Venovenous bypass in adult liver transplant recipients: A single-center observational case series.

BACKGROUND: Very little information is currently available on the use and outcomes of venovenous bypass (VVB) in liver transplantation (LT) in adults in Australia. In this study, we explored the indications, intraoperative course, and postoperative outcomes of patients who underwent VVB in a high-volume LT unit. METHODS: The study was a single-center, retrospective observational case series of adult patients who underwent VVB during LT at Austin Health in Melbourne, Australia between March 2008 and March 2022. Information on baseline preoperative status and intraoperative variables, including specific VVB characteristics as well as postoperative and VVB-related complications was collected. The lengths of intensive care unit and hospital stays as well as intraoperative and in-hospital mortality were recorded. RESULTS: Of the 900 LTs performed at this center during the aforementioned 14-year period, 27 (3%) included a VVB procedure. VVB was performed electively in 16 of these 27 patients (59.3%) and as a rescue technique to control massive bleeding in the other 11 (40.1%). The median (interquartile range [IQR]) age of those who underwent VVB procedures was 48 (39-55) years; the median age was 56 (47-62) years in the non-VVB group (p<0.0001). The median model for end-stage liver disease (MELD) scores were similar between the two patient groups. Complete blood data was available for 622 non-VVB patients. Twenty-six VVB (96.3%) and 603 non-VVB (96.9%) patients required intraoperative blood transfusions. The median (IQR) number of units of packed red blood cells transfused was 7 (4.8-12.5) units in the VVB group compared to 3.0 units (1.0-6.0) in the non-VVB group (p<0.0001). Inpatient mortality was 18.5% and 1.1% for the VVB and non-VVB groups, respectively (p<0.0001). There were no significant differences in length of hospital stay or incidence of acute kidney injury, primary graft dysfunction, or long-term graft failure between the two groups. Patients in the VVB group experienced a higher rate of postoperative non-anastomotic biliary stricture compared to patients in the non-VVB group (33% and 7.9%, respectively; p = 0.0003). CONCLUSIONS: VVB continues to play a vital role in LT. This case series highlights the heightened risk of major complications linked to VVB. However, the global transition to selective use of VVB underscores the urgent need for collaborative multi-center studies designed to address outstanding questions and parameters related to the safe implementation of this procedure.

Anaesthetic and perioperative considerations for extrapleural pneumonectomy and extended pleurectomy/decortication: a scoping review protocol.

INTRODUCTION: Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps. METHODS AND ANALYSIS: This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care. ETHICS AND DISSEMINATION: Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.

Development and validation of 'Patient Optimizer' (POP) algorithms for predicting surgical risk with machine learning.

BACKGROUND: Pre-operative risk assessment can help clinicians prepare patients for surgery, reducing the risk of perioperative complications, length of hospital stay, readmission and mortality. Further, it can facilitate collaborative decision-making and operational planning. OBJECTIVE: To develop effective pre-operative risk assessment algorithms (referred to as Patient Optimizer or POP) using Machine Learning (ML) that predict the development of post-operative complications and provide pilot data to inform the design of a larger prospective study. METHODS: After institutional ethics approval, we developed a base model that encapsulates the standard manual approach of combining patient-risk and procedure-risk. In an automated process, additional variables were included and tested with 10-fold cross-validation, and the best performing features were selected. The models were evaluated and confidence intervals calculated using bootstrapping. Clinical expertise was used to restrict the cardinality of categorical variables (e.g. pathology results) by including the most clinically relevant values. The models were created with logistic regression (LR) and extreme gradient-boosted trees using XGBoost (Chen and Guestrin, 2016). We evaluated performance using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Data was obtained from a metropolitan university teaching hospital from January 2015 to July 2020. Data collection was restricted to adult patients undergoing elective surgery. RESULTS: A total of 11,475 adult admissions were included. The performance of XGBoost and LR was very similar across endpoints and metrics. For predicting the risk of any post-operative complication, kidney failure and length-of-stay (LOS), POP with XGBoost achieved an AUROC (95%CI) of 0.755 (0.744, 0.767), 0.869 (0.846, 0.891) and 0.841 (0.833, 0.847) respectively and AUPRC of 0.651 (0.632, 0.669), 0.336 (0.282, 0.390) and 0.741 (0.729, 0.753) respectively. For 30-day readmission and in-patient mortality, POP with XGBoost achieved an AUROC (95%CI) of 0.610 (0.587, 0.635) and 0.866 (0.777, 0.943) respectively and AUPRC of 0.116 (0.104, 0.132) and 0.031 (0.015, 0.072) respectively. CONCLUSION: The POP algorithms effectively predicted any post-operative complication, kidney failure and LOS in the sample population. A larger study is justified to improve the algorithm to better predict complications and length of hospital stay. A larger dataset may also improve the prediction of additional specific complications, readmission and mortality.

