Performance and usability of pre-operative prediction models for 30-day peri-operative mortality risk: a systematic review.

Estimating pre-operative mortality risk may inform clinical decision-making for peri-operative care. However, pre-operative mortality risk prediction models are rarely implemented in routine clinical practice. High predictive accuracy and clinical usability are essential for acceptance and clinical implementation. In this systematic review, we identified and appraised prediction models for 30-day postoperative mortality in non-cardiac surgical cohorts. PubMed and Embase were searched up to December 2022 for studies investigating pre-operative prediction models for 30-day mortality. We assessed predictive performance in terms of discrimination and calibration. Risk of bias was evaluated using a tool to assess the risk of bias and applicability of prediction model studies. To further inform potential adoption, we also assessed clinical usability for selected models. In all, 15 studies evaluating 10 prediction models were included. Discrimination ranged from a c-statistic of 0.82 (MySurgeryRisk) to 0.96 (extreme gradient boosting machine learning model). Calibration was reported in only six studies. Model performance was highest for the surgical outcome risk tool (SORT) and its external validations. Clinical usability was highest for the surgical risk pre-operative assessment system. The SORT and risk quantification index also scored high on clinical usability. We found unclear or high risk of bias in the development of all models. The SORT showed the best combination of predictive performance and clinical usability and has been externally validated in several heterogeneous cohorts. To improve clinical uptake, full integration of reliable models with sufficient face validity within the electronic health record is imperative.

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.

Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass. METHODS: Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs. RESULTS: The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P<0.001 vs baseline], whereas this reduction was not seen in the imatinib group. In the control group, the number of perfused capillaries remained low throughout the experiment, whilst perfusion remained normal after imatinib administration. Microvascular oxygen saturation was less impaired after imatinib treatment compared with controls. Imatinib reduced vascular leakage and decreased fluid resuscitation compared with control [3 (3-6) vs 12 ml (7-16); P=0.024]. Plasma neutrophil-gelatinase-associated-lipocalin concentrations were reduced by imatinib. CONCLUSIONS: Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib-induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers.

Choice of fluid type: physiological concepts and perioperative indications.

The consensus that i.v. resuscitation fluids should be considered as drugs with specific dose recommendations, contraindications, and side-effects has led to an increased attention for the choice of fluid during perioperative care. In particular, the debate concerning possible adverse effects of unbalanced fluids and hydroxyethyl starches resulted in a re-evaluation of the roles of different fluid types in the perioperative setting. This review provides a concise overview of the current knowledge regarding the efficacy and safety of distinct fluid types for perioperative use. First, basic physiological aspects and possible side-effects are explained. Second, we focus on considerations regarding fluid choice for specific perioperative indications based on an analysis of available randomized controlled trials.

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.