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Endothelial dysfunction and myocardial injury after major emergency abdominal surgery: a prospective cohort study.

ABSTRACT: BACKGROUND:Preoperative endothelial dysfunction is a predictor of myocardial injury and major adverse cardiac events. Non-cardiac surgery is known to induce acute endothelial changes. The aim of this explorative cohort study was to assess the extent of systemic endothelial dysfunction after major emergency abdominal surgery and the potential association with postoperative myocardial injury. METHODS:Patients undergoing major emergency abdominal surgery were included in this prospective cohort study. The primary outcome was the change in endothelial function expressed as the reactive hyperemia index from 4-24 h after surgery until postoperative day 3-5. The reactive hyperemia index was assessed by non-invasive digital pulse tonometry. Secondary outcomes included changes in biomarkers of nitric oxide metabolism and bioavailability. All assessments were performed at the two separate time points in the postoperative period. Clinical outcomes included myocardial injury within the third postoperative day and major adverse cardiovascular events within 30?days of surgery. RESULTS:Between October 2016 and June 2017, 83 patients were included. The first assessment of the endothelial function, 4-24?h, was performed 15.8 (SD 6.9) hours after surgery and the second assessment, postoperative day 3-5, was performed 83.7 (SD 19.8) hours after surgery. The reactive hyperemia index was suppressed early after surgery and did not increase significantly; 1.64 (95% CI 1.52-177) at 4-24?h after surgery vs. 1.75 (95% CI 1.63-1.89) at postoperative day 3-5, p =?0.34. The L-arginine/ADMA ratio, expressing the nitric oxide production, was reduced in the perioperative period and correlated significantly with the reactive hyperemia index. A total of 16 patients (19.3%) had a major adverse cardiovascular event, of which 11 patients (13.3%) had myocardial injury. The L-arginine/ADMA ratio was significantly decreased at 4-24?h after surgery in patients suffering myocardial injury. CONCLUSION:This explorative pathophysiological study showed that acute systemic endothelial dysfunction was present early after major emergency abdominal surgery and remained unchanged until day 3-5 after the procedure. Early postoperative disturbances in the nitric oxide bioavailability might add to the pathogenesis of myocardial injury. This pathophysiological link should be confirmed in larger studies. TRIAL REGISTRATION:clinicaltrials.gov no. NCT03010969.

SUBMITTER: Ekeloef S

PROVIDER: S-EPMC7075012 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Endothelial dysfunction and myocardial injury after major emergency abdominal surgery: a prospective cohort study.

Ekeloef Sarah S Oreskov Jakob Ohm JO Falkenberg Andreas A Burcharth Jakob J Schou-Pedersen Anne Marie V AMV Lykkesfeldt Jens J Gögenur Ismail I

BMC anesthesiology 20200316 1

<h4>Background</h4>Preoperative endothelial dysfunction is a predictor of myocardial injury and major adverse cardiac events. Non-cardiac surgery is known to induce acute endothelial changes. The aim of this explorative cohort study was to assess the extent of systemic endothelial dysfunction after major emergency abdominal surgery and the potential association with postoperative myocardial injury.<h4>Methods</h4>Patients undergoing major emergency abdominal surgery were included in this prospec ...[more]

PMID: 32178626

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Project description:BackgroundMajor abdominal surgery is associated with endothelial glycocalyx disruption. The anti-inflammatory effects of lidocaine were recently associated with endothelial barrier protection.MethodsThis was a single-centre, parallel group, randomized, controlled, double blind, pilot trial. Forty adult patients scheduled for major abdominal surgery were included between December 2016 and March 2017 in the setting of a University Hospital in Brussels (Belgium); reasons for non-inclusion were planned liver resection and conditions associated to increased risk of local anesthetics systemic toxicity. Patients were randomized to receive either lidocaine by continuous intravenous administration or an equivalent volume of 0.9% saline. The primary endpoint was the postoperative syndecan-1 concentration (difference between groups). Near-infrared spectroscopy of the thenar eminence in association with the vascular occlusion test, and contemporary analysis of flow-mediated dilation of the brachial artery were the secondary outcomes, along with haemodynamic data. Blood samples and data were collected before surgery (T0), and at 1-3 h (T1) and 24 h (T2) post-surgery.ResultsSyndecan-1 concentration increased significantly post-surgery (P < 0.001), but without any difference between groups. The near-infrared spectroscopy-derived and flow-mediated dilation-derived variables showed minor changes unrelated to group assignment. Compared with the placebo group, the intervention group had a significantly lower peri-operative mean arterial pressure and cardiac index, despite equally conducted goal-directed haemodynamic management. Postoperative lactate concentrations were similar between groups.ConclusionsLidocaine failed to have any effect on endothelial function. Since in comparisons to other types of clinical situations, syndecan-1 was only slightly upregulated, endothelial dysfunction after major abdominal surgery might be overestimated.Trial registration« ISRCTN Registry » identifier: ISRCTN63417725. Date: 15/06/2020. Retrospectively registered.

