Potential of Urine Biomarkers CHI3L1, NGAL, TIMP-2, IGFBP7, and Combinations as Complementary Diagnostic Tools for Acute Kidney Injury after Pediatric Cardiac Surgery: A Prospective Cohort Study.

Acute kidney injury (AKI) is common after pediatric cardiac surgery (CS). Several urine biomarkers have been validated to detect AKI earlier. The objective of this study was to evaluate urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® as predictors for AKI ≥ 1 in pediatric CS after 48 h and AKI ≥ 2 after 12 h. Pediatric patients (age < 18 year; body weight ≥ 2 kg) requiring CS were prospectively included. Urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® were measured during surgery and intensive care unit (ICU) stay and corrected for urine dilution. One hundred and one pediatric patients were included. AKI ≥ 1 within 48 h after ICU admission occurred in 62.4% and AKI ≥ 2 within 12 h in 30.7%. All damage biomarkers predicted AKI ≥ 1 within 48 h after ICU admission, when corrected for urine dilution: CHI3L1 (AUC-ROC: 0.642 (95% CI, 0.535-0.741)), NGAL (0.765 (0.664-0.848)), TIMP-2 (0.778 (0.662-0.868)), IGFBP7 (0.796 (0.682-0.883)), NephroCheck® (0.734 (0.614-0.832)). Similarly, AKI ≥ 2 within 12 h was predicted by all damage biomarkers when corrected for urine dilution: uCHI3L1 (AUC-ROC: 0.686 (95% CI, 0.580-0.780)), NGAL (0.714 (0.609-0.804)), TIMP-2 (0.830 (0.722-0.909)), IGFBP7 (0.834 (0.725-0.912)), NephroCheck® (0.774 (0.658-0.865)). After pediatric cardiac surgery, the damage biomarkers urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® reliably predict AKI after correction for urine dilution.

Video-assisted thoracic surgery in critically ill COVID-19 patients on venovenous extracorporeal membrane oxygenation.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) leads to thoracic complications requiring surgery. This is challenging, particularly in patients supported with venovenous extracorporeal membrane oxygenation (VV-ECMO) due to the need for continuous therapeutic anticoagulation. We aim to share our experience regarding the safety and perioperative management of video-assisted thoracic surgery for this specific population. METHODS: Retrospective, single-center study between November 2020 and January 2022 at the ICU department of a 1.061-bed tertiary care and VV-ECMO referral center during the COVID-19 pandemic. RESULTS: 48 COVID-19 patients were supported with VV-ECMO. A total of 14 video-assisted thoracic surgery (VATS) procedures were performed in seven patients. Indications were mostly hemothorax (85.7%). In eight procedures heparin was stopped at least 1 h before incision. A total of 10 circuit changes due to clot formation or oxygen transfer failure were required in six patients (85.7%). One circuit replacement seemed related to the preceding VATS procedure, although polytransfusion might be a contributing factor. None of the mechanical complications was fatal. Four VATS-patients (57.1%) died, of which two (50%) immediately perioperatively due to uncontrollable bleeding. All three survivors were treated with additional transarterial embolization. CONCLUSION: (1) Thoracic complications in COVID-19 patients on VV-ECMO are common. (2) Indication for VATS is mostly hemothorax (3) Perioperative mortality is high, mostly due to uncontrollable bleeding. (4) Preoperative withdrawal of anticoagulation is not directly related to a higher rate of ECMO circuit-related complications, but a prolonged duration of VV-ECMO support and polytransfusion might be. (5) Additional transarterial embolization to control postoperative bleeding may further improve outcomes.

Impact of mean perfusion pressure and vasoactive drugs on occurrence and reversal of cardiac surgery-associate acute kidney injury: A cohort study.

PURPOSE: Low cardiac output and kidney congestion are associated with acute kidney injury after cardiac surgery (CSA-AKI). This study investigates hemodynamics on CSA-AKI development and reversal. MATERIALS AND METHODS: Adult patients undergoing cardiac surgery were retrospectively included. Hemodynamic support was quantified using a new time-weighted vaso-inotropic score (VISAUC), and hemodynamic variables expressed by mean perfusion pressure and its components. The primary outcome was AKI stage ≥2 (CSA-AKI ≥2) and secondary outcome full AKI reversal before ICU discharge. RESULTS: 3415 patients were included. CSA-AKI ≥2 occurred in 37.4%. Mean perfusion pressure (MPP) (OR 0.95,95%CI 0.94-0.96, p < 0.001); and central venous pressure (CVP) (OR 1.17, 95%CI 1.13-1.22, p < 0.001) are associated with CSA-AKI ≥2 development, while VISAUC/h was not (p = 0.104). Out of 1085 CSA-AKI ≥2 patients not requiring kidney replacement therapy, 76.3% fully recovered of AKI. Full CSA-AKI reversal was associated with MPP (OR 1.02 per mmHg (95%CI 1.01-1.03, p = 0.003), and MAP (OR = 1.01 per mmHg (95%CI 1.00-1.02), p = 0.047), but not with VISAUC/h (p = 0.461). CONCLUSION: Development and full recovery of CSA-AKI ≥2 are affected by mean perfusion pressure, independent of vaso-inotropic use. CVP had a significant effect on AKI development, while MAP on full AKI reversal.

