Volatile Anesthetics versus Propofol for Cardiac Surgery with Cardiopulmonary Bypass: Meta-analysis of Randomized Trials.

BACKGROUND: The aim of this systematic review and meta-analysis was to assess the effect of anesthesia maintenance with volatile agents compared with propofol on both short- and long-term mortality (primary outcomes) and major clinical events in adults undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Randomized clinical trials on the effects of current volatile anesthetics versus propofol in adults undergoing cardiac surgery with cardiopulmonary bypass were searched (1965 to September 30, 2019) in PubMed, the Cochrane Library, and article reference lists. A random effect model on standardized mean difference for continuous outcomes and odds ratio for dichotomous outcomes were used to meta-analyze data. RESULTS: In total, 37 full-text articles (42 studies, 8,197 participants) were included. The class of volatile anesthetics compared with propofol was associated with lower 1-yr mortality (5.5 vs. 6.8%; odds ratio, 0.76 [95% CI, 0.60 to 0.96]; P = 0.023), myocardial infarction (odds ratio, 0.60 [95% CI, 0.39 to 0.92]; P = 0.023), cardiac troponin release (standardized mean difference, -0.39 [95% CI, -0.59 to -0.18], P = 0.0002), need for inotropic medications (odds ratio, 0.40 [95% CI, 0.24 to 0.67]; P = 0.0004), extubation time (standardized mean difference, -0.35 [95% CI, -0.68 to -0.02]; P = 0.038), and with higher cardiac index/output (standardized mean difference, 0.70 [95% CI, 0.37 to 1.04]; P < 0.0001). The class of volatile anesthetics was not associated with changes in short-term mortality (1.63 vs. 1.65%; odds ratio, 1.04 [95% CI, 0.73 to 1.49]; P = 0.820) and acute kidney injury (odds ratio, 1.25 [95% CI, 0.77 to 2.03]; P = 0.358). CONCLUSIONS: In adults undergoing cardiac surgery with cardiopulmonary bypass, the class of volatile anesthetics was superior to propofol with regard to long-term mortality, as well as to many secondary outcomes indicating myocardial protection.

Protein-energy wasting and mortality in chronic kidney disease.

Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with an increased death risk from cardiovascular diseases. However, while even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis, PEW becomes clinically manifest at an advanced stage, early before or during the dialytic stage. Mechanisms causing loss of muscle protein and fat are complex and not always associated with anorexia, but are linked to several abnormalities that stimulate protein degradation and/or decrease protein synthesis. In addition, data from experimental CKD indicate that uremia specifically blunts the regenerative potential in skeletal muscle, by acting on muscle stem cells. In this discussion recent findings regarding the mechanisms responsible for malnutrition and the increase in cardiovascular risk in CKD patients are discussed. During the course of CKD, the loss of kidney excretory and metabolic functions proceed together with the activation of pathways of endothelial damage, inflammation, acidosis, alterations in insulin signaling and anorexia which are likely to orchestrate net protein catabolism and the PEW syndrome.

Apoptosis and myostatin mRNA are upregulated in the skeletal muscle of patients with chronic kidney disease.

Apoptosis and myostatin are major mediators of muscle atrophy and might therefore be involved in the wasting of uremia. To examine whether they are expressed in the skeletal muscle of patients with chronic kidney disease (CKD), we measured muscle apoptosis and myostatin mRNA and their related intracellular signal pathways in rectus abdominis biopsies obtained from 22 consecutive patients with stage 5 CKD scheduled for peritoneal dialysis. Apoptotic loss of myonuclei, determined by anti-single-stranded DNA antibody and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays, was significantly increased three to fivefold, respectively. Additionally, myostatin and interleukin (IL)-6 gene expressions were significantly upregulated, whereas insulin-like growth factor-I mRNA was significantly lower than in controls. Phosphorylated JNK (c-Jun amino-terminal kinase) and its downstream effector, phospho-c-Jun, were significantly upregulated, whereas phospho-Akt was markedly downregulated. Multivariate analysis models showed that phospho-Akt and IL-6 contributed individually and significantly to the prediction of apoptosis and myostatin gene expression, respectively. Thus, our study found activation of multiple pathways that promote muscle atrophy in the skeletal muscle of patients with CKD. These pathways appear to be associated with different intracellular signals, and are likely differently regulated in patients with CKD.

Amino acid and protein metabolism in the human kidney and in patients with chronic kidney disease.

The progressive loss of kidney function in patients with chronic kidney disease (CKD) is associated with a number of complications, including cardiovascular diseases, anemia, hyperparathyroidism, inflammation, metabolic acidosis, malnutrition and protein-energy wasting. The excess cardiovascular risk related to CKD is due in part to a higher prevalence of traditional atherosclerotic risk factors, in part to non-traditional, emerging risk factors peculiar to CKD. While even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis, nutritional changes are more often observed in an advanced setting. In addition, factors related to renal-replacement treatment may be implicated in the pathogenesis of heart disease and protein-energy wasting in dialysis-treated patients. Progressive alterations in kidney metabolism may cause progressive effects on cardiovascular status and nutrition. Altered kidney amino acid/protein metabolism and or excretion may be a key factor in the homeostasis of several vasoactive compounds and hormones in patients with more advanced disease. In this discussion recent research regarding the kidney handling of amino acids and protein turnover and their potential link with cardiovascular disease, progressive kidney dysfunction and nutritional status are reviewed.