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.

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.

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.

Financial and environmental costs of reusable and single-use anaesthetic equipment.

BACKGROUND.: An innovative approach to choosing hospital equipment is to consider the environmental costs in addition to other costs and benefits. METHODS.: We used life cycle assessment to model the environmental and financial costs of different scenarios of replacing reusable anaesthetic equipment with single-use variants. The primary environmental costs were CO 2 emissions (in CO 2 equivalents) and water use (in litres). We compared energy source mixes between Australia, the UK/Europe, and the USA. RESULTS.: For an Australian hospital with six operating rooms, the annual financial cost of converting from single-use equipment to reusable anaesthetic equipment would be an AUD$32 033 (£19 220), 46% decrease. In Australia, converting from single-use to reusable equipment would result in an increase of CO 2 emissions from 5095 (95% CI: 4614-5658) to 5575 kg CO 2 eq (95% CI: 5542-5608), a 480 kg CO 2 eq (9%) increase. Using the UK/European power mix, converting from single-use (5575 kg CO 2 eq) to reusable anaesthetic equipment (802 kg CO 2 eq) would result in an 84% reduction (4873 kg CO 2 eq) in CO 2 emissions, whilst in the USA converting to reusables would have led to a 2427 kg CO 2 eq (48%) reduction. In Australia, converting from single-use to reusable equipment would more than double water use from 34.4 to 90.6 kilolitres. CONCLUSIONS.: For an Australian hospital with six operating rooms, converting from single-use to reusable anaesthetic equipment saved more than AUD$30 000 (£18 000) per annum, but increased the CO 2 emissions by almost 10%. The CO 2 offset is highly dependent on the power source mix, while water consumption is greater for reusable equipment.

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.

A randomised controlled trial of peri-operative pregabalin vs. placebo for video-assisted thoracoscopic surgery.

We allocated 52 participants to oral pregabalin 300 mg and 48 participants to placebo tablets before thoracoscopic surgery and for five postoperative days. The median (IQR [range]) cumulative pain scores at rest for nine postoperative months were 184 (94-274 [51-1454]) after pregabalin and 166 (66-266 [48-1628]) after placebo, p = 0.39. The corresponding scores on deep breathing were 468 (281-655 [87-2870]) and 347 (133-561 [52-3666]), respectively, p = 0.16. After three postoperative months, 29/100 participants had persistent surgical site pain, 19/52 after pregabalin and 10/48 after placebo, p = 0.12, of whom four and five, respectively, attended a pain management clinic, p = 0.24. The median (IQR [range]) morphine equivalent consumption six days after surgery was 273 (128-619 [39-2243]) mg after pregabalin and 319 (190-663 [47-2258]) mg after placebo, p = 0.35.

A randomised controlled trial of peri-operative lidocaine infusions for open radical prostatectomy.

We allocated 76 men scheduled for radical retropubic prostatectomy to peri-operative lidocaine 2% or saline 0.9%: a pre-operative 0.075 ml.kg(-1) intravenous bolus; an intra-operative intravenous infusion at 0.075 ml.kg(-1) .h(-1) ; and 24 hours' postoperative subcutaneous infusion at 0.075 ml.kg(-1) .h(-1) . Lidocaine reduced the postoperative hospital stay by a mean (95% CI) of 1.3 (0.3-2.4) days, p = 0.017, from a mean (SD) of 4.6 (3.2) days with saline. There were no significant differences in pain at rest or on coughing at 24 h. [corrected]. Lidocaine reduced 24-h morphine consumption by a mean (95% CI) of 13.9 (2.2-25.7) mg, p = 0.021, from a mean (SD) of 52.3 (26.9) mg with saline. There were no differences in other outcomes.

Strong ion and weak acid analysis in severe preeclampsia: potential clinical significance.

