hospital mortality (OR: 6.7, 95% CI: 3.8 to 11.8, p < 0.001), critical care admission (incidence rate ratio: 8.18, 95% CI: 5.23 to 12.77, p < 0.001), and longer median length of hospital stay (12 days vs. 2 days, p < 0.001) compared to no RRT activation. CONCLUSION: After major gastrointestinal surgery, one in 14 patients had an RRT activation, almost half within 24 h of surgery. Such activation was independently associated with increased morbidity and mortality. Identified associations may guide more pre-emptive management for those at an increased risk of RRT activation.

Postoperative anaemia and patient-centred outcomes after major abdominal surgery: a retrospective cohort study.

BACKGROUND: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown. METHODS: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery. RESULTS: A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval [CI], 76.7-80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio [RR]=1.51; 95% CI, 1.10-2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87-119) vs 114 (95% CI, 99-128; P<0.001), and 130 (95% CI, 112-140) vs 139 (95% CI, 121-144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55-42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65-4.23; P<0.001); and longer median (inter-quartile range [IQR]) hospital stays, 6.6 (4.4-12.4) vs 3.7 (2.5-6.5) days (P<0.001). CONCLUSIONS: Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated. CLINICAL TRIAL REGISTRATION: NCT04978285 (ClinicalTrials.gov).

Associations between non-anaemic iron deficiency and outcomes following elective cardiac surgery (IDOCS): a prospective cohort study.

BACKGROUND: One in two adults undergoing cardiac surgery are iron deficient, best practice guidelines and consensus statements recommend routine investigation and treatment of iron deficiency before elective cardiac surgery, even in the absence of anaemia; however, it is not clear if non-anaemic iron deficiency is associated with worse outcomes in this patient population. We hypothesised that iron deficiency would be associated with worse postoperative outcomes than an iron replete state in adults without anaemia undergoing elective cardiac surgery. METHODS: We performed a prospective, cohort study at two hospitals in Australia. We recruited adults (ie, people 18 years and older) undergoing elective cardiac surgery without anaemia (defined as a haemoglobin of less than 130 g/L for men and less than 120 g/L for women), concomitant haemoglobinopathy, bone marrow pathology, haemochromatosis, or end-stage renal failure requiring dialysis. Participants were stratified as iron deficient or iron replete on the basis of preoperative testing. Iron deficiency was defined as a serum ferritin of less than 100 µg/L or 100-300 µg/L if transferrin saturation was less than 20% or C-reactive protein was more than 5 mg/L. The primary endpoint was days alive and at home at postoperative day 30. The primary analysis included all patients with data available for the primary endpoint and was adjusted for risk measured using EuroSCORE-II and body surface area. The study was prospectively registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12618000185268. FINDINGS: We conducted the study between Feb 21, 2018, and May 7, 2021. We assessed 1171 patients for eligibility and 691 were ineligible; therefore, we enrolled and followed up 480 participants. 240 (50%) were iron deficient and 240 (50%) were iron replete, 95 (20%) were women, 385 (80%) were men, and 453 (94%) were White. Complete data was available for 479 individuals (240 in the iron deficient group and 239 in the iron replete group) for the primary endpoint. The iron deficient group had a median of 22·87 days (IQR 20·65 to 24·06) alive and at home at postoperative day 30, and the iron replete group had a median of 23·18 days (IQR 20·69 to 24·70). The unadjusted difference in medians between the groups was -0·18 days (95% CI -0·73 to 0·36; p=0·51) and the adjusted difference in medians between the groups was -0·11 days (95% CI -0·66 to 0·45; p=0·70). INTERPRETATION: In non-anaemic adults undergoing elective cardiac surgery, our findings suggest that patients with iron deficiency do not have a reduction in days alive and at home at postoperative day 30 compared with patients who have a normal iron status. Routine preoperative investigation for iron deficiency in patients without anaemia undergoing elective cardiac surgery using the definitions we tested might be low-value care. FUNDING: Australian and New Zealand College of Anaesthetists Foundation.

Inclusion, characteristics, and outcomes of male and female participants in large international perioperative studies.

