Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery.

BACKGROUND: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated. METHODS: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus. RESULTS: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229). CONCLUSIONS: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit.

Effect of liver resection-induced increases in hepatic venous pressure gradient on development of postoperative acute kidney injury.

BACKGROUND: The impact of changes in portal pressure before and after liver resection (defined as ΔHVPG) on postoperative kidney function remains unknown. Therefore, we investigated the effect of ΔHVPG on (i) the incidence of postoperative AKI and (ii) the renin-angiotensin system (RAAS) and sympathetic nervous system (SNS) activity. METHODS: We included 30 patients undergoing partial liver resection. Our primary outcome was postoperative AKI according to KDIGO criteria. For our secondary outcome we assessed the plasma renin, aldosterone, noradrenaline, adrenaline, dopamine and vasopressin concentrations prior and 2 h after induction of anaesthesia, on the first and fifth postoperative day. HVPG was measured prior and immediately after liver resection. RESULTS: ΔHVPG could be measured in 21 patients with 12 patients HVPG showing increases in HVPG (∆HVPG≥1 mmHg) while 9 patients remained stable. AKI developed in 7/12 of patients with increasing HVPG, but only in 2/9 of patients with stable ΔHVPG (p = 0.302). Noradrenalin levels were significantly higher in patients with increasing ΔHVPG than in patients with stable ΔHVPG. (p = 0.009). Biomarkers reflecting RAAS and SNS activity remained similar in patients with increasing vs. stable ΔHVPG. CONCLUSIONS: Patients with increased HVPG had higher postoperative creatinine concentrations, however, the incidence of AKI was similar between patients with increased versus stable HVPG.

The effect of mannitol on oxidation-reduction potential in patients undergoing deceased donor renal transplantation-A randomized controlled trial.

BACKGROUND: Mannitol, an osmotic diuretic, is proposed to be an oxygen radical scavenger. Mannitol is often used in renal transplantation to attenuate oxidative stress and thus to protect renal graft function. We tested the hypothesis that mannitol reduces overall oxidative stress during deceased donor renal transplantation. METHODS: We randomly assigned 34 patients undergoing deceased donor renal transplantation to receive a solution of mannitol or placebo shortly before graft reperfusion until the end of surgery. We evaluated oxidative stress by measuring the static oxidative-reduction potential (sORP) and the capacity of the oxidative-reduction potential (cORP). sORP and cORP were measured pre-operatively, before and within 10 minutes after graft reperfusion, and post-operatively. RESULTS: Seventeen patients were enrolled in the mannitol group and 17 patients were enrolled in the placebo group. Mannitol had no significant effect on sORP (148.5 mV [136.2; 160.2]) as compared to placebo (143.6 mV [135.8; 163.2], P = .99). There was also no significant difference in cORP between the mannitol (0.22 µC [0.16; 0.36]) and the placebo group (0.22 µC [0.17; 0.38], P = .76). CONCLUSION: Mannitol showed no systemic redox scavenging effects during deceased donor renal transplantation. To evaluate the direct effect of mannitol on the renal graft further studies are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02705573.

Mannitol and renal graft injury in patients undergoing deceased donor renal transplantation - a randomized controlled clinical trial.

