AcumenTM hypotension prediction index guidance for prevention and treatment of hypotension in noncardiac surgery: a prospective, single-arm, multicenter trial.

BACKGROUND: Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient's likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min. METHODS: Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort. (2) A post hoc analysis of a subset of trial participants versus a propensity score-weighted contemporaneous comparison group, using external data from the Multicenter Perioperative Outcomes Group (MPOG). The trial included 485 subjects in 11 sites; 406 were in the final effectiveness analysis. The post hoc analysis included 457 trial participants and 15,796 comparison patients. Patients were eligible if aged 18 years or older, American Society of Anesthesiologists (ASA) physical status 3 or 4, and scheduled for moderate- to high-risk noncardiac surgery expected to last at least 3 h. MEASUREMENTS: minutes of mean arterial pressure (MAP) below 65 mmHg and area under MAP < 65 mmHg. RESULTS: Analysis 1: Trial subjects (n = 406) experienced a mean of 9 ± 13 min of MAP below 65 mmHg, compared with the MPOG historical control mean of 25 ± 41 min, a 65% reduction (p < 0.001). Subjects with at least one episode of hypotension (n = 293) had a mean of 12 ± 14 min of MAP below 65 mmHg compared with the MPOG historical control mean of 28 ± 43 min, a 58% reduction (p< 0.001). Analysis 2: In the post hoc inverse probability treatment weighting model, patients in the trial demonstrated a 35% reduction in minutes of hypotension compared to a contemporaneous comparison group [exponentiated coefficient: - 0.35 (95%CI - 0.43, - 0.27); p < 0.001]. CONCLUSIONS: The use of prediction software for blood pressure management was associated with a clinically meaningful reduction in the duration of intraoperative hypotension. Further studies must investigate whether predictive algorithms to prevent hypotension can reduce adverse outcomes. TRIAL REGISTRATION: Clinical trial number: NCT03805217. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03805217 . Principal investigator: Xiaodong Bao, MD, PhD. Date of registration: January 15, 2019.

Feasibility pilot trial for the Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anesthesia (THRIVE) pragmatic randomised controlled trial.

INTRODUCTION: Millions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient experience, safety and outcomes. The aim of this pilot study is to assess the feasibility of conducting a large comparative effectiveness trial assessing patient experiences and outcomes after receiving propofol TIVA or INVA. METHODS AND ANALYSIS: This protocol was cocreated by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 300-patient, two-centre, randomised, feasibility pilot trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to propofol TIVA or INVA, stratified by centre and procedural complexity. The feasibility endpoints include: (1) proportion of patients approached who agree to participate; (2) proportion of patients who receive their assigned randomised treatment; (3) completeness of outcomes data collection and (4) feasibility of data management procedures. Proportions and 95% CIs will be calculated to assess whether prespecified thresholds are met for the feasibility parameters. If the lower bounds of the 95% CI are above the thresholds of 10% for the proportion of patients agreeing to participate among those approached and 80% for compliance with treatment allocation for each randomised treatment group, this will suggest that our planned pragmatic 12 500-patient comparative effectiveness trial can likely be conducted successfully. Other feasibility outcomes and adverse events will be described. ETHICS AND DISSEMINATION: This study is approved by the ethics board at Washington University (IRB# 202205053), serving as the single Institutional Review Board for both participating sites. Recruitment began in September 2022. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. TRIAL REGISTRATION NUMBER: NCT05346588.

Positron emission tomography myocardial perfusion imaging (PET MPI) findings predictive of post-liver transplant major adverse cardiac events.

Positron emission tomography myocardial perfusion imaging (PET MPI) is a noninvasive diagnostic test capable of detecting coronary artery disease, structural heart disease, and myocardial flow reserve (MFR). We aimed to determine the prognostic utility of PET MPI to predict post-liver transplant (LT) major adverse cardiac events (MACE). Among the 215 LT candidates that completed PET MPI between 2015 and 2020, 84 underwent LT and had 4 biomarker variables of clinical interest on pre-LT PET MPI (summed stress and difference scores, resting left ventricular ejection fraction, global MFR). Post-LT MACE were defined as acute coronary syndrome, heart failure, sustained arrhythmia, or cardiac arrest within the first 12 months post-LT. Cox regression models were constructed to determine associations between PET MPI variable/s and post-LT MACE. The median LT recipient age was 58 years, 71% were male, 49% had NAFLD, 63% reported prior smoking, 51% had hypertension, and 38% had diabetes mellitus. A total of 20 MACE occurred in 16 patients (19%) at a median of 61.5 days post-LT. One-year survival of MACE patients was significantly lower than those without MACE (54% vs. 98%, p =0.001). On multivariate analysis, reduced global MFR ≤1.38 was associated with a higher risk of MACE [HR=3.42 (1.23-9.47), p =0.019], and every % reduction in left ventricular ejection fraction was associated with an 8.6% higher risk of MACE [HR=0.92 (0.86-0.98), p =0.012]. Nearly 20% of LT recipients experienced MACE within the first 12 months of LT. Reduced global MFR and reduced resting left ventricular ejection fraction on PET MPI among LT candidates were associated with increased risk of post-LT MACE. Awareness of these PET-MPI parameters may help improve cardiac risk stratification of LT candidates if confirmed in future studies.