Prediction of cardiac surgery associated - acute kidney injury (CSA-AKI) by healthcare professionals and urine cell cycle arrest AKI biomarkers [TIMP-2]*[IGFBP7]: A single center prospective study (the PREDICTAKI trial).

PURPOSE: Cardiac surgery associated acute kidney injury (CSA-AKI) is a contributor to adverse outcomes. Preventive measures reduce AKI incidence in high risk patients, identified by biomarkers [TIMP-2]*[IGFBP7] (Nephrocheck®). This study investigate clinical AKI risk assessment by healthcare professionals and the added value of the biomarker result. MATERIALS AND METHODS: Adult patients were prospectively included. Healthcare professionals predicted CSA-AKI, with and without biomarker result knowledge. Predicted outcomes were AKI based on creatinine, AKI stage 3 on urine output, anuria and use of kidney replacement therapy (KRT). RESULTS: One-hundred patients were included. Consultant and ICU residents were best in AKI prediction, respectively AUROC 0.769 (95% CI, 0.672-0.850) and 0.702 (95% CI, 0.599-0.791). AUROC of NephroCheck® was 0.541 (95% CI, 0.438-0.642). AKI 3 occurred in only 4 patients; there was no anuria or use of KRT. ICU nurses and ICU residents had an AUROC for prediction of AKI 3 of respectively 0.867 (95% CI, 0.780-0.929) and 0.809 (95% CI, 0.716-0.883); for NephroCheck® this was 0.838 (95% CI, 0.750-0.904). CONCLUSIONS: Healthcare professionals performed poor or fair in predicting CSA-AKI and knowledge of Nephrocheck® result did not improved prediction. No conclusions could be made for prediction of severe AKI, due to limited number of events.

Discharge from hospital with newly administered antipsychotics after intensive care unit delirium - Incidence and contributing factors.

PURPOSE: Delirium in the intensive care unit (ICU) is often treated with haloperidol or atypical antipsychotics. Antipsychotic treatment can lead to severe adverse effects and excess mortality. After initiation in the ICU, patients are at risk of having their antipsychotics continued unnecessarily at ICU and hospital discharge. This study aims to determine the incidence of, and risk factors for antipsychotic continuation at hospital discharge after ICU delirium. METHODS: This retrospective observational study was performed in a tertiary care center. Adult patients who received antipsychotics for ICU delirium during 2016 were included. Data was extracted from patient records. After univariate testing, a multivariate binary logistic regression model was used to identify independent risk factors for antipsychotic continuation. RESULTS: A total of 196 patients were included, of which 104 (53.1%) and 41 (20.9%) had their antipsychotics continued at ICU and hospital discharge respectively. Medical ICU admission (odds ratio [95% confidence interval] 2.97 [1.37-6.41]) and quetiapine treatment (5.81 [1.63-20.83]) were independently associated with antipsychotic continuation at hospital discharge. CONCLUSIONS: Approximately one in five patients were discharged from the hospital with continued antipsychotics. Hospital policies should implement strategies for systematic antipsychotic tapering and better follow-up of antipsychotics at transitions of care.

A recurrent and transesophageal echocardiography-associated outbreak of extended-spectrum ß-lactamase-producing Enterobacter cloacae complex in cardiac surgery patients.

Background: We report a recurrent outbreak of postoperative infections with extended-spectrum ß-lactamase (ESBL)-producing E. cloacae complex in cardiac surgery patients, describe the outbreak investigation and highlight the infection control measures. Methods: Cases were defined as cardiac surgery patients in Ghent University Hospital who were not known preoperatively to carry ESBL-producing E. cloacae complex and who postoperatively had a positive culture for this multiresistant organism between May 2017 and January 2018. An epidemiological investigation, including a case-control study, and environmental investigation were conducted to identify the source of the outbreak. Clonal relatedness of ESBL-producing E. cloacae complex isolates collected from case patients was assessed using whole-genome sequencing-based studies. Results: Three separate outbreak episodes occurred over the course of 9 months. A total of 8, 4 and 6 patients met the case definition, respectively. All but one patients developed a clinical infection with ESBL-producing E. cloacae complex, most typically postoperative pneumonia. Overall mortality was 22% (4/18). Environmental cultures were negative, but epidemiological investigation pointed to transesophageal echocardiography (TEE) as the outbreak source. Of note, four TEE probes showed a similar pattern of damage, which very likely impeded adequate disinfection. The first and second outbreak episode were caused by the same clone, whereas a different strain was responsible for the third episode. Conclusions: Health professionals caring for cardiac surgery patients and infection control specialists should be aware of TEE as possible infection source. Caution must be exercised to prevent and detect damage of TEE probes.