Project description:BackgroundCardiac surgery is known to induce acute endothelial dysfunction, which may be central to the pathophysiology of postoperative complications. Preoperative endothelial dysfunction could also be implicated in the pathophysiology of postoperative complications after cardiac surgery. However, the relationship between preoperative endothelial function and postoperative outcomes remains unknown. The primary objective was to describe the relationship between a preoperative microcirculatory dysfunction identified by iontophoresis of acetylcholine (ACh), and postoperative organ injury in patients scheduled for cardiac surgery using cardiopulmonary bypass (CPB).MethodsSixty patients undergoing elective cardiac surgery using CPB were included in the analysis of a prospective, observational, single-center cohort study conducted from January to April 2019. Preoperative microcirculation was assessed with reactivity tests on the forearm (iontophoresis of ACh and nitroprusside). Skin blood flow was measured by laser speckle contrast imaging. Postoperative organ injury, the primary outcome, was defined as a Sequential Organ Failure Assessment score (SOFA) 48 h after surgery greater than 3.ResultsOrgan injury at 48 h occurred in 29 cases (48.3%). Patients with postoperative organ injury (SOFA score > 3 at 48 h) had a longer time to reach the peak of preoperative iontophoresis of acetylcholine (133 s [104-156] vs 98 s [76-139] than patients without, P = 0.016), whereas endothelium-independent vasodilation to nitroprusside was similar in both groups. Beyond the proposed threshold of 105 s for time to reach the peak of preoperative endothelium-dependent vasodilation, three times more patients presented organ dysfunction at 48 h (76% vs 24% below or equal 105 s). In multivariable model, the time to reach the peak during iontophoresis of acetylcholine was an independent predictor of postoperative organ injury (odds ratio = 4.81, 95% confidence interval [1.16-19.94]; P = 0.030).ConclusionsPatients who postoperatively developed organ injury (SOFA score > 3 at 48 h) had preoperatively a longer time to reach the peak of endothelium-dependent vasodilation. Trial registration Clinical-Trials.gov, NCT03631797. Registered 15 August 2018, https://clinicaltrials.gov/ct2/show/NCT03631797.

Project description:BackgroundElevated plasma or serum troponin, indicating perioperative myocardial injury (PMI), is common after noncardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident.MethodsWe performed a nested case control study of samples obtained before and after noncardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with or without PMI, matched for age, gender, and comorbidity. Real-time polymerase chain reaction quantified (qRT-PCR) relative microRNA expression (cycle quantification [Cq] threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq 500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO).ResultsMicroRNAs were detectable in all 59 patients (median age 67 yr [61-75]; 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, serum microRNA expression increased after surgery (mean fold-change) hsa-miR-1-3p: 3.99 (95% confidence interval [CI: 1.95-8.19]; hsa-miR-133-3p: 5.67 [95% CI: 2.94-10.91]; P<0.001). These changes were not associated with PMI. Bioinformatic analysis of differentially expressed microRNAs from cohorts one (n=48) and two (n=11) identified pathways associated with adrenergic stress and calcium dysregulation, rather than ischaemia.ConclusionsCirculating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury.

Project description:ObjectivesTo quantify preoperative illness burden in older adults undergoing emergency major abdominal surgery (EMAS), to examine the association between illness burden and postoperative outcomes, and to describe end-of-life care in the year after discharge.DesignRetrospective study using data from Health and Retirement Study interviews linked to Medicare claims (2000-2012).SettingNational population-based dataset.ParticipantsMedicare beneficiaries who underwent EMAS.MeasurementsHigh illness burden, defined as ≥2 of the following vulnerabilities: functional dependence, dementia, use of helpers, multimorbidity, poor prognosis, high healthcare utilization. In-hospital outcomes were complications and mortality. Postdischarge outcomes included emergency department (ED) visits, hospitalization, intensive care unit (ICU) stay, and 365-day mortality. For individuals discharged alive who died within 365 days of surgery, outcomes included hospice use, hospitalization, ICU use, and ED use in the last 30 days of life. Multivariable regression was used to determine the association between illness burden and outcomes.ResultsOf 411 participants, 57% had high illness burden. More individuals with high illness burden had complications (45% vs 28% p=0.00) and in-hospital death (20% vs 9%, p=0.00) than those without. After discharge (n=349), individuals with high illness burden experienced more ED visits (57% vs 46%, P=.04) and were more likely to die (35% vs 13%, p=0.00). Of those who died after discharge (n=86), 75% had high illness burden, median survival was 67 days (range 21-141 days), 48% enrolled in hospice, 32% died in the hospital, 23% were in the ICU in the last 30 days of life and 37% had an ED visit in the last 30 days of life.ConclusionMost older adults undergoing EMAS have preexisting high illness burden and experience high mortality and healthcare use in the year after surgery, particularly near the end of life. Concurrent surgical and palliative care may improve quality of life and end-of-life care in these people. J Am Geriatr Soc 66:2072-2078, 2018.

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Endothelial dysfunction and myocardial injury after major emergency abdominal surgery: a prospective cohort study.

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Endothelial dysfunction and myocardial injury after major emergency abdominal surgery: a prospective cohort study.

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