Multicenter evaluation of the Quantra with the QStat Cartridge in adult patients undergoing liver transplantation.

Blood loss and transfusion of blood products are key concerns during liver transplantation. Whole-blood viscoelastic testing devices have been used to monitor hemostatic function and guide the transfusion of blood products in this patient population. The Quantra System with the QStat Cartridge is a new point-of-care, closed-system viscoelastic testing device that measures changes in clot stiffness during coagulation and fibrinolysis using ultrasound detection of resonance. The aim of this multicenter prospective observational study was to evaluate the Quantra System against the ROTEM delta device in monitoring coagulation and fibrinolysis in patients undergoing liver transplantation. One hundred twenty-five (125) adult subjects (above 18 y old) were enrolled across 5 medical centers in the US. Blood samples were collected at a minimum of 3-time points: preincision (baseline), during the anhepatic phase, and after the start of reperfusion. Performance was assessed as the correlation of equivalent measurements from the QStat Cartridge and ROTEM delta INTEM, EXTEM, and FIBTEM assays. In addition, a clinical concordance analysis was performed to assess the agreement between the 2 devices related to the detection of fibrinolysis. The correlation between the 2 viscoelastic testing devices was strong, with r -values ranging between 0.88 and 0.95, and the overall agreement with respect to detecting fibrinolysis was 90.3% (CI, 86.9%-93.2%). The results indicate that the Quantra with the QStat Cartridge provides comparable information as the ROTEM delta in the assessment of hemostatic function during a liver transplant. Quantra's simplicity of use and availability of rapid results may provide clinicians with a faster, more convenient means to assess coagulation and fibrinolysis status in the operating room and critical care setting.

Successful living donor liver transplantation in a patient with hemophilia A and factor VIII inhibitor: A case report with perioperative recommendations.

Liver transplantation in patients with end-stage liver disease and coexisting hemophilia A has been described. Controversy exists over perioperative management of patients with factor VIII inhibitor predisposing patients to hemorrhage. We describe the case of a 58-year-old man with a history of hemophilia A and factor VIII inhibitor, eradicated with rituximab prior to living donor liver transplantation without recurrence of inhibitor. We also provide perioperative management recommendations from our successful multidisciplinary approach.

Intraoperative risk factors of acute kidney injury after liver transplantation.

Acute kidney injury (AKI) is one of the most common complications of liver transplantation (LT). We examined the impact of intraoperative management on risk for AKI following LT. In this retrospective observational study, we linked data from the electronic health record with standardized transplant outcomes. Our primary outcome was stage 2 or 3 AKI as defined by Kidney Disease Improving Global Outcomes guidelines within the first 7 days of LT. We used logistic regression models to test the hypothesis that the addition of intraoperative variables, including inotropic/vasopressor administration, transfusion requirements, and hemodynamic markers improves our ability to predict AKI following LT. We also examined the impact of postoperative AKI on mortality. Of the 598 adult primary LT recipients included in our study, 43% (n = 255) were diagnosed with AKI within the first 7 postoperative days. Several preoperative and intraoperative variables including (1) electrolyte/acid-base balance disorder (International Classification of Diseases, Ninth Revision codes 253.6 or 276.x and International Classification of Diseases, Tenth Revision codes E22.2 or E87.x, where x is any digit; adjusted odds ratio [aOR], 1.917, 95% confidence interval [CI], 1.280-2.869; p = 0.002); (2) preoperative anemia (aOR, 2.612; 95% CI, 1.405-4.854; p = 0.002); (3) low serum albumin (aOR, 0.576; 95% CI, 0.410-0.808; p = 0.001), increased potassium value during reperfusion (aOR, 1.513; 95% CI, 1.103-2.077; p = 0.01), and lactate during reperfusion (aOR, 1.081; 95% CI, 1.003-1.166; p = 0.04) were associated with posttransplant AKI. New dialysis requirement within the first 7 days postoperatively predicted the posttransplant mortality. Our study identified significant association between several potentially modifiable variables with posttransplant AKI. The addition of intraoperative data did not improve overall model discrimination.

