End-tidal carbon dioxide in the early phase of cardiopulmonary exercise testing prior to major colorectal cancer surgery associates with postoperative outcome.

BACKGROUND: Cardiopulmonary exercise testing (CPET) objectively informs preoperative risk stratification prior to major surgery. CPET facilities are resource intensive and therefore more cost-effective triage methods are desirable for scalability. We tested two dynamic CPET parameters (end-tidal CO2 (PetCO2) and heart rate (HR)) to early phase exercise and resting diffusion capacity (DLCO) as potential point of care assessments that could be used outside of formal CPET testing facilities. METHODS: We conducted a retrospective cohort study including 84 patients who underwent CPET prior to elective major abdominal cancer surgery. Data were analyzed for PetCO2 and HR in response to early phase (2 minutes) exercise as well as resting DLCO against postoperative complications and two-year survival. Complications were classified according to Clavien-Dindo classification into less severe and severe (CD>IIIb) grades. Optimal cut points for predicting outcomes were determined using the Youden Index of receiver operating characteristic (ROC) curves. Multivariate regression modeling including both logistic and Cox proportional-hazards model adjusted to age and comorbidity burden was used to analyse the association between the selected parameters and postoperative outcomes. RESULTS: PetCO2, in response to two minutes of loaded exercise was higher in survivors than in non-survivors (median (IQR) 40.0 (4.2) mmHg vs. 34.5 (5.2) mmHg, P<0.001). There was no association between chronotropic response and postoperative outcome. The optimal cut point for predicting postoperative complications and survival was 38 mmHg and 37.1 mmHg for PetCO2, respectively. Low PetCO2 was associated with considerably lower odds of survival (OR 0.12; 95% CI 0.03, 0.47; P=0.003) and additionally increased odds of severe postoperative complications (OR 6.77; 95% CI 1.45, 38.4; P=0.019). Reduced age-predicted DLCO% <80% was associated with increased mortality (HR 5.27; 95% CI 1.09, 25.5; P=0.039). CONCLUSIONS: Assessment of DLCO at rest and dynamic assessment of PetCO2 during the early phase of exercise may potentially be developed as inexpensive point-of-care triage tools to scale objective preoperative risk assessment.

Clinical covariates that improve surgical risk prediction and guide targeted prehabilitation: an exploratory, retrospective cohort study of major colorectal cancer surgery patients evaluated with preoperative cardiopulmonary exercise testing.

BACKGROUND: Preoperative risk stratification is used to derive an optimal treatment plan for patients requiring cancer surgery. Patients with reversible risk factors are candidates for prehabilitation programmes. This pilot study explores the impact of preoperative covariates of comorbid disease (Charlson Co-morbidity Index), preoperative serum biomarkers, and traditional cardiopulmonary exercise testing (CPET)-derived parameters of functional capacity on postoperative outcomes after major colorectal cancer surgery. METHODS: Consecutive patients who underwent CPET prior to colorectal cancer surgery over a 2-year period were identified and a minimum of 2-year postoperative follow-up was performed. Postoperative assessment included: Clavien-Dindo complication score, Comprehensive Complication Index, Days at Home within 90 days (DAH-90) after surgery, and overall survival. RESULTS: The Charlson Co-morbidity Index did not discriminate postoperative complications, or overall survival. In contrast, low preoperative haemoglobin, low albumin, or high neutrophil count were associated with postoperative complications and reduced overall survival. CPET-derived parameters predictive of postoperative complications, DAH-90, and reduced overall survival included measures of VCO2 kinetics at anaerobic threshold (AT), peakVO2 (corrected to body surface area), and VO2 kinetics during the post-exercise recovery phase. Inflammatory parameters and CO2 kinetics added significant predictive value to peakVO2 within bi-variable models for postoperative complications and overall survival (P < 0.0001). CONCLUSION: Consideration of modifiable 'triple low' preoperative risk (anaemia, malnutrition, deconditioning) factors and inflammation will improve surgical risk prediction and guide prehabilitation. Gas exchange parameters that focus on VCO2 kinetics at AT and correcting peakVO2 to body surface area (rather than absolute weight) may improve CPET-derived preoperative risk assessment.

