Intraoperative measurement of the respiratory exchange ratio predicts postoperative complications after liver transplantation

Background: During surgery, any mismatch between oxygen delivery (DO2) and consumption (VO2) can promote the development of postoperative complications. The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide (CO2) production (VCO2) to VO2, may be a useful noninvasive tool for detecting inadequate DO2. The primary objective of this study was to test the hypothesis that RER measured during liver transplantation may predict postoperative morbidity. Secondary objectives were to assess the ability of other variables used to assess the DO2/VO2 relationship, including arterial lactate, mixed venous oxygen saturation, and veno-arterial difference in the partial pressure of carbon dioxide (VAPCO2gap), to predict postoperative complications. Methods: This retrospective study included consecutive adult patients who underwent liver transplantation for end stage liver disease from June 27th, 2020, to September 5th, 2021. Patients with acute liver failure were excluded. All patients were routinely equipped with a pulmonary artery catheter. The primary analysis was a receiver operating characteristic (ROC) curve constructed to investigate the discriminative ability of the mean RER measured during surgery to predict postoperative complications. RER was calculated at five standardized time points during the surgery, at the same time as measurement of blood lactate levels and arterial and mixed venous blood gases, which were compared as a secondary analysis. Results: Of the 115 patients included, 57 developed at least one postoperative complication. The mean RER (median [25–75] percentiles) during surgery was significantly higher in patients with complications than in those without (1.04[0.96–1.12] vs 0.88[0.84–0.94]; p < 0.001). The area under the ROC curve was 0.87 (95%CI: 0.80–0.93; p < 0.001) with a RER value (Youden index) of 0.92 giving a sensitivity of 91% and a specificity of 74% for predicting the occurrence of postoperative complications. The RER outperformed all other measured variables assessing the DO2/VO2 relationship (arterial lactate, SvO2, and VAPCO2gap) in predicting postoperative complications. Conclusion: During liver transplantation, the RER can reliably predict postoperative complications. Implementing this measure intraoperatively may provide a warning for physicians of impending complications and justify more aggressive optimization of oxygen delivery. Further studies are required to determine whether correcting the RER is feasible and could reduce the incidence of complications.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Intraoperative measurement of the respiratory exchange ratio predicts postoperative complications after liver transplantation

Abstract Background During surgery, any mismatch between oxygen delivery (DO2) and consumption (VO2) can promote the development of postoperative complications. The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide (CO2) production (VCO2) to VO2, may be a useful noninvasive tool for detecting inadequate DO2. The primary objective of this study was to test the hypothesis that RER measured during liver transplantation may predict postoperative morbidity. Secondary objectives were to assess the ability of other variables used to assess the DO2/VO2 relationship, including arterial lactate, mixed venous oxygen saturation, and veno-arterial difference in the partial pressure of carbon dioxide (VAPCO2gap), to predict postoperative complications. Methods This retrospective study included consecutive adult patients who underwent liver transplantation for end stage liver disease from June 27th, 2020, to September 5th, 2021. Patients with acute liver failure were excluded. All patients were routinely equipped with a pulmonary artery catheter. The primary analysis was a receiver operating characteristic (ROC) curve constructed to investigate the discriminative ability of the mean RER measured during surgery to predict postoperative complications. RER was calculated at five standardized time points during the surgery, at the same time as measurement of blood lactate levels and arterial and mixed venous blood gases, which were compared as a secondary analysis. Results Of the 115 patients included, 57 developed at least one postoperative complication. The mean RER (median [25–75] percentiles) during surgery was significantly higher in patients with complications than in those without (1.04[0.96–1.12] vs 0.88[0.84–0.94]; p < 0.001). The area under the ROC curve was 0.87 (95%CI: 0.80–0.93; p < 0.001) with a RER value (Youden index) of 0.92 giving a sensitivity of 91% and a specificity of 74% for predicting the occurrence of postoperative complications. The RER outperformed all other measured variables assessing the DO2/VO2 relationship (arterial lactate, SvO2, and VAPCO2gap) in predicting postoperative complications. Conclusion During liver transplantation, the RER can reliably predict postoperative complications. Implementing this measure intraoperatively may provide a warning for physicians of impending complications and justify more aggressive optimization of oxygen delivery. Further studies are required to determine whether correcting the RER is feasible and could reduce the incidence of complications

Native Chemical Ligation via N-Acylurea Thioester Surrogates Obtained by Fmoc Solid-Phase Peptide Synthesis

Native chemical ligation (NCL) enables the direct chemical synthesis and semisynthesis of proteins of different sizes and compositions, streamlining the access to proteins containing posttranslational modifications (PTMs). NCL assembles peptide fragments through the chemoselective reaction of a C-terminal α-thioester peptide, prepared either by chemical synthesis or via intein-splicing technology, and a recombinant or synthetic peptide containing an N-terminal Cys. Whereas the generation of C-terminal α-thioester proteins can be achieved via the recombinant fusion of the sequence of interest to an intein domain, chemical methods can also be used for synthetically accessible proteins. The use of Fmoc solid-phase peptide synthesis (Fmoc-SPPS) to obtain α-thioester peptides requires the development of novel strategies to overcome the lability of the thioester bond toward piperidine Fmoc-removal conditions. These new synthetic methods enable the easy introduction of PTMs in the thioester fragment. In this chapter, we describe an approach for the synthesis and use of C-terminal α-N-acylbenzimidazolinone (Nbz) and α-N-acyl-N′-methylbenzimidazolinone (MeNbz) peptides in NCL. Following stepwise peptide elongation, acylation with p-nitrophenylchloroformate and cyclization affords the Nbz/MeNbz peptides. The optimization of the coupling conditions allows the chemoselective incorporation of the C-terminal amino acid (aa) on the 3,4-diaminobenzoyl (Dbz) and prevents undesired diacylations of the resulting o-aminoanilide. Following synthesis, these Nbz/MeNbz peptides undergo NCL straightforwardly at neutral pH catalyzed by the presence of arylthiols. Herein, we apply the Nbz technology solid phase synthesis, NCL-mediated cyclization and folding of the heterodimeric RTD-1 defensin, an antimicrobial peptide isolated from the rhesus macaque leukocytes.This work was supported by the Spanish Ministerio de Economía y Competitividad (grants CTQ2012-31197 and RYC-2011-09001). J.P.-P. acknowledges an FPI scholarship (BES-2013-065237).Peer reviewe