BACKGROUND: We compared baseline characteristics and outcomes and evaluated the subgroup effects of randomised interventions by sex in males and females in large international perioperative trials. METHODS: Nine randomised trials and two cohort studies recruiting adult patients, conducted between 1995 and 2020, were included. Baseline characteristics and outcomes common to six or more studies were evaluated. Regression models included terms for sex, study, and an interaction between the two. Comparing outcomes without adjustment for baseline characteristics represents the 'total effect' of sex on the outcome. RESULTS: Of 54 626 participants, 58% were male and 42% were female. Females were less likely to have ASA physical status ≥3 (56% vs 64%), to smoke (15% vs 23%), have coronary artery disease (21% vs 32%), or undergo vascular surgery (10% vs 23%). The pooled incidence of death was 1.6% in females and 1.8% in males (risk ratio [RR] 0.92; 95% confidence interval [CI]: 0.81-1.05; P=0.20), of myocardial infarction was 4.2% vs 4.5% (RR 0.92; 95% CI: 0.81-1.03; P=0.10), of stroke was 0.5% vs 0.6% (RR 1.03; 95% CI: 0.79-1.35; P=0.81), and of surgical site infection was 8.6% vs 8.3% (RR 1.03; 95% CI: 0.79-1.35; P=0.70). Treatment effects of three interventions demonstrated statistically significant effect modification by sex. CONCLUSIONS: Females were in the minority in all included studies. They were healthier than males, but outcomes were comparable. Further research is needed to understand the reasons for this discrepancy. CLINICAL TRIAL REGISTRATION: International Registry of Meta-Research (UID: IRMR_000011; 5 January 2021).

The association between unanticipated prolonged post-anaesthesia care unit length of stay and early postoperative deterioration: A retrospective cohort study.

This study aimed to investigate whether there was an association between an unanticipated prolonged post-anaesthesia care unit (PACU) length of stay and early postoperative deterioration, as defined as the need for a rapid response team activation, within the first seven days of surgery. We conducted a single-centre retrospective cohort study of adult surgical patients, who stayed at least one night in hospital, and were not admitted to critical care immediately postoperatively, between 1 July 2017 and 30 June 2019. A total of 11,885 cases were analysed. PACU length of stay was significantly associated with rapid response team activation on both univariate (odds ratio (OR) per increment 1.57, 95% confidence intervals (CI) 1.45 to 1.69, P < 0.001) and multivariate analysis (OR per increment 1.41, 95% CI 1.28 to 1.55, P < 0.001). Patients who stayed less than one hour were at low risk of deterioration (absolute risk 3.7%). In patients staying longer than one hour, the absolute increase in risk was small but observable within six hours of PACU discharge. Compar\ed to a one-hour length of stay, a five-hour stay had a relative risk of 4.9 (95% CI 3.7 to 6.1). Other factors associated with rapid response team activation included non-elective surgery (OR 1.78, P < 0.001) and theatre length of stay (OR per increment 1.61, P < 0.001). PACU length of stay was also independently associated with predefined complications and unplanned intensive care unit admission postoperatively. In our cohort, an unanticipated prolonged PACU length of stay of over one hour was associated with an increased incidence of rapid response team activation in the first seven days postoperatively.

An audit of perioperative end-of-life care practices and documentation relating to patients who died in a surgical unit in three Victorian hospitals.

The number of older, frail patients undergoing surgery is increasing, prompting consideration of the benefits of intensive treatment. Despite collaborative decision-making processes such as advance care planning being supported by recent Australian legislation, their role in perioperative care is yet to be defined. Furthermore, there has been little evaluation of the quality of end-of-life care in the surgical population. We investigated documentation of the premorbid functional status, severity of illness, intensity of treatment, operative management and quality of end-of-life care in patients who died in a surgical unit, with a retrospective study of surgical mortality which was performed across three hospitals over a 23-month period in Victoria, Australia. Among 99 deceased patients in the study cohort, 68 had a surgical operation. Preoperative functional risk assessment by medical staff was infrequently documented in the medical notes (5%) compared with activities of daily living (69%) documented by nursing staff. Documented preoperative discussions regarding the risk of death were rarely and inconsistently done, but when done were extensive. Documented end-of-life care discussions were identified in 71%, but were frequently brief, inconsistent, and in 60% did not occur until 48 hours from death. In 35.4% of instances, documented discussions involved junior staff (registrars or residents), and 43.4% involved intensive care unit staff. Palliative or terminal care referrals also occurred late (1-2 days prior to death). Not-for-resuscitation orders were frequently changed when approaching the end of life. Overall, 57% of deceased patients had a documented opportunity for farewell with family. We conclude that discussions and documentation of end-of-life care practices could be improved and recommend that all surgical units undertake similar audits to ensure that end-of-life care discussions occur for high-risk and palliative care surgical patients and are documented appropriately.