A randomised controlled trial of succinylated gelatin (4%) fluid on urinary acute kidney injury biomarkers in cardiac surgical patients.

BACKGROUND: Fluid resuscitation is frequently required for cardiac surgical patients admitted to the intensive care unit. The ideal fluid of choice in regard to efficacy and safety remains uncertain. Compared with crystalloid fluid, colloid fluid may result in less positive fluid balance. However, some synthetic colloids are associated with increased risk of acute kidney injury (AKI). This study compared the effects of succinylated gelatin (4%) (GEL) with compound sodium lactate (CSL) on urinary AKI biomarkers in patients after cardiac surgery. METHODS: Cardiac surgical patients who required an intravenous fluid bolus of at least 500 mL postoperatively were randomly allocated to receive GEL or CSL as the resuscitation fluid of choice for the subsequent 24 h. Primary outcomes were serial urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C concentrations measured at baseline, 1 h, 5 h and 24 h after enrolment, with higher concentrations indicating greater kidney injury. Secondary biomarker outcomes included urinary clusterin, α1-microglobulin and F2-isoprostanes concentrations. Differences in change of biomarker concentration between the two groups over time were compared with mixed-effects regression models. Statistical significance was set at P < 0.05. RESULTS: Forty cardiac surgical patients (n = 20 per group) with similar baseline characteristics were included. There was no significant difference in the median volume of fluid boluses administered over 24 h between the GEL (1250 mL, Q1-Q3 500-1750) and CSL group (1000 mL, Q1-Q3 500-1375) (P = 0.42). There was a significantly greater increase in urinary cystatin C (P < 0.001), clusterin (P < 0.001), α1-microglobulin (P < 0.001) and F2-isoprostanes (P = 0.020) concentrations over time in the GEL group, compared to the CSL group. Change in urinary NGAL concentration (P = 0.68) over time was not significantly different between the groups. The results were not modified by adjustment for either urinary osmolality or EuroSCORE II predicted risk of mortality. CONCLUSIONS: This preliminary randomised controlled trial showed that use of succinylated gelatin (4%) for fluid resuscitation after cardiac surgery was associated with increased biomarker concentrations of renal tubular injury and dysfunction, compared to crystalloid fluid. These results generate concern that use of intravenous gelatin fluid may contribute to clinically relevant postoperative AKI. Trial registration ANZCTR.org.au, ACTRN12617001461381. Registered on 16th October, 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373619&isReview=true .

Associations Between Nutrition Markers and Muscle Mass on Bioimpedance Analysis in Patients Receiving Parenteral Nutrition.

BACKGROUND: Parenteral nutrition (PN) is used for malnourished patients and those intolerant of enteral nutrition. This pilot study assessed repeatability of bioimpedance analysis (BIA) in critically ill patients and association with nutrition markers and patients' length of hospital stay. METHODS: Twenty-two patients receiving PN, after major surgery or during critical illness, were enrolled and underwent serial BIA and Subjective Global Assessment (SGA) by a dietitian. Repeatability of BIA was assessed by repeating BIA measurements within 10 minutes in 18 of the 22 study patients (82%). RESULTS: All BIA parameters were repeatable with strong intraclass correlation coefficients (>0.78). Phase angle (PhA), reflective of muscle mass, was significantly associated with serum albumin (R2 = 0.198, P < .001), total lymphocyte count (R2 = 0.083, P = .018), and body mass index (R2 = 0.084, P = .015). Of the 48 SGAs performed, 4 were considered severely malnourished, and all were associated with low PhA (<5°) compared with only 53% and 33% for those considered to be moderately malnourished and well nourished, respectively (χ2 test: P = .042). Low PhA was significantly associated with an increased length of hospital stay compared with those without low PhA (median 36 vs 16 days, respectively; P < .001). CONCLUSION: BIA is repeatable in critically ill patients receiving PN. Low PhA was prevalent for those judged as severely malnourished and was associated with reduced total lymphocyte count and serum albumin and prolonged length of hospital stay compared with those with a higher PhA.