Augmented renal clearance: a common condition in critically ill children.

BACKGROUND: Augmented renal clearance (ARC), an increase in kidney function with enhanced elimination of circulating solute, has been increasingly recognized in critically ill adults. In a pediatric intensive care setting, data are scarce. The primary objective of this study was to investigate the prevalence of ARC in critically ill children. Secondary objectives included a risk factor analysis for the development of ARC and a comparison of two methods for assessment of renal function. METHODS: In 105 critically ill children between 1 month and 15 years of age, glomerular filtration rate (GFR) was measured by means of a daily 24-h creatinine clearance (24 h ClCr) and compared to an estimated GFR using the revised Schwartz formula. Logistic regression analysis was used to identify risk factors for ARC. RESULTS: Overall, 67% of patients expressed ARC and the proportion of ARC patients decreased during consecutive days. ARC patients had a median ClCr of 142.2 ml/min/1.73m2 (IQR 47.1). Male gender and antibiotic treatment were independently associated with the occurrence of ARC. The revised Schwartz formula seems less appropriate for ARC detection. CONCLUSIONS: A large proportion of critically ill children develop ARC during their stay at the intensive care unit. Clinicians should be cautious when using Schwartz formula to detect ARC. Our findings require confirmation from large study cohorts and investigation of the relationship with clinical outcome.

Low flow extracorporeal CO2 removal in ARDS patients: a prospective short-term crossover pilot study.

BACKGROUND: Lung protective mechanical ventilation (MV) is the corner stone of therapy for ARDS. However, its use may be limited by respiratory acidosis. This study explored feasibility of, effectiveness and safety of low flow extracorporeal CO2 removal (ECCO2R). METHODS: This was a prospective pilot study, using the Abylcap® (Bellco) ECCO2R, with crossover off-on-off design (2-h blocks) under stable MV settings, and follow up till end of ECCO2R. Primary endpoint for effectiveness was a 20% reduction of PaCO2 after the first 2-h. Adverse events (AE) were recorded prospectively. We included 10 ARDS patients on MV, with PaO2/FiO2 < 150 mmHg, tidal volume ≤ 8 mL/kg with positive end-expiratory pressure ≥ 5 cmH2O, FiO2 titrated to SaO2 88-95%, plateau pressure ≥ 28 cmH2O, and respiratory acidosis (pH <7.25). RESULTS: After 2-h of ECCO2R, 6 patients had a ≥ 20% decrease in PaCO2 (60%); PaCO2 decreased 28.4% (from 58.4 to 48.7 mmHg, p = 0.005), and pH increased (1.59%, p = 0.005). ECCO2R was hemodynamically well tolerated. During the whole period of ECCO2R, 6 patients had an AE (60%); bleeding occurred in 5 patients (50%) and circuit thrombosis in 3 patients (30%), these were judged not to be life threatening. CONCLUSIONS: In ARDS patients, low flow ECCO2R significantly reduced PaCO2 after 2 h, Follow up during the entire ECCO2R period revealed a high incidence of bleeding and circuit thrombosis. TRIAL REGISTRATION: https://clinicaltrials.gov identifier: NCT01911533 , registered 23 July 2013.