Association of perioperative transfusion of fresh frozen plasma and outcomes after cardiac surgery.

BACKGROUND: Fresh frozen plasma (FFP) transfusion is used to manage coagulopathy and bleeding in cardiac surgery patients despite uncertainty about its safety and effectiveness. METHODS: We performed a propensity score matched analysis of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database including patients from 39 centres from 2005 to 2018. We investigated the association of perioperative FFP transfusion with mortality and other clinical outcomes. RESULTS: Of 119,138 eligible patients, we successfully matched 13,131 FFP recipients with 13,131 controls. FFP transfusion was associated with 30-day mortality (odds ratio (OR), 1.41; 99% CI, 1.17-1.71; p < .0001), but not with long-term mortality (hazard ratio (HR), 0.92; 99% CI, 0.85-1.00; p = .007, Holm-Bonferroni α = 0.0004). FFP was also associated with return to theatre for bleeding (OR, 1.97; 99% CI, 1.66-2.34; p < .0001), prolonged intubation (OR, 1.15; 99% CI, 1.05-1.26; p < .0001) and increased chest tube drainage (Mean difference (MD) in mL, 131; 99% CI, 120-141; p < .0001). It was also associated with reduced postoperative creatinine levels (MD in g/L, -6.33; 99% CI, -10.28 to -2.38; p < .0001). CONCLUSION: In a multicentre, propensity score matched analysis, perioperative FFP transfusion was associated with increased 30-day mortality and had variable associations with secondary clinical outcomes.

Quantifying Perioperative Risks for Antireflux and Hiatus Hernia Surgery: A Multicenter Cohort Study of 4301 Patients.

OBJECTIVE: Using a comprehensive Australian cohort, we quantified the incidence and determined the independent predictors of intraoperative and postoperative complications associated with antireflux and hiatus hernia surgeries. In addition, we performed an in-depth analysis to understand the complication profiles associated with each independent risk factor. BACKGROUND: Predicting perioperative risks for fundoplication and hiatus hernia repair will inform treatment decision-making, hospital resource allocation, and benchmarking. However, available risk calculators do not account for hernia anatomy or technical aspects of surgery in estimating perioperative risk. METHODS: Retrospective analysis of all elective antireflux and hiatus hernia surgeries in 36 Australian hospitals over 10 years. Hierarchical multivariate logistic regression analyses were performed to determine the independent predictors of intraoperative and postoperative complications accounting for patient, surgical, anatomic, and perioperative factors. RESULTS: A total of 4301 surgeries were analyzed. Of these, 1569 (36.5%) were large/giant hernias and 292 (6.8%) were revisional procedures. The incidence rates of intraoperative and postoperative complications were 12.6% and 13.3%, respectively. The Charlson Comorbidity Index, hernia size, revisional surgery, and baseline anticoagulant usage independently predicted both intraoperative and postoperative complications. These risk factors were associated with their own complication profiles. Finally, using risk matrices, we visualized the cumulative impact of these 4 risk factors on the development of intraoperative, overall postoperative, and major postoperative complications. CONCLUSIONS: This study has improved our understanding of perioperative morbidity associated with antireflux and hiatus hernia surgery. Our findings group patients along a spectrum of perioperative risks that inform care at an individual and institutional level.