Utility of the Cell Index in Predicting External Ventricular Drain-Related Ventriculo-Meningitis.

BACKGROUND/OBJECTIVE: Ventriculo-meningitis (VM) is an important complication of external ventricular drains (EVDs) in neurosurgical patients. Consequences include increased morbidity, mortality, and duration of hospital stay. Early diagnosis of EVD-associated VM allows earlier treatment intervention. The cell index (CI) may provide a simple measure that overcomes the limitations of isolated cerebrospinal fluid (CSF) parameters and other diagnostic tests, allowing earlier prediction of VM. METHODS: All patients admitted to a tertiary hospital and requiring EVD insertion during 2015 and 2016 were assessed for inclusion in this retrospective case-control study. Patients with a known or suspected intracranial infection were excluded. Of the 186 patients who underwent EVD insertion, 95 patients were included in the final cohort. Data pertaining to patient characteristics and laboratory indices were extracted from health records and the microbiology laboratory database. The CI was calculated as the ratio of temporally related CSF leukocytes/erythrocytes to peripheral blood leukocytes/erythrocytes. Data from patients with microbiologically confirmed VM were analyzed in comparison with those not developing VM during the course of their stay. Categorical and continuous variables with skewed distributions were analyzed by Chi square and Mann-Whitney tests, respectively. RESULTS: EVD-associated VM developed in 7.4% of patients. The highest CSF CI (within 3 days prior to diagnosis of VM or at any time for those not developing VM) differed significantly between the two groups (16; IQR 10.8-48.5 vs. 3.3; IQR 1.0-12.8, respectively; p = .046). The area under the receiver operating characteristic curve (AUROC) for the highest CI was 0.727 (95% confidence interval [CI] 0.526-0.929; p = .027). A CI of 10.4 provided a sensitivity and specificity of 80.5% and 70.5%, respectively, for the early diagnosis of VM. CONCLUSIONS: In neurosurgical patients with an EVD, the CSF CI significantly predicted the development of VM.

Intermittent pneumatic compression is a cost-effective method of orthopedic postsurgical venous thromboembolism prophylaxis.

BACKGROUND: Venous thromboembolism (VTE) is a major complication after lower-limb arthroplasty that increases costs and reduces patient's quality of life. Using anticoagulants for 10-35 days following arthroplasty is the standard prophylaxis, but its cost-effectiveness after accounting for bleeding complications remains unproven. METHODS: A comprehensive, clinical model of VTE was created using the incidences, clinical effects (including bleeding), and costs of VTE and prophylaxis from randomized controlled trials, meta-analyses, and large observational studies. Over 50 years, the total health care costs and clinical impact of three prophylaxis strategies, that are as follows, were compared: low-molecular-weight heparin (LMWH) alone, intermittent pneumatic compression (IPC), and IPC with LMWH (IPC+LMWH). The cost per VTE event that was avoided and cost per quality-adjusted life year (QALY) gained in both the US and Australian health care settings were calculated. RESULTS: For every 2,000 patients, the expected number of VTE and major bleeding events with LMWH were 151 and 6 in the USA and 160 and 46 in Australia, resulting in a mean of 11.3 and 9.1 QALYs per patient, respectively. IPC reduced the expected VTE events by 11 and 8 in the USA and Australia, respectively, compared to using LMWH alone. IPC reduced major bleeding events compared to LMWH, preventing 1 event in the US and 7 in Australia. IPC+LMWH only reduced VTE events. Neither intervention substantially impacted QALYs but both increased QALYs versus LMWH. IPC was cost-effective followed by IPC+LMWH. CONCLUSION: IPC and IPC+LMWH are cost-effective versus LMWH after lower-limb arthroplasty in the USA and Australia. The choice between IPC and IPC+LMWH depends on expected bleeding risks.

