Postoperative systemic inflammation after major abdominal surgery: patient-centred outcomes.

Postoperative systemic inflammation is strongly associated with surgical outcomes, but its relationship with patient-centred outcomes is largely unknown. Detection of excessive inflammation and patient and surgical factors associated with adverse patient-centred outcomes should inform preventative treatment options to be evaluated in clinical trials and current clinical care. This retrospective cohort study analysed prospectively collected data from 3000 high-risk, elective, major abdominal surgery patients in the restrictive vs. liberal fluid therapy for major abdominal surgery (RELIEF) trial from 47 centres in seven countries from May 2013 to September 2016. The co-primary endpoints were persistent disability or death up to 90 days after surgery, and quality of recovery using a 15-item quality of recovery score at days 3 and 30. Secondary endpoints included: 90-day and 1-year all-cause mortality; septic complications; acute kidney injury; unplanned admission to intensive care/high dependency unit; and total intensive care unit and hospital stays. Patients were assigned into quartiles of maximum postoperative C-reactive protein concentration up to day 3, after multiple imputations of missing values. The lowest (reference) group, quartile 1, C-reactive protein ≤ 85 mg.l-1 , was compared with three inflammation groups: quartile 2 > 85 mg.l-1 to 140 mg.l-1 ; quartile 3 > 140 mg.l-1 to 200 mg.l-1 ; and quartile 4 > 200 mg.l-1 to 587 mg.l-1 . Greater postoperative systemic inflammation had a higher adjusted risk ratio (95%CI) of persistent disability or death up to 90 days after surgery, quartile 4 vs. quartile 1 being 1.76 (1.31-2.36), p < 0.001. Increased inflammation was associated with increasing decline in risk-adjusted estimated medians (95%CI) for quality of recovery, the quartile 4 to quartile 1 difference being -14.4 (-17.38 to -10.71), p < 0.001 on day 3, and -5.94 (-8.92 to -2.95), p < 0.001 on day 30. Marked postoperative systemic inflammation was associated with increased risk of complications, poor quality of recovery and persistent disability or death up to 90 days after surgery.

Non-Invasive Positive airway Pressure thErapy to Reduce Postoperative Lung complications following Upper abdominal Surgery (NIPPER PLUS): a pilot randomised control trial.

OBJECTIVES: Postoperative pulmonary complications (PPCs) are a common serious complication following upper abdominal surgery. Postoperatively, physiotherapy-led non-invasive ventilation (NIV) may be a promising method to reduce PPC incidence. The objectives of this pilot trial were to examine preliminary effectiveness, feasibility and safety of additional intermittent physiotherapy-led NIV compared to continuous high-flow nasal cannula oxygen therapy (HFNC) alone. DESIGN: Single-centre, assessor-blinded, parallel-group, pilot randomised control trial. SETTING: Primary-referral hospital in Australia. PARTICIPANTS: 130 high-risk patients undergoing upper abdominal surgery. INTERVENTIONS: Continuous HFNC for 48-hours following surgical extubation, or HFNC plus five 30-minute physiotherapy-led NIV sessions. OUTCOMES: PPC incidence, trial feasibility and safety. RESULTS: PPC incidence was similar between groups (HFNC alone 12/65 (18%) vs HFNC plus NIV 10/64 (16%) adjusted HR 0.95; 95% CI 0.40-2.29). Delivery of HFNC as per-protocol was achieved in 81% (n = 105) of all participants. Physiotherapy-led NIV initiated within four-hours of surgical extubation was achieved in 81% (n = 52) of intervention group participants, with a mean 4.2 (SD 1.3) total number of NIV sessions delivered in the first two postoperative days. NIV was delivered as per-protocol in 52% of this cohort. Two episodes of severe hypotension during NIV requiring medical intervention were reported. CONCLUSION: Delivery of continuous HFNC was feasible. Delivery of NIV within four-hours of extubation was achieved and delivered safely with< 1% adverse events. The planned NIV intervention of five sessions within two postoperative days was not feasible. The results of this pilot study have informed the decision not to proceed to a fully powered trial. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au ACTRN12617000269336. CONTRIBUTION OF THE PAPER.