Enhancing pre-transplant cardiac assessment: Validation and utility of the CAD-LT score with CCTA in liver transplant candidates.

BACKGROUND: Coronary computed tomography angiography (CCTA) is increasingly being used in the preoperative workup for liver transplantation (LT). We sought to assess the utility of integrating CCTA with the novel CAD-LT (Coronary Artery Disease in Liver Transplantation) score and its impact on reducing the need for invasive coronary angiography prior to LT. METHODS: We conducted a retrospective cohort study of consecutive patients (age ≥ 18 years) who underwent CCTA for LT workup between 2011 and 2018 at the Victorian Liver Transplant Unit, Melbourne, Australia. CAD-LT scores, a traditional risk factor-based criteria, were calculated, and patients stratified as low-, intermediate- or high-risk. RESULTS: Overall, 229 patients underwent CCTA. The mean age was 66 ± 5 years (82% male) with a modest-to-high risk factor burden (diabetes, 53%; hypertension, 46%; current or former smoker, 62%). The mean CAD-LT score of our cohort was 12.4 ± 4.0. No patients were classified as low-risk, 49 patients (21.4%) were deemed intermediate-risk and 180 patients (78.6%) were deemed high-risk. A high CAD-LT score (≥ 9) showed high sensitivity (95.3% [95% CI 86-98%]) and modest specificity (27.8% [95% CI 21-35%]) for the detection of obstructive coronary artery disease on CCTA, with a negative predictive value of 94%. Following multidisciplinary discussions, only 41 patients (18%) of patients proceeded to ICA of which 27% received percutaneous coronary intervention. CONCLUSIONS: The use of CCTA in patients deemed intermediate- to high-risk by the CAD-LT score has the potential to reduce the need for invasive coronary angiography in patients undergoing LT workup.

The hospital costs of complications following major abdominal surgery: a retrospective cohort study.

OBJECTIVE: Postoperative complications following major abdominal surgeries is a pressing concern for hospital care and health economics. Given the paucity of available cost data for patients undergoing major abdominal surgery, we evaluated the number and the severity of postoperative complications following major abdominal surgeries and calculated the costs borne by a single centre university hospital within an Australian healthcare system. RESULTS: The overall incidence of postoperative complications for 1790 adult patients undergoing major abdominal surgeries (i.e., colonic, liver, small bowel resections and Whipple procedures) between January 2013 and June 2018 was 75.2%. Of these complications, 56.9% were minor (Clavien-Dindo (CVD) Grades I or II) and 15.5% were major (CVD Grades III or IV). As the severity of complications increased, median adjusted total hospital costs rose significantly, with a median (interquartile range [IQR]) of AUD 29,519.70 (IQR 21,828.80-40,527.90) in CVD Grade II versus AUD 50,702.40 (IQR 35,866.00-69,296.80) in CVD Grade III (p <.001). Further, developing one, two or three complications resulted in significantly increased hospital costs by AUD 2618.30 (13.3% increase), AUD 3605.50 (16.2% increase) and AUD 3173.00 (12.3% increase) (p <.0001), respectively, with an exponential spike in costs incurred by patients who developed more than three complications (AUD 23,719.70; 81.7% increase; p < 0001).

Platelet versus fresh frozen plasma transfusion for coagulopathy in cardiac surgery patients.

BACKGROUND: Platelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown. METHODS: We conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005-2021 across 58 sites were included. The primary outcome was operative mortality. RESULTS: Of 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P<0.001) and 1-year (RR, 1.50; 95% CI, 1.32 to 1.71; P<0.001) mortality. FFP was associated with increased rates of 4-hour chest drain tube output (Adjusted mean difference in ml, 28.37; 95% CI, 19.35 to 37.38; P<0.001), AKI (RR, 1.13; 95% CI, 1.01 to 1.27; P = 0.033) and readmission to ICU (RR, 1.24; 95% CI, 1.09 to 1.42; P = 0.001). CONCLUSION: In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting.