Comparison of Duke Activity Status Index with cardiopulmonary exercise testing in cancer patients.

PURPOSE: The Duke Activity Status Index (DASI), a patient-administered questionnaire, is used to quantify functional capacity in patients undergoing cancer surgery. METHODS: This retrospective cohort study assessed whether the DASI was accurate in predicting peak oxygen consumption (pVO2) that was objectively measured using cardiopulmonary exercise testing (CPET) in 43 consecutive patients scheduled for elective major cancer surgery at a tertiary cancer centre. The primary outcome measured the limits of agreement between DASI-predicted pVO2 and actual measured pVO2. RESULTS: The study population was elderly (median 63 years, interquartile range 18), 58% were male, with the majority having intraabdominal cancer surgery. Although the DASI scores were statistically related to the measured pVO2 (N = 43, adjusted R2 = 0.20, p = 0.002), both the bias (8 ml kg- 1 min- 1) and 95% limits of agreement (19.5 to - 3.4 ml kg- 1 min- 1) between the predicted and measured pVO2 were large. Using some of the individual components, recalibrating the intercept and regression coefficient of the total DASI score did not substantially improve its ability to predict the measured pVO2. CONCLUSION: In summary, both the limits of agreement and bias between the measured and DASI-predicted pVO2 were substantial. The DASI-predicted pVO2 based on patient's assessment of their functional status could not be considered a reliable surrogate of measured pVO2 during CPET for the population of patients pending major cancer surgery and cannot, therefore, be used as a triage tool for referral to CPET centres for objective risk assessment.

Out-of-office hours' elective surgical intensive care admissions and their associated complications.

BACKGROUND: The 'weekend' effect is a controversial theory that links reduced staffing levels, staffing seniority and supportive services at hospitals during 'out-of-office hours' time periods with worsening patient outcomes. It is uncertain whether admitting elective surgery patients to intensive care units (ICU) during 'out-of-office hours' time periods mitigates this affect through higher staffing ratios and seniority. METHODS: Over a 3-year period in Western Australia's largest private hospital, this retrospective nested-cohort study compared all elective surgical patients admitted to the ICU based on whether their admission occurred 'in-office hours' (Monday-Friday 08.00-18.00 hours) or 'out-of-office hours' (all other times). The main outcomes were surgical complications using the Dindo-Clavien classification and length-of-stay data. RESULTS: Of the total 4363 ICU admissions, 3584 ICU admissions were planned following elective surgery resulting in 2515 (70.2%) in-office hours and 1069 (29.8%) out-of-office hours elective ICU surgical admissions. Out-of-office hours ICU admissions following elective surgery were associated with an increased risk of infection (P = 0.029), blood transfusion (P = 0.020), total parental nutrition (P < 0.001) and unplanned re-operations (P = 0.027). Out-of-office hours ICU admissions were also associated with an increased hospital length-of-stay, with (1.74 days longer, P < 0.0001) and without (2.8 days longer, P < 0.001) adjusting for severity of acute and chronic illnesses and inter-hospital transfers (12.3 versus 9.8%, P = 0.024). Hospital mortality (1.2 versus 0.7%, P = 0.111) was low and similar between both groups. CONCLUSION: Out-of-office hours ICU admissions following elective surgery is common and associated with serious post-operative complications culminating in significantly longer hospital length-of-stays and greater transfers with important patient and health economic implications.

Incidence and outcomes after bariatric surgery in older patients: a state-wide data-linked cohort study.