Association of intraoperative hyperglycemia and postoperative outcomes in patients undergoing non-cardiac surgery: a multicenter retrospective study.

BACKGROUND: While pre and postoperative hyperglycemia is associated with increased risk of surgical site infection, myocardial infarction, stroke and risk of death, there are no multicenter data regarding the association of intraoperative blood glucose levels and outcomes for the non-cardiac surgical population. METHODS: We conducted a retrospective cohort study from the Michigan Surgical Quality Collaborative, a network of 64 hospitals that prospectively collects validated data on surgical patients for the purpose of quality improvement. We included data for adult general, vascular, endocrine, hepatobiliary, and gastrointestinal operations between 2013 and 2015. We assessed the risk-adjusted, independent relationship between intraoperative hyperglycemia (glucose > 180) and the primary outcome of 30-day morbidity/mortality and secondary outcome of infectious complications using multivariable logistic regression modelling. Post hoc sensitivity analysis to assess the association between blood glucose values ≥250 mg/dL and outcomes was also performed. RESULTS: Ninety-two thousand seven hundred fifty-one patients underwent surgery between 2013 and 2015 and 5014 (5.4%) had glucose testing intra-operatively. Of these patients, 1647 patients (32.9%) experienced the primary outcome, and 909 (18.1%) the secondary outcome. After controlling for patient comorbidities and surgical factors, peak intraoperative glucose > 180 mg/dL was not an independent predictor of 30-day mortality/morbidity (adjusted OR 1.05, 95%CI:0.86 to 1.28; p-value 0.623; model c-statistic of 0.720) or 30-day infectious complications (adjusted OR 0.93, 95%CI:0.74,1.16; p 0.502; model c-statistic of 0.709). Subgroup analysis for patients with or without diabetes yielded similar results. Sensitivity analysis demonstrated blood glucose of 250 mg/dL was a predictor of 30-day mortality/morbidity (adjusted OR: 1.59, 95% CI: 1.24, 2.05; p < 0.001). CONCLUSIONS: Among more than 5000 patients across 64 hospitals who had glucose measurements during surgery, there was no difference in postoperative outcomes between patients who had intraoperative glucose > 180 mg/ dL compared to patients with glucose values ≤180 mg/ dL.

Intraoperative glycemic control in patients undergoing Orthotopic liver transplant: a single center prospective randomized study.

BACKGROUND: Perioperative hyperglycemia is associated with poor outcomes yet evidence to guide intraoperative goals and treatment modalities during non-cardiac surgery are lacking. End-stage liver disease is associated with altered glucose homeostasis; patients undergoing liver transplantation display huge fluctuations in blood glucose (BG) and represent a population of great interest. Here, we conduct a randomized trial to compare the effects of strict versus conventional glycemic control during orthotopic liver transplant (OLT). METHODS: Following approval by the Institutional Review Board of the University of Michigan Medical School and informed consent, 100 adult patients undergoing OLT were recruited. Patients were randomized to either strict (target BG 80-120 mg/dL) or conventional (target BG 180-200 mg/dL) BG control with block randomization for diabetic and nondiabetic patients. The primary outcomes measured were 1-year patient and graft survival assessed on an intention to treat basis. Graft survival is defined as death or needing re-transplant (www.unos.org). Three and 5-year patient and graft survival, infectious and biliary complications were measured as secondary outcomes. Data were examined using univariate methods and Kaplan-Meir survival analysis. A sensitivity analysis was performed to compare patients with a mean BG of ≤120 mg/dL and those > 120 mg/dL regardless of treatment group. RESULTS: There was no statistically significant difference in patient survival between conventional and strict control respectively;1 year, 88% vs 88% (p-0.99), 3 years, 86% vs 84% (p- 0.77), 5 years, 82% vs 78. % (p-0.36). Graft survival was not different between conventional and strict control groups at 1 year, 88% vs 84% (p-0.56), 3 years 82% vs 76% (p-0.46), 5 years 78% vs 70% (p-0.362). CONCLUSION: There was no difference in patient or graft survival between intraoperative strict and conventional glycemic control during OLT. TRIAL REGISTRATION: Clinical trial number and registry: www.clinicaltrials.gov NCT00780026. This trial was retrospectively registered on 10/22/2008.

Photobiomodulation at 660 nm Stimulates Fibroblast Differentiation.