BACKGROUND: The influence of common disturbances seen in preeclampsia, such as changes in strong ions and weak acids (particularly albumin) on acid-base status, has not been fully elucidated. The aims of this study were to provide a comprehensive acid-base analysis in severe preeclampsia and to identify potential new biological predictors of disease severity. METHODS: Fifty women with severe preeclampsia, 25 healthy non-pregnant- and 46 healthy pregnant controls (26-40 weeks' gestation), were enrolled in this prospective case-control study. Acid-base analysis was performed by applying the physicochemical approach of Stewart and Gilfix. RESULTS: Mean [sd] base excess was similar in preeclamptic- and healthy pregnant women (-3.3 [2.3], and -2.8 [1.5] mEq/L respectively). In preeclampsia, there were greater offsetting contributions to the base excess, in the form of hyperchloraemia (BE(Cl) -2 [2.3] vs -0.4 [2.3] mEq/L, P<0.001) and hypoalbuminaemia (BE(Alb) 3.6 [1] vs 2.1 [0.8] mEq/L, P<0.001). In preeclampsia, hypoalbuminaemic metabolic alkalosis was associated with a non-reassuring/abnormal fetal heart tracing (P<0.001). Quantitative analysis in healthy pregnancy revealed respiratory and hypoalbuminaemic alkalosis that was metabolically offset by acidosis, secondary to unmeasured anions and dilution. CONCLUSIONS: While the overall base excess in severe preeclampsia is similar to that in healthy pregnancy, preeclampsia is associated with a greater imbalance offsetting hypoalbuminaemic alkalosis and hyperchloraemic acidosis. Rather than the absolute value of base excess, the magnitude of these opposing contributors may be a better indicator of the severity of this disease. Hypoalbuminaemic alkalosis may also be a predictor of fetal compromise. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT 02164370.

Patient frailty: the elephant in the operating room.

For most surgeons and many anaesthetists, patient frailty is currently the 'elephant in the (operating) room': it is easy to spot, but is often ignored. In this paper, we discuss different approaches to the measurement of frailty and review the evidence regarding the effect of frailty on peri-operative outcomes. We explore the limitations of 'eyeballing' patients to quantify frailty, and consider why the frail older patient, challenged by seemingly minor insults in the postoperative period, may suffer falls or delirium. Frailty represents a state of increased vulnerability to stressors, and older inpatients are exposed to multiple stressors in the peri-operative setting. Quantifying frailty is likely to increase the precision of peri-operative risk assessment. The Frailty Index derived from Comprehensive Geriatric Assessment is a simple and robust way to quantify frailty, but is yet to be systematically investigated in the pre-operative setting. Furthermore, the optimal care for frail patients and the reversibility of frailty with prehabilitation are fertile areas for future research.

The microbiological and sustainability effects of washing anaesthesia breathing circuits less frequently.

In the presence of single-use airway filters, we quantified anaesthetic circuit aerobic microbial contamination rates when changed every 24 h, 48 h and 7 days. Microbiological samples were taken from the interior of 305 anaesthetic breathing circuits over a 15-month period (3197 operations). There was no significant difference in the proportion of contaminated circuits when changed every 24 h (57/105 (54%, 95% CI 45-64%)) compared with 48 h (43/100 (43%, 95% CI 33-53%, p = 0.12)) and up to 7 days (46/100 (46%, 95% CI 36-56%, p = 0.26)). Median bacterial counts were not increased at 48 h or 7 days provided circuits were routinely emptied of condensate. Annual savings for one hospital (six operating theatres) were $AU 5219 (£3079, €3654, $US 4846) and a 57% decrease in anaesthesia circuit steriliser loads associated with a yearly saving of 2760 kWh of electricity and 48 000 l of water. Our findings suggest that extended circuit use from 24 h up to 7 days does not significantly increase bacterial contamination, and is associated with labour, energy, water and financial savings.

Postoperative hypothermia and patient outcomes after major elective non-cardiac surgery.

Using a multicentre adult patient database from Australia and New Zealand, we obtained the lowest and highest temperature in the first 24 h after admission to the intensive care unit after elective non-cardiac surgery. Hypothermia was defined as core temperature < 36 °C; transient hypothermia as a temperature < 36 °C that was corrected within 24 h, and persistent hypothermia as hypothermia not corrected within 24 h. We studied 50,689 patients. Hypothermia occurred in 23,165 (46%) patients, was transient in 22,810 (45%), and was persistent in 608 (1.2%) patients. On multivariate analysis, neither transient (OR = 1.07, 95% CI 0.96-1.20) nor persistent (OR = 1.50. 95% CI 0.96-2.33) hypothermia was independently associated with increased hospital mortality.