Atherosclerosis on CT coronary angiography and the risk of long-term cardiovascular events after liver transplantation.

Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5-13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2-4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3-6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6-20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24-0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.

Textbook outcomes after oesophagectomy: a single-centre observational study.

BACKGROUND: Textbook outcomes is a composite quality assurance tool assessing the ideal perioperative and postoperative course as a unified measure. Currently, its definition and application in the context of oesophagectomy in Australia is unknown. The aim of this study was to assess the textbook outcomes after oesophagectomy in a single referral centre of Australia and investigate the association between textbook outcomes and patient, tumour, and treatment characteristics. METHODS: An observational study was retrospectively performed on patients undergoing open, laparoscopic, or hybrid oesophagectomy between January 2010 and December 2019 in a single cancer referral centre. A textbook outcome was defined as the fulfillment of 10 criteria: R0 resection, retrieval of at least 15 lymph nodes, no intraoperative complications, no postoperative complications greater than Clavien-Dindo grade III, no anastomotic leak, no readmission to the ICU, no hospital stay beyond 21 days, no mortality within 90 days, no readmission related to the surgical procedure within 30 days from admission and no reintervention related to the surgical procedure. The proportion of patients who met each criterion for textbook outcome was calculated and compared. Selected patient-related parameters (age, gender, BMI, ASA score, CCI score), tumour-related factors (tumour location, tumour histology, AJCC clinical T and N stage and treatment-related factor [neoadjuvant chemotherapy and surgical approach]) were assessed. Disease recurrence and one year survival were also evaluated. RESULTS: 110 patients who underwent oesophagectomy were included. The overall textbook outcome rate was 24%. The difference in rates across the years was not statistically significant. The most achieved textbook outcome parameters were 'no mortality in 90 days' (96%) and 'R0 resection' (89%). The least frequently met textbook outcome parameter was 'no severe postoperative complications' (58%), followed by 'no hospital stays over 21 days' (61%). No significant association was found between patient, tumour and treatment characteristics and the rate of textbook outcome. Tumour recurrence rate and overall long term survival was similar between textbook outcome and non-textbook outcome groups. Patients with R0 resection, no intraoperative complication and a hospital stay less than 21 days had reduced mortality rates. CONCLUSIONS: Textbook outcome is a clinically relevant indicator and was achieved in 24% of patients. Severe complications and a prolonged hospital stay were the key criteria that limited the achievement of a textbook outcome. These findings provide meticulous evaluation of oesophagectomy perioperative care and provide a direction for the utilisation of this concept in identifying and improving surgical and oncological care across multiple healthcare levels.

Financial burden of postoperative complications following oesophagectomy: a scoping review protocol.

INTRODUCTION: The rapid rise in the incidence of oesophageal adenocarcinoma has resulted in an increasing number of patients undergoing oesophagectomy. Although novel surgical techniques are enhancing surgical outcomes, postoperative complications remain pervasive. Despite this, there are limited reviews mapping the cost of postoperative complications following oesophagectomy, and none has compared cost differences between patient groups. Such information would be invaluable in appreciating the financial burden on the healthcare system and serving to guide hospital financing decisions. This scoping review protocol outlines an approach to reviewing the literature to precipitate and inform discussions surrounding financing oesophagectomy procedures as well as funding requirements for upper gastrointestinal surgical units. METHODS AND ANALYSIS: Adhering to the pertinent components of the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols guidelines, a systematic exploration will be conducted across electronic databases, including MEDLINE, EMBASE, the Cochrane Library and Econolit, with further reference tracking of eligible studies. This review will encompass studies related to the costs associated with complications following oesophagectomy. All studies published prior to 31 October 2023 are eligible for inclusion. The process of screening and extracting data will be undertaken by two independent reviewers. Subsequently, the amassed data will be pooled and subjected to comprehensive analysis and presented descriptively, using both a mixed methods and a narrative approach. ETHICS AND DISSEMINATION: Ethics approval was not required. The results will be communicated through established professional networks, conference presentations and publication in peer-reviewed journals.