BACKGROUND AND OBJECTIVES: Among many of the different complications that diabetic patients suffer, foot ulcers are the most challenging, and in many cases result in non-traumatic lower limb amputation and permanent disability. To alleviate this burden, new interventions such as photobiomodulation (PBM) have been utilized. However, the cellular pathways affected by PBM have not yet been fully recognized. The differentiation of fibroblasts into myofibroblasts forms a vital part of wound healing and is often impaired under diabetic conditions. Therefore, this study sought to investigate the effects of PBM at 660 nm on the transforming growth factor-ß1 (TGF-ß1)/Smad pathway and the differentiation of fibroblasts into myofibroblasts. STUDY DESIGN/MATERIALS AND METHODS: WS1 fibroblasts were treated with PBM using a wavelength of 660 nm at a fluence of 5 J/cm2 in normal, normal wounded, diabetic, and diabetic wounded models. Post-irradiation cellular responses were observed at 24, 48, and 72 hours to ascertain morphological changes and cell viability, and the expression of fibroblast differentiation markers (Thy-1 or CD90, extra domain A fibronectin or EDA-FN and α-smooth muscle actin or α-SMA), TGF-ß1, phosphorylated (p)TGF-ß receptor 1 (R1), and p-Smad2/3. RESULTS: There was a significant increase in cell viability in all irradiated cell models, and no real significant changes in TGF-ß1, pTGF-ß1R1, and p-Smad2/3. As incubation time post-irradiation increased, Thy-1 (CD90) decreased, while EDA-FN and α-SMA increased in wounded models. CONCLUSIONS: PBM at 660 nm with 5 J/cm2 was successful in stimulating the differentiation of fibroblasts into myofibroblasts in diabetic wounded cells, which was independent of the TGF-ß1/Smad pathway. Fibroblast transition into myofibroblasts is vital to wound healing, failure of which results in impaired healing; PBM is able to foster such a transition. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

The impact of intraoperative fluid management during laparoscopic donor nephrectomy on donor and recipient outcomes.

BACKGROUND: Intraoperative fluid management during laparoscopic donor nephrectomy (LDN) may have a significant effect on donor and recipient outcomes. We sought to quantify variability in fluid management and investigate its impact on donor and recipient outcomes. METHODS: A retrospective review of patients who underwent LDN from July 2011 to January 2016 with paired kidney recipients at a single center was performed. Patients were divided into tertiles of intraoperative fluid management (standard, high, and aggressive). Donor and recipient demographics, intraoperative data, and postoperative outcomes were analyzed. RESULTS: Overall, 413 paired kidney donors and recipients were identified. Intraoperative fluid management (mL/h) was highly variable with no correlation to donor weight (kg) (R = 0.017). The aggressive fluid management group had significantly lower recipient creatinine levels on postoperative day 1. However, no significant differences were noted in creatinine levels out to 6 months between groups. No significant differences were noted in recipient postoperative complications, graft loss, and death. There was a significant increase (P < 0.01) in the number of total donor complications in the aggressive fluid management group. CONCLUSIONS: Aggressive fluid management during LDN does not improve recipient outcomes and may worsen donor outcomes compared to standard fluid management.

Intraoperative hyperglycemia is independently associated with infectious complications after non-cardiac surgery.

BACKGROUND: Perioperative hyperglycemia and its associated increase in morbidity and mortality have been well studied in the critical care and cardiac surgery literature. However, there is little data regarding the impact of intraoperative hyperglycemia on post-operative infectious complications in non-cardiac surgery. METHODS: All National Surgery Quality Improvement Program patients undergoing general, vascular, and urological surgery at our tertiary care center were reviewed. After integrating intraoperative glucose measurements from our intraoperative electronic health record, we categorized patients as experiencing mild (8.3-11.0 mmol/L), moderate (11.1-16.6 mmol/L), and severe (≥ 16.7 mmol/L) intraoperative hyperglycemia. Using multiple logistic regression to adjust for patient comorbidities and surgical factors, we evaluated the association of hyperglycemia with the primary outcome of postoperative surgical site infection, pneumonia, urinary tract infection, or sepsis within 30 days. RESULTS: Of 13,954 patients reviewed, 3150 patients met inclusion criteria and had an intraoperative glucose measurement. 49% (n = 1531) of patients experienced hyperglycemia and 15% (n = 482) patients experienced an infectious complication. Patients with mild (adjusted odds ratio 1.30, 95% confidence interval [1.01 to 1.68], p-value = 0.04) and moderate hyperglycemia (adjusted odds ratio 1.57, 95% confidence interval [1.08-2.28], p-value = 0.02) had a statistically significant risk-adjusted increase in infectious complications. The model c-statistic was 0.72 [95% confidence interval 0.69-0.74]. CONCLUSIONS: This is one of the first studies to demonstrate an independent relationship between intraoperative hyperglycemia and postoperative infectious complications. Future studies are needed to evaluate a causal relationship and impact of treatment.