BACKGROUND: Ischaemia/reperfusion (I/R) injury is associated with renal tissue damage during deceased donor renal transplantation. The effect of mannitol to reduce I/R injury during graft reperfusion in renal transplant recipients is based on weak evidence. We evaluated the effect of mannitol to reduce renal graft injury represented by 16 serum biomarkers, which are indicators for different important pathophysiological pathways. Our primary outcome were differences in biomarker concentrations between the mannitol and the placebo group 24 h after graft reperfusion. Additionally, we performed a linear mixed linear model to account biomarker concentrations before renal transplantation. METHODS: Thirty-four patients undergoing deceased donor renal transplantation were randomly assigned to receive either 20% mannitol or 0.9% NaCl placebo solution before, during, and after graft reperfusion. Sixteen serum biomarkers (MMP1, CHI3L1, CCL2, MMP8, HGF, GH, FGF23, Tie2, VCAM1, TNFR1, IGFBP7, IL18, NGAL, Endostatin, CystC, KIM1) were measured preoperatively and 24 h after graft reperfusion using Luminex assays and ELISA. RESULTS: Sixteen patients in each group were analysed. Tie2 differed 24 h after graft reperfusion between both groups (p = 0.011). Change of log2 transformed concentration levels over time differed significantly in four biomarkers (VCAM1,Endostatin, KIM1, GH; p = 0.007; p = 0.013; p = 0.004; p = 0.033; respectively) out of 16 between both groups. CONCLUSION: This study showed no effect of mannitol on I/R injury in patients undergoing deceased renal transplantation. Thus, we do not support the routinely use of mannitol to attenuate I/R injury. TRIAL REGISTRATION: NCT02705573 . Registered on 10th March 2016.

A comparison of intraoperative goal-directed intravenous administration of crystalloid versus colloid solutions on the postoperative maximum N-terminal pro brain natriuretic peptide in patients undergoing moderate- to high-risk noncardiac surgery.

BACKGROUND: N-terminal pro brain natriuretic peptide (NT-proBNP) and troponin T are released during myocardial wall stress and/or ischemia and are strong predictors for postoperative cardiovascular complications. However, the relative effects of goal-directed, intravenous administration of crystalloid compared to colloid solutions on NT-proBNP and troponin T, especially in relatively healthy patients undergoing moderate- to high-risk noncardiac surgery, remains unclear. Thus, we evaluated in this sub-study the effect of a goal-directed crystalloid versus a goal-directed colloid fluid regimen on postoperative maximum NT-proBNP concentration. We further evaluated the incidence of myocardial injury after noncardiac surgery (MINS) between both study groups. METHODS: Thirty patients were randomly assigned to receive additional intravenous fluid boluses of 6% hydroxyethyl starch 130/0.4 and 30 patients to receive lactated Ringer's solution. Intraoperative fluid management was guided by oesophageal Doppler-according to a previously published algorithm. The primary outcome were differences in postoperative maximum NT-proBNP (maxNT-proBNP) between both groups. As our secondary outcome we evaluated the incidence of MINS between both study groups. We defined maxNT-proBNP as the maximum value measured within 2 h after surgery and on the first and second postoperative day. RESULTS: In total 56 patients were analysed. There was no significant difference in postoperative maximum NT-proBNP between the colloid group (258.7 ng/L (IQR 199.4 to 782.1)) and the crystalloid group (440.3 ng/L (IQR 177.9 to 691.2)) during the first 2 postoperative days (P = 0.29). Five patients in the colloid group and 7 patients in the crystalloid group developed MINS (P = 0.75). CONCLUSIONS: Based on this relatively small study goal-directed colloid administration did not decrease postoperative maxNT-proBNP concentration as compared to goal-directed crystalloid administration. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01195883 ) Registered on 6th September 2010.

The effect of intraoperative goal-directed crystalloid versus colloid administration on perioperative inflammatory markers - a substudy of a randomized controlled trial.

