Frailty as a growing challenge for anesthesiologists - results of a Dutch national survey.

BACKGROUND: Frailty is a multidimensional condition characterized by loss of functional reserve, which results in increased vulnerability to adverse outcomes following surgery. Anesthesiologists can reduce adverse outcomes when risk factors are recognized early and dedicated care pathways are operational. As the frail elderly population is growing, we investigated the perspective on the aging population, familiarity with the frailty syndrome and current organization of perioperative care for elderly patients among Dutch anesthesiologists. METHODS: A fifteen-item survey was distributed among anesthesiologists and residents during the annual meeting of the Dutch Society of Anesthesiology. The first section included questions on self-reported competence on identification of frailty, acquaintance with local protocols and attitude towards the increasing amounts of elderly patients presenting for surgery. The second part included questions on demographic features of the participant such as job position, experience and type of hospital. Answers are presented as percentages, using the total number of replies for the question per group as a denominator. RESULTS: A sample of 132 surveys was obtained. The increasing number of elderly patients was primarily perceived as challenging by 76% of respondents. Ninety-nine percent agreed that frailty should influence anesthetic management, while 85% of respondents claimed to feel competent to recognize frailty. Thirty-four percent of respondents reported the use of a dedicated pathway in the preoperative approach of frail elderly patients. However, only 30% of respondents reported to know where to find the frailty screening in the patient file and appointed that frailty is not consistently documented. Interestingly, only 43% of respondents reported adequate collaboration with geriatricians. This could include for example a standardized preoperative multidisciplinary approach or dedicated pathway for the elderly patient. CONCLUSIONS: This survey demonstrated that the increasing number of frail elderly patients is perceived as important and relevant for anesthetic management. Opportunities lie in improving the organization and effectuation of perioperative care by more consistent involvement of anesthesiologists.

Postoperative microcirculatory perfusion and endothelial glycocalyx shedding following cardiac surgery with cardiopulmonary bypass.

We investigated microcirculatory perfusion disturbances following cardiopulmonary bypass in the early postoperative period and whether the course of these disturbances mirrored restoration of endothelial glycocalyx integrity. We performed sublingual sidestream dark field imaging of the microcirculation during the first three postoperative days in patients who had undergone on-pump coronary artery bypass graft surgery. We calculated the perfused vessel density, proportion of perfused vessels and perfused boundary region. Plasma was obtained to measure heparan sulphate and syndecan-1 levels as glycocalyx shedding markers. We recruited 17 patients; the mean (SD) duration of non-pulsatile cardiopulmonary bypass was 103 (18) min, following which 491 (29) ml autologous blood was transfused through cell salvage. Cardiopulmonary bypass immediately decreased both microcirculatory perfused vessel density; 11 (3) vs. 16 (4) mm.mm-2 , p = 0.052 and the proportion of perfused vessels; 92 (5) vs. 69 (9) %, p < 0.0001. The proportion of perfused vessels did not increase after transfusion of autologous salvaged blood following cardiopulmonary bypass; 72 (7) %, p = 0.19 or during the first three postoperative days; 71 (5) %, p < 0.0001. The perfused boundary region increased after cardiopulmonary bypass; 2.2 (0.3) vs. 1.9 (0.3) µm, p = 0.037 and during the first three postoperative days; 2.4 (0.3) vs. 1.9 (0.3) µm, p = 0.003. Increased plasma heparan sulphate levels were inversely associated with the proportion of perfused vessels during cardiopulmonary bypass; R = -0.49, p = 0.02. Plasma syndecan-1 levels were inversely associated with the proportion of perfused vessels during the entire study period; R = -0.51, p < 0.0001. Our study shows that cardiopulmonary bypass-induced acute microcirculatory perfusion disturbances persist in the first three postoperative days, and are associated with prolonged endothelial glycocalyx shedding. This suggests prolonged impairment and delayed recovery of both microcirculatory perfusion and function after on-pump cardiac surgery.

Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats.

BACKGROUND: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. METHODS: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. RESULTS: CPB immediately impaired microcirculatory perfusion [5 (4-8) vs 10 (7-12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8-25) vs 7 (1-12) µg g-1, P=0.04] and lung [and 23 (13-60) vs 6 (4-16) µg g-1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6-28) µg g-1vs 23 (13-60) µg g-1, P=0.04], but not in kidney [10 (3-23) vs 12 (8-25) µg g-1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. CONCLUSIONS: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.

Endothelial hyperpermeability after cardiac surgery with cardiopulmonary bypass as assessed using an in vitro bioassay for endothelial barrier function.