BACKGROUND: The burgeoning problem of obesity is seen most profoundly in older populations. Despite the dramatic increase in bariatric surgery rates over the last 20 years, weight reduction surgery is largely restricted to younger patients. METHODS: This retrospective, longitudinal, self-matched, population-based cohort study assessed the incidence and outcomes of all patients undergoing bariatric surgery who were ≥55 years old in Western Australia between 2007 and 2011. The mean preoperative and post-operative follow-up periods were 2.5 years and 3.4 years, respectively. RESULTS: Of the 12 062 bariatric surgical operations recorded during the study period, 2179 (18.1%) were performed in patients aged ≥55 years old. Older bariatric patients were statistically more likely to require longer hospital admissions (2.85 versus 2.65 days, P < 0.001), have post-operative complications (12.0 versus 6.3%, P < 0.001) and require intensive care admissions (8.2 versus 4.3%, P = 0.001) compared to patients <55 years old. However, both 30-day (no deaths in the older cohort) and long-term mortality rates (1.07 versus 0.42 deaths per 1000 patient-years, P = 0.10) remained relatively low. All-cause long-term hospitalization rates were also significantly reduced (P < 0.001) after bariatric surgery for patients who were older than 55 years compared to before surgery. CONCLUSION: Despite older age being associated with a higher risk of complications and longer hospital stays, there was a reduction in subsequent overall hospitalizations for older patients after bariatric surgery, suggesting that bariatric surgery may still confer health benefits to carefully selected obese older patients who cannot achieve weight loss by other means.

Transapical Versus Transaortic Transcatheter Aortic Valve Implantation: A Systematic Review.

Two alternative approaches for transcatheter aortic valve implantation (TAVI) exist for patients unsuitable for the transfemoral approach; the transapical and the transaortic approaches. It is unclear as to which approach has superior short-term outcomes. A systematic review and meta-analysis was performed to answer this question. Mortality was equivalent in the 2 groups. There was a trend toward a lower rate of stroke in the transaortic group (0.9% vs 2.1%) but this was not statistically significant. Conversion to surgical aortic valve replacement, paravalvular leak, pacemaker requirement, and major bleeding occurred at equivalent rates.

A comparison of long-term outcomes after meticillin-resistant and meticillin-sensitive Staphylococcus aureus bacteraemia: an observational cohort study.

BACKGROUND: Findings from previous studies have suggested that outcomes after meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia are worse than after meticillin-sensitive S. aureus (MSSA) bacteraemia. We assessed whether patients who had MRSA bacteraemia had a higher risk of death and recurrent infections than those who had MSSA bacteraemia. METHODS: For this observational cohort study, we assessed data from the microbiology laboratory database at the Royal Perth Hospital (WA, Australia). Data were for all patients who had an episode of MRSA bacteraemia between July 1, 1997, and June 30, 2007, and, by use of a computer-generated randomisation sequence, a randomly selected subgroup of patients who had an episode of MSSA bacteraemia (patients with one or more set of blood cultures positive for S. aureus). The primary outcomes were survival time and subsequent infection-related hospital readmissions, analysed by Cox proportional hazards regression with adjustment for important prognostic factors. FINDINGS: Of the 583 patients who had an episode of MRSA or MSSA bacteraemia, we used data for the 582 who had complete data linkage: 185 patients who had MRSA bacteraemia and 397 patients who had MSSA bacteraemia. The crude survival time of patients after MRSA bacteraemia was shorter than it was for patients with MSSA bacteraemia (14 months [IQR 1-86] vs 54 months [3-105]; hazard ratio 1·46, 95% CI 1·18-1·79; p=0·01). The adverse association between MRSA and all-cause mortality (0·98, 0·77-1·30; p=0·87) or infection-related mortality (1·22, 0·89-1·69; p=0·22) were not statistically significant after adjustment for important prognostic factors including age, comorbidities, severity of acute illness, metastatic infections, and long-term care facility resident status. After adjustment for these confounding factors, we saw no difference in infection-related hospital readmissions between patients who had MRSA bacteraemia and those who had MSSA bacteraemia (odds ratio 0·95, 95% CI 0·59-1·53; p=0·83). INTERPRETATION: Long-term outcomes after MRSA bacteraemia were worse than those after MSSA bacteraemia through its confounding associations with other prognostic factors. Our findings might have implications for management strategies to control MRSA colonisation. FUNDING: The Medical Research Foundation of Royal Perth Hospital.