BACKGROUND: Excessive perioperative fluid administration may result in iatrogenic endothelial dysfunction and tissue edema, transducing inflammatory markers into the bloodstream. Colloids remain longer in the circulation, requiring less volume to reach similar hemodynamic endpoints compared to crystalloids. Thus, we tested the hypothesis that a goal-directed colloid regimen attenuates the inflammatory response compared to a goal-directed crystalloid regime. METHODS: Patients undergoing moderate- to high-risk open abdominal surgery were randomly assigned to goal-directed lactated Ringer's solution (n = 58) or a hydroxyethyl starch 6% 130/0.4 (n = 62) fluid regimen. Our primary outcome was perioperative levels of pro- and anti-inflammatory cytokines. Secondary outcome was perioperative levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP). Measurements were performed preoperatively, immediate postoperatively, on postoperative day one, two and four. RESULTS: The areas under the curve of Interleukin (IL) 6 (p = 0.60), IL 8 (p = 0.46), IL 10 (p = 0.68) and tumor necrosis factor α (p = 0.47) levels did not differ significantly between the groups. WBC, CRP and PCT values were also comparable. LBP, although significantly higher in the crystalloid group, remained in the normal range. Patients assigned to crystalloids received a median (IQR) amount of 3905 mL (2880-5288) of crystalloid. Patients assigned to colloids received 1557 mL (1207-2116) of crystalloid and 1250 mL (750-1938) of colloid. CONCLUSION: Cytokine and inflammatory marker levels did not differ between goal-directed crystalloid and colloid administration after moderate to high-risk abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT00517127 ). Registered 16th August 2007.

Effect of goal-directed crystalloid- versus colloid-based fluid strategy on tissue oxygen tension: a randomised controlled trial.

BACKGROUND: Sufficient tissue oxygen tension may reduce the risk of postoperative wound infections. Supplemental administration of crystalloids increases subcutaneous oxygen tension (Psqo2). Colloids remain longer in the intravascular system and might therefore increase Psqo2 even more than crystalloids. Therefore, we tested the hypothesis that goal-directed colloid administration increases the perioperative Psqo2 more compared with crystalloid administration. METHODS: We randomly assigned 80 patients undergoing elective open abdominal surgery to receive fluid boluses of hydroxyethyl starch (HES) or lactated Ringer's (LR) solution guided by oesophageal Doppler. Intraoperative Psqo2 was measured in the upper arm. After operation, we measured the Psqo2 in the upper arm and in the surgical wound. RESULTS: Forty patients were enrolled in each group. Patients in the colloid group received HES solution 750 ml (500; 1000) and LR solution 1500 ml (1000; 2000). Patients in the crystalloid group received LR solution 2825 ml (2000; 3960). The goal-directed administration of colloids did not improve intraoperative Psqo2 in the arm compared with crystalloid administration (11.4 kPa [9.0; 16.6] vs 11.2 kPa [8.6; 15.1], respectively; P=0.58). Postoperative arm Psqo2 was 8.1 kPa (6.5; 9.6) in the colloid group and 7.3 kPa (5.7; 9.1) in the crystalloid group (P=0.11). Postoperative surgical wound Psqo2 was 10.7 kPa (8.6; 13.4) in the colloid group and 10.1 kPa (8.1; 12.7) in the crystalloid group (P=0.68). CONCLUSIONS: Goal-directed colloid administration did not increase Psqo2 compared with goal-directed crystalloid administration in patients undergoing open abdominal surgery. CLINICAL TRIAL REGISTRATION: NCT00517127.

Perioperative Supplemental Oxygen Does Not Worsen Long-Term Mortality of Colorectal Surgery Patients.

BACKGROUND: A follow-up analysis from a large trial of oxygen and surgical-site infections reported increased long-term mortality among patients receiving supplemental oxygen, especially those having cancer surgery. Although concerning, there is no obvious mechanism linking oxygen to long-term mortality. We thus tested the hypothesis that supplemental oxygen does not increase long-term mortality in patients undergoing colorectal surgery. Secondarily, we evaluated whether the effect of supplemental oxygen on mortality depended on cancer status. METHODS: Mortality data were obtained for 927 patients who participated in 2 randomized trials evaluating the effect of supplemental oxygen on wound infection. We assessed the effect of 80% vs 30% oxygen on long-term mortality across 4 clinical sites in the 2 trials using a Cox proportional hazards regression model stratified by study and site. Kaplan-Meier survival estimates were calculated for each trial. Finally, we report site-stratified hazard ratios for patients with and without cancer at baseline. RESULTS: There was no effect of 80% vs 30% oxygen on mortality, with an overall site-stratified hazard ratio of 0.93 (95% confidence interval [CI], 0.72-1.20; P = 0.57). The treatment effect was consistent across the 2 original studies (interaction P = 0.88) and across the 4 sites (P = 0.84). There was no difference between patients with (n = 451) and without (n = 450) cancer (interaction P = 0.51), with hazard ratio of 0.85 (95% CI, 0.64-1.1) for cancer patients and 0.97 (0.53-1.8) for noncancer patients. CONCLUSIONS: In contrast to the only previous publication, we found that supplemental oxygen had no influence on long-term mortality in the overall surgical population or in patients having cancer surgery.