BACKGROUND: The mechanisms causing increased endothelial permeability after cardiopulmonary bypass (CPB) have not been elucidated. Using a bioassay for endothelial barrier function, we investigated whether endothelial hyperpermeability is associated with alterations in plasma endothelial activation and adhesion markers and can be attenuated by the use of pulsatile flow during CPB. METHODS: Patients undergoing cardiac surgery were randomized to non-pulsatile (n=20) or pulsatile flow CPB (n=20). Plasma samples were obtained before (pre-CPB) and after CPB (post-CPB), and upon intensive care unit (ICU) arrival. Changes in plasma endothelial activation and adhesion markers were determined by enzyme-linked immunosorbent assay. Using electric cell-substrate impedance sensing of human umbilical vein endothelial monolayers, the effects of plasma exposure on endothelial barrier function were assessed and expressed as resistance. RESULTS: Cardiopulmonary bypass was associated with increased P-selectin, vascular cell adhesion molecule-1, and von Willebrand factor plasma concentrations and an increase in the angiopoietin-2 to angiopoietin-1 ratio, irrespective of the flow profile. Plasma samples obtained after CPB induced loss of endothelial resistance of 21 and 23% in non-pulsatile and pulsatile flow groups, respectively. The negative effect on endothelial cell barrier function was still present with exposure to plasma obtained upon ICU admission. The reduction in endothelial resistance after exposure to post-CPB plasma could not be explained by CPB-induced haemodilution. CONCLUSION: The change in the plasma fingerprint during CPB is associated with impairment of in vitro endothelial barrier function, which occurs irrespective of the application of a protective pulsatile flow profile during CPB. CLINICAL TRIAL REGISTRATION: NTR2940.

Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis.

INTRODUCTION: Female sex may provide a survival benefit after trauma, possibly attributable to protective effects of estrogen. This study aims to compare markers of coagulation between male and female trauma patients across different ages. METHODS: Secondary analysis of a prospective cohort study at six trauma centers. Trauma patients presenting with full trauma team activation were eligible for inclusion. Patients with a penetrating trauma or traumatic brain injury were excluded. Upon hospital arrival, blood was drawn for measurement of endothelial and coagulation markers and for rotational thromboelastometry (ROTEM) measurement.Trauma patients were divided into four categories: males <45 years, males ≥45 years, females <45 years and females ≥45 years. In a sensitivity analysis, patients between 45 - 55 years were excluded to control for menopausal transitioning. Groups were compared with a Kruskall-Wallis test with Bonferroni correction. A logistic regression was performed to assess whether the independent effect of sex and age on mortality. RESULTS: 1345 patients were available for analysis. Compared to the other groups, mortality was highest in females ≥45, albeit not independent from injury severity and shock. In the group of females ≥45 there was increased fibrinolysis, demonstrated by increased levels of plasmin-antiplasmin complexes with a concomitant decrease in α2-antiplasmin. Also, a modest decrease in coagulation factors II and X was observed. Fibrinogen levels were comparable between groups. The sensitivity analysis in 1104 patients demonstrated an independent relationship between female sex and age ≥ 55 years and mortality. ROTEM profiles did not reflect the changes in coagulation tests. CONCLUSION: Female trauma patients past their reproductive age have an increased risk of mortality compared to younger females and males, associated with augmented fibrinolysis and clotting factor consumption. ROTEM parameters did not reflect coagulation differences between groups. LEVEL OF EVIDENCE: Level III prognostic and epidemiological data.

Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification.

AIMS/HYPOTHESIS: Changes in cardiac substrate utilisation leading to altered energy metabolism may underlie the development of diabetic cardiomyopathy. We studied cardiomyocyte substrate uptake and utilisation and the role of the fatty acid translocase CD36 in relation to in vivo cardiac function in rats fed a high-fat diet (HFD). METHODS: Rats were exposed to an HFD or a low-fat diet (LFD). In vivo cardiac function was monitored by echocardiography. Substrate uptake and utilisation were determined in isolated cardiomyocytes. RESULTS: Feeding an HFD for 8 weeks induced left ventricular dilation in the systolic phase and decreased fractional shortening and the ejection fraction. Insulin-stimulated glucose uptake and proline-rich Akt substrate 40 phosphorylation were 41% (p < 0.001) and 45% (p < 0.05) lower, respectively, in cardiomyocytes from rats on the HFD. However, long-chain fatty acid (LCFA) uptake was 1.4-fold increased (p < 0.001) and LCFA esterification into triacylglycerols and phospholipids was increased 1.4- and 1.5-fold, respectively (both p < 0.05), in cardiomyocytes from HFD compared with LFD hearts. In the presence of the CD36 inhibitor sulfo-N-succinimidyloleate, LCFA uptake and esterification were similar in LFD and HFD cardiomyocytes. In HFD hearts CD36 was relocated to the sarcolemma, and basal phosphorylation of a mediator of CD36-trafficking, i.e. protein kinase B (PKB/Akt), was increased. CONCLUSIONS/INTERPRETATION: Feeding rats an HFD induced cardiac contractile dysfunction, which was accompanied by the relocation of CD36 to the sarcolemma, and elevated basal levels of phosphorylated PKB/Akt. The permanent presence of CD36 at the sarcolemma resulted in enhanced rates of LCFA uptake and myocardial triacylglycerol accumulation, and may contribute to the development of insulin resistance and diabetic cardiomyopathy.