A protocol for prospective observational study to determine if non-anaemic iron deficiency worsens postoperative outcome in adult patients undergoing elective cardiac surgery: the IDOCS study.

BACKGROUND: Pre-operative anaemia has been associated independently with worse outcomes after cardiac surgery in adults and is often caused by absolute or functional iron deficiency. Iron deficiency is a continuum ending with anaemia, and therefore it is plausible that pre-operative early or 'non-anaemic' iron deficiency may also be associated with worse outcomes in patients undergoing cardiac surgery. METHODS: We have designed a prospective, observational study to determine if there is an association between non-anaemic iron deficiency and worse outcomes after cardiac surgery in adults. Patients without anaemia undergoing elective cardiac surgery will be allocated to an iron-deficient and an iron-replete group based on standard pre-operative blood tests (ferritin, transferrin saturation and C-reactive protein). The primary outcome is days alive and at home on postoperative day 30. The key secondary outcomes are days alive and at home on postoperative day 90 and readmission to acute care. Other secondary outcomes include health-related quality of life questionnaires, quality of postoperative recovery, postoperative complications, changes in haemoglobin concentration, and requirement for allogeneic blood products. The planned study sample size is 240 patients per group, which has 83% power to detect a median difference of 1.25 days in the primary outcome. The study commenced in March 2018, and recently completed recruitment, with data audit and cleaning ongoing. DISCUSSION: This study will be conducted using a rigorous, prospective observational design; it will provide peak bodies and clinicians with high-quality evidence concerning the associations between non-anaemic iron deficiency and patient-centred outcomes after elective cardiac surgery. Our primary and key secondary outcomes are known to have great importance to clinicians and patients alike and align with the recommendations of the StEP-COMPAC group for outcomes in prospective peri-operative research. The definition used for iron deficiency accounts for both absolute and functional iron deficiency and make use of standard pre-operative blood tests to make this determination, easing the transition of results into clinical practice. The study will be conducted in two relatively high-volume centres in a single high-income country. This limits the generalisability of study results to similar centres. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ACTRN12618000185268 ). Registered 5 February 2018.

Sugammadex, neostigmine and postoperative pulmonary complications: an international randomised feasibility and pilot trial.

BACKGROUND: Sugammadex reduces residual neuromuscular blockade after anaesthesia, potentially preventing postoperative pulmonary complications. However, definitive evidence is lacking. We therefore conducted a feasibility and pilot trial for a large randomised controlled trial of sugammadex, neostigmine, and postoperative pulmonary complications. METHODS: Patients aged ≥40 years having elective or expedited abdominal or intrathoracic surgery were recruited in Australia and Hong Kong. Perioperative care was at the discretion of clinicians, except for the use of rocuronium and/or vecuronium for neuromuscular blockade and the randomised intervention (sugammadex or neostigmine) for reversal. Feasibility measurements included recruitment, crossover, acceptability, completeness, and workload. Trial coordinator feedback was systematically sought. Patient-reported quality of life was measured using the EQ-5D-5L score. The primary pilot outcome was the incidence of new pulmonary complications up to hospital discharge (or postoperative day 7 if still in hospital). RESULTS: Among 150 eligible patients, 120 consented to participate (recruitment rate 80%, 95% confidence interval [CI] 73 to 86%). The randomised intervention was administered without crossover to 115 of 117 patients who received reversal (98%, 95% CI 94 to 100%). The protocol was acceptable or highly acceptable to the anaesthetist in 108 of 116 cases (93%, 95% CI 87 to 97%; missing = 4). Four patients of the 120 patients were lost to follow-up at 3 months (3.3%, 95% CI 0.9 to 8.3%). Case report forms were complete at 3 months for all remaining patients. The median time to complete trial processes was 3.5 h (range 2.5-4.5 h). Trial coordinators reported no barriers to trial processes. Patients were aged 64 (standard deviation 11) years, 70 (58%) were male and 50 (42%) were female, and planned surgeries were thoracic (23 [19%]), upper abdominal (41 [34%]), and lower abdominal (56 [47%]). The primary outcome was observed in 5 (8.5%) of the 59 sugammadex patients and 5 (8.2%) of the 61 neostigmine patients (odds ratio 1.02, 95% CI 0.28 to 3.67). CONCLUSIONS: A large international randomised controlled trial of sugammadex, neostigmine and postoperative pulmonary complications in adult patients having abdominal and intrathoracic surgery, including collection of cost-effectiveness evidence for Health Technology Appraisal, is feasible. TRIAL REGISTRATION: Prospectively registered at the Australian and New Zealand Clinical Trials Registry ( ACTRN12620001313921 ) on December 7, 2020. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380645&isReview=true .

