Description

This project is based on a predictive alghorithm (Multifactorial Dynamic Perfusion Index-MDPI) already published and covered by a patent. The MDPI is based on a dynamic collection of 7 different variables during cardiopulmonary bypass (CPB) and provides a probability index for postoperative acute kidney injury. Multicenter observational prospective trial developed through 3 work packages, addressing (1) external validation of the MDPI in a series of 800 adult cardiac surgery patients collected in 2 Institutions (2) development of a novel MDPI to be applied in infants < 20 kg undergoing cardiac surgery (200 patients) and (3) verification of of other possible outcomes that may be predicted by the MDPI. Since many of the predictive variables are modifiable by the perfusionist/anesthesiologist during CPB, it is a tool that allows therapeutic manouvres. Ultimately, the MDPI will be incorporated in a dedicated monitor to provide an on-line "flight control" during CPB. Cardiac surgery associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications, associated with an increased mortality risk. Several risk scores for CSA-AKI exist. They are based on preoperative risk factors and severity of the procedure. They define a static risk (SR) based on non-modifiable risk factors. As so, they do not consider intraoperative variables, that include potentially modifiable risk factors (dynamic risk, DR). In a previous study we have developed a new model for prediction of CSA-AKI that is inclusive of the SR and the DR, producing the Multifactorial Dynamic Perfusion Index (MDPI). The MDPI is based on 7 factors collected during cardiopulmonary bypass (CPB): oxygen delivery time spent on a low oxygen delivery, hematocrit, time on CPB, mean arterial pressure, transfusions and lactate values. The MDPI showed a better discrimination (AUC 0.769) than the other existing models, and a good calibration until a risk of 60%. Of notice 5 out of the 7 predictors composing the MDPI are modifiable risk factors and therefore can be considered as a ¿flight control¿, on-line measure of the quality of perfusion, to prompt interventions by the perfusionist and the anesthesiologist. The MDPI is covered by an Italian patent (n. 102022000012893) owned by the IRCCS Policlinico San Donato with Marco Ranucci as inventor. The patent covers the inclusion of the MDPI into a dedicated monitor collecting the variables on CPB and producing the MDPI. The activities are separated into 3 work-packages (WP).

WP 1: The MDPI has been developed in a single Institution. Additionally, its validation was performed on the same development series using a bootstrap technique. To make this algorithm exportable in different Institutions, a different new series of patients is required (internal validation) and a new series collected in an external Institution (external validation). Additionally, it cannot be excluded that additional risk factors may be identified and included in the MDPI algorithm; moreover, there is the hypothesis that other outcome measures of morbidity and even mortality may be predicted by the MDPI. WP 1 includes the operative Units 1 and 2 and is based on the collection of a new series of consecutive adult patients requiring cardiac surgery with CPB. The study protocol has been already submitted to the Ethics Committee (166/int/2022) and Clinical Trial. Gov for the internal validation at the operative unit 1 and includes 400 patients. An additional amount of 400 patients will be collected at the operative unit 2. In this series, the MDPI parameters will be collected and assessed for discrimination and calibration properties in predicting CSA-AKI (defined as AKI of any kind, AKI stage and AKI stage 2 or greater). Appropriate tools will be applied to define discrimination (ROC analysis) and calibration (calibration plot using LOWESS) properties of the MDPI. This WP is essentially a validation of the existing MDPI as patented by IRCCS Policlinico San Donato WP2: The MDPI has been develop in the adult patient population. There is little information available in the literature about the CSA-AKI risk factors in infants and newborns weighing < 20 kgs. However, CSA-AKI in this segment of population is present at a rate that is equal or even higher than in the adults. It can be hypothesized that above 20 kgs, the patient is probably comparable to the adult patient, whereas there is a gap in knowledge in infants and newborns. WP2 is intended to cover this gap in knowledge by addressing a series of 200 patients weighing < 20 kgs and receiving cardiac surgery with CPB for palliation or correction of congenital heart defects, producing an MDPI for infants (I MDPI). This WP will be totally performed at the operative unit 2, that is the largest congenital heart center in Italy. A new patent on the I-MDPI is anticipated.

WP3: This WP is based on the same patient population of WP 1, but has a complementary aim. It is in fact possible that (a) other factors apart from the seven included in the MDPI may be associated with CSA-AKI, therefore deserving to be included in the model (MDPI 2.0) and (b) other outcomes, and namely 30-days mortality may be predicted by the MDPI. Once defined these aims, this WP (that includes the 2 operative units) includes the preliminary steps for the implementation of the MDPI into existing or newly developed monitoring systems for CPB. Dedicated patents are anticipated for MDPI 2.0.