An evaluation of the outcome metric 'days alive and at home' in older patients after hip fracture surgery.

'Days alive and at home' is a validated measure that estimates the time spent at home, defined as the place of residence before admission to hospital. We evaluated this metric in older adults after hip fracture surgery and assessed two follow-up durations, 30 and 90 days. Patients aged ≥ 70 years who underwent hip fracture surgery were identified retrospectively via hospital admission and government mortality records. Patients who successfully returned home and were still alive within 90 days of surgery were distinguished from those who were not. Regression models were used to examine which variables were associated with failure to return home and number of days at home among those who did return, within 90 days of surgery. We analysed the records of 825 patients. Median (IQR [range]) number of days at home within 90 days (n = 788) was 54 (0-76 [0-88]) days and within 30 days (n = 797) it was 2 (0-21 [0-28]) days. Out of these, 274 (35%) patients did not return home within 90 days and 374 (47%) within 30 days after surgery. Known peri-operative risk-factors such as older age, pre-operative anaemia and postoperative acute renal impairment were associated with failure to return home. This study supports days alive and at home as a useful patient-centred outcome measure in older adults after hip fracture surgery. We recommend that this metric should be used in clinical trials and measured at 90, rather than 30, postoperative days. As nearly half of this patient population did not return home within 30 days, the shorter time-period catches fewer meaningful events.

Effects of preoperative physiotherapy on signs and symptoms of pulmonary collapse and infection after major abdominal surgery: secondary analysis of the LIPPSMAck-POP multicentre randomised controlled trial.

BACKGROUND: Preoperative education and breathing exercise training by a physiotherapist minimises pulmonary complications after abdominal surgery. Effects on specific clinical outcomes such as antibiotic prescriptions, chest imaging, sputum cultures, oxygen requirements, and diagnostic coding are unknown. METHODS: This post hoc analysis of prospectively collected data within a double-blinded, multicentre, randomised controlled trial involving 432 participants having major abdominal surgery explored effects of preoperative education and breathing exercise training with a physiotherapist on postoperative antibiotic prescriptions, hypoxemia, sputum cultures, chest imaging, auscultation, leukocytosis, pyrexia, oxygen therapy, and diagnostic coding, compared to a control group who received a booklet alone. All participants received standardised postoperative early ambulation. Outcomes were assessed daily for 14 postoperative days. Analyses were intention-to-treat using adjusted generalised multivariate linear regression. RESULTS: Preoperative physiotherapy was associated with fewer antibiotic prescriptions specific for a respiratory infection (RR 0.52; 95% CI 0.31 to 0.85, p = 0.01), less purulent sputum on the third and fourth postoperative days (RR 0.50; 95% CI 0.34 to 0.73, p = 0.01), fewer positive sputum cultures from the third to fifth postoperative day (RR 0.17; 95% CI 0.04 to 0.77, p = 0.01), and less oxygen therapy requirements (RR 0.49; 95% CI 0.31 to 0.78, p = 0.002). Treatment effects were specific to respiratory clinical coding domains. CONCLUSIONS: Preoperative physiotherapy prevents postoperative pulmonary complications and is associated with the minimisation of signs and symptoms of pulmonary collapse/consolidation and airway infection and specifically results in reduced oxygen therapy requirements and antibiotic prescriptions. TRIAL REGISTRATION: ANZCTR 12613000664741 ; 19/06/2013.

Associations between preoperative anaemia and hospital costs following major abdominal surgery: cohort study.