An acetate-buffered balanced crystalloid versus 0.9% saline in patients with end-stage renal disease undergoing cadaveric renal transplantation: a prospective randomized controlled trial.

BACKGROUND: Recent studies have shown a decline in glomerular filtration rate and increased renal vasoconstriction after administration of normal saline when compared with IV solutions with less chloride. In this study, we investigated the impact of normal saline versus a chloride-reduced, acetate-buffered crystalloid on the incidence of hyperkalemia during cadaveric renal transplantation. The incidence of metabolic acidosis and kidney function were secondary aims. METHODS: In this prospective randomized controlled trial, 150 patients received normal saline or an acetate-buffered balanced crystalloid during and after cadaveric renal transplantation. Venous blood gases were obtained at the start of anesthesia and every 30 minutes until discharge from the postoperative surveillance unit. Serum creatinine and 24-hour urine output were obtained on postoperative days 1, 3, and 7. RESULTS: Patients received a similar amount of fluid (median: 2625mL [interquartile range: 2000 to 3100] vs 2500 mL [2000 to 3050], P = 0.83). Hyperkalemia, defined as serum potassium >5.9 mmol/L, occurred in 13 patients (17%) in the saline and 15 (21%) in the balanced group (P = 0.56; difference between proportions -0.037 [-16.5% to 8.9%]). Minimum base excess was lower in the saline group compared with the balanced regimen (-4.5 mmol/L [-6 to -2.4] vs -2.6 mmol/L [-4 to -1], P < 0.001) and maximum chloride was significantly higher in the saline group (109 mmol/L [107 to 111] vs 107 mmol/L [105 to 109], P < 0.001). No difference in creatinine or urine output was seen postoperatively. Significantly more patients needed catecholamines in the saline group (30% vs 15%, P = 0.03). CONCLUSIONS: The incidence of hyperkalemia differed by less than 17% between groups. Use of balanced crystalloid resulted in less hyperchloremia and metabolic acidosis. Significantly more patients in the saline group required administration of catecholamines for circulatory support.

The effect of goal-directed crystalloid versus colloid administration on postoperative spirometry parameters: a substudy of a randomized controlled clinical trial.

BACKGROUND: Pulmonary function is impaired after major abdominal surgery and might be less impaired by restrictive fluid administration. Under the assumption of a fluid-sparing effect of colloids, we tested the hypothesis that an intraoperative colloid-based goal-directed fluid management strategy impairs postoperative pulmonary function parameters less compared to goal-directed crystalloid administration. METHODS: We performed a preplanned, single-center substudy within a recently published trial evaluating the effect of goal-directed crystalloids versus colloids on a composite of major complications. Sixty patients undergoing major open abdominal surgery were randomized to Doppler-guided intraoperative fluid replacement therapy with lactated Ringer's solution (n = 31) or unbalanced 6% hydroxyethyl starch 130/0.4 (n = 29). A blinded investigator performed bedside spirometry (Spirobank-G, Medical International Research, Rome, Italy) preoperatively as well as 6, 24, and 48 h postoperatively. RESULTS: Median total intraoperative fluid requirements were significantly higher during crystalloid administration compared to patients receiving colloids (4567 ml vs. 3044 ml, p = 0.01). Six hours after surgery, pulmonary function parameters did not differ significantly between the crystalloid - and the colloid group: forced vital capacity (FVC): 1.6 l (1.2-2 l) vs. 1.9 l (1.5-2.4 l), p = 0.15; forced expiratory volume in 1 second (FEV1): 1.1 l (0.9-1.6 l) vs. 1.4 l (1.2-1.7 l), p = 0.18; and peak expiratory flow (PEF): 2 l.sec-1 (1.5 - 3.6 l.sec -1) vs. 2.3 l.sec -1 (1.8 - 3.4 l.sec -1), p = 0.23. Moreover, postoperative longitudinal time × group interactions of FVC, FEV1, and PEF between 6 and 48 postoperative hours did not differ significantly. CONCLUSION: Postoperative pulmonary function parameters were similarly impaired in patients receiving goal-directed crystalloid administration as compared to goal-directed colloid administration during open abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT00517127 , registered on August 16, 2007) and EudraCT (2005-004602-86).