The impact of intraoperative and postoperative fluid balance on complications for transthoracic esophagectomy: a retrospective analysis.

OBJECTIVE: Transthoracic esophagectomy is associated with significant morbidity and mortality. Therefore, it is imperative to optimize perioperative management and minimize complications. In this retrospective analysis, we evaluated the association between fluid balance and esophagectomy complications at a tertiary hospital in Melbourne, Australia, with a particular focus on respiratory morbidity and anastomotic leaks. Cumulative fluid balance was calculated intraoperatively, postoperatively in recovery postoperative day (POD) 0, and on POD 1 and 2. High and low fluid balance was defined as greater than or less than the median fluid balance, respectively, and postoperative surgical complications were graded using the Clavien-Dindo classification. RESULTS: In total, 109 patients, with an average age of 64 years, were included in this study. High fluid balance on POD 0, POD1 and POD 2 was associated with a higher incidence of anastomotic leak (OR 8.59; 95%CI: 2.64-39.0). High fluid balance on POD 2 was associated with more severe complications (of any type) (OR 3.33; 95%CI: 1.4-8.26) and severe pulmonary complications (OR 3.04; 95%CI: 1.27-7.67). For every 1 L extra cumulative fluid balance in POD 1, the odds of a major complication increase by 15%, while controlling for body mass index (BMI) and American Society of Anaesthesiologists (ASA) class. The results show that higher cumulative fluid balance is associated with worsening postoperative outcomes in patients undergoing transthoracic esophagectomy. Restricted fluid balance, especially postoperatively, may mitigate the risk of postoperative complications - however prospective trials are required to establish this definitively.

The transit of oral premedication beyond the stomach in patients undergoing laparoscopic sleeve gastrectomy: a retrospective observational multicentre study.

BACKGROUND: Antiemetic and analgesic oral premedications are frequently prescribed preoperatively to enhance recovery after laparoscopic sleeve gastrectomy. However, it is unknown whether these medications transit beyond the stomach or if they remain in the sleeve resection specimen, thereby negating their pharmacological effects. METHODS: A retrospective cohort study was performed on patients undergoing laparoscopic sleeve gastrectomy and receiving oral premedication (slow-release tapentadol and netupitant/palonosetron) as part of enhanced recovery after bariatric surgery program. Patients were stratified into the Transit group (premedication absent in the resection specimen) and Failure-to-Transit group (premedication present in the resection specimen). Age, sex, body mass index, and presence of diabetes were compared amongst the groups. The premedication lead time (time between premedications' administration and gastric specimen resection), and the premedication presence or absence in the specimen was evaluated. RESULTS: One hundred consecutive patients were included in the analysis. Ninety-nine patients (99%) were morbidly obese, and 17 patients (17%) had Type 2 diabetes mellitus. One hundred patients (100%) received tapentadol and 89 patients (89%) received netupitant/palonosetron. One or more tablets were discovered in the resected specimens of 38 patients (38%). No statistically significant differences were observed between the groups regarding age, sex, diabetes, or body mass index. The median (Q1‒Q3) premedication lead time was 80 min (57.8‒140.0) in the Failure-to-Transit group and 119.5 min (85.0‒171.3) in the Transit group; P = 0.006. The lead time required to expect complete absorption in 80% of patients was 232 min (95%CI:180‒310). CONCLUSIONS: Preoperative oral analgesia and antiemetics did not transit beyond the stomach in 38% of patients undergoing laparoscopic sleeve gastrectomy. When given orally in combination, tapentadol and netupitant/palonosetron should be administered at least 4 h before surgery to ensure transition beyond the stomach. Future enhanced recovery after bariatric surgery guidelines may benefit from the standardization of premedication lead times to facilitate increased absorption. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry; number ACTRN12623000187640; retrospective registered on 22/02/2023.