BACKGROUND: Determining the cost-effectiveness and sustainability of patient blood management programmes relies on quantifying the economic burden of preoperative anaemia. This retrospective cohort study aimed to evaluate the hospital costs attributable to preoperative anaemia in patients undergoing major abdominal surgery. METHODS: Patients who underwent major abdominal surgery between 2010 and 2018 were included. The association between preoperative patient haemoglobin (Hb) concentration and hospital costs was evaluated by curve estimation based on the least-square method. The in-hospital cost of index admission was calculated using an activity-based costing methodology. Multivariable regression analysis and propensity score matching were used to estimate the effects of Hb concentration on variables related directly to hospital costs. RESULTS: A total of 1286 patients were included. The median overall cost was US $18 476 (i.q.r.13 784-27 880), and 568 patients (44.2 per cent) had a Hb level below 13.0 g/dl. Patients with a preoperative Hb level below 9.0 g/dl had total hospital costs that were 50.6 (95 per cent c.i. 14.1 to 98.9) per cent higher than those for patients with a preoperative Hb level of 9.0-13.0 g/dl (P < 0.001), 72.5 (30.6 to 128.0) per cent higher than costs for patients with a Hb concentration of 13.1-15.0 g/dl (P < 0.001), and 62.4 (21.8 to 116.7) per cent higher than those for patients with a Hb level greater than 15.0 g/dl (P < 0.001). Multivariable general linear modelling showed that packed red blood cell (PRBC) transfusions were a principal cost driver in patients with a Hb concentration below 9.0 g/dl. CONCLUSION: Patients with the lowest Hb concentration incurred the highest hospital costs, which were strongly associated with increased PRBC transfusions. Costs and possible complications may be decreased by treating preoperative anaemia, particularly more severe anaemia.

The effect of advanced recovery room care on postoperative outcomes in moderate-risk surgical patients: a multicentre feasibility study.

Postoperative complications are common and may be under-recognised. It has been suggested that enhanced postoperative care in the recovery room may reduce in-hospital complications in moderate- and high-risk surgical patients. We investigated the feasibility of providing advanced recovery room care for 12-18 h postoperatively in the post-anaesthesia care unit. The primary hypothesis was that a clinical trial of advanced recovery room care was feasible. The secondary hypothesis was that this model may have a sustained impact on postoperative in-hospital and post-discharge events. This was a multicentre, prospective, feasibility before-and-after trial of moderate-risk patients (predicted 30-day mortality of 1-4%) undergoing non-cardiac surgery and who were scheduled for postoperative ward care. Patients were managed using defined assessment checklists and goals of care in an advanced recovery room care setting in the immediate postoperative period. This utilised existing post-anaesthesia care unit infrastructure and staffing, but extended care until the morning of the first postoperative day. The advanced recovery room care trial was deemed feasible, as defined by the recruitment and per protocol management of > 120 patients. However, in a specialised cancer centre, recruitment was slow due to low rates of eligibility according to narrow inclusion criteria. At a rural site, advanced recovery room care could not be commenced due to logistical issues in establishing a new model of care. A definitive randomised controlled trial of advanced recovery room care appears feasible and, based on the indicative data on outcomes, we believe this is warranted.

Attitudes of anesthetists towards an anesthesia-led nurse practitioner model for low-risk colonoscopy procedures: a cross-sectional survey.

BACKGROUND: The mounting pressure on the Australian healthcare system is driving a continual exploration of areas to improve patient care and access and to maximize utilization of our workforce. We hypothesized that there would be support by anesthetists employed at our hospital for the design, development, and potential implementation of an anesthesia-led nurse practitioner (NP) model for low-risk colonoscopy patients. METHODS: We conducted a cross-sectional, mixed methods study to ascertain the attitudes and acceptability of anesthetists towards a proposed anesthesia-led NP model for low-risk colonoscopy patients. An online survey using commercial software and theoretical questions pertaining to participants' attitudes towards an anesthesia-led NP model was e-mailed to consultant anesthetists. Participants were also invited to participate in a voluntary 20-min face-to-face interview. RESULTS: A total of 60 survey responses were received from a pool of 100 anesthetists (response rate = 60%, accounting for 8.04% margin of error). Despite the theoretical benefits of improved patient access to colonoscopy services, most anesthetists were not willing to participate in the supervision and training of NPs. The predominant themes underlying their lack of support for the program were a perception that patient safety would be compromised compared to the current model of anesthesia-led care, the model does not meet the Australian and New Zealand College of Anesthetists guidelines for procedural sedation and analgesia, and the program may be a public liability prone to litigation in the event of an adverse outcome. Concerns about consumer acceptance and cost-effectiveness were also raised. Finally, participants thought the model should be pilot tested to better understand consumer attitudes, logistical feasibility, patient and proceduralist attitudes, clinical governance, and, importantly, patient safety. CONCLUSIONS: Most anesthetists working in a single-center university hospital did not support an anesthesia-led NP model for low-risk colonoscopy patients. Patient safety, violations of the current Australian and New Zealand College of Anesthetists guidelines on procedural sedation, and logistical feasibility were significant barriers to the acceptance of the model. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, 12619001036101.