Acute Kidney Injury in Cardiorenal Syndrome Type 1 Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: We evaluated the epidemiology and outcome of acute kidney injury (AKI) in patients with cardiorenal syndrome type 1 (CRS-1) and its subgroups: acute heart failure (AHF), acute coronary syndrome (ACS) and after cardiac surgery (CS). SUMMARY: We performed a systematic review and meta-analysis. CRS-1 was defined by AKI (based on RIFLE, AKIN and KDIGO), worsening renal failure (WRF) and renal replacement therapy (RRT). We investigated the three most common clinical causes of CRS-1: AHF, ACS and CS. Out of 332 potential papers, 64 were eligible - with AKI used in 41 studies, WRF in 25 and RRT in 20. The occurrence rate of CRS-1, defined by AKI, WRF and RRT, was 25.4, 22.4 and 2.6%, respectively. AHF patients had a higher occurrence rate of CRS-1 compared to ACS and CS patients (AKI: 47.4 vs. 14.9 vs. 22.1%), but RRT was evenly distributed among the types of acute cardiac disease. AKI was associated with an increased mortality rate (risk ratio = 5.14, 95% CI 3.81-6.94; 24 studies and 35,227 patients), a longer length of stay in the intensive care unit [LOSICU] (median duration = 1.37 days, 95% CI 0.41-2.33; 9 studies and 10,758 patients) and a longer LOS in hospital [LOShosp] (median duration = 3.94 days, 95% CI 1.74-6.15; 8 studies and 35,227 patients). Increasing AKI severity was associated with worse outcomes. The impact of CRS-1 defined by AKI on mortality was greatest in CS patients. RRT had an even greater impact compared to AKI (mortality risk ratio = 9.2, median duration of LOSICU = 10.6 days and that of LOShosp = 20.2 days). KEY MESSAGES: Of all included patients, almost one quarter developed AKI and approximately 3% needed RRT. AHF patients experienced the highest occurrence rate of AKI, but the impact on mortality was greatest in CS patients.

A multiscale entropy-based tool for scoring severity of systemic inflammation.

OBJECTIVE: Early detection and start of appropriate treatment are highly correlated with survival of sepsis and septic shock, but the currently available predictive tools are not sensitive enough to identify patients at risk. DESIGN: Linear (time and frequency domain) and nonlinear (unifractal and multiscale complexity dynamics) measures of beat-to-beat interval variability were analyzed in two mouse models of inflammatory shock to determine if they are sensitive enough to predict outcome. SETTING: University research laboratory. SUBJECTS: Blood pressure transmitter-implanted female C57BL/6J mice. INTERVENTIONS: IV administration of tumor necrosis factor (n = 11) or lipopolysaccharide (n = 14). MEASUREMENTS AND MAIN RESULTS: Contrary to linear indices of variability, unifractal dynamics, and absolute heart rate or blood pressure, quantification of complex beat-to-beat dynamics using multiscale entropy was able to predict survival outcome starting as early as 40 minutes after induction of inflammatory shock. Based on these results, a new and clinically relevant index of multiscale entropy was developed that scores the key features of a multiscale entropy profile. Contrary to multiscale entropy, multiscale entropy scoring can be followed as a function of time to monitor disease progression with limited loss of information. CONCLUSIONS: Analysis of multiscale complexity of beat-to-beat dynamics at high temporal resolution has potential as a sensitive prognostic tool with translational power that can predict survival outcome in systemic inflammatory conditions such as sepsis and septic shock.

Implementation of a structured information transfer checklist improves postoperative data transfer after congenital cardiac surgery.

BACKGROUND: During one hospital stay, a patient can be cared for by five different units. With patient transfer from one unit to another, it is of prime importance to convey a complete picture of the patient's situation to minimise the risk of medical errors and to provide optimal patient care. OBJECTIVE(S): This study was designed to test the hypothesis that the implementation of a standardised checklist used during verbal patient handover could improve postoperative data transfer after congenital cardiac surgery. DESIGN: Prospective, pre/postinterventional clinical study. SETTING: Cardiac centre of a university hospital. PATIENTS: Forty-eight patients younger than 16 years undergoing heart surgery. INTERVENTIONS: A standardised checklist was developed containing all data that, according to the investigators, should be communicated during the handover of a paediatric cardiac surgery patient from the operating room to the ICU. MAIN OUTCOME MEASURES: Data transfer during the postoperative handover before and after implementation of the checklist was evaluated. Duration of handover, number of interruptions, number of irrelevant data and number of confusing pieces of information were noted. Assessment of the handover process by ICU medical and nursing staff was quantified. RESULTS: After implementation of the information transfer checklist, the overall data transfer increased from 48 to 73% (P < 0.001). The duration of data transfer decreased from a median (range) of 6 (2 to 16) to 4 min (2 to 19) (P = 0.04). The overall handover assessment by the intensive care nursing staff improved significantly after implementation of the checklist. CONCLUSION: Implementation of an information transfer checklist in postoperative paediatric cardiac surgery patients resulted in a more complete transfer of information, with a decrease in the handover duration.

Cold histidine-tryptophan-ketoglutarate solution and repeated oxygenated warm blood cardioplegia in neonates with arterial switch operation.