Desflurane Versus Sevoflurane and Postoperative Cardiac Biomarkers in Older Adults Undergoing Low- to Moderate-Risk Noncardiac Surgery-Secondary Analysis of a Prospective, Observer-Blinded, Randomized Clinical Trial.

Background/Objectives: Previous preclinical studies have shown that desflurane might have the most significant cardioprotective effect of all volatile anesthetics. However, data regarding the cardioprotective effects of desflurane versus sevoflurane are lacking. Therefore, we evaluated the effect of the maintenance of anesthesia using desflurane versus sevoflurane on the postoperative maximum concentrations of cardiac biomarkers in older adults undergoing low- to moderate-risk noncardiac surgery. Methods: In this secondary analysis of a prospective randomized trial, we included all 190 older adults undergoing low- to moderate-risk noncardiac surgery. Patients were randomized to receive desflurane or sevoflurane for the maintenance of anesthesia. We administered desflurane or sevoflurane, aiming at a BIS value of 50 ± 5. The cardiac-specific biomarkers included troponin T, NT-proBNP, and copeptin, which were measured preoperatively, within one hour after surgery, and on the second postoperative day. Results: There were no significant differences between the desflurane and sevoflurane groups in the postoperative maximum concentrations of troponin T (11 ng.L-1 [8; 16] versus 13 ng.L-1 [9; 18]; p = 0.595), NT-proBNP (196 pg.mL-1 [90; 686] versus 253 pg.mL-1 [134; 499]; p = 0.288), or copeptin (19 pmol.L-1 [7; 58] versus 12 pmol.L-1 [6; 41]; p = 0.096). We also observed no significant differences in the troponin T, NT-proBNP, or copeptin concentrations between the desflurane and sevoflurane groups at any measured timepoint (all p > 0.05). Conclusions: In contrast to preclinical studies, we did not observe a significant difference in the postoperative maximum concentrations of cardiac biomarkers. It seems likely that desflurane does not exert significant clinical meaningful cardioprotective effects in older adults. Thus, our results do not support the use of desflurane in patients undergoing low- to moderate-risk noncardiac surgery.

Desflurane versus sevoflurane anesthesia and postoperative recovery in older adults undergoing minor- to moderate-risk noncardiac surgery - A prospective, randomized, observer-blinded, clinical trial.