Borderline anaemia and postoperative outcome in women undergoing major abdominal surgery: a retrospective cohort study.

Pre-operative anaemia is typically diagnosed with a haemoglobin concentration < 120 g.l-1 for women and < 130 g.l-1 for men on the basis of limited evidence. This retrospective cohort study stratified women undergoing elective, major abdominal surgery based on pre-operative haemoglobin concentration: anaemic (< 120 g.l-1 ); borderline anaemic (120-129 g.l-1 ); and non-anaemic (> 130 g.l-1 ). Data from 1554 women were analysed. Women with borderline anaemia had a greater incidence of postoperative complications (55 (16%) vs. 110 (11%); p = 0.026), longer duration of hospital stay (median (IQR [range]) 3 (1-6 [0-69]) days vs. 2 (1-5 [0-80]) days; p = 0.017) and fewer days alive and out of hospital at postoperative day 30 (median (IQR [range]) 27 (23-29 [0-30]) vs. 28 (25-29 [0-30]) days; p = 0.017) compared with non-anaemic women. However, after matched cohort analysis, these outcome differences no longer remained statistically significant. After multivariable adjustment for procedure, Charlson comorbidity index and patient age, a negative relationship between logarithmic pre-operative haemoglobin concentration and duration of stay was found (parameter estimate (standard error) -0.006 (0.003) vs. 0.003 (0.003) for a haemoglobin concentration < 130 g.l-1 vs. > 130 g.l-1 , respectively; p = 0.03); the difference in duration of stay was approximately 50% greater for women with a haemoglobin concentration of 120 g.l-1 compared with those with a haemoglobin concentration of 130 g.l-1 . Although the contribution of borderline anaemia to the incidence of postoperative complications is uncertain, the current diagnostic criteria should be re-assessed.

Transplantation of mesenchymal stem cells genetically engineered to overexpress interleukin-10 promotes alternative inflammatory response in rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause for long-term disability, yet the treatments available that improve outcomes after TBI limited. Neuroinflammatory responses are key contributors to determining patient outcomes after TBI. Transplantation of mesenchymal stem cells (MSCs), which release trophic and pro-repair cytokines, represents an effective strategy to reduce inflammation after TBI. One such pro-repair cytokine is interleukin-10 (IL-10), which reduces pro-inflammatory markers and trigger alternative inflammatory markers, such as CD163. In this study, we tested the therapeutic effects of MSCs that were engineered to overexpress IL-10 when transplanted into rats following TBI in the medial frontal cortex. METHODS: Thirty-six hours following TBI, rats were transplanted with MSCs and then assessed for 3 weeks on a battery of behavioral tests that measured motor and cognitive abilities. Histological evaluation was then done to measure the activation of the inflammatory response. Additionally, immunomodulatory effects were evaluated by immunohistochemistry and Western blot analyses. RESULTS: A significant improvement in fine motor function was observed in rats that received transplants of MSCs engineered to overexpress IL-10 (MSCs + IL-10) or MSCs alone compared to TBI + vehicle-treated rats. Although tissue spared was unchanged, anti-inflammatory effects were revealed by a reduction in the number of glial fibrillary acidic protein cells and CD86 cells in both TBI + MSCs + IL-10 and TBI + MSC groups compared to TBI + vehicle rats. Microglial activation was significantly increased in the TBI + MSC group when compared to the sham + vehicle group. Western blot data suggested a reduction in tumor necrosis factor-alpha in the TBI + MSCs + IL-10 group compared to TBI + MSC group. Immunomodulatory effects were demonstrated by a shift from classical inflammation expression (CD86) to an alternative inflammation state (CD163) in both treatments with MSCs and MSCs + IL-10. Furthermore, co-labeling of both CD86 and CD163 was detected in the same cells, suggesting a temporal change in macrophage expression. CONCLUSIONS: Overall, our findings suggest that transplantation of MSCs that were engineered to overexpress IL-10 can improve functional outcomes by providing a beneficial perilesion environment. This improvement may be explained by the shifting of macrophage expression to a more pro-repair state, thereby providing a possible new therapy for treating TBI.