COVID-19 risk in elective surgery during a second wave: a prospective cohort study.

BACKGROUND: The COVID-19 pandemic has greatly affected access to elective surgery, largely because of concerns for patients and healthcare workers. A return to normal surgery workflow depends on the prevalence and transmission of coronavirus in elective surgical patients. The aim of this study was to determine the prevalence of active SARS-coronavirus-2 infection during a second wave among patients admitted to hospital for elective surgery in Victoria. METHODS: Prospective cohort study across eight hospitals in Victoria during July-August 2020 was conducted enrolling adults and children admitted to hospital for elective surgery or interventional procedure requiring general anaesthesia. Study outcomes included a positive polymerase chain reaction (PCR) test for SARS-CoV-2 in the preoperative period (primary outcome), and for those with a negative test preoperatively, the incidence of a positive PCR test for SARS-CoV-2 in the post-operative period. RESULTS: We enrolled 4965 elective adult and paediatric surgical patients from 15 July to 31 August 2020. Four patients screened negative on questionnaire but had a positive PCR test for coronavirus, resulting in a Bayesian estimated prevalence of 0.12% (95% probability interval 0-0.26%). There were no reports of healthcare worker infections linked to elective surgery during and up to 2 weeks after the study period. CONCLUSION: The prevalence of SARS-CoV-2 in asymptomatic elective surgical patients during a second wave was approximately 1 in 833. Given the very low likelihood of coronavirus transmission, and with existing current hospital capacity, recommencement of elective surgery should be considered. A coronavirus screening checklist should be mandated for surgical patients.

Preoperative communication between anaesthetists and patients with obesity regarding perioperative risks and weight management: a structured narrative review.

BACKGROUND: Individuals with obesity frequently present for anaesthesia and surgery. Good communication during the preoperative consultation can optimise the provision of relevant health information and guide improvement of health status preoperatively. METHODS: We planned a systematic literature review to assess existing guidelines and evidence of effectiveness for how anaesthetists should communicate with patients who have obesity in the preoperative period about perioperative risks and weight management. Database searches used keywords related to perioperative weight loss conversations. We found no papers that directly addressed our aim. The literature identified as most relevant was analysed in the form of a narrative review. RESULTS: The majority of suggestions for weight loss conversations came from primary care. Four primary themes potentially relevant to anaesthetists were identified: barriers to such conversations, communication tools, language and communication and specific recommendations. Identified barriers included lack of skills, training, poor remuneration, pessimism and time constraints for clinicians. Established discussion tools including the '5A's' approach (Assess, Advise, Agree, Assist, Arrange) and motivational interviewing may hold promise to improve preoperative conversations. The papers highlighted a need for empathetic language, including use of patient-specific language where possible. CONCLUSIONS: There are currently no published guidelines for how anaesthetists could most effectively discuss weight in the perioperative period with patients who have obesity. Much of the literature for obesity communication is based on the primary care setting. The perioperative period may represent an increased time of receptiveness for patients. Guidelines for discussions about weight management and associated perioperative risk are suggested.