STUDY OBJECTIVE: The effect of volatile anesthetics on postoperative recovery in older adults is still not entirely clear. Thus, we evaluated the effect of desflurane versus sevoflurane anesthesia on speed of postoperative recovery in older adults eligible for same-day discharge. We further evaluated the incidence of postoperative nausea and vomiting (PONV), bispectral index (BIS) values, and S100B concentrations. DESIGN: Single-center, prospective, observer-blinded, randomized clinical trial. SETTING: Operating room. PATIENTS: 190 patients ≥65 years of age and scheduled for minor- to moderate-risk noncardiac surgeries. INTERVENTIONS: Goal-directed administration of desflurane versus sevoflurane for maintenance of anesthesia with an intraoperative goal of BIS 50 ± 5. MEASUREMENTS: The primary outcome was the time to anesthesia recovery, which was defined as the time between arrival at the post-anesthesia care unit (PACU) and reaching criteria for discharge from PACU, based on modified Aldrete score ≥ 12 points. Modified Aldrete scores were assessed at PACU arrival and thereafter in five-minute intervals. PONV was evaluated during PACU stay and the first three postoperative days, BIS values were recorded during PACU stay, and S100B values were measured before and after surgery, and on the second postoperative day. MAIN RESULTS: 95 patients were randomized to receive desflurane, and 95 patients to receive sevoflurane. We did not observe a significant difference in median duration of postoperative recovery between the groups (desflurane: 0 min [0;0]; sevoflurane: 0 min [0;0]; p = 0.245). 77 patients (81.1%) in the desflurane group and 84 patients (88.4%) in the sevoflurane group already had Aldrete scores ≥12 points upon arrival at PACU (p = 0.277). There was also no significant difference in the incidences of PONV (p = 0.606), postoperative BIS values (p = 0.197), and postoperative maximum S100B concentrations (p = 0.821) between the groups. CONCLUSIONS: Despite previous reports, we did not observe significant faster recovery times after desflurane anesthesia. Both volatile anesthetics may be appropriate for same-day discharge in older adults.

PerIoperative iNflammatory reSponse assessment In hiGH-risk patienTs undergoing non-cardiac surgery (INSIGHT): study protocol of a prospective non-interventional observational study.

INTRODUCTION: Increased inflammatory processes after non-cardiac surgery are very common. The association between postoperative inflammation and the occurrence of cardiovascular complications after non-cardiac surgery are still not entirely clear. Therefore, we will evaluate the association between postoperative inflammation and the occurrence of major cardiovascular complications in patients at-risk for cardiovascular complications undergoing non-cardiac surgery. We will further evaluate the association of postoperative inflammation and days-at-home within 30 days after surgery (DAH30), the incidence of acute kidney injury, postoperative N-terminal probrain natriuretic peptide (NT-proBNP) concentrations and neurocognitive decline. METHODS AND ANALYSIS: In this multicentre study, we will include 1400 patients at-risk for cardiovascular complications undergoing non-cardiac surgery. Our primary aim is to evaluate the association of postoperative maximum C-reactive protein concentration and the occurrence of a composite of five major cardiovascular complications (myocardial infarction, myocardial injury after non-cardiac surgery, new onset of atrial fibrillation, stroke and death) within 30 days after surgery using a Mann-Whitney-U test as well as a logistic regression model. As our secondary aim, we will evaluate the association of a composite of three inflammatory biomarkers (interleukin 6, procalcitonin and copeptin) on the occurrence of our composite of five cardiovascular complications within 30 days and 1 year after surgery, acute kidney injury, DAH30 and NT-proBNP concentrations using linear or logistic regression models. We will measure inflammatory biomarkers before surgery, and on the first, second, third and fifth postoperative day. We will check medical records and conduct a telephone survey 30 days and 1 year after surgery. We evaluate neurocognitive function, using a Montreal Cognitive Assessment, before and 1 year after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees at the Medical University of Vienna (2458/2020) and at the Medical University of Graz (33-274 ex 20/21). TRIAL REGISTRATION NUMBER: NCT04753307.

Effect of Supplemental Oxygen on von Willebrand Factor Activity and Ristocetin Cofactor Activity in Patients at Risk for Cardiovascular Complications Undergoing Moderate-to High-Risk Major Noncardiac Surgery-A Secondary Analysis of a Randomized Trial.