Postoperative outcomes following cardiac surgery in non-anaemic iron-replete and iron-deficient patients - an exploratory study.

Iron deficiency anaemia is strongly associated with poor outcomes after cardiac surgery. However, pre-operative non-anaemic iron deficiency (a probable anaemia precursor) has not been comprehensively examined in patients undergoing cardiac surgery, despite biological plausibility and evidence from other patient populations of negative effect on outcome. This exploratory retrospective cohort study aimed to compare an iron-deficient group of patients undergoing cardiac surgery with an iron-replete group. Consecutive non-anaemic patients undergoing elective coronary artery bypass grafting or single valve replacement in our institution between January 2013 and December 2015 were considered for inclusion. Data from a total of 277 patients were analysed, and were categorised by iron status and blood haemoglobin concentration into iron-deficient (n = 109) and iron-replete (n = 168) groups. Compared with the iron-replete group, patients in the iron-deficient group were more likely to be female (43% vs. 12%, iron-replete, respectively); older, mean (SD) age 64.4 (9.7) vs. 63.2 (10.3) years; and to have a higher pre-operative EuroSCORE (median IQR [range]) 3 (2-5 [0-10]) vs. 3 (2-4 [0-9]), with a lower preoperative haemoglobin of 141.6 (11.6) vs. 148.3 (11.7) g.l-1 . Univariate analysis suggested that iron-deficient patients had a longer hospital length of stay (7 (6-9 [2-40]) vs. 7 (5-8 [4-23]) days; p = 0.013) and fewer days alive and out of hospital at postoperative day 90 (83 (80-84 [0-87]) vs. 83 (81-85 [34-86]), p = 0.009). There was no evidence of an association between iron deficiency and either lower nadir haemoglobin or higher requirement for blood products during inpatient stay. After adjusting the model for pre-operative age, sex, renal function, EuroSCORE and haemoglobin, the mean increase in hospital length of stay in the iron-deficient group relative to the iron-replete group was 0.86 days (bootstrapped 95%CI -0.37 to 2.22, p = 0.098). This exploratory study suggests there is weak evidence of an association between non-anaemic iron deficiency and outcome after cardiac surgery after controlling for potentially confounding variables.

Effects of intraoperative and early postoperative normal saline or Plasma-Lyte 148® on hyperkalaemia in deceased donor renal transplantation: a double-blind randomized trial.

BACKGROUND: Administration of saline in renal transplantation is associated with hyperchloraemic metabolic acidosis, but the effect of normal saline (NS) on the risk of hyperkalaemia or postoperative graft function is uncertain. METHODS: We compared NS with Plasma-Lyte 148® (PL) given during surgery and for 48 h after surgery in patients undergoing deceased donor renal transplantation. The primary outcome was hyperkalaemia within 48 h after surgery. Secondary outcomes were need for hyperkalaemia treatment, change in acid-base status, and graft function. RESULTS: Twenty-five subjects were randomized to NS and 24 to PL. The incidence of hyperkalaemia in the first 48 h after surgery was higher in the NS group; 20 patients (80%) vs 12 patients (50%) in the PL group (risk difference: 0.3; 95% confidence interval: 0.05, 0.55; P=0.037). The mean (sd) peak serum potassium was NS 6.1 (0.8) compared with PL 5.4 (0.9) mmol litre-1 (P=0.009). Sixteen participants (64%) in the NS group required treatment for hyperkalaemia compared with five (21%) in the PL group (P=0.004). Participants receiving NS were more acidaemic [pH 7.32 (0.06) vs 7.39 (0.05), P=0.001] and had higher serum chloride concentrations (107 vs 101 mmol litre-1, P<0.001) at the end of surgery. No differences in the rate of delayed graft function were observed. Subjects receiving PL who did not require dialysis had a greater reduction in creatinine on day 2 (P=0.04). CONCLUSIONS: Compared with PL, participants receiving NS had a greater incidence of hyperkalaemia and hyperchloraemia and were more acidaemic. These biochemical differences were not associated with adverse clinical outcomes. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000023853.