Multimodal intrathecal analgesia (MITA) with morphine for reducing postoperative opioid use and acute pain following hepato-pancreato-biliary surgery: A multicenter retrospective study.

INTRODUCTION: The optimal analgesic modality for patients undergoing hepato-pancreato-biliary (HPB) surgery remains unknown. The analgesic effects of a multimodal intrathecal analgesia (MITA) technique of intrathecal morphine (ITM) in combination with clonidine and bupivacaine compared to ITM alone have not been investigated in these patients. METHODS: We performed a multicenter retrospective study of patients undergoing complex HPB surgery who received ITM, bupivacaine, and clonidine (MITA group) or ITM-only (ITM group) as part of their perioperative analgesia strategy. The primary outcome was the unadjusted oral morphine equivalent daily dose (oMEDD) in milligrams on postoperative day 1. After adjusting for age, body mass index, hospital allocation, type of surgery, operation length, and intraoperative opioid use, postoperative oMEDD use was investigated using a bootstrapped quantile regression model. Other prespecified outcomes included postoperative pain scores, opioid-related adverse events, major complications, and length of hospital stay. RESULTS: In total, 118 patients received MITA and 155 patients received ITM-only. The median (IQR) cumulative oMEDD use on postoperative day 1 was 20.5 mg (8.6:31.0) in the MITA group and 52.1 mg (18.0:107.0) in the ITM group (P < 0.001). There was a variation in the magnitude of the difference in oMEDD use between the groups for different quartiles. For the MITA group, on postoperative day 1, patients in the 25th percentile required 14.0 mg less oMEDD (95% CI: -25.9 to -2.2; P = 0.025), patients in the 50th percentile required 27.8 mg less oMEDD (95% CI: -49.7 to -6.0; P = 0.005), and patients in the 75th percentile required 38.7 mg less oMEDD (95% CI: -72.2 to -5.1; P = 0.041) compared to patients in the same percentile of the ITM group. Patients in the MITA group had significantly lower pain scores in the postoperative recovery unit and on postoperative days 1 to 3. The incidence of postoperative respiratory depression was low (<1.5%) and similar between groups. Patients in the MITA group had a significantly higher incidence of postoperative hypotension requiring vasopressor support. However, no significant differences were observed in major postoperative complications, or the length of hospital stay. CONCLUSION: In patients undergoing complex HPB surgery, the use of MITA, consisting of ITM in combination with intrathecal clonidine and bupivacaine, was associated with reduced postoperative opioid use and resulted in superior postoperative analgesia without risk of respiratory depression when compared to patients who received ITM alone. A randomized prospective clinical trial investigating these two intrathecal analgesic techniques is justified.

Concentrated urine, low urine flow, and postoperative elevation of plasma creatinine: A retrospective analysis of pooled data.

Elevations of plasma creatinine are common after major surgery, but their pathophysiology is poorly understood. To identify possible contributing mechanisms, we pooled data from eight prospective studies performed in four different countries to study circumstances during which elevation of plasma creatinine occurs. We included 642 patients undergoing mixed major surgeries, mostly open gastrointestinal. Plasma and urinary creatinine and a composite index for renal fluid conservation (Fluid Retention Index, FRI) were measured just before surgery and on the first postoperative morning. Urine flow was measured during the surgery. The results show that patients with a postoperative increase in plasma creatinine by >25% had a high urinary creatinine concentration (11.0±5.9 vs. 8.3±5.6 mmol/L; P< 0001) and higher FRI value (3.2±1.0 vs. 2.9±1.1; P< 0.04) already before surgery was initiated. Progressive increase of plasma creatinine was associated with a gradually lower urine flow and larger blood loss during the surgery (Kruskal-Wallis test, P< 0.001). The patients with an elevation > 25% also showed higher creatinine and a higher FRI value on the first postoperative morning (P< 0.001). Elevations to > 50% of baseline were associated with slightly lower mean arterial pressure (73 ± 10 vs. 80 ± 12 mmHg; P< 0.005). We conclude that elevation of plasma creatinine in the perioperative period was associated with low urine flow and greater blood loss during surgery and with concentrated urine both before and after the surgery. Renal water conservation-related mechanisms seem to contribute to the development of increased plasma creatinine after surgery.

Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial.

BACKGROUND: The role of the renin-angiotensin-aldosterone axis in vasoplegia after cardiac surgery remains unclear. We tested the hypothesis that, compared with norepinephrine, infusion of angiotensin II titrated to achieve similar mean arterial pressure (MAP) would suppress plasma renin concentration (PRC) while maintaining aldosterone levels. METHODS: In a double-blind, randomised controlled trial, subjects received either an infusion of angiotensin II or norepinephrine to maintain MAP 70-80 mm Hg from induction of anaesthesia. We compared PRC, aldosterone, dipeptidyl peptidase-3, and angiotensin-converting enzyme 2 activity between treatment groups, before surgery, on ICU admission, and 24 h after surgery. RESULTS: In 60 patients (11.7% female; mean age 68 yr [11 yr]), norepinephrine increased median PRC at ICU admission (median difference [MD] 46 [inter-quartile range, IQR, 3-88] µU ml-1; P<0.001) but angiotensin II did not (MD -3 [IQR -62 to 35] µU ml-1; P=0.36). Aldosterone levels increased with both. The aldosterone:PRC ratio did not change with norepinephrine (MD -0.01 [IQR -0.14 to 0.03] µU ml-1 per ng dl-1, P=0.76) but increased with angiotensin II (MD 0.05 [IQR 0.004-0.26] µU ml-1 per ng dl-1, P<0.001). The upper quartile of PRC before surgery was associated with higher vasopressor requirements when norepinephrine was used to maintain MAP, but not angiotensin II. Dipeptidyl peptidase-3 levels and angiotensin-converting enzyme 2 activities were similar at all time points. CONCLUSIONS: Angiotensin II suppressed renin release while maintaining aldosterone levels compared with norepinephrine. Higher plasma renin concentration before surgery was associated with greater vasopressor requirement for norepinephrine, but not angiotensin II. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry-ACTRN12621000195853 23/02/2021.

Changes in SedLine-derived processed electroencephalographic parameters during hypothermia in patients undergoing cardiac surgery with cardiopulmonary bypass.

Objective: Processed electroencephalography (pEEG) is used to monitor depth-of-anesthesia during cardiopulmonary bypass (CPB). The SedLine device has been recently introduced for pEEG monitoring. However, the effect of hypothermia on its parameters during CPB is unknown. Accordingly, we aimed to investigate temperature-induced changes in SedLine-derived pEEG parameters during CPB. Design: Prospective observational study. Setting: Cardiac surgery operating theatre. Participants: 28 patients undergoing elective cardiac surgery with CPB. Interventions: We continuously measured patient state index (PSI), suppression ratio (SR), bilateral spectral edge frequency (SEF) and temperature. We used linear mixed modelling with fixed and random effects to study the interactions between pEEG parameters and core temperature. Measurements and main results: During CPB maintenance, the median temperature was 32.1°C [interquartile range (IQR): 29.8-33.6] at the end of cooling and 32.8°C (IQR: 30.1-34.0) at rewarming initiation. For each degree Celsius change in temperature during cooling and rewarming the PSI either decreased by 0.8 points [95% confidence interval (CI): 0.7-1.0; p < 0.001] or increased by 0.7 points (95% CI: 0.6-0.8; p < 0.001). The SR increased by 2.9 (95% CI: 2.3-3.4); p < 0.001) during cooling and decreased by 2.2 (95% CI: 1.7-2.7; p < 0.001) during rewarming. Changes in the SEF were not related to changes in temperature. Conclusions: During hypothermic CPB, temperature changes led to concordant changes in the PSI. The SR increased during cooling and decreased during rewarming. Clinicians using SedLine for depth-of-anesthesia monitoring should be aware of these effects when interpreting the PSI and SR values.