Increased von Willebrand Factor (vWF) activity mediates platelet adhesion and might be a contributor to the development of thrombotic complications after surgery. Although in vitro studies have shown that hyperoxia induces endovascular damage, the effect of perioperative supplemental oxygen as a possible trigger for increased vWF activity has not been investigated yet. We tested our primary hypothesis that the perioperative administration of 80% oxygen concentration increases postoperative vWF activity as compared to 30% oxygen concentration in patients at risk of cardiovascular complications undergoing major noncardiac surgery. A total of 260 patients were randomly assigned to receive 80% versus 30% oxygen throughout surgery and for two hours postoperatively. We assessed vWF activity and Ristocetin cofactor activity in all patients shortly before the induction of anesthesia, within two hours after surgery and on the first and third postoperative day. Patient characteristics were similar in both groups. We found no significant difference in vWF activity in the overall perioperative time course between both randomization groups. We observed significantly increased vWF activity in the overall study population throughout the postoperative time course. Perioperative supplemental oxygen showed no significant effect on postoperative vWF and Ristocetin cofactor activity in cardiac risk patients undergoing major noncardiac surgery. In conclusion, we found no significant influence of supplemental oxygen in patients undergoing major non-cardiac surgery on postoperative vWF activity and Ristocetin cofactor activity.

Hemodynamic effects of intraoperative 30% versus 80% oxygen concentrations: an exploratory analysis.

Background: Supplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate. Methods: We present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO2 of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate. Results: There was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate -0.16 mmHg, CI -1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min-1 [58, 72], and in the 30% oxygen group: 64 beats.min-1 [58; 70]; effect estimate: 0.12 beats.min-1, CI -2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected. Conclusion: In contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients. Clinical Trail Registration: https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

Prognostic significance of mean corpuscular volume in patients with pancreatic ductal adenocarcinoma and multimodal treatment.

AIM OF THE STUDY: Mean corpuscular volume (MCV) has shown mounting evidence as a prognostic indicator in a number of malignancies. The aim of this study was to examine the prognostic potential of pretherapeutic MCV among patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection after neoadjuvant treatment (NT). PATIENTS AND METHODS: Consecutive patients with PDAC who underwent pancreatic resection between 1997 and 2019 were included in this study. Neoadjuvantly treated patients' serum MCV was measured before NT and before surgery. In patients undergoing upfront resection serum MCV was measured before surgery. Median MCV values were used as cut-off to distinguish high from low MCV values. RESULTS: Five hundred and forty-nine (438 upfront resected and 111 neoadjuvantly treated) patients were included in this study. Multivariate analysis revealed, that high MCV before and after NT, were independent negative prognostic factors for overall survival (P<0.01, respectively). Furthermore, the median MCV value from before to after NT increased significantly (P<0.001, Wilcoxon signed-rank test) and was (P=0.03, Wilcoxon rank sum test) associated with tumor response to NT. CONCLUSION: High MCV is an independent adverse prognostic factor in patients with resectable neoadjuvantly treated PDAC and may qualify as useful indicator to help physicians to provide personalized prognostication.

Perioperative supplemental oxygen and oxidative stress in patients undergoing moderate- to high-risk major abdominal surgery - A subanalysis of randomized clinical trial.