BACKGROUND: The present study aimed to compare myocardial protection, as assessed by cardiac troponin-I release, and short-term outcomes between two groups of neonates undergoing the arterial switch operation (ASO) with either Custodiol cardioplegia (Custodiol HTK, Köhler Chemie GmbH, Bensheim, Germany) or repeated oxygenated warm blood cardioplegia. METHODS: A total of 218 neonates were enrolled retrospectively from February 2007 through February 2011. All analyses were stratified on the type of procedure (ASO±ventricular septal defect closure ± aortic arch repair). Troponin concentrations within the first week of surgery were analyzed using mixed models for repeated measurements. To counteract the confounding effect of the coronary anatomy, a sensitivity analysis was conducted after 1:1 matching. RESULTS: Overall 30 patients had Custodiol cardioplegia, and 188 had warm blood cardioplegia. High-risk coronary anatomy (single right coronary artery giving rise to the left, intramural course) was associated with higher troponin concentrations and a higher 30-day mortality rate postoperatively, and was more prevalent in the Custodiol group when compared with the warm blood cardioplegia group. Postoperative troponin concentrations were higher in the Custodiol group both before (p<0.001) and after matching on the coronary anatomy (p=0.03). The 30-day mortality rate was higher in the Custodiol group, 10% versus 1.1% (p=0.009), but only a nonsignificant trend was noted after matching. CONCLUSIONS: The use of Custodiol cardioplegia in neonates undergoing ASO was associated with a larger troponin release when compared with warm blood cardioplegia, suggesting poor myocardial protection. The difference noted in 30-day mortality was not due to the use of Custodiol.

Early elevation of cardiac troponin I is predictive of short-term outcome in neonates and infants with coronary anomalies or reduced ventricular mass undergoing cardiac surgery.

OBJECTIVE: The present study aimed to assess the usefulness of routine monitoring of cardiac troponin I concentrations within 24 hours of surgery (cTn-I<24h) in neonates and infants undergoing cardiac surgery. METHODS: The added predictive ability of a high peak cTn-I<24h (within the upper quintile per procedure) for a composite outcome, including 30-day mortality and severe morbidity, was assessed retrospectively. The predicted risk for the composite outcome was estimated from a logistic regression model including preoperative and intraoperative variables. Adding a high peak cTn-I<24h to the risk model resulted in reclassification of the predicted risk. It also allowed quantification of the improvement in reclassification and discrimination by the difference between c-indexes, the Net Reclassification and the Integrated Discrimination Indexes (NRI and IDI). RESULTS: Overall, 1023 consecutive patients were included. Adding a high peak cTn-I<24h to the model resulted in no improvement in reclassification or discrimination in the overall population (difference between c-indexes: 0.011 [-0.004 to 0.029], NRI = 0.06, P = .22, IDI = 0.02, P = .06), except in a subgroup of patients undergoing the arterial switch operation with or without ventricular septal defect closure and/or aortic arc repair, anomalous origin of the left coronary artery from the pulmonary artery repair, truncus arteriosus repair, Norwood procedure, and Sano modification, in whom NRI = 0.23 (P = .005) and IDI = 0.05 (P < .001). CONCLUSIONS: Patients with coronary anomalies and patients with reduced ventricular mass should benefit from the routine monitoring of cTn-I concentrations after surgery for congenital cardiac disease.

High-dose aprotinin, blood product transfusions, and short-term outcome in neonates and infants: a pediatric cardiac surgery center experience.

BACKGROUND: The efficacy of aprotinin, the most popular antifibrinolytic agent in congenital cardiac surgery, was still uncertain in small infants when its prophylactic use was suspended for safety reasons. The aim of this study is to describe associations between the prophylactic use of high-dose aprotinin, the need for blood product transfusions, and short-term outcome in neonates and infants with cardiac surgery. METHODS/MATERIALS: This retrospective study included all patients younger than 1 year undergoing surgery with cardiopulmonary bypass through 42 months, before and after withdrawal of aprotinin. Each patient who received aprotinin was matched with a control with similar baseline and surgical characteristics, who have not received any antifibrinolytic agent. Associations between the use of aprotinin and the exposure to red blood cells, fresh frozen plasma, and platelet transfusions were estimated from a logistic regression model, and the exposure to additional transfusions from a polytomous regression model. RESULTS: Matching resulted in two groups of 283 patients each, well balanced except for the priming volume and the ultrafiltration rate, larger in the aprotinin group. After adjustment for the priming volume and ultrafiltration rate, there was no significant association between the use of aprotinin, the exposure to any blood product transfusion, or the exposure to additional transfusions, the rate of re-exploration for bleeding, and short-term outcome. Two patients in the control group required re-exploration for bleeding. CONCLUSIONS: No association was found between the prophylactic use of aprotinin, blood product transfusions, and short-term outcome in this population of neonates and infants.