STUDY OBJECTIVE: Oxidative stress plays a pivotal role in the development and aggravation of cardiovascular diseases. The influence of intraoperative inspired oxygen concentrations on oxidative stress is still not entirely known. Therefore, we evaluated in this sub-study if supplemental oxygen affects the oxidation-reduction potential in patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. DESIGN: Sub-study of a prospective parallel-arm double-blinded single-center superiority randomized trial. SETTING: Operating room and postoperative recovery area. INTERVENTION: Administration of 0.8 FiO2 versus 0.3 FiO2 throughout surgery and for the first two postoperative hours. MEASUREMENTS: The primary outcome was the static oxidation-reduction potential (sORP) and the oxidation-reduction potential capacity (cORP) between both groups. The secondary outcome was the trend of sORP and cORP in the overall study population. We assessed sORP and cORP before induction of anesthesia, 2 h after induction of anesthesia, within 2 h after surgery and on the first and third postoperative day. MAIN RESULTS: 258 patients were analyzed. 128 patients were randomly assigned to the 80% oxygen group and 130 patients were randomly assigned to the 30% oxygen group. Postoperative sORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: -1.162 mV,95% CI: -2.584 to 0.260; p = 0.109). On average, we observed a change in sORP of 5.288 mV (95% CI:4.633 to 5.913, p < 0.001) per day. cORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: -0.015µC, (95%CI: -0.062 to 0.032; p = 0.524). On average, we observed a change in cORP values of -0.170µC (95%CI: -0.194 to -0.147, p < 0.001) per day. CONCLUSION: In contrast to previous reports, we could not find any evidence of an association between intraoperative supplemental oxygen and perioperative oxidative stress assessed by sORP and cORP. TRIAL REGISTRATION: clinicaltrials.gov: NCT03366857https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

Perioperative Supplemental Oxygen and Postoperative Copeptin Concentrations in Cardiac-Risk Patients Undergoing Major Abdominal Surgery-A Secondary Analysis of a Randomized Clinical Trial.

Noncardiac surgery is associated with hemodynamic perturbations, fluid shifts and hypoxic events, causing stress responses. Copeptin is used to assess endogenous stress and predict myocardial injury. Myocardial injury is common after noncardiac surgery, and is often caused by myocardial oxygen demand-and-supply mismatch. In this secondary analysis, we included 173 patients at risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. Patients were randomly assigned to receive 80% or 30% oxygen throughout surgery and the first two postoperative hours. We evaluated the effect of supplemental oxygen on postoperative Copeptin concentrations. Copeptin concentrations were measured preoperatively, within two hours after surgery, on the first and third postoperative days. In total, 85 patients received 0.8 FiO2, and 88 patients received 0.3 FiO2. There was no significant difference in postoperative Copeptin concentrations between both study groups (p = 0.446). Copeptin increased significantly within two hours after surgery, compared with baseline in the overall study population (estimated effect: −241.7 pmol·L−1; 95% CI −264.4, −219.1; p < 0.001). Supplemental oxygen did not significantly attenuate postoperative Copeptin release. Copeptin concentrations showed a more immediate postoperative increase compared with previously established biomarkers. Nevertheless, Copeptin concentrations did not surpass Troponin T in early determination of patients at risk for developing myocardial injury after noncardiac surgery.

Perioperative Supplemental Oxygen and Plasma Catecholamine Concentrations after Major Abdominal Surgery-Secondary Analysis of a Randomized Clinical Trial.

Perioperative stress is associated with increased sympathetic activity that leads to increases in heart rate and blood pressure, which are associated with the development of perioperative myocardial ischemia. In healthy volunteers, it was shown that the administration of supplemental oxygen attenuated sympathetic nerve activity and subsequently led to lower plasma catecholamine concentrations. We therefore tested the hypothesis that perioperative supplemental oxygen attenuates sympathetic nerve in patients at risk for cardiovascular complications undergoing major abdominal surgery. We randomly assigned 81 patients to receive either 80% or 30% inspired oxygen concentration throughout surgery and the first two postoperative hours. We assessed noradrenaline, adrenaline, and dopamine plasma concentrations before the induction of anesthesia, two hours after surgery and on the third postoperative day. There was no significant difference in postoperative noradrenaline (effect estimated: -41.5 ng·L-1, 95%CI -134.3, 51.2; p = 0.38), adrenaline (effect estimated: 11.2 ng·L-1, 95%CI -7.6, 30.1; p = 0.24), and dopamine (effect estimated: -1.61 ng·L-1, 95%CI -7.2, 3.9; p = 0.57) concentrations between both groups. Based on our results, it seems unlikely that supplemental oxygen influences endogenous catecholamine release in the perioperative setting.